US 2014O161955A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0161955 A1 Wadhwa (43) Pub. Date: Jun. 12, 2014

(54) LIQUID DIETARY SUPPLEMENT (57) ABSTRACT FORMULATION COMPOSITIONS This invention relates to liquid dietary Supplement formula tion compositions that provide dietary minerals and addi (71) Applicant: Manpreet S. Wadhwa, Thousand Oaks, tional optional ingredients beneficial for health; methods of CA (US) design and manufacture of Such compositions; and methods to enable convenient oral ingestion of the formulation ingre (72) Inventor: Manpreet S. Wadhwa, Thousand Oaks, dients, by adding the formulations to drinking water, bever CA (US) ages, foods, or meals. The formulation compositions of this invention generally include water, water-soluble calcium (21) Appl. No.: 13/712,328 compound(s), water-soluble magnesium compound(s), and additional optional ingredients, wherein the Sum of the con centrations of the calcium and magnesium compounds is (22) Filed: Dec. 12, 2012 most preferably 2 molar or more, up . the point of No. The formulations of this invention possess inherent resistance Publication Classification to microbial growth. The formulations of this invention and variations thereof can be used as dietary Supplements to (51) Int. Cl. increase intake of beneficial minerals, to mineralize water, to A2.3L I/304 (2006.01) fortify foods or beverages, and can also be used to prepare a (52) U.S. Cl. variety of additional liquid formulations by varying the cal CPC ...... A2.3L I/304 (2013.01) cium and magnesium compounds, and/or by adding one or USPC ...... 426/590: 426/648 more compatible ingredient(s). US 2014/01 6 1955 A1 Jun. 12, 2014

LIQUID DIETARY SUPPLEMENT and antineoplastic medications may cause excessive loss of FORMULATION COMPOSITIONS magnesium. Diabetes may result in magnesium loss due to increased magnesium loss in urine due to hyperglycemia. CROSS REFERENCE TO RELATED Alcoholism is associated with low blood levels of magne APPLICATION sium, and individuals with chronic malabsorptive problems Such as those with Chrohn's disease, gluten sensitive enter 0001. This application claims the benefit of priority to opathy, regional enteritis, or intestinal Surgery are also at risk U.S. Provisional Application Ser. No. 61/569,790 filed on for magnesium deficiency. Dec. 13, 2011. 0006 Given the number of people at risk for calcium and magnesium deficiency, there is an ongoing need for effective FIELD OF THE INVENTION dietary Supplements that can provide or improve an intake of 0002 The present invention relates generally to dietary these minerals to help meet nutritional requirements while Supplements and more specifically it relates to liquid dietary being convenient and easy to use for the consumer. There are Supplement formulation compositions that generally include many dietary Supplements containing calcium and magne water-soluble dietary minerals and additional optional ingre sium compounds that are commercially available or dients that are beneficial for health; methods of designing and described in prior literature. The vast majority of these are producing Such formulation compositions, and methods to Solid dosage forms, such as tablets, capsules, or powders. enable convenient oral ingestion of the formulation ingredi Although these Supplements are relatively inexpensive, they ents, by adding the formulations to drinking water, beverages, have some disadvantages. Absorption of the nutrients from or meals. these Supplements tends to be quite variable, and large tablets or capsules are frequently not suitable for pediatric, geriatric BACKGROUND OF THE INVENTION and some patient populations. Liquid dosage forms of cal 0003 Calcium is the most abundant mineral in the body cium and magnesium possess Some advantages over the Solid and plays both a structural and functional role in maintaining dosage forms in terms of better absorption, convenience of human health. While most of the body's calcium is stored in use and dosing flexibility, but are less commonly available. the bones and teeth, calcium also serves a critical role in The liquid formulations tend to have stability limitations and processes such as vascular contraction and vasodilation, are vulnerable to microbial growth in the absence of addi muscle function, nerve transmission, and hormonal Secretion. tional preservatives. Almost all marketed liquid formulations The calcium ion is also a ubiquitous cellular messenger, and of calcium and magnesium are particulate suspensions that stimulates a variety of enzymes and other target proteins. tend to settle, and carry a requirement to “shake well before 0004. There are a number of factors that put people at risk use’. These products can have variable absorption, depending for diseases associated with inadequate calcium intake. Cal upon the Suspension characteristics, and can lead to incorrect cium absorption decreases in adulthood and continues to dosing if not shaken well prior to use. There are few liquid decrease as people age. In aging adults, bone breakdown products where the calcium and magnesium are completely exceeds formation, resulting in bone loss. In women, meno dissolved in water and present in an ionic state to provide pause leads to bone loss because decreases in estrogen pro optimal absorption upon ingestion. However, the calcium and duction both increase bone resorption and decrease calcium magnesium mineral concentrations of Such formulations are absorption. Negative effects on calcium balance have also relatively low compared to those of the Suspension liquid been observed in amenorrhic women of childbearing age. products, and thus require relatively large Volume dosages to Further, a number of people who avoid dairy products due to meet the recommended daily allowances. Thus, there is a lactose intolerance or veganism are also at risk for calcium need for improved liquid dietary Supplement formulations inadequacy. Bone health measures serve as a basis for deriv where calcium and magnesium are present in relatively high ing measures Such as Recommended Dietary Allowances for concentrations, are completely dissolved, and are inherently calcium, and inadequate calcium intake increases the risk for stable and resistant to microbial growth. osteoporosis, a disorder characterized by porous and fragile BRIEF SUMMARY OF THE INVENTION bones which affects more than 10 million U.S. adults. In addition to its effects on bone health, calcium intake has been 0007. The invention generally relates to liquid dietary proposed to have beneficial effects on reducing cardiovascu Supplement compositions which include water, water-soluble lar disease risk, lowering blood pressure, and prevention of calcium compound(s), water-soluble magnesium compound colorectal cancer and prostate cancer. (S), and optional ingredients. The total sum of concentrations 0005 Magnesium is another essential mineral in the body. of the dissolved calcium and magnesium compounds is About half of total body magnesium is found in bone, while higher than the dissolved concentrations found in currently the other half is found within body tissues. Magnesium is available liquid supplements, and is at least 1 Molar. These required for more than 300 biochemical reactions in the body, compositions possess resistance to microbial growth which and is important for maintaining the function of muscles and allows reduction or elimination of additional preservatives in nerves, Supporting the immune system, maintaining bone the compositions. Thus the compositions possess Some useful health, regulating blood Sugar levels, maintaining normal features that are not found in the existing soluble liquid com blood pressure, and playing a role in energy metabolism and positions of calcium and magnesium. protein synthesis. Dietary studies suggest that many Ameri 0008. There have thus been outlined, rather broadly, some cans do not get adequate amounts of magnesium. As magne of the features of the invention in order that the detailed sium absorption is regulated by the intestines and excretion is description thereof may be better understood, and in order regulated by the kidneys, conditions affecting these organs that the present contribution to the art may be better appreci may result in magnesium deficiency. For example, medicines ated. There are additional features of the invention that will be that affect the kidneys such as diuretics and some antibiotics described hereinafter. In this respect, it is to be understood US 2014/01 6 1955 A1 Jun. 12, 2014

that the invention is not limited in its application to the details 0020 “Water solubility” as used herein means the maxi of construction or to the arrangements of the components set mum amount of a compound or ingredient that will dissolve forth in the following description. The invention is capable of in pure water at a given temperature. other embodiments and of being practiced and carried out in (0021 “Water soluble” (or “water-soluble') as used herein various ways. Also, it is to be understood that the phraseology means an ingredient, element or material capable of dissolv and terminology employed herein are for the purpose of the ing in water, by going into a liquid aqueous state, either description and should not be regarded as limiting. spontaneously or by employing commonly used methods to 0009. An object of the invention is to provide liquid aid dissolution Such as shaking, mixing, heating, cooling, and dietary Supplement formulation compositions that are benefi adjusting water pH with an acid or base to make the water cial for health, and a convenient method of orally ingesting acidic or alkaline. these Supplements by adding to drinking water or other Suit 0022. The term “stable' as used herein means formula able beverages. tions capable of maintaining their dissolved ingredients in 0010. Another object is to provide formulation composi Solution without precipitating those ingredients out for a tions that are useful for adding beneficial minerals to distilled, minimum of 3 months, more preferably at least 6 months, reverse-osmosis filtered or otherwise deionized waters, in even more preferably 9 months and most preferably 12 order to make these waters more beneficial for health. months or more. 0011. Another object is to provide formulation composi 0023 The term “room temperature' as used herein is the tions that can be used as liquid dietary Supplements to commonly accepted range from 59° to 77° F (15° to 25°C.) increase intake of minerals that are beneficial for human which is Suitable for human occupancy and at which labora health. tory experiments are usually performed. 0012 Another object is to provide liquid formulation 0024. The term “beverage' as used herein means water or compositions that inhibit or prevent microbial growth, and any other potable liquid Suitable for human or animal con into which additional compatible minerals, vitamins, and/or Sumption in a ready-to-serve, drinkable form. other useful ingredients can be added to enable a variety of 0025. The term “clear as used herein means transparent, liquid dietary Supplements. with few or no visible particulates present, and indicative of formulations with fully dissolved ingredients. 0013 Another object is to provide a method of designing 0026 “Saturation” or “point of saturation' as used herein a variety of additional formulation compositions by building means the point at which water will not dissolve any more of upon the basic calcium and magnesium formulation compo a chemical in Solution. sitions disclosed in this invention, and variations thereof. 0027. As used herein, an ingredient of a formulation com 0014) Another object is to provide methods of preparing or position of the invention is “compatible' with the composi manufacturing the above-mentioned formulations. tion when it can be incorporated into the composition without 0015. Another object is to provide formulation composi making the resulting composition unsuitable for its intended tions that allow convenient methods of oral consumption of SC. the formulation ingredients by diluting or mixing relatively 0028 “Compound as used herein refers to a material, Small quantities of the formulation compositions into drink element or ingredient. For example, a calcium compound ing water, juices, other beverages, or foods. refers to a calcium containing material that is either naturally 0016. Another object is to provide methods of fortifying a occurring or chemically synthesized, either organic or inor beverage or food by adding relatively small quantities of the ganic in nature, and includes materials or ingredients referred formulation compositions into drinking water, juices, other to by specialized terms such as chemicals, salts, complexes, beverages, foods or meals. chelates, isomers, acids, bases etc. 0017. Another object is to provide kits as a convenient (0029 “Molar” or “Molarity” as used herein is a unit of means for fortifying a beverage or food at point of consump concentration, and refers to the number of moles of solute tion, or for fortifying a beverage or food at point manufacture divided by the number of liters of solution. for subsequent distribution. 0030 "Cup' as used herein means a volume of 8 fluid 0018. Other objects, advantages and variations of the ounces or about 240 milliliters. “Cup' may also refer to a present invention will become obvious to those familiar with drinking vessel that holds the same Volume. the art, and it is intended that these objects, advantages and 0031) “Serving of food as used herein refers to the por variations are within the scope of the present invention. To the tion of food used as a reference on its nutrition label, or is the accomplishment of the above and related objects, this inven typical recommended portion of that food to be eaten. tion may be embodied in the form described in the accompa 0032 “RDA' as used herein refers to recommended nying embodiments and examples, attention being called to dietary (or daily) allowance, the amount of nutrient intake per the fact however, that these are illustrative only and non day considered necessary for maintenance of good health as limiting. set forth in the Recommended Dietary Daily Allowance— Food and Nutrition Board, National Academy of Sciences— DETAILED DESCRIPTION OF THE INVENTION National Research Council. 0033 "Juice' as used herein has a meaning ascribed to it A. Definitions by a person of ordinary skill in the art and includes a full strength juice, a juice drink containing less than 100% juice, 0019 “Water” as used herein refers to purified water a concentrate of juice, or a diluted juice from fruits, Veg which is suitable for drinking and is reasonably free of con etables or other produce, which can be squeezed and/or tamination from extraneous matter or dissolved substances crushed to produce a juice. that could react unfavorably with the other ingredients of the 0034 “Fruit flavor as used herein refers to those flavors formulations described. derived from the edible reproductive part of a seed plant, US 2014/01 6 1955 A1 Jun. 12, 2014

especially one having a Sweet pulp associated with the seed. Purified water may also be obtained from a natural, reason Also included within the term “fruit flavor are synthetically ably pure source Such as from rain or Snow. prepared flavors made to simulate fruit flavors derived from 0046 2. Water-Soluble Calcium Compound(s) natural sources. 0047 Water-soluble calcium compound(s) such as cal 0035 “Botanical flavor as used herein refers to flavors cium chloride comprises the second main element. The sec derived from parts of a plant other than the fruit. As such, ond main element provides calcium which is an essential botanical flavors can include those flavors derived from mineral for human and animal health. There are many water essential oils and extracts of nuts, bark, roots and leaves. Also soluble calcium compounds Suitable for oral ingestion within included within the term “botanical flavor are synthetically a dietary Supplement. The water-soluble compounds may be prepared flavors made to simulate botanical flavors derived inorganic or organic, and may exist as anhydrous or hydrated from natural sources. forms, or as D or L isomers. These may all be used in the 0036 “Flavonoid as used herein refers to a group of phe formulation compositions of the invention, either as a single nol-containing compounds found in plants that may be ben calcium compound, or as a combination of calcium com eficial for health, and are also sometimes referred to as biofla pounds, provided that the selected ingredients are water vonoids, flavanols, flavonols, flavones, isoflavonoids, soluble to some extent and are compatible with the other neoflavonoids, and polyphenols. dissolved ingredients in the formulation. Various examples of 0037 “Emulsion” as used herein refers to a dispersion of calcium compounds are provided later in this application. minute droplets of one liquid in another liquid, the two liquids 0048. 3. Water-Soluble Magnesium Compound(s) being poorly miscible or immiscible with each other, and 0049. Water-soluble magnesium compound(s) such as "emulsification” refers to any process of producing an emul magnesium chloride comprises the third main element. The S1O. third main element provides magnesium which is an essential 0038 'Suspension” as used herein refers to a dispersion of mineral for human and animal health. There are many water Small particles of a solid in a liquid, the solid being poorly soluble magnesium compounds Suitable for oral ingestion soluble or insoluble in the liquid. “Suspension' may also refer within a dietary Supplement. The water-soluble compounds to any process of producing a Suspension. may be inorganic or organic, and may exist as anhydrous or 0039. “Solubilization' or “Solubilize' as used herein hydrated forms, or as D or L isomers. These may all be refers to making insoluble or poorly soluble Substance more included in the formulation compositions of the invention, soluble, by the addition of solubilizing agent(s) such as deter either as a single magnesium compound, or as a combination gents or co-solvents. of magnesium compounds, provided that the selected ingre 0040 “Fortify” as used herein refers to increasing, dients are water soluble to some extent, and are compatible improving or Supplementing the nutritious value of a food or with the other dissolved ingredients in the formulation. Vari beverage by adding minerals, vitamins etc. ous examples of magnesium compounds are provided later in 0041. In certain jurisdictions, there may not be any gener this application. ally accepted definition of the term “comprising.” As used 0050. 4. Optional Ingredients herein, the term “comprising is intended to represent “open’ 0051. The formulation compositions of this invention may language which permits the inclusion of any additional ele have additional optional ingredients or compounds compat mentS. ible with the above-mentioned main elements (i.e. water, 0042 Additional self-explanatory terms, and terms com water-soluble calcium compound(s) and water-soluble mag monly used in the art are utilized at various places in the nesium compound(s)). The optional ingredients may be application. added, for example, to enhance the nutritional profile of the composition or improve its organoleptic or physicochemical B. Main Elements of the Formulation Compositions properties. These optional ingredients may include one or 0043. The formulation compositions of this invention more additional compatible mineral(s), vitamin(s), antioxi have four major categories of ingredients that are described in dant(s), herbal extract(s), flavonoid(s), flavoring agent(s), more detail below. These comprise water, water-soluble cal Sweetener(s), bracer(s), buffering agent(s), coloring agent(s), cium compound(s), water-soluble magnesium compound(s), pH modifier(s), preservative(s), and the like. There is no limit and optional compounds or ingredients that will be described to the type or number of optional ingredients which may be further. The calcium and magnesium compounds are dis included, provided that they are suitable for use within a solved within water so that the sum of their concentrations is dietary Supplement, and are compatible with the other dis at least 1 Molar or more; and additional compounds may also solved ingredients in the formulation. Although it is prefer be present. All of the compounds or ingredients are preferably able that the optional ingredients are water soluble, even obtained from food grade or higher quality sources. Alterna poorly soluble or water-insoluble ingredients may be added, tively, the compounds are from lower quality sources, but by utilizing co-solvents or Solubilizing agents, or by prepar amenable to purification to make them suitable for human or ing Suspensions or emulsions. Various examples of optional animal use. The compounds may be inorganic or organic, may compounds are provided later in this application. exist as anhydrous or hydrated forms, as D or L isomers, as C. Some Examples of Calcium-, Magnesium-, and mixtures, and in liquid, Solid or gas states. Optional Compounds 0044) 1. Water 0045 Water (of suitable purity) is chemically denoted as 0052 Some examples of calcium compounds, magnesium HO and comprises the first main element. Water is required compounds, and optional compounds (including compatible as a solvent vehicle for the various formulation compositions mineral(s), vitamin(s), antioxidant(s), herbal extract(s), fla described in this invention. Various methods of producing vonoid(s), flavoring agent(s), Sweetener(s), bracer(s), buffer purified water are known in the art and include filtration, ing agent(s), coloring agent(s), pH modifier(s), preservative deionization, reverse-osmosis, distillation, among others. (S), and the like) that may be included in the compositions of US 2014/01 6 1955 A1 Jun. 12, 2014

the invention are listed below. It is to be understood that the sium hydroxide, magnesium hypophosphite, magnesium listing of compounds is not comprehensive, and represents iodate, magnesium iodide, magnesium lactate, magnesium commonly used compounds of varying water solubility that lactate gluconate, magnesium ketoglutarate, magnesium lysi may be suitable for human or animal use. When present, the nate, magnesium malate, magnesium nitrate, magnesium optional mineral(s), vitamin(s) etc. are typically present in nitrite, magnesium orotate, magnesium oxide, magnesium amounts sufficient to provide at least about 1%, more prefer perchlorate, magnesium permanganate, magnesium perOX ably at least about 5%, still more preferably at least about ide, magnesium picolinate, magnesium pidolate, mono-, di 10%, even more preferably at least about 20%, and most and tri-magnesium phosphate, magnesium propionate, mag preferably at least about 30% of the RDA in a convenient nesium pyruvate, magnesium saccharin, magnesium salicy ingestable Volume (e.g. about 1 teaspoon to 2 tablespoons, or late, magnesium selenate, magnesium potassium selenate, about 5 to 30 ml) of the formulation composition, where such magneisum silicate, magnesium Succinate, magnesium Sul RDAs are established. In cases where no RDAs are estab fate, magnesium tartrate, magnesium taurate. lished, such as in the case of many types of optional com 0057 3A. Other Mineral Compounds pound(s) such as antioxidants, herbal extracts, flavonoids, 0.058 Minerals other than calcium and magnesium are flavoring agents, Sweeteners, bracers, buffering agents, col well-known in the art. Examples of additional optional min oring agents, pH modifiers and preservatives, those skilled in eral(s) that may be included include, but are not limited to, the art will understand and utilize amounts that are generally compounds of boron, cobalt, copper, chromium, fluorine, safe and effective in providing the desired results. Much iodine, iron, manganese, molybdenum, nickel, phosphorus, information is available in the art that allows selection of such potassium, Selenium, silicon, silver, sodium, strontium, Sul amounts, and further, Such amounts can also be selected or phur, Vanadium, Zinc and other trace minerals. These may all varied by means of systematic experimentation. be used in the formulation compositions of the invention, 0053 1. Calcium Compounds either as a single compound, or as a combination of com 0054 Non-limiting example of calcium compounds that pounds, or by in-situ formation Such as by a reaction between may be included include calcium acetate, calcium acetylsali acid and base, provided that the selected ingredients are com cylate, calcium amino acid complexes, calcium ascorbate, patible with the other dissolved ingredients in the formula calcium aspartate, calcium asparginate, calcium benzoate, tion. calcium bicarbonate, calcium bisglycinate, calcium bisulfite, 0059 Non-limiting example of forms of boron that may be calcium borogluconate, calcium bromate, calcium bromide, optionally included include boric acid, boric anhydride, calcium bromolactobionate, calcium carbonate, calcium boron ascorbate, boron gluconate, boric tartrate, sodium caseinate, calcium chlorate, calcium chloride, calcium cit borate, sodium tetrahydroborate, boron citrate, boron glyci rate, calcium citrate malate, calcium hydroxycitrate, calcium nate, boron aspartate and boron amino acid complexes. potassium citrate, calcium cyclamate, calcium diethylacetate, 0060. Non-limiting example of forms of cobalt that may calcium ferrous citrate, calcium formate, calcium fumarate, be optionally included include cobalt acetate, cobalt carbon calcium glubionate, calcium glucarate, calcium gluceptate, ate, cobalt chloride, cobalt glucoheptonate, cobalt gluconate, calcium gluconate, calcium glutamate, calcium glycerophos cobalt Sulfate, cobalt amino acid complexes, cobalamin, phate, calcium glycinate, calcium hexametaphosphate, cal cyanocobalamin, hydroxycobalamin and methylcobalamin. cium histidinate, calcium hydroxyapatite, calcium hydrox 0061 Non-limiting forms of copper that may be option ide, calcium hypophosphite, calcium iodate, calcium iodide, ally included include, copper bisglycinate, copper citrate, calcium ketoglutarate, calcium lactate, calcium lactate glu copper hydroxide carbonate, copper sebacate, copper lysi conate, calcium lactate gluconate citrate, calcium lactobion nate, copper gluconate, copper Sulfate, copper oxide and cop ate, calcium laevulinate, calcium lysinate, calcium magne per amino acid complexes. sium acetate, calcium methionate, calcium malate, calcium 0062. Non-limiting examples of forms of chromium that methylfolate, calcium nitrate, calcium nitrite, calcium oro may be optionally included include chromic acetate, chromic tate, calcium oxide, calcium pantothenate, calcium perchlo chloride, chromic lactate hydroxide, chromium nicotinate, rate, calcium permanganate, calcium picolinate, calcium chromic nitrate, chromium picolinate, chromic sulfate, and pidolate, mono-, di- and tri-calcium phosphate, calcium pro chromium amino acid complexes. pionate, calcium pyruvate, calcium saccharin, calcium sili 0063) Non-limiting examples of forms of fluorine that cate, calcium sodium lactate, calcium Sorbate, calcium spir may be optionally included include calcium fluoride, potas ulina chelate, calcium Stearate, calcium Stelate, calcium sium fluoride, Sodium fluoride, and sodium monofluorophos Succinate, calcium Sulphate, calcium sulfite, calcium tartrate, phate. calcium threonate, and calcium ureidosuccinate. 0064. Non-limiting examples of forms of iodine that may 0055 2. Magnesium Compounds be optionally included include potassium iodide, Sodium 0056. Non-limiting example of magnesium compounds iodide, potassium iodate, sodium iodate, and iodine casein. that may be included include magnesium acetate, magnesium 0065. Non-limiting examples of forms of iron (ferrous acetylsalicylate, magnisium amino acid complexes, magne and/or ferric) that may be optionally included include iron sium ascorbate, magnesium asparaginate, magnesium aspar bisglycinate, iron carbonate, iron gluconate, iron Sulfate, iron tate, magnesium benzoate, magnesium bicarbonate, magne fumarate, iron Succinate, iron gluconate, iron lactate, iron sium bisglycinate, magnesium bromate, magnesium tartrate, irontaurate, iron ammonium citrate, iron citrate, iron bromide, magnesium carbonate, magnesium chlorate, mag pidolate, iron picolinate, iron pyrophosphate, iron saccharate, nesium chloride, magnesium citrate, magnesium citrate and iron amino acid complexes. malate, magnesium potassium citrate, magnesium formate, 0.066 Non-limiting examples of forms of manganese that magnesium fumarate, magnesium gluceptate, magnesium may be optionally included include manganese aminoate, gluconate, magnesium glutamate, magnesium glycerophos manganese ascorbate, manganese bisglycinate, manganese phate, magnesium glycinate, magnesium histidinate, magne aspartate, manganese arginate, manganese picolinate, man US 2014/01 6 1955 A1 Jun. 12, 2014

ganese carbonate, manganese chloride, manganese citrate, Vitamin B (thiamine), Vitamin B (cobalamin, cyanocobal manganese dioxide, manganese gluconate, manganese glyci amin, dibencozide, hydroxocobalamin, methylcobalamin), nate, manganese glycerophosphate, manganese pidolate, Vitamin B (riboflavin), vitamin B (niacin, niacinamide), manganese Sulfate and manganese amino acid complexes. vitamin B (pantothenic acid, sodium pantothenate, calcium 0067. Non-limiting examples of forms of molybdenum pantothenate, pantethine), Vitamin B (pyridoxine, pyridoxal, that may be optionally included include ammonium molyb pyridoxal-5-phosphate, pyridoxamine), Vitamin C (ascorbic date, molybdenum citrate, molybdenum picolinate, potas acid, ascorbate salts), Vitamin D (cholecalciferol, ergocalcif sium molybdate and Sodium molybdate. erol), Vitamin E (tocopherols, tocotrienols), and vitamin K 0068. Non-limiting examples of nickel compounds that (phylloquinone, phtyomenadione, menaquinone). may be optionally included include nickel chloride and nickel 0081 3C. Herbal Extracts and Flavonoids sulfate. 0082 Herbal extracts are well known in the art and are also 0069. Non-limiting examples of forms of phosphorus that referred to as botanical extracts. Flavonoids are natural Sub may be optionally included include Sodium, potassium, cal stances present in a variety of plant sources (e.g., fruits, cium and magnesium salts of phosphoric acids and hydroxy Vegetables, and flowers), and are suggested to be beneficial lapatite. for health. They may also have antioxidant activity. Herbal 0070. Non-limiting examples of forms of potassium that extracts and flavonoid(s) which may be optionally included in may be optionally included include potassium bicarbonate, the present invention can be extracted from, for example, potassium carbonate, potassium chloride, potassium glucon fruit, vegetables, green tea, plant parts or mixtures thereof, by ate, potassium glycerophosphate, potassium hydroxide, any suitable method well known to those skilled in the art. potassium phosphate, potassium citrate, potassium lactate, Alternatively, specific herbal compound(s) or flavonoid(s) potassium malate, potassium pyruvate, and potassium amino may be prepared by synthetic or other appropriate biochemi acid complexes. cal methods and incorporated into the present compositions. 0071 Non-limiting examples of forms of selenium that Non-limiting examples of the most common flavonoids may be optionally included include selenium oxide, sodium which are extracted from tea plants and other plants include, Selenite, sodium selenate, potassium selenide, and organic for example, apigenin, catechins, epicatechin, gallocatechin, forms such as selenomethonine and selenocysteine. epigallocatechin, epicatechin gallate, epigallocatechin gal 0072. Non-limiting examples of forms of silicon that may late, kaempferol, luteolin, myricetin, quercetin, rutin, tan be optionally included include orthosilicic acid, silica nins, theaflavins. hydride, silicon dioxide, potassium silicate and sodium sili I0083 3D. Flavoring Agents Cate. I0084. Non-limiting examples of flavoring agents that may 0073. Non-limiting examples of forms of silver that may be included include fruit flavors, botanical flavors, and the be optionally included include colloidal silver and silver che like. Non-limiting examples of fruit flavors include orange, late complexes. lemon, lime, grapefruit, apple, grape, cherry, pineapple, fruit 0074 Non-limiting examples of forms of sodium that may punch, Strawberry, kiwi, tangerine, raspberry, mango, cocoa, be optionally included include sodium bicarbonate, sodium papaya, apricot, passion fruit, and cupuacu. Non-limiting carbonate, Sodium citrate, Sodium chloride, Sodium glucon examples of botanical flavors include kola, tea, aloe Vera, ate, Sodium lactate, Sodium hydroxide, Sodium phosphate and guarana, ginseng, ginkgo, hawthorn, hibiscus, rose hips, cha Sodium amino acid complexes. momile, peppermint, fennel, ginger, licorice, lotus, Schizan 0075 Non-limiting examples of strontium that may be dra, saw palmetto, sarsaparilla, safflower, St. Johns Wort, optionally included include strontium carbonate, strontium curcuma, cardamom, nutmeg, cassia bark, bunchu, cinna lactate, strontium citrate, strontium ralenate, and strontium mon, jasmine, chrysanthemum, water chestnut, Sugar cane, gluconate. lychee, bamboo shoots, Vanilla, and coffee. 0076 Non-limiting examples of forms of sulphur that may 0085 3E. Sweeteners be optionally included include cysteine, methionine, and I0086. The compositions of the present invention may methylsulfonylmethane. optionally contain an appropriate amount of one or more 0077. Non-limiting examples of forms of vanadium that Sweetener(s), including carbohydrate Sweeteners and natural may be optionally included include bis-oxovanadium, and/or artificial no/low calorie Sweeteners. The amount of the Sodium metavanadate, Vanadium amino acid complexes, Sweetener used in the compositions of the present invention Vanadium aspartate, Vanadium citrate, Vanadium glycinate, typically depends upon the particular Sweetener used and the Vanadyl nicotinate, Vanadyl Sulfate. Sweetness intensity desired. 0078. Non-limiting examples of forms of zinc that may be I0087. The compositions of the present invention can be optionally included include Zinc lactate, Zinc sulfate, Zinc sweetened with any of the carbohydrate sweeteners, prefer chloride, Zinc acetate, Zinc gluconate, Zinc glycinate, Zinc ably monosaccharides and/or disaccharides. Preferred Sugar ascorbate, Zinc citrate, Zinc arginate, Zinc ascorbate, Zinc Sweeteners for use in compositions of the present invention aspartate, Zinc bisglycinate, Zinc lysinate, Zinc malate, Zinc are sucrose, unrefined cane Sugars, honey, agave nectar, fruc picolinate, Zinc pidolate, Zinc orotate, Zinc oxide and Zinc tose, glucose, and mixtures thereof, particularly Sucrose and amino acid complexes. fructose. Fructose can be obtained or provided as liquid fruc 0079 3B. Vitamins and Antioxidants tose, high fructose corn syrup, dry fructose or fructose syrup, 0080. Non-limiting examples of vitamins, antioxidants but is preferably provided as high fructose corn syrup. and related compounds that may be optionally included in the I0088. Non-caloric or low calorie sweeteners may option formulation compositions of the invention include biotin, ally be used in the compositions of the present invention to carnitine, coenzyme Q10, choline, folic acid, inositol, lyco Sweeten such compositions. Non-limiting examples of Such pene, lutein, astaxanthin, Zeaxanthin, vitamin A (beta-caro Sweeteners include Stevia, erythritol, glycerin, licorice, gly tene, carotenoids, retinol, retinol-acetate, retinol-palmitate), cyrrhizins, aspartame, saccharine, cyclamates, acesulfame K. US 2014/01 6 1955 A1 Jun. 12, 2014

L-aspartyl-L-phenylalanine lower alkyl ester Sweeteners, 0098. 3.J. Preservatives L-aspartyl-D-alanine amides, L-aspartyl-D-serine amides, 0099 Non-limiting examples of preservatives that may be L-aspartyl-hydroxymethyl alkane amide Sweeteners, L-as optionally included in the formulation compositions of the partyl-1-hydroxyethylalkane amide Sweeteners, and Syn invention include acetic acid, citric acid, benzoic acid, Sorbic thetic alkoxy aromatics. acid, Sulphur dioxide, potassium benzoate, potassium Sor 0089 3F. Bracers bate, Sodium benzoate, sodium Sorbate, calcium benzoate, 0090. As is commonly known in the art, bracers can have calcium Sorbate, Sodium citrate, potassium citrate, sodium a beneficial physiological effect such as increased mental hexametaphosphate, nitrites, sulfites etc. Preservatives may alertness. Bracers can be obtained by extraction from a natu also include antioxidants such as ascorbic acid, EDTA BHA, ral Source or can be synthetically produced. Non-limiting BHT TBHQ, dehydroacetic acid, dimethydicarbonate, examples of bracers that may be optionally included include ethoxyquin, and parabens. methyl Xanthines, e.g., caffeine, theobromine, and theophyl line. Additionally, one or more of these bracers are present in, D. Some Embodiments of the Formulation for example, coffee, tea, kola nut, cacao pod, mate, yaupon, Compositions guarana, puerh, and yoco. Natural plant extracts from the 0100 1x. In one embodiment, the formulation composi above sources are the preferred sources of bracers as they may tion is an aqueous composition comprising the following contain other compounds that are also desirable. ingredients, such that the Sum of concentrations of the dis 0091. The most preferred methylxanthine is caffeine. Caf Solved calcium and magnesium compounds is between about feine may be obtained from the aforementioned plants or, 1 molar to the point of Saturation: alternatively, may be synthetically prepared. Preferred 01.01 a. water: botanical sources of caffeine which may be utilized as a 0102) b. one or more dissolved calcium compound(s): complete or partial source of caffeine include green tea, and guarana, puerh, mate, black tea, cola nuts, cocoa, and coffee. 0.103 c. one or more dissolved magnesium compound As used herein, green tea, guarana, coffee, and mate are the (s). most preferred botanical sources of caffeine, most preferably 0104. The sum of the concentrations of the dissolved cal green tea, guarana, and coffee. Any bracer utilized herein is cium and magnesium compounds is required to be at least preferably present in physiologically relevant amounts, about 1 molar or more since this provides relatively high which means that the sources used in the practice of this quantities of calcium and/or magnesium in Small Volumes, invention provide a safe and effective quantity. while also providing microbial resistance, as shown later in 0092) 3G. Buffering Agents more detail. 0093 Buffering agents are well known in the art; non 0105 2x. The composition of embodiment 1X, wherein the limiting examples include carbonic acid, citric acid, acetic Sum of the concentrations of the dissolved calcium compound acid, phosphoric acid, Succinic acid and various salts of Such (s) and dissolved magnesium compound(s) is in the range of acids. about 1.5 molar to the point of saturation. 0094) 3H. Coloring Agents 0106 3x. The composition of embodiment 1X, wherein the 0095 One or more coloring agent(s) may also be option Sum of the concentrations of the dissolved calcium compound ally included in the formulation compositions of the inven (s) and dissolved magnesium compound(s) is in the range of tion. Coloring agents may include FD&C Dyes, FD&C about 2 molar to the point of Saturation. Lakes, or natural coloring agents. Non-limiting examples of 0107 4X. The composition of embodiment 1X, wherein the FD&C Dyes include FD&C yellow #5, FD&C blue #2, and Sum of the concentrations of the dissolved calcium compound FD&C red #40. Non limiting examples of FD&C Lakes (s) and dissolved magnesium compound(s) is in the range of include FD&C Lake red #40, FD&C Lake yellow #6, and about 1 molar to about 4.2 molar. FD&C Lake blue #1. Non-limiting examples of natural col 0.108 5x. The composition of embodiment 1X, wherein the oring agents include fruit, vegetable, and/or plant extracts Sum of the concentrations of the dissolved calcium compound from Sources such as grape, black currant, aronia, carrot, (s) and dissolved magnesium compound(s) is in the range of beetroot, red cabbage, and hibiscus. about 1.5 molar to about 4.2 molar. 0.096 3I. pH Modifiers 0109 6x. The composition of embodiment 1X, wherein the 0097. Optionally, one or more pH modifier(s) may be Sum of the concentrations of the dissolved calcium compound included to raise or lower the pH of the formulation compo (s) and dissolved magnesium compound(s) is in the range of sitions of the invention. The pH of the formulation composi about 2.0 molar to about 4.2 molar. tions may be lowered or raised for organoleptic effects, or 0110) 7x. The composition of embodiment 1X, wherein improving physicochemical properties such as increasing calcium and magnesium are present in a molar ratio in the solubility of the dissolved compounds. The pH modifers can range of about 0.01 to 100 calcium to magnesium. be referred to as acidulants or alkalizing agents. Non-limiting 0111 8x. The composition of embodiment 1X, wherein examples of acidulants are food grade edible acids such as calcium and magnesium are present in a molar ratio in the lactic acid, citric acid, malic acid, fumaric acid, adipic acid, range of about 0.1 to 10 calcium to magnesium. phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, 0112 9x. The composition of embodiment 1X, wherein acetic acid. Succinic acid, and maleic acid. The pH of the calcium and magnesium are present in a molar ratio in the formulation compositions can be adjusted by varying the ratio range of about 0.3 to about 3.2 calcium to magnesium. of cations (e.g. calcium, magnesium, Sodium and potassium 0113 10x. The composition of embodiment 1x, wherein cations) to acid components. Non-limiting examples of alka the one or more dissolved calcium compound(s) are selected lizing agents are compounds such as Sodium hydroxide, from calcium chloride, calcium acetate, calcium amino acid potassium hydroxide, calcium hydroxide and magnesium complexes, calcium aminoethyl phosphate, calcium arginate, hydroxide. calcium aspartate, calcium ascorbate, calcium citrate, cal US 2014/01 6 1955 A1 Jun. 12, 2014

cium glubionate, calcium gluceptate, calcium gluconate, cal I0121 18x. The composition of embodiment 14x, wherein cium bromide, calcium iodide, calcium lactate, calcium the additional compatible bracer(s) is one or more of caffeine, malate, calcium orotate, and calcium pyruvate; and the one theobromine, theophylline, extracts of cocoa, coffee, tea, more dissolved magnesium compound(s) are selected from green tea, black tea, guarana, kola nuts, cacao pods, mate, magnesium chloride, magnesium acetate, magnesium amino puerh, yaupon, and yoco. acid complexes, magnesium arginate, magnesium aspartate, 0.122 19X. The composition of embodiment 14x, wherein magnesium ascorbate, magnesium citrate, magnesium glu the additional compatible buffering agent(s), coloring agent conate, magnesium glycinate, magnesium lactate, magne (S), pH modifier(s), or preservative(s) is one or more of sium lysinate, magnesium malate, magnesium orotate, mag buffering agent of carbonic acid, citric acid, acetic acid, phos nesium bromide, magnesium iodide, magnesium pyruvate phoric acid, Succinic acid and various salts of Such acids; and magnesium Succinate. coloring agent of FD&C Dyes, FD&C Lakes, or natural col 0114 11x. The composition of embodiment 1x, wherein oring agents such as fruit, vegetable, and/or plant extracts of the one or more dissolved calcium compound(s) are selected grape, black currant, aronia, carrot, beetroot, red cabbage, from calcium chloride and calcium acetate; and the one or and hibiscus; pH modifier of lactic acid, citric acid, malic more dissolved magnesium compound(s) are selected from acid, fumaric acid, adipic acid, phosphoric acid, gluconic magnesium chloride and magnesium acetate. acid, tartaric acid, ascorbic acid, acetic acid, Succinic acid, 0115 12x. The composition of embodiment 1x, compris maleic acid, sodium hydroxide, potassium hydroxide, cal ing the dissolved compounds of calcium chloride and mag cium hydroxide and magnesium hydroxide; preservative of nesium chloride. acetic acid, citric acid, benzoic acid, Sorbic acid, Sulphur 0116 13x. The composition of embodiment 1x, compris dioxide, potassium benzoate, potassium Sorbate, sodium ben ing the dissolved compounds of calcium chloride, magne Zoate, sodium Sorbate, TBIIQ, calcium benzoate, calcium sium chloride, and potassium chloride. Sorbate, sodium citrate, potassium citrate, Sodium hexameta 0117 14X. The composition of embodiment 1x, further phosphate, nitrites, sulfites, ascorbic acid, EDTA BHA, comprising one or more additional compatible mineral(s), BHT TBHQ, dehydroacetic acid, dimethydicarbonate, Vitamin(s), antioxidant(s), herbal extract(s), flavonoid(s), fla ethoxyquin, and parabens. Voring agent(s), Sweetener(s), bracer(s), buffering agent(s), I0123 20x. The composition of embodiment 1x, wherein coloring agent(s), pH modifier(s), preservative(s). one or more additional compatible ingredient(s) are dis 0118 15x. The composition of embodiment 14x, wherein solved, solubilized, emulsified or suspended within the com the additional compatible mineral(s) is one or more com position. pound(s) of boron, cobalt, copper, chromium, fluorine, 0.124 21x. The composition of embodiment 1x, wherein iodine, iron, manganese, molybdenum, nickel, phosphorus, one or more of the calcium or magnesium compound, chelate potassium, Selenium, silicon, silver, sodium, strontium, Vana or complex is formed in situ, as may occur due to an acid-base dium, and zinc. reaction in water. 0119) 16x. The composition of embodiment 14x, wherein 0.125 22x. The composition of embodiment 20x, wherein the additional compatible vitamin(s), antioxidant(s), herbal one or more of the compound, chelate or complex is formed extract(s) or flavonoid(s) is one or more of biotin, carnitine, in situ, as may occur due to an acid-base reaction in water. coenzyme Q10, choline, folic acid, inositol, lycopene, lutein, astaxanthin, Zeaxanthin, vitamin A, Vitamin B, Vitamin B2, E. Properties of the Compositions of the Invention vitamin B. vitamin B. vitamin Bs, vitamin B vitamin C. 0.126 The elements of the formulation compositions need Vitamin D. Vitamin E, and vitamin K, apigenin, catechins, to be suitable for consumption within a dietary Supplement, epicatechin, gallocatechin, epigallocatechin, epicatechingal sufficiently water soluble to provide at least about 1 molar or late, epigallocatechin gallate, kaempferol, luteolin, myrice higher Summed concentration of calcium and magnesium tin, quercetin, rutin, tannins, and theaflavins. compounds dissolved in water, and compatible with the other 0120 17x. The composition of embodiment 14x, wherein ingredients of the formulation. There are several consider the additional compatible flavor(s) or sweetener(s) is one or ations for developing useful liquid dietary Supplement formu more of fruit flavors of orange, lemon, lime, grapefruit, lations. The major considerations include Sufficient physico apple, grape, cherry, pineapple, fruit punch, Strawberry, kiwi, chemical stability of the formulation, and also resistance of tangerine, raspberry, mango, cocoa, papaya, apricot, passion the formulation to microbial growth over time during storage fruit, and cupuacu; botanical flavors of kola, tea, aloe Vera, and use. There are many liquid dietary Supplements contain guarana, ginseng, ginkgo, hawthorn, hibiscus, rose hips, cha ing calcium and magnesium compounds that are commer momile, peppermint, fennel, ginger, licorice, lotus seed, Schi cially available or described in prior literature. However, to Zandra, saw palmetto, Sarsaparilla, Safflower, St. Johns Wort, the inventor's knowledge there are no prior art examples of curcuma, cardamom, nutmeg, cassia bark, bunchu, cinna aqueous liquid formulations that have relatively high concen mon, jasmine, chrysanthemum, water chestnut, Sugar cane, trations (e.g. at least 1 Molar) of dissolved calcium and mag lychee, bamboo shoots, vanilla, and coffee; carbohydrate nesium compounds in combination, are reasonably stable, Sweeteners of Sucrose, unrefined cane Sugars, honey, agave and also have inherent resistance to microbial growth in the nectar, fructose, glucose, high fructose corn syrup; non-ca absence of additional preservatives. The present invention loric Sweeteners of Stevia, erythritol, glycerin, licorice, gly discloses formulation compositions that have these afore cyrrhizins, aspartame, saccharine, cyclamates, acesulfame K. mentioned characteristics, and therefore are new and useful L-aspartyl-L-phenylalanine lower alkyl ester Sweeteners, compositions not previously available in prior art. Although it L-aspartyl-D-alanine amides, L-aspartyl-D-serine amides, is possible to add optional preservatives to the formulations L-aspartyl-hydroxymethyl alkane amide Sweeteners, L-as described in this invention, a very useful feature of these partyl-1-hydroxyethylalkane amide Sweeteners, and Syn formulations is an inherent resistance to microbial growth, thetic alkoxy aromatics. and thus the need for adding preservatives can be reduced, US 2014/01 6 1955 A1 Jun. 12, 2014

minimized or eliminated. This in turn makes the formulation solved in water, wherein the sum of the concentrations of compositions simpler, more versatile, and more Suitable for these compounds is about 1 molar or more, and wherein regular use. additional optional ingredients may be present. Several 0127. In order to achieve this inherent resistance to micro embodiments of the compositions have already been bial growth, the formulation compositions of this invention described. Some practical uses are described below. contain calcium and magnesium compounds dissolved at 0.132. The compositions may be used to mineralize drink suitable concentrations in water such that the sum of the ing water with calcium and magnesium compounds, along concentrations of the dissolved calcium compound(s) and with other optional minerals, vitamins or other ingredients dissolved magnesium compound(s) is at least about 1 molar, that are beneficial for health. This is especially useful when more preferably at least about 1.5 molar, and most preferably the water to be mineralized is deficient in minerals, such as in at least about 2 molar or more, up to the point of Saturation. the case of distilled or reverse-osmosis filtered waters, rain 0128. In another embodiment, the formulation composi water, etc. Mineralizing of water is achieved by adding Small tion comprises dissolved calcium compound(s) and dissolved quantities of the formulation compositions to drinking water. magnesium compound(s) in a range of about 1 molar to I0133. There are many methods by which a formulation of saturation along with excess undissolved solids being this invention can be added to water or other beverages. For present, as in a suspension, or undissolved non-aqueous liq example, the formulation may be dispensed directly from a uid droplets being present, as in an emulsion. Although fully bottle thru a dispensing cap, or it may be added to the water dissolved and clear liquid formulations are preferable, the using a dropper, Syringe, spoon, Small measuring cup, dis compositions of the invention have useful characteristics pensing pump etc. The quantity to be added depends on the Such as beneficial amounts of dissolved calcium and magne amount of water that needs to be mineralized, and the level of sium, along with inherent microbial resistance, even if some mineralization required. Since the formulations of this inven ingredients are present that are poorly soluble. Thus the cal tion are aqueous liquids, mixing with water is easily achieved. cium & magnesium compositions of this invention can be If needed. Some mechanical mixing may be employed to considered as useful liquid vehicles for the delivery of addi provide a homogenous solution of the mineralized water. tional nutritional compounds, whether those additional com 0.134. The formulations described in this invention can pounds are sufficiently water soluble or not. also be used as a dietary Supplement to increase intake of calcium, magnesium and other optional beneficial ingredi F. Kits of the Invention ents that may be present in the formulation. Using the Supple 0129. The compositions of the present invention may be ment in this manner is especially useful when the individual utilized in kits as described herein. The kits of the present taking the Supplement has a calcium and/or magnesium min invention comprise one or more compositions of the present eral deficiency, or has a diet or condition that can lead to Such invention together with information which informs a user of deficiencies. Since the formulations have high concentrations the kit, by words, pictures, and/or the like, that use of the kit of calcium and magnesium compounds, they are intended to will provide supplementation of a beverage or food with be ingested only after dilution into water, juice or some other calcium and magnesium, and with additional beneficial com beverage, Soup, food or meal. This is achieved simply by pounds where applicable. adding a measured amount of the formulation into a cup or 0130. In a particularly preferred embodiment, the infor other Suitable quantity of water, juice or other beverage, Soup, mation is printed on a container holding the composition, e.g., food or meal. The measured amount of the formulation com a bottle. These preferred kits may be in the form of one bottle position added to the cup of beverage or serving of food may containing the composition, or may be obtained as a plurality be at least about 1 ul, preferably at least about 5 ul, more of bottles each containing the composition. For example, the preferably at least about 25 ul, and most preferably at least kits may be obtained as one bottle, or cases of four, six, seven, about 50 ul, which is the approximate volume of one water or eight bottles co-packaged together. The preferred kits may drop. The measured amount of the formulation composition also include one or more dispensing means, such as dispens added to the cup of beverage or serving of food may be up to ing cap, dropper, Syringe, dispensing pump, Small measuring about 60 ml (4 tablespoons), preferably up to about 30 ml (2 cup, or spoon, for providing a measured amount of the for tablespoons), more preferably up to about 15 ml (1 table mulation into a cup or other Suitable quantity of water, juice, spoon), still more preferably up to 10 ml (2 teaspoons), and other beverage, or food. The preferred kits may also include most preferably up to about 5 mls (1 teaspoon). instructions for dispensing and mixing the composition into a 0.135 The formulations of this invention can also be pre beverage or food. In another preferred embodiment, a kit may pared and used at a large scale. For example, measured provide a large quantity of a formulation composition of the amounts of formulation can be added to a large vessel or tank present invention to be utilized during manufacture of a for to mineralize water, or to manufacture a dietary Supplement tified beverage or food, for subsequent distribution. In or fortified food. During Such manufacturing processes, the another embodiment, a kit may comprise one or more of the formulations can be added by either weight or volume, on a formulation composition(s) of the present invention, contain continuous or intermittent basis, manually or by using a ing instructions to use in combination with, or preferably metering device. co-packaged with, one or more commercially available 0.136 The calcium and magnesium formulations dietary Supplement(s) such as a vitamin product, a multivita described in this invention can also be used as a base or min product, a mineral product, a trace mineral product, a vehicle for dietary supplement formulations with additional herbal product etc. optional ingredients. The added ingredients would provide additional desirable characteristics to the basic formulations, G. Methods of the Invention Such as including additional beneficial minerals, vitamins, 0131 The formulation compositions described in this antioxidants, herbal extracts, flavonoids, bracers, and/or other invention comprise calcium and magnesium compounds dis beneficial ingredients, including pleasant flavors, visually US 2014/01 6 1955 A1 Jun. 12, 2014

attractive colors, etc. As a simple illustration of this, Some of 0148 33X. A method offortifying a beverage or food with the formulations described in Examples 2 and 3 provide the calcium, magnesium and additional optional ingredient(s), beneficial mineral potassium, along with calcium and mag comprising: nesium. 0149 adding at least 1 drop or about 50 ul, up to about 30 0137 The methods of the invention also include methods ml of the composition of embodiment 20x to one cup of the of designing a formulation composition. In one embodiment, beverage or one serving of the food, or adding correspond the invention provides a method of designing an aqueous ingly larger or Smalleramounts of the composition to larger or composition comprising one or more dissolved calcium com Smaller quantities of the beverage or food. pound(s) and one or more dissolved magnesium compound 0150 34X. A method of designing an aqueous composi (S), comprising: tion comprising one or more dissolved calcium compound(s) 0.138 a. Selecting one or more calcium compound(s) and one or more dissolved magnesium compound(s), com and one or more magnesium compound(s) for the com prising: position; and 0151 a. selecting one or more calcium compound(s) and 0.139 b. Determining the amounts of the individual cal one or more magnesium compound(s) to be included in the cium and magnesium compounds to be included in the composition; and composition so that the Sum total dissolved concentra 0152 b. selecting or determining the amounts of the indi tion of the calcium and magnesium compound(s) is at vidual calcium and magnesium compounds to be included in least about 1 molar, preferably at least about 1.5 molar, the composition so that the dissolved compounds remain and more preferably at least about 2 molar. soluble and compatible upon storage at room temperature, 0140 c. Optionally, selecting or determining amounts while the Sum total concentration of the calcium compound of one or more optional ingredient(s) so that these are (s) and the magnesium compound(s) is at least about 1 molar. compatible with the dissolved calcium and magnesium 0153. 35x. The method of embodiment 34x, wherein one formulations. or more additional ingredient(s) are included within the com 0141. The methods of the invention include methods of position by a) selecting one or more additional ingredient(s) preparation or manufacture. Various processes may be used to to be included within the composition and b) selecting or prepare the compositions that have been described. Prefer determining the amount(s) of the additional ingredients such ably the compositions are prepared by one or more simple that the dissolved compound(s) remain soluble and compat processes comprising dissolution or mixing of the ingredients ible upon storage at room temperature. into water. However other processes may also be employed. 0154 36x. The method of embodiment 34x, wherein one Non-limiting examples of commonly used processes may or more additional ingredient(s) are included within the com include mixing of ingredient(s) into an aqueous solution; position by a) selecting one or more additional ingredient(s) mixing of one or more aqueous solution(s); removal of water to be included within the composition and b) selecting or from dilute composition(s) by evaporation, dialysis, ultrafil determining the amount(s) of the additional ingredient(s) tration or freeze-drying to reach the desired concentrations of Such that the additional ingredient(s) are dissolved, solubi the calcium and magnesium compounds and optional ingre lized, emulsified or Suspended within the composition. dients; and by utilizing combinations of these processes. Fur 0155 37x. The method of embodiment 34x, wherein the ther, in the case of poorly soluble optional ingredient(s), one or more calcium compound(s) are selected from calcium solubilization, Suspension and/or emulsification processes chloride, calcium acetate, calcium amino acid complexes, may be employed. calcium aminoethyl phosphate, calcium arginate, calcium 0142. In the methods of designing or manufacturing com aspartate, calcium ascorbate, calcium citrate, calcium glu positions of the invention, non-limiting examples of the com bionate, calcium gluceptate, calcium gluconate, calcium bro pounds that may be selected include one or more of the mide, calcium iodide, calcium lactate, calcium malate, cal calcium compounds, the magnesium compounds, or the cium orotate, and calcium pyruvate; and the one more optional compounds listed earlier in Section C of the detailed dissolved magnesium compound(s) are selected from mag description. nesium chloride, magnesium acetate, magnesium amino acid complexes, magnesium arginate, magnesium aspartate, mag H. Additional Embodiments of the Invention nesium ascorbate, magnesium citrate, magnesium gluconate, magnesium glycinate, magnesium lactate, magnesium lysi 0143 Based on the prior sections, additional non-limiting nate, magnesium malate, magnesium orotate, magnesium embodiments of the present inventions are described below: bromide, magnesium iodide, magnesium pyruvate and mag 0144 31x. A method offortifying a beverage or food with nesium Succinate calcium and magnesium comprising: 0156 38x. A method of manufacture of the composition of 0145 adding at least about 1 ul up to about 60 ml of the embodiment 1X, wherein the composition is prepared by a composition of embodiment 1X to about one cup of the bev process comprising one or more of mixing of ingredient(s) erage or about one serving of the food, or adding correspond into water or aqueous solution; mixing of one or more aque ingly larger or Smalleramounts of the composition to larger or ous solutions; or removal of water from dilute composition(s) Smaller quantities of the beverage or food. by evaporation, dialysis, ultrafiltration, or freeze-drying. 0146 32X. A method offortifying a beverage or food with 0157 39x. A method of manufacture of the composition of calcium and magnesium comprising: embodiment 20x, wherein the composition is prepared by a 0147 adding at least 1 drop or about 50 ul, up to about 30 process comprising one or more of: mixing of ingredient(s) ml of the composition of embodiment 1X to one cup of the into water or aqueous solution; mixing of one or more aque beverage or one serving of the food, or adding correspond ous solution(s); removal of water from dilute composition(s) ingly larger or Smalleramounts of the composition to larger or by evaporation, dialysis, ultrafiltration, or freeze-drying: Smaller quantities of the beverage or food. incorporation of poorly soluble ingredient(s) by solubiliza US 2014/01 6 1955 A1 Jun. 12, 2014 10 tion; incorporation of poorly soluble liquid ingredient(s) by mixing the same E. coli Suspension in distilled water. The emulsification; or incorporation of poorly soluble Solid ingre spiked samples were incubated for 1 day at room temperature, dient(s) by Suspension. and dilutions were then plated on Petrifilm plates (designed 0158 40x. A kit comprising the composition of embodi for total aerobic counts) to evaluate microbial growth or inhi ment 1X bition. The results are summarized in Table 1. Relative to the 0159 41x. A kit comprising the composition of embodi positive control, microbial growth was somewhat reduced ment 20X. (approx 2-fold) in the formulations having a total calcium & 0160 42x. A kit comprising the embodiment of 1x or 20x, magnesium compound concentration of 1M. In contrast, copackaged with one or more commercially available vitamin microbial growth was significantly reduced (approx 10-fold product, multivitamin product, mineral product or herbal reduction) in the formulations having total Summed concen product. tration of 1.5M. The microbial count reduction observed was approx 100-fold or greater, and practically no bacterial counts EXAMPLES were observed for the spiked formulations where the sum of 0161 The examples provided below explain the composi the calcium and magnesium compounds was 2M, 2.5M or tions of the invention further, and also demonstrate several of 3M, irrespective of the ratio of calcium to magnesium. TABLE 1 Calcium Magnesium % RDA chloride chloride Calcium to in Formulation concentration concentration Magnesium Total salt Visual Microbial 5 ml Code (M) (M) ratio conc. (M) appearance inhibition (Ca,Mg) CM2A1.O O.76 O.24 3.2 1.O Clear Slight 15, 7 CM2B1.0 O6 0.4 .5 1.O Clear Slight 12, 12 CM2C1.0 O.S O.S O 1.O Clear Slight 10, 15 CM2D1.0 0.4 O.6 0.7 1.O Clear Slight 8, 18 CM2E1.0 O.24 O.76 O.3 1.O Clear Slight 5, 23 CM2A1.5 1.14 O.36 3.2 1.5 Clear Significant 23, 11 CM2B1.5 O.89 O.61 .5 1.5 Clear Significant 18, 18 CM2C1.5 0.75 0.75 O 1.5 Clear Significant 15, 23 CM2D1.5 O.61 O.89 0.7 1.5 Clear Significant 12, 27 CM2E1.5 O.36 1.14 O.3 1.5 Clear Significant 7,35 CM2A2.O 52 O.48 3.2 2.0 Clear High 31, 14 CM2B2.O 19 O.81 .5 2.0 Clear High 24, 25 CM2C2.O O 1.O O 2.0 Clear High 20, 30 CM2D2.0 O.81 1.19 0.7 2.0 Clear High 16, 36 CM2E2.0 O48 1.52 O.3 2.0 Clear High 10, 46 CM2A2.5 9 O.6 3.2 2.5 Clear High 38, 18 CM2B2.5 49 1.01 .5 2.5 Clear High 30, 31 CM2C2.5 25 1.25 O 2.5 Clear High 25, 38 CM2D2.5 O1 1.49 0.7 2.5 Clear High 20, 45 CM2E2.5 O6 1.9 O.3 2.5 Clear High 12, 58 CM2A3.O 2.29 O.71 3.2 3.0 Clear High 46, 22 CM2B3.0 .79 1.21 .5 3.0 Clear High 36,37 CM2C3.0 .5 1.5 O 3.0 Clear High 30, 46 CM2D3.0 .21 1.79 0.7 3.0 Clear High 24, 54 CM2E3.0 O.71 2.29 O.3 3.0 Clear High 14, 69 *RDA: recommended daily allowance, based on a standard 2000 calorie diet the embodiments. The examples are illustrative only, and Example 2 variations may be made in the specific compositions as 0163 Sixteen formulation compositions were prepared in described within the scope of this application. four sets as described below, and shown in Table 2. The first set of formulations was prepared with calcium chloride and Example 1 magnesium acetate dissolved in distilled water. The second set was prepared with calcium acetate and magnesium chlo 0162 Twenty five formulations were made with different ride dissolved in distilled water. The third set was prepared with calcium chloride, magnesium chloride, calcium acetate concentrations of calcium chloride and magnesium chloride and magnesium acetate dissolved in distilled water. The dissolved in distilled water. The formulations contained vari fourth set was prepared with calcium chloride, magnesium ous ratios of elemental calcium to elemental magnesium in chloride, and potassium chloride dissolved in distilled water. the formulations, as shown in Table 1. For each of these ratios, Within each set, four formulations were prepared at a total formulations were prepared at a total concentration (sum of Summed calcium and magnesium compound concentration calcium and magnesium compound concentrations) of 1M, of 1M, 1.5M, 2.0M, and 2.5M. All formulations were visually 1.5M, 2.0M, 2.5M, and 3.0M. All the formulations were clear, demonstrating full dissolution of the compounds. A visually clear, demonstrating full dissolution of the calcium bacterial Suspension of E. coli was spiked into aliquots of and magnesium compounds. A bacterial Suspension of E. coli each of these 16 formulations and mixed. A positive control was spiked into aliquots of each of these 25 formulations and was also prepared, by spiking and mixing the same E. coli mixed. A positive control was also prepared, by spiking and Suspension in distilled water. The spiked samples were incu US 2014/01 6 1955 A1 Jun. 12, 2014 11 bated for 1 day at room temperature, and dilutions were then optional ingredient. The formulations were passed thru a 0.2 plated on Petrifilm plates (designed for total aerobic counts) micron pore-size filter to remove any extraneous particulates, to evaluate microbial growth or inhibition. The results are and stored at room temperature in plastic bottles with dis summarized in Table 2. Relative to the positive control, pensing caps. These formulations were testeda) for mineral microbial growth was somewhat reduced (approx 2-fold) in izing reverse-osmosis (RO) filtered drinking water, and b) for the formulations having a total Summed concentration of 1M. dietary Supplementation. Mineralization of water was accom In contrast, microbial growth was significantly reduced (ap plished by adding one or more drop(s) of formulation to an empty cup of water, and then filling the cup with RO filtered, proX 10-fold) in the formulations having total Summed con or distilled water. Mineralized water consistently tasted better centration of 1.5 M. Further, the microbial count reduction (normal) as compared to RO filtered or distilled waters, due to was approx 100-fold or greater, and there were practically no the presence of added minerals. The presence of added min bacterial counts observed for the spiked formulations where erals was confirmed by conductivity measurements to esti the Sum of the calcium and magnesium compounds was 2M mate total dissolved solids (TDS). Typically, the TDS value of or 2.5M, irrespective of the ratio of calcium to magnesium, or RO filtered water was 5 ppm and the TDS value of distilled the specific type of compound used. These results were con water was less than 1 ppm. The addition of a single drop sistent with the results seen earlier in Example 1, and show (approx 50 uL) of any one of the two formulations of this that the formulations behaved consistently when other com example to a standard size 8 oz. cup of RO or distilled water pounds of calcium and magnesium were used in various resulted in a TDS of about 100 ppm. Additional dietary combinations, and also when an additional optional com Supplementation of calcium and magnesium was accom pound was added. Further, the 16 formulations were passed plished in a manner similar to the mineralization of water, by thru a 0.2 micron pore-size filter to remove any extraneous adding larger quantities (up to one teaspoon) of formulation particulates, and stored at room temperature in plastic tubes to a cup of water or juice, and then drinking the entire con with caps. They were inspected after 3 months and then again tents. The formulations taken in this manner had a distinct after 13 months, and all the formulations remained clear and taste when diluted in water. However, the taste was masked soluble, with no evidence of microbial growth. when diluted in juice. TABLE 2

Calcium Magnesium Ca & Mg % RDA CaCl2 MgCl2 acetate acetate KCI salts sum in Formula conc. conc. COC. COC. COC. COC. Visual Microbial 5 ml Code (M) (M) (M) (M) (M) (M) Appearance inhibition (Ca,Mg)

CM3A1.O 0.67 O.33 O Clear Sligh 13, 10 CM3A1.5 1.O O.S .5 Clear Significant 20, 15 CM3A2O 134 O.66 2.0 Clear High 27, 20 CM3A2.5 1.67 O.83 2.5 Clear High 33, 25 CM4A1.O 0.67 O.33 O Clear Sligh 7, 20 CM4A1.5 1.O O.S 5 Clear Significant 10,30 CM4A2.O 1.34 O.66 2.0 Clear High 13, 41 CM4A2.5 1.67 O.83 2.5 Clear High 17,51 CMSA1.O O.4 0.4 O.1 O.1 O Clear Sligh 10, 15 CMSA1.5 0.6 O.6 O.15 O.15 5 Clear Significant 15, 23 CMSA2.O O.8 O.8 O.2 O.2 2.0 Clear High 20, 30 CMSA2.5 1.O 1.O O.25 O.25 2.5 Clear High 25, 38 CM6A1.O O.S O.S O.25 O Clear Sligh 10, 15 CM6A1.5 0.75 0.75 O.3 .5 Clear Significant 15, 23 CM6A2O 1.O 1.O 0.4 2.0 Clear High 20, 30 CM6A2.5 1.25 1.25 O.S 2.5 Clear High 25, 38

Example 3 0.165. The formulations were inspected after 3 months and 0164. Two formulations were prepared in distilled water, remained as clear liquids, with no evidence of microbial with even greater concentrations of calcium and magnesium growth. The formulations were inspected again after 13 compounds as compared to prior examples (total Summed months, and remained clear liquids with no evidence of concentration of about 4.2 M) as compared to the earlier microbial growth. Since these formulations contain simple examples. It should be noted that the formulations presented compounds of calcium and magnesium, there is no concern of in this example are close to the point of Saturation. One of these formulations was prepared with calcium chloride and any chemical degradation. Since these formulations also magnesium chloride; and the other formulation included a inhibit any microbial growth, they are expected to have a long third compound (potassium chloride) along with the calcium shelf life of several years when stored in closed containers, and magnesium compounds, as shown in Table 3. It should be and refrigeration is not needed. Thus these formulations are noted that inclusion of the potassium compound within one of physically and chemically stable, do not allow bacterial the formulations demonstrates inclusion of an additional growth, and are convenient to store and use. US 2014/01 6 1955 A1 Jun. 12, 2014 12

TABLE 3 Typical TDS* (ppm) of % RDA of mineralized Calcium, water, after Magnesium, Microbial adding 2 drops Potassium MgCl2. KCl Visual growth after (approx 100LL) in Formula CaCl2 conc. conc. appearance after 13 months of formulation to 1 teaspoon Code conc. (M) (M) (M) 13 months storage storage 8 OZ RO* water (5 ml) CM1 2.5 1.65 Clear No 205 50, 50, NA CMK1 2.5 1.65 O.45 Clear No 220 50, 50, 2.5 *TDS: Total dissolved solids, based on conductivity (with sodium chloride reference) **RO water: reverse-osmosis filtered (purified and demineralized) water, TDS of RO water was typically 5 ppm.

Example 4 in which all terms are meant in their broadest, reasonable 0166 Two drops of formulation CM1 mentioned in Table sense unless otherwise indicated. Any headings utilized 3 are added to one 8 oz cup of water. Drinking 8 such cups of within the description are for convenience only and have no mineralized water a day will provide about 8% of the recom legal or limiting effect. mended intake of calcium and magnesium, based on a stan The invention claimed is: dard 2000 calorie diet. If two drops of formulation CMK1 1. An aqueous composition comprising: mentioned in Table 3 are used instead of CM1, drinking 8 a. Water, such cups of mineralized water a day will provide about 8% of b. one or more dissolved calcium compound(s); and the recommended intake of calcium and magnesium, along c. one or more dissolved magnesium compound(s): with a trace quantity of potassium, which also helps to wherein the sum of the concentrations of the dissolved cal slightly improve the water taste. cium compound(s) and dissolved magnesium compound(s) is in the range of about 1 molar to the point of Saturation. Example 5 2. The composition of claim 1, wherein the sum of the (0167. In the case of formulation CMK1 mentioned in concentrations of the dissolved calcium compound(s) and Table 3, 1 teaspoon is added into a cup of water. Consuming dissolved magnesium compound(s) is in the range of about the entire contents of the cup will provide 50% of the recom 1.5 molar to the point of saturation. mended daily intake amount of calcium and magnesium, 3. The composition of claim 1, wherein the sum of the along with about 2.5% of the recommended intake of potas concentrations of the dissolved calcium compound(s) and sium, based on a standard 2000 calorie diet. Alternatively, the dissolved magnesium compound(s) is in the range of about 2 formulation is added to a cup of juice or beverage, or added to molar to the point of Saturation. a serving of soup or some other Suitable food, if taste masking 4. The composition of claim 1, wherein the sum of the of the formulation ingredients is desired. As described in an concentrations of the dissolved calcium compound(s) and earlier section, it is also possible to add sweeteners or flavors dissolved magnesium compound(s) is in the range of about 1 for improved taste. Further, as described in an earlier section, molar to about 4.2 molar. a variety of optional ingredients may be added to the basic 5. The composition of claim 1, wherein the sum of the calcium and magnesium compositions described in this and concentrations of the dissolved calcium compound(s) and the earlier examples. Therefore, the calcium and magnesium dissolved magnesium compound(s) is in the range of about compositions of the invention, described in earlier embodi 1.5 molar to about 4.2 molar. ments and within the examples shown in the above tables, 6. The composition of claim 1, wherein the sum of the serve as a useful base vehicle for additional ingredients, allow concentrations of the dissolved calcium compound(s) and convenient storage while inhibiting microbial growth, and dissolved magnesium compound(s) is in the range of about allow consumption in a convenient manner while providing 2.0 molar to about 4.2 molar. useful minerals along with additional dietary ingredients. 0168 The examples provided in the above section dem 7. The composition of claim 1, wherein calcium and mag onstrate several of the embodiments, and also provide several nesium are present in a molar ratio in the range of about 0.01 variations of the formulation compositions of the invention. to 100 calcium to magnesium. Further, formulations within the scope of the invention can be 8. The composition of claim 1, wherein calcium and mag varied easily by changing concentrations of calcium or mag nesium are present in a molar ratio in the range of about 0.1 to nesium compounds, and by adding additional optional ingre 10 calcium to magnesium. dients. Variations or alternative embodiments of the present 9. The composition of claim 1, wherein calcium and mag invention will be obvious to those skilled in the art and it is nesium are present in a molar ratio in the range of about 0.3 to intended that these variations are within the scope of the about 3.2 calcium to magnesium. present invention. 10. The composition of claim 1, wherein the one or more 0169. What has been described and illustrated herein are dissolved calcium compound(s) are selected from calcium preferred embodiments of the invention along with some chloride and calcium acetate and the one or more dissolved variations. The terms and descriptions used herein are set magnesium compound(s) are selected from magnesium chlo forth by way of illustration only and are not meant as limita ride and magnesium acetate. tions. Those skilled in the art will recognize that many varia 11. The composition of claim 1, comprising the dissolved tions are possible within the spirit and scope of the invention compounds of calcium chloride and magnesium chloride. US 2014/01 6 1955 A1 Jun. 12, 2014

12. The composition of claim 1, comprising the dissolved a. Selecting one or more calcium compound(s) and one or compounds of calcium chloride, magnesium chloride, and more magnesium compound(s) to be included in the potassium chloride. composition; and 13. The composition of claim 1, wherein one or more b. Selecting or determining the amounts of the individual additional compatible ingredients are dissolved, Solubilized, calcium and magnesium compounds to be included in the composition so that the dissolved compounds remain emulsified, or Suspended within the composition. Soluble and compatible upon storage at room tempera 14. The composition of claim 1, wherein one or more of the ture, while the Sum total concentration of the calcium dissolved compounds is formed in situ within the composi compound(s) and the magnesium compound(s) is at tion. least about 1 molar. 15. A method offortifying a beverage or food with calcium 19. The method of claim 18, wherein one or more addi and magnesium utilizing the composition of claim 1 compris tional ingredient(s) are included within the composition by a) ing: selecting one or more additional ingredient(s) to be included adding at least about 1 Jul up to about 60 ml of the compo within the composition and b) selecting or determining the sition of claim 1 to about one cup of the beverage or to amount(s) of the additional ingredients such that the dis about one serving of the food, or adding correspondingly Solved compound(s) remain soluble and compatible upon Smaller or larger amounts of the composition to Smaller storage at room temperature. or larger quantities of the beverage or food. 20. The method of claim 18, wherein one or more addi tional ingredient(s) are included within the composition by a) 16. A method offortifying a beverage or food with calcium selecting one or more additional ingredient(s) to be included and magnesium utilizing the composition of claim 1 compris within the composition and b) selecting or determining the 1ng: amount(s) of the additional ingredient(s) such that the addi adding at least about 50 ul up to about 30 ml of the com tional ingredient(s) are dissolved, solubilized, emulsified or position of claim 1 to about one cup of the beverage or to Suspended within the composition. about one serving of the food, or adding correspondingly 21. A kit comprising the composition of claim 1. Smaller or larger amounts of the composition to Smaller 22. A kit comprising the composition of claim 13. or larger quantities of the beverage or food. 23. A method of manufacture of the composition of claim 17. A method offortifying a beverage or food with calcium, 1, wherein the composition is prepared by a process compris magnesium and additional optional ingredients, utilizing the ing one or more of mixing of ingredient(s) into water or composition of claim 13, comprising: aqueous solution; mixing of one or more aqueous Solution(s): adding at least about 50 ul up to about 30 ml of the com or removing water from dilute composition(s). position of claim 13 to about one cup of the beverage or 24. A method of manufacture of the composition of claim to about one serving of the food, or adding correspond 13, wherein the composition is prepared by a process com ingly smaller or larger amounts of the composition to prising one or more of mixing of ingredient(s) into water or Smaller or larger quantities of the beverage or food. aqueous solution; mixing of one or more aqueous Solution(s): 18. A method of designing an aqueous composition com removing water from dilute composition(s); or incorporating prising one or more dissolved calcium compound(s) and one poorly soluble ingredient(s). or more dissolved magnesium compound(s), comprising: k k k k k