COMPOSITIONS FOR MAINTAINING ELECTROLYTE BALANCE AND URINARY TRACT HEALTH

Abstract

An electrolyte supplement/replacement, in particular a gel capsule, comprises an electrolyte formulation for facilitating sufficient electrolyte replenishment and compounds for maintaining urinary tract health in dehydrated persons, including but not limited to persons who lose substantial amounts of electrolytes due to illness or those who engage in strenuous physical activities in hot climates and/or work environments, such as military personnel, construction workers, sports training, athletes and the like, to improve electrolyte balance, extend endurance, prevent muscle cramps and other effects of dehydration. The supplement comprises sufficient types and amounts of electrolytes to facilitate rapid return to electrolyte homeostasis in a dehydrated person.

Claims

1. An electrolyte supplement consisting of: a. sodium, b. calcium c. potassium, d. magnesium, and e. a bladder anti-infective, wherein the electrolyte supplement is provided in the form of a gel cap, and wherein the gel cap disintegrates in about fifteen minutes under a standard USP disintegration test.

2. The electrolyte supplement of claim 1, wherein sodium is provided as sodium chloride, wherein calcium is provided as calcium carbonate, wherein potassium is provided as potassium chloride, and wherein magnesium is provided as magnesium oxide.

3. The electrolyte supplement of claim 1, wherein the anti-infective comprises D-mannose, lauricidin, nattokinase, apolactoferrin, lactoferrin, cranberry extract, polyphenols, probiotics, ascorbic acid, or urinary acidifiers.

4. The electrolyte supplement of claim 2, wherein sodium chloride is present in an amount of at least 200 mg per gel capsule, wherein calcium carbonate is present in an amount of at least 100 mg per capsule, wherein potassium chloride is present in an amount of at least 100 mg per capsule, wherein magnesium oxide is present in an amount of at least 25 mg per capsule.

5. The electrolyte supplement of claim 4, wherein the ratio of potassium to magnesium is at least 4:1.

6. A gel capsule comprising an electrolyte supplement for preventing, reducing or treating dehydration, wherein the electrolyte supplement consists of: a. sodium chloride present at 250 mg/gel capsule, b. calcium carbonate present at 139 mg/gel capsule, c. potassium chloride present at 108 mg/gel capsule, d. magnesium oxide present at 25 mg/gel capsule, and e. D-Mannose present at 75 mg/gel capsule.

7. A method of treating dehydration comprising the step of: administering two of the gel capsules according to claim 6 to a dehydrated subject.

8. A method of preventing or reducing the incidence of dehydration associated with strenuous physical exercise comprising the step of: administering two of the gel capsules according to claim 6 to a human subject prior to or during strenuous physical exercise.

9. A method of preventing or reducing the incidence of dehydration associated with strenuous physical exercise in hot climates or work environments, comprising the step of: administering two of the gel capsules according to claim 6 to a human subject prior to or during strenuous physical exercise.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0040] The invention is directed to an electrolyte supplement (replacement) for use in the prevention, reduction and/or treatment of electrolyte loss associated with dehydration, particularly in those persons who undertake strenuous physical activity in hot environments. The electrolyte supplement is provided in an easy-to-use gel cap form, requiring no preparation and no need to carry water or other liquid supplements in the field. The electrolyte supplement provides gastrointestinal protection from high salt content but unexpectedly is well absorbed and readily bioavailable to the user. The inventive formulation replenishes electrolytes necessary for bodily functions. An added advantage is that, by fulfilling electrolyte requirements, it improves performance by allowing muscle cells to extend duration time thus reducing muscle fatigue. In some instances, the combination of potassium, calcium and magnesium may help offset any blood pressure increases caused by sodium ingestion.

[0041] Because it is in gel cap form, the concentration of electrolytes in the inventive formulation can be and is greater than that typically found in known electrolyte supplements and thus reduces the amount required to prevent, reduce and/or treat electrolyte loss associated with dehydration. The gel cap provides unexpected bioavailability comparable to that achieved with liquid preparations. An added advantage is the inclusion of an anti-infective to prevent bladder irritation and/or urinary tract infections commonly encountered with dehydration.

[0042] The following definitions are used herein:

[0043] “Electrolyte” shall mean and include salts and minerals that can conduct electrical impulses in the body. Electrolytes control fluid balance in the body and are important for fluid balance, acid-base balance, delivery of oxygen to cells, cell wall integrity, the nervous system, cardiac system, muscle contraction, energy generation, and almost every major biochemical reaction in the body. In short, electrolytes allow the body to function and work. Electrolytes include but are not limited to sodium, potassium, magnesium, calcium and chloride.

[0044] “Supplement” or “replacement” with respect to the invention means and includes providing additional electrolytes lost through any situation or condition that leads to water loss and associated dehydration states. “Supplement” and “replacement” with respect to electrolytes are used interchangeably herein.

[0045] Electrolyte disorders are not only associated with dehydration but may be implicated in a number of disease and clinical states. Dehydration disturbs electrolyte balance creating an “imbalance”. Lack of electrolyte homeostasis can have serious consequences on a cellular level. If not resolved, cellular activity may be impaired, as well as action and resting membrane potentials. Electric instability in cells can lead to a number of serious consequences.

[0046] Electrolyte deficiencies may not always be determined through simple serum evaluations, particularly for potassium and magnesium. Only about 2 percent of total body potassium and about 1 percent of total body magnesium is accessible in the extracellular space where it may be assessed by measuring plasma or serum levels. When dehydration with loss of electrolytes occurs, the body attempts to maintain serum concentrations of electrolytes by transporting electrolytes from intracellular stores to the extracellular space, often at the expense of muscle, cardiac, bone and liver cells. This transport, coupled with concomitant water loss, results in normal serum electrolyte levels or a “hyper” level of electrolytes. As a result, it is often difficult to determine electrolyte deficiencies, particularly for potassium and magnesium. Accordingly, for electrolyte loss due to dehydration, a preferred approach is to prevent or reduce electrolyte loss in the field with electrolyte supplements.

[0047] It is known that magnesium is important in the functioning of the Na/K pump, the Ca-pump and Na/Ca exchange. (See Schroll, A., “Importance of magnesium for the electrolyte homeostasis—an overview”, 2002, available online at mgwater.com and Hans-Jurgen, A. et al., “Modulation of the Na, K-ATPase by Magnesium Ions”, Biochemistry 56(7): 1005-1016 (2017), doi:10.1021/acs.biochem.6b01243.Epub 2017 Feb. 9). The Na/K pump maintains cellular potassium concentration by active transport across a gradient. It has been well-known that Mg.sup.2+ is an essential cofactor for activation of enzymatic ATP hydrolysis by ATPase, without being transported through the cell membrane. (Hans-Jurgen, A., supra). In short, magnesium is responsible for the function of ATPase, the enzyme involved in the Na/K pump. When magnesium is deficient, ATPase demonstrates reduced activity. While not wishing to be bound by theory, regardless of mechanism, magnesium plays an important role in the function of the Na/K pump. Similarly, magnesium deficiency is implicated in the efficient functioning of the calcium pump (Ca-pump) and the sodium/calcium exchange (Na/Ca exchange). In short, magnesium facilitates the transport of potassium and calcium in and out of cells and may aid in the absorption of these critical electrolytes.

[0048] Further, magnesium deficiency and potassium deficiency are often concurrent. Magnesium deficiency is often followed by potassium deficiency. And it is known that potassium deficiency, i.e., hypokalemia, can be refractory, and not resolved by administration of potassium alone. Additional magnesium may be needed to restore potassium balance. It is therefore critical to assure that adequate magnesium is provided to facilitate the efficient and rapid return to electrolyte homeostasis.

[0049] The inventive electrolyte supplement includes not only sodium and potassium, but also magnesium and calcium, all of which work in concert to restore electrolyte homeostasis, in amounts sufficient to replenish electrolytes in dehydration states. Although various salt forms of each electrolyte exist and may be used, preferably the formulation comprises sodium (as sodium chloride), potassium (as potassium chloride or potassium gluconate), calcium (as calcium carbonate, calcium chloride or calcium gluconate) and magnesium (as magnesium oxide, chloride, sulfate or citrate). Although the use of a gel cap for the inventive electrolyte supplement improves gastrointestinal tolerance, both calcium carbonate and magnesium oxide may also facilitate digestion and/or prevent gastrointestinal upset from high salt content.

[0050] Because the inventive electrolyte formulation is included in a gel cap, the amounts of each electrolyte as well as total electrolytes that can be incorporated into one gel cap are limited to an extent, but higher than what is typically found in known electrolyte supplements. As such, the inventive electrolyte formulation may require at least two capsules per serving to assure adequate supplementation. Even so, it is far easier to take two fast acting, readily available capsules to achieve electrolyte balance than to prepare multiple powders or carry large amounts of liquid. By way of example only, 60 capsules (2 capsules per serving) is generally equal to 90 bottles of typical sports drinks. A user can carry a 30-day supply of electrolytes in a small light weight container, as compared to carrying more powder packets and the water required for mixing or large volumes of liquid preparations.

[0051] The inventive formulation also comprises anti-infectives known to be useful to reduce or eliminate urinary tract infections (UTI's). Suitable anti-infectives include D-mannose, lauricidin, nattokinase, apolactoferrin or lactoferrin, cranberry extract, polyphenols, probiotics, ascorbic acid and other urinary acidifiers. D-mannose is preferred as it is effective against Escherichia coli, which is believed to be responsible for about 90% or UTI's.

[0052] The amount of sodium, calcium, potassium and magnesium contained in the inventive electrolyte supplement can vary depending on capsule size. Preferably, sodium is present in the inventive electrolyte formulation in amounts of at least 200 mg per capsule; calcium is present in at least 100 mg per capsule; potassium is present in at least 100 mg per capsule; and magnesium is present in at least 25 mg per capsule. Ideally, the ratio of potassium to magnesium in any one capsule should be at least 4:1. This ratio approximates normal potassium to magnesium ratios in the extracellular fluid.

[0053] A particularly preferred embodiment comprises (per capsule): [0054] Sodium chloride 250 mg/capsule [0055] Calcium carbonate 139 mg/capsule [0056] Potassium chloride 108 mg/capsule [0057] Magnesium oxide 25 mg/capsule [0058] D-mannose 75 mg/capsule

[0059] Other amounts may be utilized and are within the scope of the invention. Amounts utilized may be limited by capsule size selected. For the purposes of the invention a minimum size for the gel cap would be a number two capsule. No particular material is required for the capsule, provided that the capsule is capable of dissolving in about fifteen minutes. For purposes of the invention, the types and amounts utilized should be adequate for the purpose of fulfilling electrolyte replenishment. The invention contemplates that adequate supplementation requires two capsules per serving of the inventive electrolyte supplement. The number of servings ingested will depend on the particular duration of physical activity and the environment. Comparisons with other electrolyte supplements discussed herein based upon “per serving”, not “per capsule”, electrolyte content.

[0060] The invention is further described by the non-limiting examples set forth below.

Example 1—Certificate of Analysis for Content and Disintegration

[0061] The inventive electrolyte supplement formulation in Table 1 below was evaluated.

TABLE-US-00001 TABLE 1 Milligrams (mg) per two Material capsule serving Sodium (as chloride) 500 mg Potassium (as chloride) 216 mg Calcium (as calcium carbonate) 279 mg Magnesium (as magnesium oxide)  50 mg D-Mannose 150 mg

[0062] The inventive formulation was incorporated into a hard gelatin capsule. Capsules were analyzed by third party testing agencies and certified for conformance to the above formulation specifications, heavy metal tests, and disintegration time. Notably, conformance to content specification was verified after disintegration thus providing an assessment of the amount of electrolytes actually delivered through the gel cap dosage form once released in the body. Results are shown in Table 2 below.

TABLE-US-00002 TABLE 2 Results per two Analysis Specification Method* capsule serving (**) Appearance Off-white/white powder blend. Visual Conforms White cap/white body capsule Capsule disintegration test NMT*** 15 minutes USP 32 <2040> Conforms Sodium (as chloride) NLT**** 500 mg/serving ICP/MS Assay 552.05 mg/Serving Potassium (as chloride) NLT 216 mg/serving ICP/MS Assay 213.04 mg/serving Calcium (as carbonate) NLT 279 mg/serving ICP/MS Assay 296.55 mg/serving Magnesium (as oxide NLT 50 mg/serving ICP/MS Assay  56.07 mg/serving D-Mannose NLT 150 mg/serving HPLC ALA626A  167.2 mg/serving *Method utilized can be either USP or other accepted compendia methods. (**) All assay testing methods had a variance of +/−10%. ***NMT = “No more than.” ****NLT + “No less than.”

[0063] Heavy metal testing (results not shown) utilizing USP test methods resulted in a “pass” rating for arsenic, cadmium, lead, and mercury. Microbiology testing (results not shown) was negative for P. aeruginosa, S. aureus, E. coli, and Salmonella sp.

[0064] Third party testing results showed that the inventive electrolyte replacement formulation does not contain any trace contaminants and that the contents were verified as specified.

[0065] The results above show that the inventive electrolyte formulation is capable of delivering sufficient types and amounts of electrolytes when incorporated into a gel capsule. The gel capsule disintegration time better than that obtained for coated and uncoated tablets. As such, it is expected that bioavailability would be comparable to that achieved when using liquid electrolyte supplements. The gel capsule has the advantage of being able to deliver higher amounts of electrolytes as compared to currently available electrolyte supplements, while at the same time reducing or eliminating palatability issues and gastrointestinal upset typically encountered with current supplements.

[0066] In addition, the inventive electrolyte formulation includes a sufficient amount of magnesium to assure proper functioning of the Na/K pump, the Ca pump and Na/Ca pump, thus improving the time in which electrolyte homeostasis can be restored.

[0067] While in accordance with the patent statutes the best mode and preferred embodiment have been set forth, the scope of the invention is not limited thereto, but rather by the scope of the attached claims.