Compositions in the form of a urea powder

Abstract

The disclosure relates to an improved composition of a mixture based on urea. The present disclosure can be broadly described as a more stable powder composition comprising an amount of urea effective for treatment of hyponatremia. The present disclosure is a urea formulation that is a sparkling Urea (may be referred to below as "UreaAide sparkling"). The usual starting dose of urea is 15 grams, twice a day. The UreaAide sparkling is a powder that can come in single use urea dose packet. In one embodiment, the UreaAide sparkling is a single use, 15 gram urea dose packet. The 15 gram urea dosage may vary. For example, the urea dosage may not be a 15 gram dose. The urea dose can be prescribed to be taken once per day or many times throughout the day.

Description

[0001] Utility Patent Application KNA-006 COMPOSITIONS IN THE FORM OF A UREA POWDER FIELD OF THE INVENTION The present disclosure relates to compositions for nutrient supplementation. The dietary supplements and pharmaceutical products, as well as the methods described, may be useful in the treatment of patients with varied etiologies and chronicity of Hyponatremia. BACKGROUND The kidneys carry out a multitude of excretory, metabolic, regulatory, and endocrine functions, including the maintenance of fluid and electrolyte homeostasis, the excretion of metabolic waste products, and the synthesis and degradation of various hormones. Additionally, the kidneys play a role in preserving the homeostatic composition of plasma. Hyponatremia, characterized by plasma sodium levels below 135 mEq / L, represents a common electrolyte imbalance associated with numerous adverse physiological signs and symptoms. These symptoms encompass headache, nausea, cognitive impairment, fatigue, and balance disturbances. The condition is correlated with an increased risk of falls, fractures, osteoporosis, seizures, and mortality. Although conventional treatments for hyponatremia such as fluid restriction and oral sodium chloride tablet administration are often employed, the empirical support for these approaches remains limited. Moreover, patient adherence to these treatments tends to be low. Sodium chloride may also elevate blood pressure, cause edema and frequently fails to adequately correct sodium levels. SUMMARY One aspect of the present disclosure pertains to a composition of a mixture incorporating urea. The disclosure addresses a stable powder composition comprising a certain amount of urea for the treatment of hyponatremia. Urea is a guideline-based therapy for hyponatremia. A known Utility Patent Application KNA-006 limitation of urea is its distaste and nausea caused by its salty / briny taste profile. This can lead to some patients discontinuing urea treatment. In one embodiment, a urea formulation is provided as a sparkling composition, referred to as “UreaAide sparkling.” The standard initial dosage of urea is 15 grams, administered twice a day. UreaAide sparkling is supplied as a powder in single-use urea dose packets. In one embodiment, UreaAide sparkling is provided as a single-use, 15-gram urea dose packet. The 15-gram dosage is variable; for instance, the prescribed urea dosage may differ from 15 grams. The urea dose can be prescribed for once-daily or multiple-times-daily administration. In one embodiment, UreaAide sparkling is formulated for the treatment of hyponatremia. The composition may be dispersed in water or another liquid prior to ingestion by the patient, or it may be incorporated into or mixes with food. UreaAide sparkling is provided as a powder in single-use 15-gram urea dose packets. The flavor profile of UreaAide sparkling aims to enhance taste and tolerability. In one embodiment, Agave powder is included in the formulation, which can impart a sweet flavor and has a low glycemic index. The Agave powder may also contain trace vitamins and minerals. Another embodiment includes lemon and orange flavoring to enhance taste and balance. The citrus flavor may combine with sodium bicarbonate, contributing a salty component and the sparkling attribute to improve flavor, texture, mouth-feel, and digestion. UreaAide sparkling is available in diverse flavors or flavor combinations, such as orange, mint, or blueberry-raspberry combinations. The UreaAide formulation may also include a bitter blocker. Additionally, the formulation can incorporate sucralose and stevia to enhance sweetness without adding calories. In one embodiment, the orange flavor of the UreaAide sparkling contains Silicon Dioxide and may or may not contain Calcium Silicate. In another embodiment, the mint flavor of the UreaAide sparkling contains Calcium Silicate and may or may not contain Silicon Dioxide. In another aspect, the disclosure relates to a powder formulation. The powder formulation includes an amount of sparkling urea effective for treatment of hyponatremia and calcium silicate. The calcium silicate has a particle size in the range of 3 to 8 microns, wherein less than Utility Patent Application KNA-006 one embodiment, the urea comprises 62.50% of the formulation weight, and the urea is a sparkling UreaAide formulation. The calcium silicate may have a particle size of 8 microns. In another aspect, the disclosure relates to a powder formulation. The powder formulation includes an amount of sparkling urea effective for treatment of hyponatremia and calcium silicate. The calcium silicate has a particle size of 8 microns. DETAILED DESCRIPTION The management of hyponatremia typically involves fluid restriction and the administration of oral sodium chloride tablets. Sodium chloride tablets may be prescribed alongside fluid restriction and / or loop diuretics to elevate plasma sodium levels. However, the concurrent need for fluid restriction and / or loop diuretics may affect long-term adherence to this therapy. The use of loop diuretics in conjunction with sodium chloride and / or fluid restriction has exhibited an increased incidence of hypokalemia and acute kidney injury events compared to fluid restriction alone, and has generally not been shown to be superior. In recent years, vasopressin receptor antagonists have been introduced as a therapeutic option for hyponatremia. However, notable safety concerns with these medications include an elevated risk of liver injury at high doses, drug interactions and the possibility of overly rapid correction of plasma sodium levels. Additionally, the high retail cost of vasopressin antagonists may limit their widespread utilization. Lastly, vasopressin receptor antagonist also have known adverse side effects that impact compliance including: excessive thirst, polyuria, nocturia and polydipsia. Various individuals with sodium imbalances use urea, which serves as a guideline-based medical food for managing hyponatremia. Urea is synthesized by the liver as a primary end product of nitrogen metabolism, then released into the blood and excreted by the kidneys. While urea presents a more cost-effective option compared to many other hyponatremia treatments, considerations regarding its application exist, such as availability and unfavorable taste, which may deter its use as a first-line therapy for hyponatremia. The present disclosure relates to an enhanced composition of a urea-based mixture. This disclosure can be characterized as a more stable powder composition containing an effective Utility Patent Application KNA-006 amount of urea for the treatment of hyponatremia. It may also pertain to treating individuals at risk of developing hyponatremia. The composition may be dispersed in water or another liquid before ingestion by the patient, or it may be incorporated into or mixed with food. Alternatively, the composition may be packaged with food until ready for use. The present disclosure describes a urea formulation referred to as "UreaAide sparkling." The starting dosage of urea is typically 15 grams, administered twice daily. UreaAide sparkling is a powder that can be provided in single-use urea dose packets. In one embodiment, UreaAide sparkling is a single-use, 15-gram urea dose packet. The 15-gram dose may vary. For example, the urea dosage may differ from the 15-gram dose. The urea dose can be prescribed to be taken once per day or multiple times throughout the day. Given that urea generally has an unfavorable taste, making it difficult for patients to tolerate, the UreaAide sparkling formulation includes a specific flavor profile to enhance taste and tolerability. In one embodiment, agave powder is included in the formulation. The agave powder, for example, may possess a sweet flavor and a low glycemic index. The agave powder may also contain trace vitamins and minerals. In one embodiment, the formulation incorporates lemon and orange flavorings to enhance taste and balance flavor. These may add a citrus sour note that, combined with sodium bicarbonate, contributes to a salty component and a sparkling element to enhance flavor, texture, mouth-feel, and digestion. UreaAide sparkling can be available in a variety of flavors or flavor combinations, such as orange, mint, or a blueberry- raspberry combination. Blocking bitter taste perception can occur throughout the taste signal cascade. A compound can act by directly antagonizing bitter taste receptors, preventing the activation of gustducin and inhibiting taste perception. The UreaAide formulation can include a bitter blocker. A bitter blocker is a substance that inhibits or masks the perception of bitterness in food and beverages. Common bitter blockers include quinine, denatonium, and gymnemic acid. In addition to the bitter blocker, the UreaAide formulation can also include sucralose and stevia to enhance sweetness without adding calories. Utility Patent Application KNA-006 UreaAide sparkling orange is a formulation low in sugar, sodium, and calories, making it suitable for individuals with diabetes and high blood pressure. In one embodiment, UreaAide sparkling orange contains only 30 calories, 3 grams of sugar, and 60 mg of sodium. It contains no fat and no cholesterol. In another embodiment, the ingredients of UreaAide sparkling orange can vary, resulting in differences in sugar, calories, fat, or other components. Although the formulation is named UreaAide sparkling orange, the flavor does not have to be orange. In one embodiment, the UreaAide sparkling formulation can be any flavor or a combination of flavors. Additionally, in one embodiment, the formulation does not have to be a sparkling formulation. UreaAide sparkling orange can utilize a specific 8-micron-sized calcium silicate powder to enhance flow through a sachet machine, reduce clumping, and ensure consistent fill of sachets. A sachet can be a small porous bag or packet. The particle size distribution of the calcium silicate is significant such that amounts of calcium silicate above the upper limit microns and below the lower limit are undesirable. For example, it is desirable that the particle size distribution of the calcium silicate should be adapted such that amounts below 3.0 microns and above 8.0 microns are avoided. It is preferred that the calcium silicate have a mean particle diameter within the range of 3.0 and 8.0 microns, with less than 10% of the particles by weight being below 3.0 microns or above 8.0 microns in diameter. In one embodiment, 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 are desirable, such as 8%, 6%, 4%, or even 1%. Table 1 is an embodiment of a specification sheet of the urea.

[0002] Utility Patent Application KNA-006 Table 1 Test Method Specification MIN MAX Description Visual White pearls Odor Olfactory Faint Ammonia Odor Assay, % USP 99.0 100.5 Identification USP To Meet Requirements Infrared Absorption <197K> Corresponds to Standard Retention Time of Major Peak <621> Corresponds to Standard Meeting Range, deg. C <741> 132 135 Residue on Ignition, % <281> 0.1 Alcohol-insoluble matter, % USP 0.04 Chloride, % <221> 0.007 Sulfate <221> 0.010 Heavy Metals, ppm <231> 20 Residual Solvents <467> To Meet Requirements Utility Patent Application KNA-006 As shown in Table 1, in one embodiment, the assay percentage is between 99% and 100.5%, the alcohol-insoluble matter is 0.04%, the chloride is .007%, the sulfate is 0.010%, and the heavy metals is 20 ppm or parts per million (the number of units of mass of a contaminant per million units of total mass). These are examples, the percentages and amounts may vary. Table 2 is an embodiment of a final formulation specification of UreaAide sparkling. Table 2 Product Name: UreaAide Orange flavor, 24 grams. Ingredient mg per serving Ingredient % Description Urea Pellets 15000 63.16% Sodium Dioxide 250 1.05% Agave Powder 4525 19.05% Lemon Juice Powder 800 3.37% Masking Flavor A19- 004379# 200 0.84% Masking Flavor A19- 005813** 500 2.11% Citric Acid 850 3.58% Baking Soda 300 1.26% Orange Flavor WONF SD A19-003935^^ 550 2.32% Orange Flavor PWD A19-003634"" 550 2.32% Stevia 95% Extract 100 0.42% Sucralose 125 0.53% 23750 100.00% Link to all the certifications and documents:Urea Aide Ingredient CofA's and Specs - Google Drive # Maltodextrin + Natural ** Potassium Bitartrate 80- Maltodextrin10-15% Natural Flavors <2% ^^ Maltodextrin, Natural Flavors, Gum Arabica "" Arabic Gun, Natural Flavors Utility Patent Application KNA-006 As shown in Table 2, the ingredient description and percentages are displayed. Urea, granule form, USP makes up 63.16% of the formulation, Prinova makes up 1.05% of the formulation, agave powder makes up 19.05% of the formulation, lemon powder makes up 3.37% of the formulation, Bitter Blocker makes up 2.95% of the formulation, citric acid makes up 3.58% of the formulation, baking soda makes up 1.26% of the formulation, orange flavor WONF (with other natural flavors) makes up 2.32% of the formulation, orange flavor PWD (powdered) makes up 2.32% of the formulation, stevia 95% extract makes up 0.42% of the formulation, and sucralose makes up 0.53% of the formulation. Table 3 is another embodiment of a final formulation specification of UreaAide sparkling. Table 3 Product Name: UreaAide Blueberry Raspberry flavor Ingredient Description Percentages Urea, USP 62.5% Agave powder 20.85% Lemon powder 4.17% Sour enhancing flavor a19-003783 0.42% Bitterblocker 655771 2.08% Citric acid 3.44% Baking soda 1.25% Blueberry flavor 2.08% Mixed berry 2.29% Utility Patent Application KNA-006 Stevia 95% Extract 0.42% Calcium Silicate 0.5% As shown in Table 3, the ingredient description and percentages in this embodiment are different than in Table 3. Agave powder makes up 20.85% of the formulation, lemon powder makes up 4.17% of the formulation, sour enhancing flavor makes up 0.42% of the formulation, Bitter Blocker makes up 2.08% of the formulation, citric acid makes up 3.44% of the formulation, baking soda makes up 1.25% of the formulation, blueberry flavor makes up 2.08% of the formulation, mixed berry makes up 2.29% of the formulation, stevia 95% extract makes up 0.42% of the formulation, and calcium silicate makes up 0.5% of the formulation. Table 4 is an embodiment of nutrition facts of UreaAide sparkling. Table 4 Product Name: UreaAide Orange flavor - Nutrition Facts Serving size (9 g) Amount per serving Calories 30 % daily value Total Fat 0 g 0% Saturated Fat 0 g 0% Utility Patent Application KNA-006 Trans Fat 0 g 0% Cholesterol 0 g 0% Sodium 60 mg 3% Total Carbohydrates 7 g 3% Dietary Fiber 0 g 0% Total Sugars 3 g 0% Includes 3 g Added Sugars 6% Protein 0 g Vitamin D 0 mcg 0% Calcium 4 mg 0% Iron 0 mg 0% Potassium 5 mg 0% The UreaAide sparkling orange has ingredients of agave powder, natural flavors, citric acid, lemon powder, sodium bicarbonate, sucralose, silicon dioxide and stevia extract. The UreaAide sparkling orange has 0 grams of fat, 0 mg. of cholesterol, 60 mg. of sodium, 7 grams of total carbohydrates, 0 grams of dietary fiber, 3 grams of total sugars, and 3 grams of added sugars. In one embodiment, the UreaAide sparkling orange has 0 mcg of vitamin D, 4 mg. of Calcium, 0 mg. of Iron, and 5 mg. of Potassium. In one embodiment, the UreaAide sparkling formulation has a net weight of 24 g and is 15g of Urea per packet. Utility Patent Application KNA-006 Table 5 is another embodiment of a UreaAide Sparkling Orange flavor composition: Formula: FV.001. Ingredient Description mg per serving Ingredient % Urea Pellets 15000 62.50% Silicon Dioxide 250 1.04% Agave Powder 4775 19.90% Lemon Juice Powder 800 3.33% Maltodextrin + Natural Flavors 200 0.83% Potassium Bitartrate (80-90%) + Maltodextrin (10-15%) + Natural Flavors <2% 500 2.08% Citric Acid 850 3.54% Baking Soda 300 1.25% Maltodextrin, Natural Flavors, Gum Arabica 550 2.29% Arabic Gum, Natural Flavors 550 2.29% Stevia 95% Extract 100 0.42% Sucralose 125 0.52% 24000 100.00% In one embodiment, the Urea granules are mill grinded to a powder.In one embodiment, immediately thereafter, the flavor ingredients are blended together with the ground Urea granules. Then, the 8-micron calcium silicate and / or Silicon Dioxide can be added to aid in flow through the sachet machine as well as aid in quality and consistency of the final product. The blend is then put through the sachet machine and filled to 24 grams of the homogenous blend. The blend is, for example, sealed one packet at a time. Table 6 is an embodiment of properties of the Sachet for Orange. Utility Patent Application KNA-006 Properties Results Value Thickness 5 mil Tensile Strength≧30N - ≧30N61N – 68NMD / TD Elongation MD / TD ≧50% - ≧15% Heat-sealing strength ≧12N / 15mm Peel strength ≧2.5N / 15mm Transmission / H2O ≦2.0g / m2·24hr (38°C,90%RH)Transmission / O2 (23°C,0%RH)≦10cm3 / m2·24h·0.1MPa0.38Width 660mm(±2mm) 660±0.5 Coefficient of Friction MD ≦0.4 0.335 Coefficient of Friction TD ≦0.4 0.295 Table 7 is an embodiment of the properties of the Sachet for Mint. Properties: Physical Property Typical Value Test Method Caliper 3.50 T411 Yield 6.88 msi / lb. ASTM D4321 Layer property Results Typical Value Test Method Exterior layer performance Properties Dimension Stability Excellent N / A N / A Flex Crack Resistance Good N / A N / A Ink Recommendation Film Inks N / A N / A Stiffness / Flexibilty Average N / A N / A Tear Propogation Not tested grams N / A Tear Resistance (grams- 57.0 / CD grams-force N / A force) MD 67.0 Barrier Layer Performance Properties Chemical Resistance Good N / A N / A Utility Patent Application KNA-006 Light Good N / A N / A Moisture Vapor Trans Rate 0.0004 Grams / 100 sq. in. / day N / A Odor Excellent N / A N / A Oxygen Trans Rate 0 cc / 100 sq. in. / day Sealant Layer Performance Properties Caulk and Flow Good N / A N / A Hot Tack Good N / A N / A Coefficient of friction 0.32 Kinetic (seal to seal) Puncture Resistance 14.2 Pounds of force Seal Initiation Temperature 260 F Seal Strength 7000 g / in. @ 350 F / 40 psi / 0.5 sec Seal through Contamination Good N / A N / A Burst Strength 58 psi N / A Table 8 is a graph of an embodiment of a heat seal curve of the sachet.

[0003] Utility Patent Application KNA-006 Table 9 is a certificate of analysis table of UreaAide Natural Sparkling Orange. Sample Name: UreaAide Natural Eurofins Sample: 14167968 Sparkling Orange Sample Pass / Fail PASS Base Date 04-Jun-2024 Project ID KIDNEYAIDE-20240483 Receipt Condition Ambient Temperature PO NumberNA Pull Date 04-Jun-2024Lot Number Date Started 04-Jun-2024 Sample Serving Size 24 g Sampled Sample results apply as received Description Version 2.0 CaliforniaNumber Composited 3Timepoint Initial Analysis Result Specifications Pass / Fail Package AppearanceCommercial foil pouchCharacteristic Odor Sweet and tart odor characteristic of citrus Caloric CalculationsCalories from Fat <1.00 Cal / 100g Calories from FatTotal Carbohydrate <0.02 g / Serving SizeNote Protein, Carbohydrate and Calories are normally calculated in foods following standard factors. Urea is nitrogen containing but is not a protein nor metabolized for any caloric content. Note The protein, carbohydrate and calories in this sample analysis excludes any contribution from the % measured as urea Fatty Acids Calculated as Triglycerides Utility Patent Application KNA-006 Saturated Fatty Acids (Acid<0.002 g / Serving SizeForm) Total Cis Unsaturated Fatty<0.002 g / Serving SizeAcids (Acid Form) Monounsaturated Fatty Acids<0.002 g / Serving Size(Acid Form) Polyunsaturated Fatty Acids<0.002 g / Serving Size(Acid Form) <0.002 g / Serving SizeTrans Fatty Acids (Acid Form) <0.002 g / Serving SizeOmega 3 Fatty Acids <0.007 %Fatty Acids Calculated as TriglyceridesOmega 6 Fatty Acids 0.007 %Omega 7 Fatty Acids <0.007 %Omega 9 Fatty Acids <0.007 %Total Fatty Acids 0.002 g / Serving Size4:0 Butyric <0.007 %6:0 Caproic <0.007 %8:0 Caprylic <0.007 %10:0 Capric <0.007 %12:0 Lauric <0.007 %14:0 Myristic <0.007 %14:1 Myristoleic <0.007 %15:0 Pentadecanoic <0.007 %15:1 Pentadecenoic <0.007 %16:0 Palmitic <0.007 %16:1 Palmitoleic <0.007 %17:0 Heptadecanoic <0.007 %17:1 Heptadecenoic <0.007 %18:0 Stearic <0.007 %9c 18:1 Oleic <0.007 %18:2 Linoleic 0.007 %18:3 Gamma Linolenic <0.007 %18:3 Alpha Linolenic <0.007 %18:4 Octadecatetraenoic <0.007 %20:0 Arachidic <0.007 %20:1 Eicosenoic <0.007 %20:2 Eicosadienoic <0.007 %Fatty Acids Calculated as Triglycerides20:3 Eicosatrienoic (n3) <0.007 %20:3 Homogamma Linolenic<0.007 %(n6)20:4 Arachidonic (n3) <0.007 %20:4 Arachidonic (n6) <0.007 %20:5 Eicosapentaenoic <0.007 %21:5 Heneicosapentaenoic <0.007 % Utility Patent Application KNA-00622:0 Behenic <0.007 %22:1 Erucic <0.007 %22:2 Docosadienoic <0.007 %22:3 Docosatrienoic <0.007 %22:4 Docosatetraenoic <0.007 %22:5 Docosapentaenoic (n3) <0.007 %22:5 Docosapentaenoic (n6) <0.007 %22:6 Docosahexaenoic <0.007 %24:0 Lignoceric <0.007 %24:1 Nervonic <0.007 %Total 18:1 trans <0.007 %Total 18:1 cis <0.007 %Total 18:2 trans <0.007 %Total 18:3 trans <0.007 %CholesterolCholesterol <0.010 mg / gTotal Dietary FiberTotal Dietary Fiber 0.508 g / Serving SizeSugar Profile By Ion ChromatographyFructose 4.36 g / Serving SizeSugar Profile By Ion Chromatography Galactose <0.02 g / Serving Size Galactose <0.02 Galactose <0.02 g / Serving Size g / Serving Size Glucose <0.02 g / Serving Size Glucose <0.02 Glucose <0.02 g / Serving g / Serving Size SizeSucrose <0.02 g / Serving Size Sucrose <0.02 Sucrose <0.02 g / Serving g / Serving Size SizeLactose <0.02 g / Serving Size Lactose <0.02 Lactose <0.02 g / Serving g / Serving Size Size Isomaltulose <0.02 g / Serving Size Isomaltulose Isomaltulose <0.02 <0.02 g / Serving g / Serving Size SizeMaltose 0.05 g / Serving Size Maltose 0.05 Maltose 0.05 g / Serving g / Serving Size SizeTotal Sugar 4.41 g / Serving Size Total Sugar 4.41 Total Sugar 4.41 g / Serving Size g / Serving Size Nitrogen, Dumas Method Nitrogen, DumasNitrogen, Dumas MethodMethod Nitrogen 29.8 % Nitrogen 29.8 % Nitrogen 29.8 % Elements by ICP Emission Elements by ICP Emission Elements by ICP Elements by ICP Spectrometry (ICP-OES) Spectrometry (ICP-OES) Emission Emission Spectrometry Spectrometry(ICP-OES)(ICP-OES)Calcium 228 ppm Calcium 228 ppm Calcium 228 ppmIron <2.50 ppm Iron <2.50 ppm Iron <2.50 ppmPotassium 4670 ppm Potassium 4670 Potassium 4670 ppm ppmSodium 3550 ppm Sodium 3550 ppm Sodium 3550 ppmAsh Ash Ash Ash 1.66 % Ash 1.66 % Ash 1.66 % Utility Patent Application KNA-006 Moisture by M100_T100 Moisture by Moisture by M100_T100 M100_T100 Moisture 16.5 % Moisture 16.5 % Moisture 16.5 % Water Activity Water Activity Water ActivityWater Activity 0.244 <= 0.6 Pass PassTemperature 25.0 °CCoagulase Positive Staph. * Coagulase Positive Staph. * Coagulase Coagulase Positive Positive Staph. * Staph. * Staphylococcus aureus <10 CFU / g <= 10 CFU / g Pass Salmonella (BAX) PCR Detection * Salmonella Negative / 25 gYeast and Mold Plate Count *Yeast Plate <10 CFU / g <= 200 CFU / g PassMold Plate Count <10 CFU / g <= 200 CFU / g PassAerobic Plate Count *Standard Plate Count 700 CFU / g <= 2000 CFU / g PassE.coli and Coliforms (Petrifilm) *Total coliforms <10 CFU / gEscherichia Coli <10 CFU / gUrea - DJUPN testing performed in E_DK_VITAM * Urea 15.6 g / Serving Size 13.5 - 16.5Passg / Serving SizeMethod References Testing LocationAerobic Plate Count (APC) EML New Berlin2345 S 170th St New Berlin, WI53151 USA FDA BAM Ch.3 FDA BAM Ch.3 FDA BAM Ch.3 FDA BAM Ch.3 AOAC 966.23 AOAC 966.23 AOAC 966.23 AOAC 966.23 CMMEF Ch.8 CMMEF Ch.8 CMMEF Ch.8 CMMEF Ch.8Ash (ASHM_S) Food IntegrityInnovation-Madison 6304 Ronald Reagan Ave Madison, WI 53704 USAOfficial Methods of Analysis of AOAC INTERNATIONAL, 18th Ed., Method 923.03, AOAC INTERNATIONAL, Gaithersburg, MD, USA, (2005). (Modified) Caloric Calculations (CALC_S)Food IntegrityInnovation-Madison 6304 Ronald Reagan Ave Madison, WI 53704 USAUnited States Department of Agriculture, “Energy Value of Foods,” Agriculture Handbook No.74, pp 2-11 (1973). Utility Patent Application KNA-006 Code of Federal Regulation, Title 21, Part 101.9, pp.24-25Method References Testing LocationCholesterol (CHOLSTRL_S) Food IntegrityInnovation-Madison 6304 Ronald Reagan Ave Madison, WI 53704 USAAOCS Official Method Ce 12-16, Sterols and Stanols in Foods and Dietary Supplements Containing Added Phytosterols (Modified). Coagulase Positive Staph. Bennett, R. W., and Lancette,EML New Ber(STAPHPC) G. A., “Chapter 12 - 2345 S 170th St NelwinBerlin, WI Staphylococcus aureus,” 53151 USA Bacteriological Analytical Manual, Eighth Ed., Revision A, U. S. Food and Drug Administration: Silver Spring, MD (1998), Revised Jan 2001. (Modified). E.coli and Coliforms (Petrifilm)AOAC 991.14 EML New Berlin(ECCOLIPET) 2345 S 170th St New Berlin, WI 53151 USA Elements by ICP Emission Official Methods of AnalysisFood IntegritySpectrometry (ICP-OES) of AOAC INTERNATIONAL, Innovation-Madison (ICP_S) Method 984.27, 985.01, and 2011.14, 6304 Ronald Reagan Ave Madison, WI 53704 USAAOAC INTERNATIONAL, Gaithersburg, MD, USA. (Modified)Fatty Acids Calculated as Official Method No.996.06, Official Methods Food Integrity Triglycerides (FALT_S) Official Methods of Analysis and Innovation-Madison of the AOAC Recommended INTERNATIONAL (modified), Practices of the 6304 Ronald Reagan Ave 19th Ed., AOAC AOCS, OfficialMadison, WI 53704 USAmethods Ce 2b-11 INTERNATIONAL: (2011), Ce 1h-05 Gaithersburg, Maryland (2009), Ce (2012). 1j-07 (2013), Ce 2-66 (2009),The American Oil Chemists' Society, Utility Patent Application KNA-006 Champaign, IL (modified). Moisture by M100_T100 Official Methods of AnalysisFood Integrity(M100T100_S) of AOAC INTERNATIONAL, Innovation-Madison 18th Ed., Methods 925.09 6304 Ronald Reagan Ave and 926.08, AOACMadison, WI 53704 USAINTERNATIONAL, Gaithersburg, MD, USA,(2005). (Modified). Nitrogen, Dumas Method Official Methods of AnalysisFood Integrity(DGEN_S) of AOAC INTERNATIONAL, Innovation-Madison 18th Ed., Methods 968.06 6304 Ronald Reagan Ave and 992.15, AOACMadison, WI 53704 USAINTERNATIONAL, Gaithersburg, MD, USA, (2005). (Modified) Organoleptic Evaluation INTERNAL SOP DESIGNEDFood Integrity(ORGE) TO SUPPLEMENT THE Innovation-Madison UNITED STATES PHARMACOPEIA, 6304 Ronald Reagan Ave 25TH EDITION, PAGE 2363,Madison, WI 53704 USAUSP CONVENTION, INC., ROCKVILLE, MD., 2002. Project Setup Fee (STABILITY) AOAC 2003.09; DuPontFood IntegrityQualicon BAX System User Innovation-Madison Guide, Part Number 2CQ-049. 13-0713-V3.3, 2005-2013. 6304 Ronald Reagan Ave Madison, WI 53704 USASalmonella (BAX) PCR AOAC 2003.09; DuPontEML New BerlinDetection (SALBAX) Qualicon BAX System User Guide, Part Number 2CQ-049. 2345 S 170th St New Berlin, WI 13-0713-V3.3, 2005-2013. 53151 USA Sugar Profile By Ion AOAC 2018.16 Sugar ProfileFood IntegrityChromatography (SGIC_2_S) in Food, Dietary Innovation-Madison Supplements, Pet Food and Animal Feeds (modified) 6304 Ronald Reagan Ave Madison, WI 53704 USATotal Dietary Fiber (TDFL_S) Official Methods of Analysis of AOAC INTERNATIONAL 18th Ed., Method 991.43, AOAC INTERNATIONAL, Gaithersburg, MD, USA, (2005). (Modified) Urea - DJUPN testing performed Test performed by a thirdExternalin E_DK_VITAM (MISC_SEND) party laboratory Water Activity (WACT_S) Official Methods of AnalysisFood Integrityof AOAC INTERNATIONAL, Innovation-Madison Method 978.18, AOAC INTERNATIONAL, 6304 Ronald Reagan Ave Gaithersburg, MD,Madison, WI 53704 USAUSA (Modified). Yeast and Mold Plate Count FDA BAM Chapter 18EML New Berlin(YM_SPRD) (modified) 2345 S 170th St New Berlin, WI 53151 USATesting Location(s) Released on Behalf of Eurofins by Utility Patent Application KNA-006 Edward Ladwig - President Eurofins Food Chemistry Testing Madison Food Integrity Innovation-Madison Eurofins Food Chemistry Testing Madison, Inc. 6304 Ronald Reagan Ave Madison WI 53704 800-675-8375 2918.01

Claims

Utility Patent Application KNA-006 What is claimed is:

1. A powder formulation comprising: (a) an amount of sparkling urea effective for treatment of hyponatremia; (b) calcium silicate, the calcium silicate having a particle size in the range of 3 to 8 microns, wherein less than 10% of the particles by weight have a diameter less than 3 microns or greater than 8 microns.

2. The composition of claim 1, wherein the urea comprises 63.16% of the formulation weight.

3. The composition of claim 1, wherein the urea is a sparkling UreaAide formulation.

4. The composition of claim 1, further comprising a flavoring agent.

5. The composition of claim 1, wherein the calcium silicate has a particle size of 8 microns.

6. The composition of claim 1, wherein the sparkling urea has a dose of 15 grams.

7. The composition of claim 1, wherein the sparkling urea is mixed with a liquid.

8. The composition of claim 1, wherein the sparkling urea is mixed with food.

9. A powder formulation comprising: (a) an amount of sparkling urea effective for treatment of hyponatremia; (b) calcium silicate, the calcium silicate having a particle size of 8 microns.

10. The powder formulation of claim 9, further comprising a flavoring agent.

11. The powder formulation of claim 9, wherein the urea comprises 63.16% of the formulation weight.

12. The powder formulation of claim 9, wherein the urea is a sparkling UreaAide formulation.

13. The powder formulation of claim 9, wherein the sparkling urea has a dose of 15 grams.

14. The powder formulation of claim 9, wherein the sparkling urea is mixed with a liquid.

15. The powder formulation of claim 9, wherein the sparkling urea is mixed with food.

16. A method of treating a subject with hyponatremia comprising: (a) administering sparkling urea effective for treatment of hyponatremia; (b) administering calcium silicate, the calcium silicate having a particle size in the range of 3 to 8 microns, wherein less than 10% of the particles by weight have a diameter less than 3 microns or greater than 8 microns, wherein the treatment is administered in single-use urea packet.Utility Patent Application KNA-006 17. The method of claim 16, wherein the sparkling urea has a dose of 15 grams.

18. The method of claim 1, wherein the sparkling urea formulation comprises a bitter blocker.

19. The method of claim 1, wherein the urea is a sparkling UreaAide formulation.

20. The composition of claim 16, further comprising a flavoring agent.