Method for neutralizing stomach acid using alginate, polylysine, and a seed preservative

Abstract

Provided is a nutritional supplement (or "digestive aid") containing alginate that is optimized for improved solubility, safety, taste and effectiveness. The present invention relates to a method for neutralizing stomach acid in a subject comprising an alginate-based nutritional product ("AP"). The AP comprises alginate as a reflux neutralizer, raft forming agent, and stabilizer, and includes polylysine, dextrose, and grapefruit seed extract preservatives. The method is intended to provide relief or prevention of acid reflux and other forms of indigestion in mammals. In some embodiments, dextrose and polylysine are combined to form a preservative for the alginate-based dietary supplement. In other embodiments, a method is provided for producing an anti-reflux raft.

Description

[Technical field]

[0001] Priority This application claims priority from U.S. Provisional Application No. 63 / 218,488, filed July 5, 2021. The disclosure of this provisional application is incorporated herein as if set forth in full. The present disclosure relates generally to methods for neutralizing stomach acid in a subject using polylysine, dextrose, and grapefruit seed extract as preservatives in alginate-based nutritional supplements and digestive aids. [Background technology]

[0002] Paraben-based compounds and synthetic substances in general are known in the art to act as effective preservatives and digestive aids.However, paraben-based compounds are known hormone disruptors and are involved in the development of certain cancers.Therefore, there is a need in the art for safe, easy to manufacture, non-carcinogenic, non-hormonally disrupting, non-paraben-based food preservatives and digestive aids.Alginate is a natural polysaccharide polymer isolated from brown algae, which may partially address this need in the art.Alginate has been safely used as a food additive for over 100 years, and its health benefits are mainly derived from stable dietary fiber that is easily digested in mammalian stomachs. The stomach can be considered an extension of the esophagus. After oral ingestion, food remains in the stomach for 1-6 hours. During that time, the chewed food becomes a thin paste or gruel, which is broken down into small pieces and flows out into the duodenum. To process this food, several enzymes are produced by the epithelial cells. In addition, the parietal cells of the stomach produce hydrochloric acid, also called gastric acid, which keeps the pH of the stomach low. This gastric acid is the first line of immune response to foreign organisms, providing a bactericidal effect against bacteria, fungi, and other microorganisms. Although essential for food digestion, reflux of stomach acid into the esophagus and upper respiratory tract is a problem in modern society. The esophagus and throat (pharynx and larynx) are not capable of processing the low pH stomach acid contents and can cause damage. While many people are genetically and physically predisposed to reflux, lifestyle habits such as stress, overeating, eating or drinking quickly, and guzzling carbonated drinks can further contribute to reflux of stomach contents into the esophagus and upper respiratory tract.

[0003] Indigestion can be broadly defined as dyspepsia or GERD (gastroesophageal reflux disease). Dyspepsia is a general term for the pain or discomfort a person may feel in the stomach and under the ribs, usually after eating or drinking alcohol (i.e. alcoholic drinks or coffee), but similar symptoms can occur on an empty stomach. GERD, on the other hand, is a digestive disorder caused by the relaxation of a ring of muscle between the human esophagus and stomach. This ring is called the lower esophageal sphincter (LES), and its relaxation can further lead to heartburn or excess stomach acid. Some people experience indigestion a few times a year, while others suffer from daily symptoms that can range from mild discomfort lasting a few minutes to severe pain lasting longer, sometimes accompanied by nausea and vomiting that can last for hours. The most common symptoms of indigestion are pain or discomfort in the stomach and under the ribs, heartburn, bloating or uncomfortable fullness after eating, stomach rumbling, stomach cramps, tightness or tightness in the stomach, excessive burping or flatulence, and nausea or vomiting. The most common symptoms of reflux of gastric contents into the upper airway, or laryngopharyngeal reflux (LPR), are sore throat, rasping, hoarseness, coughing, and the feeling of a lump in the throat.

[0004] This disorder is experienced by an increasing number of people in developed countries. At least one third of the population suffers from episodic dyspepsia. Indigestion can generally be alleviated by antacids, which act as bases or acid buffers to raise the pH of the stomach contents. Antacids are usually available over the counter and can be purchased at any pharmacy. Calcium carbonate is commonly used as the active ingredient in antacids. Some calcium-based antacids also have other ingredients added, such as magnesium or aluminum. Common over the counter antacids include Tums® (which is simply calcium carbonate) sold by GlaxoSmithKline of Brentford, UK, Rennie® (which has magnesium added to it to counteract the possible side effect of constipation from consuming too much calcium) and Maalox® (which has aluminum added to it and is available in liquid or tablet form) sold by Novartis. Antacids can be useful as self-medication for indigestion sufferers with mild or moderate heartburn, but because they are fast-acting and short-acting, they are less helpful for frequent or severe heartburn and do not work very well as a preventative measure.

[0005] Acid blockers, such as H2 blockers and proton pump inhibitors (PPIs), are commonly used for severe, chronic conditions. These drugs work by blocking stomach acid from being produced. Although these acid blockers are not as fast acting as antacids, they are long-lasting and can be effective for several hours at a time. Over-the-counter acid blockers include Axid®, Pepcid®, Tagamet®, and Zantac®. These brands are also available in prescription strengths if the milder forms do not provide sufficient relief. The clinical efficacy of H2 blockers and proton pump inhibitors is well known. (Hurlimann S, Michel K, Inauen W, Halter F: Effect of Rennie Liquid versus Maalox Liquid on intragastric pH in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers. Am J. Gastroenterol. 1996; 91: 1173-1180;Feldman M: Pros and cons of over-the-counter availability of histamine2-receptor antagonists. Arch Intern Med 1993; 153: 2415-2424;Netzer P, Brabetz-Hoefliger A, Bruendler R, Flogerzi B, Huesler J, Halter F: Comparison of the effect of the antacid Rennie versus low dose; and H2-receptor antagonists (ranitidine, famotidine) on intragastric pH. acidity. Aliment Pharmacol Ther 1998; 12: 337-342).

[0006] Acid blockers, such as Pepcid®, Tagamet®, and Zantac®, work by blocking one of the histamines produced in the stomach, which then blocks the production of acid. These histamine blockers are typically most effective when taken twice daily, 30-60 minutes before meals. Unfortunately, some histamine blockers have been implicated in the development of certain cancers, as well as many other serious, life-threatening and / or life-altering side effects.

[0007] Another class of acid-blocking drugs, called proton pump inhibitors, or PPIs, stop the tiny proton pumps in the stomach that produce acid, dramatically lowering acid levels. They are often used when histamine blockers do not provide sufficient relief or when a person has erosions in the esophagus or other complications of GERD (gastroesophageal reflux disease). One proton pump inhibitor, Prilosec®, is available commercially in the United States as well as many other countries. Other PPIs, such as Aciphex®, Nexium®, Prevacid®, Protonix®, and other forms of Prilosec®, may require a doctor's prescription depending on local requirements. Reglan® is another prescription drug that works to reduce acid reflux by speeding up the emptying of the stomach. Reglan® strengthens the digestive contractions that move food through the esophagus, thus speeding up digestion, which may be associated with reduced heartburn. Prokinetic drugs, including Reglan®, have potentially deadly side effects and have received a "black box" warning from the Food and Drug Administration (FDA), the agency's strongest warning.

[0008] Alginate is a natural product of kelp (brown algae) that has been used safely as a natural food additive for over 100 years. Alginate is a common household ingredient used to thicken foods and make jellies. When consumed, alginate also coats the lining of the esophagus and stomach, creating a protective mucosal layer and forming protective alginate rafts that float on top of the stomach contents and bind with bicarbonate in the stomach to relieve acid reflux. One of the major challenges in developing natural alginate products to help relieve reflux is that alginate can form a medium for bacterial and fungal growth and is very difficult to preserve. For this reason, the main preservative used in modern alginate-based products is paraben. Parabens are synthetic preservatives that are known hormone disruptors and have been implicated in hair loss, allergic reactions, and the development of many cancers. As an example, British Patent No. 2324725 discloses a pharmaceutical composition suitable for forming a mucoadhesive lining in the digestive tract. It comprises alginic acid or an alginate salt with at least a unitary M / G ratio. The composition can be formulated as a liquid for the treatment of reflux esophagitis. In the examples, 32 g of calcium carbonate or 100 g of 10% aluminum hydroxide gel per 100 g of sodium alginate are used to form an anti-reflux raft that floats on the stomach. However, alginate products suffer from several adverse effects, including hormone disruption and potential carcinogenic effects due to the paraben preservatives required to prevent bacterial and fungal growth.

[0009] Relatedly, WO2001 / 087282A3 and US2007 / 0281015 describe an antacid pharmaceutical composition that has mucosal protective activity and quickly and long-lastingly neutralizes gastric acid. The pharmaceutical is intended as a liquid preparation for oral ingestion. It contains at least 30% sodium alginate, an antacid soluble drug, and a proton pump inhibitor such as omeprazole. The antacid soluble drug of choice is sodium bicarbonate, which acts directly in the digestive tract to neutralize gastric hyperacidity, the alginate forms a viscous suspension or gel after entering the gastric environment and exerts protective activity over the gastric mucosa, and the proton pump inhibitor acts by selectively blocking the H+ / K+_ATPase enzyme in the gastric parietal cells of the stomach. The objective of the present invention is to disclose a nutritional supplement / supplement (or "digestive aid") containing alginate optimized for improved solubility, safety, taste and efficacy. In contrast to the prior art, said digestive aid has the advantage of acting almost instantly as well as having a longer lasting neutralizing effect on stomach acid. Thus, the invention described herein fulfills the need in the art for a safer, more palatable, non-hormonally disrupting, non-carcinogenic digestive aid, which is furthermore natural, paraben-free and safe. Summary of the Invention

[0010] In order to minimize the limitations found in existing systems and methods, as well as other limitations which will become apparent upon reading this specification, the present invention includes polylysine, dextrose, and grapefruit seed extract as preservatives in an alginate-based nutritional supplement product ("AP" or "digestive aid").

[0011] The present disclosure provides a method for neutralizing gastric acid in a subject, comprising administering to the subject an effective amount of an alginate-based product (AP), wherein the AP forms anti-reflux rafts in the subject's stomach, the AP comprising alginate and polylysine. In some embodiments, the AP is further adapted to neutralize acid reflux, and the AP further comprises a stabilizer, an alkaline salt, a secondary alkaline agent, and a salt comprising calcium.

[0012] In other embodiments, the AP is adapted to counteract reflux esophagitis, and the alginate is formulated to inhibit proteolytic enzymes. In embodiments, inhibiting proteolytic enzymes comprises inhibiting the proteolytic activity of pepsin and / or gastric juices. In some embodiments, the AP is further adapted to counteract indigestion, and the AP further comprises polylysine, dextrose, and grapefruit seed extract. In some embodiments, the AP is adapted to act as both an antacid and an anti-reflux raft, the anti-reflux raft comprising a foam barrier adapted to react with gastric acid and float in the stomach contents of a subject, thereby neutralizing gastric acid, acid reflux, GERD, and / or indigestion. In embodiments, the AP forms a foam raft formulation in 2.0-12.0% w / v low viscosity grade dextrose blended with sugar as a secondary preservative.

[0013] In other embodiments, administering an effective amount of dextrose sugar contributes to the dryness of the product, which promotes its action as a preservative. In particular, the AP may be formulated as a powder, syrup, and / or capsule. Also provided is a method for producing an anti-reflux raft. Further provided is a method for neutralizing reflux in a subject, comprising administering to the subject an effective amount of an alginate-based product (AP), wherein the AP is administered in combination with at least a carrier and an MTOR compound. It is a primary object of the present invention to provide methods for making and using a natural, safe, non-hormone disrupting, non-carcinogenic digestive aid. A second object of the present invention is to provide a method of using a digestive aid or alginate product ("AP") that is more palatable to users, offered in a variety of unique natural flavors optimized by world-class chefs. It is another object of the present invention to optimize the alginate raft technology so that lower concentrations of the alginate active ingredient are required to obtain a therapeutic effect. Yet another object of the present invention is to optimize the manufacture of the indigestion related nutritional supplement / digestion aid claimed herein and improve the solubility of some of the ingredients including salts. These and other advantages and features of the present invention are described with particularity to enable those skilled in the art to understand the present invention, and a better understanding of the nature and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying drawings, in which: To improve clarity and understanding of the various elements and embodiments of the present invention, elements in the drawings are not necessarily drawn to scale. Additionally, elements that are commonly known and well understood by those skilled in the art have not been drawn to clearly illustrate the various embodiments of the present invention. Thus, the drawings are in a generalized format for clarity and conciseness. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 shows the chemical structure of polylysine according to a preferred embodiment of the present invention. [Diagram 2] FIG. 2 shows the chemical structure of dextrose in accordance with a preferred embodiment of the present invention. [Diagram 3] FIG. 3 shows the chemical structure of alginic acid ("alginate") in accordance with a preferred embodiment of the present invention. [Figure 4] Figure 4 shows a schematic diagram of alginate raft precipitation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] In the following discussion addressing several embodiments and applications of the present invention, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and changes may be made without departing from the scope of the present invention. Various inventive features are described below that can each be used independently of one another or in combination with other features. However, any single inventive feature may not address any of the problems discussed above, or may only address one of the problems discussed above. Furthermore, one or more of the problems discussed above may not be fully addressed by any of the features described below.

[0016] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. "And," as used herein, is used interchangeably with "or," unless expressly stated otherwise. As used herein, the term "about" refers to ±5% of the recited parameter. All embodiments of any aspect of the invention can be used in combination, unless the context clearly dictates otherwise. Unless the context clearly requires otherwise, throughout this specification and the claims, words such as "comprise," "comprising," and the like are to be construed in an inclusive sense, i.e., "including but not limited to," as opposed to an exclusive or exhaustive sense. Words using the singular or plural also include the plural and singular, respectively. Additionally, when used in this application, the words "herein," "herein," "wherein," "wherein," "above," and "below," and similar words, refer to this application as a whole and not to any particular portions of this application.

[0017] The description of the embodiments of the present disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. While specific embodiments and examples of the present disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the present disclosure, as those skilled in the relevant art will recognize. In some embodiments, the use of polylysine 10, dextrose 20 and grapefruit seed extract as preservatives in alginate-based products is contemplated. In a preferred embodiment, the alginate-based product (hereinafter referred to as "AP" or "alginate supplement") is a composition comprising an alginate-based product that uses alginate 30 as a stabilizer in addition to polylysine 10, dextrose 20 and grapefruit seed extract preservatives. In some embodiments, dextrose 20 (or other common sugars known in the art) and polylysine 10 are combined to form a preservative for alginate-based products. In other embodiments, dextrose 20 (or other common sugars known in the art), grapefruit seed extract and polylysine 10 are combined to form a preservative for alginate-based products.

[0018] In some embodiments, dextrose 20 sugar and / or other sugars contribute to the dryness of the product, which aids in its action as a preservative. Additionally, in some embodiments, the AP forms a thinning (protective) barrier on the mucosal lining of the user's throat and esophagus to provide relief from the partially refluxed low pH components of the small intestine and stomach characteristic of gastroesophageal reflux. Once in the stomach, as shown in FIG. 4, the AP forms a stable protective raft 40 of foam composition (also referred to herein as a "gel raft", "foam" or "foam raft") that acts as a pH-neutral mechanical barrier to reduce gastric reflux from the stomach to the esophagus and throat. Reducing reflux reduces the exposure of the user's throat to the low pH contents of the stomach that would otherwise contribute to local inflammation, DNA damage, pain, bad breath, and poor sleep. In a preferred embodiment, the AP comprises 200 mg sodium alginate, 170 mg vitamin B5, 200 mg sodium bicarbonate, dextrose 20, polylysine 10, and grapefruit seed extract. In a preferred embodiment, the alginate gel coats the tissues of the throat and esophagus, providing relief from acid reflux and other forms of indigestion as described above. In particular, 200 mg sodium alginate is used as a food additive to form a foamy and / or viscous solution or gel. Additionally, 170 mg vitamin B5 (calcium pantothenate) enhances the strength and cohesiveness of the foamy raft. Calcium increases raft strength by cross-linking the alginate polymers 30. In some embodiments, vitamin B5 provides the unexpected result of enhanced raft strength and reduced acid reflux. Additionally, vitamin B5 helps the body convert masticated carbohydrates into glucose, which the body uses to produce adenosine triphosphate (ATP) through aerobic metabolism. These B vitamins, often called vitamin B complex, help the body metabolize fats and proteins and contribute to improved nervous system function. AP also fills the stomach and can be used as a dietary supplement.

[0019] Further to the above, 200 mg of sodium bicarbonate enhances the availability and efficacy of raft formation. In particular, in the presence of gastric acid, bicarbonate forms carbon dioxide bubbles within the alginate gel matrix, buffering the acid in the process. This feature induces effervescent action within the rafts, allowing the gel to further float to the surface of the gastric contents. Carbon dioxide also contributes to the acid neutralizing effect of AP. In some embodiments, dextrose 20 functions as a natural sweetener and an essential preservative. As mentioned above, dextrose 20 also reduces the moisture content of AP, which is essential for the preservative function of AP. The unique combination of alginate 30 and dextrose 20 significantly enhances the acid reflux suppression effect of AP in a manner not contemplated in the art. As mentioned above, polylysine 10 also functions as an essential natural preservative. In some embodiments, grapefruit seed extract ("GSE extract") serves as an essential natural preservative, antifungal agent, and sweetener, providing a uniquely high concentration of antioxidants.

[0020] In some embodiments, AP is a low sodium, iodine free, potassium free alternative to many anti-reflux compositions known in the art. Other products known in the art contain high salt content, high levels of potassium, which contribute to high blood pressure and kidney damage in some patients, as well as potential carcinogens such as parabens, which are known hormone disruptors. In contrast, all the components of AP are non-synthetic, which alleviates digestive and organ filtration problems.In another embodiment, AP functions as a dietary supplement, and the usefulness of AP comes mainly from its fibrous compounds.In the user's stomach, said compounds expand, giving the user a feeling of fullness, while contributing to a balanced pH environment.

[0021] Further expanding on the usefulness of vitamin B5, besides its digestive function, the compound is highly water soluble and essential for the manufacture of red blood cells. Additionally, vitamin B5 acts as a substrate for the synthesis of stress-related hormones produced in the adrenal glands. In some embodiments, vitamin B5 in AP promotes the maintenance of a healthy digestive tract and aids in the body's use of other vitamins, particularly B2 (also called riboflavin). In particular, the miscibility of calcium and vitamin B5 was contemplated by the inventors. In some embodiments, the ideal ingredient composition (optimized for solubility) included a Chilean seaweed sourcing of alginate 30 (specifically, lessonia nigrescens) formulated in a 60 / 40 (M / G) ratio.

[0022] In some embodiments, various dosages of each of the above ingredients are contemplated and are optimized for each particular food product with respect to buffering capacity, antioxidant capacity, etc. As noted above, in a preferred embodiment, the AP comprises 200 mg sodium alginate, 170 mg vitamin B5, 200 mg sodium bicarbonate, dextrose 20, polylysine 10, and grapefruit seed extract. In another embodiment, the AP comprises sodium alginate in the range of 75-400 mg, 100-350 mg vitamin B5, 100-300 mg sodium bicarbonate, with dextrose 20, polylysine 10, and grapefruit seed extract included in non-specific dosage amounts.

[0023] In some embodiments, the AP relates to the relief of reflux esophagitis using alginate 30 specially formulated to inhibit proteolytic enzymes. In some embodiments, the invention relates to the inhibition of the proteolytic activity of pepsin and / or gastric juice. In other embodiments, one or more dextrose molecules 20 with a preferred molecular weight of less than 500 kDa are used in combination with polylysine 10, dextrose 20 and grapefruit seed extract preservatives. The composition may be in the form of a dry powder that can be mixed with water. Additionally, the preparation may be configured in a liquid form, preferably containing dextrose 20 in an amount of 0.1-15% w / v. In some embodiments, the composition further comprises a neutralizing agent for neutralizing gastric acid, such as sodium hydroxide.

[0024] In some embodiments, the composition preferably contains a divalent or trivalent metal cation to enhance the formation of foam rafts. The cation may be, for example, a calcium ion or an aluminum ion. For example, the composition may contain 10-80 g of calcium carbonate per 100 g of dextrose 20. In some embodiments, the AP exerts its effect by dissolving solid calcium carbonate salts in the stomach under the influence of acid gastric juice, in addition to polylysine 10, dextrose 20 and grapefruit seed extract. High calcium concentrations stimulate the gelation of alginate, as calcium ions and polysaccharides form a rigid matrix. Furthermore, the dissolution of calcium carbonate and sodium bicarbonate increases the CO 2 Gas is generated and traps the alginate matrix, thereby forming foam rafts. Apart from being potential carcinogens and hormone disruptors known in the art, and in addition to the inconvenience of consuming a non-uniform product, the products known in the prior art have the drawback that the consumer cannot obtain an adequate dose of calcium salt to proceed with optimal gelation. More importantly, the sodium alginate salt used in the prior art is occupied by calcium ions in a cage-like structure, and therefore cannot react with the acid present in the stomach.

[0025] To remedy this problem, in some embodiments, the AP can act as both an antacid and a foam-like barrier or raft that allows the esophagus to pour into the upper part of the stomach. When the tablet is swallowed or the liquid is ingested, the antacid, polylysine 10, dextrose 20 and grapefruit seed extract neutralize the stomach acid, while the effervescent creates a physical barrier to aid in relief from acid reflux. The composition can be orally administered in the form of a dry powder or an aqueous suspension, which may also contain suspending agents and / or preservatives. The antacid / effervescent formulation reacts with the stomach acid to form a raft on the stomach contents. In some embodiments, the AP comprises an effervescent formulation comprising 2.0-12.0% w / v low viscosity grade dextrose mixed with a secondary preservative sugar. Relatedly, the liquid formulation of the antacid / effervescent formulation comprises an aqueous medium containing 1.5-10.0% w / v low viscosity grade dextrose 20 mixed with other sugars known in the art. To suspend the calcium carbonate particles in the aqueous medium, a suspending agent such as an acrylic polymer crosslinked with 1% dextrose 20 can be used. In another embodiment, improved pourability is obtained in AP formulations using liquid compositions containing potassium bicarbonate instead of other bicarbonates and at least 10% w / v sodium alginate in combination with polylysine 10, dextrose 20 and grapefruit seed extract as preservatives. The compositions achieve a viscosity that does not cause thickening problems even when stored at low temperatures. A salt of a divalent metal ion such as calcium carbonate is generally included in the above compositions in an amount of 5-40 g / 100 g dextrose 20 to obtain optimal foam raft formation.

[0026] In some embodiments, a method is contemplated for providing relief from GERD and dyspepsia using all natural polylysine 10, dextrose 20 and grapefruit seed extract as preservatives. As noted above, the method further relates to the preparation of an injectable liquid sodium alginate composition. The composition preferably comprises a total dextrose 20 content of 8-15% w / v. In this embodiment, the composition further comprises an amount of bicarbonate, which may be required to generate adequate carbon dioxide in the stomach to obtain adequate raft formation 20.

[0027] In some embodiments, the compositions of the invention can optionally contain small amounts of alkali salts containing crosslinkable multivalent metal ions to support foam rafts when contacted with gastric fluids. In some embodiments, rafts act mechanically, meaning that their anti-reflux effect results from physically obscuring access to substrates. In particular, the crosslinkable multivalent metal ions can be ions of calcium and aluminum, and salts include, by way of example only, calcium carbonate, CaHPO 4 , aluminum carbonate and aluminum hydroxide. The salt containing crosslinkable polyvalent metal ions is usually present in an amount of less than 12% by weight, such as less than 5% by weight, such as less than 1% by weight, such as less than 0.3% by weight, preferably less than 0.1% by weight, based on the weight of the alginate. The salt is generally solid in the composition, but is suitably highly soluble at the pH present in the stomach. In one aspect of the invention, the salt provides less than 200 ppm of polyvalent metal ions when the pH of the composition is changed to about pH=2. In one aspect, the amount of calcium salt in the composition provides less than 50 ppm of dissolved calcium ions when the pH is changed to about pH=2.

[0028] In some embodiments, the AP further comprises an alkaline salt, the alkaline salt being a disintegrant selected from the group consisting of sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3), and mixtures thereof. In some embodiments, the AP further comprises at least 2%, 4%, 8%, 10% or more by weight of an additional alkaline agent selected from the group consisting of magnesium hydroxide (Mg(OH)2), potassium hydroxide (KOH), sodium hydroxide (NaOH), sodium acetate (C2H3O2Na), and mixtures thereof, based on the weight of sodium alginate. In some embodiments, the AP further comprises less than 10%, less than 8%, less than 6%, or less than 4% by weight of a calcium-containing salt, based on the weight of sodium alginate. In some embodiments, the composition further comprises an alkaline agent, such as magnesium hydroxide. In some embodiments, the composition further comprises sodium bicarbonate in an amount of 10%, 12%, 15%, or 20% or more by weight in total, based on the weight of sodium alginate. In other embodiments, the amount of magnesium hydroxide is greater than or equal to 1%, 2%, or 3% by weight based on the weight of sodium alginate. As mentioned above, in a preferred embodiment, the alginate-based product ("AP") is a composition that includes alginate 30 as a stabilizer, in addition to polylysine 10, dextrose 20, grapefruit seed extract preservatives, and optionally minor amounts of salts. However, in other aspects, the composition of the present invention ("AP") does not contain added salts, including cross-linking polyvalent metal ions, such as calcium salts, which are soluble at the pH present in the stomach. Small amounts of calcium salts may be present, for example, in tap water ingested by the user of the composition. In one embodiment, at least 70%, such as 80%, and preferably at least 90% of the alkali metal carboxylate groups of the alkali metal alginate are available to react with stomach acid, i.e., do not react with cross-linking polyvalent metal ions. In some embodiments, the calcium-containing agent is vitamin B5 and / or another vitamin B complex known in the art. Calcium pantothenate, alternatively known as pantothenic acid or vitamin B5 or panthenol, is a composition of 8% calcium and 92% pantothenic acid.

[0029] The composition according to the present invention may contain one or more acceptable carriers in addition to the above-mentioned active ingredient.The carrier must be "acceptable" in the sense that it is compatible with other components of the composition and is not harmful to its recipient.In certain embodiments, the alginate is purified.The composition can be formulated as tablets, pills, syrups, capsules, gummies, powders, etc.

[0030] It will be understood that the amount of the composition required for treatment or prevention varies depending on the form of administration, the disorder to be addressed, the condition, age, medical history of the subject, and the composition formulation.When a person seeks relief from a certain affliction, the amount of active ingredient is preferably an amount effective to provide relief to the individual.With increasing age, it is often necessary to increase the dosage of AP to provide the mitigating effect of GSE antioxidant. The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which active ingredient is administered.The carrier in the composition may include a binder such as microcrystalline cellulose, polyvinylpyrrolidone (polyvidone or povidone), tragacanth gum, gelatin, starch, lactose or lactose monohydrate; a lubricant or surfactant such as magnesium stearate or sodium lauryl sulfate; a lubricant such as colloidal silicon dioxide; a sweetener such as dextrose 20, sucrose or saccharin; and / or a flavoring such as peppermint, methyl salicylate, orange flavor, and / or other natural flavors.

[0031] In some embodiments, the AP formulation further comprises one or more enzyme cofactors and / or one or more essential nutrients. Exemplary cofactors include vitamin C, biotin, vitamin B5, vitamin E, and vitamin K. Exemplary essential nutrients are amino acids and fatty acids. The AP can also comprise one or more excipients known in the art, such as dispersing agents, wetting agents, and suspending agents. The AP solution, suspension, or emulsion can also contain one or more excipients known in the art, such as dispersing agents, wetting agents, and suspending agents.

[0032] Therapeutic formulations suitable for oral administration, such as tablets and pills, can be obtained by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by mixing the ingredients and compressing the mixture in a suitable device to form tablets of suitable size. In one embodiment, the alkali metal alginate can be mixed with a binder, a lubricant, an inert diluent and / or a disintegrant, and the alkali salt can be mixed with a diluent, a lubricant and / or a surfactant, before mixing. In some embodiments, when one or more carriers are present, the free-flowing alkali metal alginate powder may be mixed with a binder, such as microcrystalline cellulose, and a surfactant, such as sodium lauryl sulfate, until a homogenous mixture is obtained. Another binder, such as polyvidone, may then be transferred to the mixture under agitation. Once a homogenous distribution is obtained, the alkali salt is added under constant agitation. The mixture is passed through a granulating screen, dried, and then compressed into tablets in standard compression equipment. Alternatively, the tablets are prepared without the addition of a carrier. According to this alternative embodiment, the free-flowing alkali metal alginate is mixed with the alkali salt before compressing the mixture into tablets. Conventional methods for producing solid forms of the composition can be found in the European Pharmacopoeia, which is incorporated herein by reference. Tablets may be coated or uncoated. Uncoated tablets may be scored. Coated tablets may be coated with sugar, shellac, film, or other enteric coating agents.

[0033] In other embodiments, the grape seed compound includes natural seed antioxidants, fiber, and MTOR compounds (e.g., compounds shown to act on the MTOR gene signaling pathway, including resveratrol). In other embodiments, the inclusion and concentration of resveratrol enhances both the strong antioxidant properties of AP, but may also contribute to neuroprotective and lifespan-extending benefits to the user. In particular, resveratrol is highly concentrated in grape skins, and when administered at high concentrations, it has been shown to extend the lifespan of certain laboratory mice by up to 50%. This observation is likely related to both the strong antioxidant effects of resveratrol and its gene signaling / gene regulatory effects, for example, acting through the MTOR signaling pathway.

[0034] In some embodiments, there are multiple flavors of AP, including vanilla caramel, mint chocolate, and / or other natural flavors. These flavors are derived in part from natural antioxidant ingredients and sugars inherent in the natural ingredients. In a preferred embodiment, the AP also has a basic pH and / or is infused with a pH buffering compound to reduce acid reflux in the user. In this way, the AP can be consumed by the user as a flavorful food and as a supplement for acid reflux. One of the inherent advantages of AP is the flavor variety (breadth of flavor) as well as the flavorful product (intensity of flavor). In some embodiments, reflux prevention rafts ("rafts") are produced by the steps of: a) preparing a functionalized natural or synthetic calcium carbonate containing minerals, said functionalized natural or synthetic calcium carbonate being a reaction product of natural or synthetic calcium carbonate with carbon dioxide and one or more acids, where the carbon dioxide is formed in situ by acid treatment and / or is provided from an external source; b) preparing at least one polylysine-containing component; c) preparing at least one formulation agent comprising an alginate; d) mixing the compounds prepared in steps a), b) and c); and e) granulating the mixture obtained in step d) by melting, dry or wet granulation, or roller compaction. In particular, step "c" may include the addition of dextrose, preservatives, grapefruit seed extract, and other secondary compounds.

[0035] Further to the above, in some embodiments, a portion of the formulation auxiliary of step c) is first mixed with the functionalized calcium carbonate of step a) and at least one polylysine-containing component of step b), then the remaining portion of the formulation auxiliary is added to the mixture, followed by granulation step e). Further to the above, in some embodiments, the natural calcium carbonate source for preparing the functionalized calcium carbonate is selected from the group of marble, calcite, chalk, vitamin B5, limestone and dolomite and / or mixtures thereof. In other embodiments, the synthetic calcium carbonate for preparing the functionalized calcium carbonate is precipitated calcium carbonate containing aragonite, vaterite or calcareous mineralogical crystal morphology, in particular prismatic, rhombohedral or scalenohedral precipitated calcium carbonate or mixtures thereof. In yet other embodiments, the acid is selected from the group of hydrochloric acid, sulfuric acid, sulfurous acid, hydrogen sulfate, phosphoric acid, a combination of phosphoric acid with acetic acid, formic acid or citric acid, or acid salts thereof, and mixtures thereof, preferably phosphoric acid.

[0036] In some embodiments, the functionalized natural or synthetic calcium carbonate has a 5m 2 / g~200m 2 / g, preferably 20m 2 / g~150m 2 / g, more preferably 40m 2 / g~100m 2 In some embodiments, the functionalized natural or synthetic calcium carbonate has a mass median particle size of 0.2-40 μm, preferably 0.6-25 μm, more preferably 0.9-18 μm, and even more preferably 1-15 μm, measured using standard means known in the art, such as a Malvern Mastersizer X long bed.

[0037] The foregoing description of preferred embodiments of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teachings. It is intended that the scope of the invention be limited not by this detailed description, but by the claims and the equivalents of the claims appended hereto.

Claims

An alginate-based product (AP) for use in a method of neutralizing the effects of gastroesophageal reflux in a subject, the method comprising: a) administering to the subject an effective amount of AP, wherein AP comprises alginate, dextrose, vitamin B5 and polylysine, dextrose, grapefruit seed extract and polylysine are combined to form a preservative for AP, and AP does not contain parabens and is composed entirely of non-synthetic ingredients, said step, b) forming a mucoadhesive barrier on the mucosae of the larynx, esophagus and stomach to reduce gastroesophageal reflux, c) creating a raft in the subject's stomach, wherein vitamin B5 crosslinks the alginate polymer to enhance the strength and cohesiveness of the raft, thereby reducing acid reflux and significantly enhancing the acid reflux inhibitory effect of AP. The AP according to claim 1, wherein the anti-reflux raft comprises a foamed barrier adapted to function as a pH-neutral mechanical barrier that reduces gastroesophageal reflux from the stomach to the esophagus and pharynx and neutralizes gastric acid, gastroesophageal reflux, reflux esophagitis, and / or dyspepsia by reacting with gastric acid and floating on the gastric contents. The AP according to claim 1, wherein administration of an effective amount of dextrose promotes drying of the product and promotes its action as a preservative. The AP according to claim 1, wherein the AP is administered in combination with one or more cofactors, excipients, vitamins, carriers, surfactants, and / or binders. An alginate-based product (AP) for use in a method of neutralizing the effects of gastroesophageal reflux, the method comprising the following steps: a) administering AP to a subject, wherein the AP comprises sodium alginate, vitamin B5, sodium bicarbonate, dextrose, polylysine, and grapefruit seed extract, dextrose and polylysine combine to form a preservative for AP, and the AP does not contain parabens and is composed entirely of non-synthetic ingredients, said step, b) A step of forming a raft of the foamy composition by AP in the stomach of the subject, wherein the raft is a pH-neutral mechanical barrier that reduces gastric reflux from the stomach to the esophagus and pharynx, vitamin B5 enhances the strength and cohesiveness of the raft, sodium bicarbonate enhances the usefulness and efficacy of raft formation, and the combination of sodium alginate and dextrose enhances the anti-corrosion effect of AP, said step. **Claim 6**: An alginate-based product (AP) for use in a method of neutralizing the effects of gastroesophageal reflux in a subject, said method comprising administering to the subject an effective amount of AP, said AP comprising sodium alginate, vitamin B5, sodium bicarbonate, dextrose, polylysine, and grapefruit seed extract; said AP forms a stable protective raft of the foamy composition that functions as a pH-neutral mechanical barrier to reduce gastric juice reflux from the stomach to the esophagus and pharynx; in the presence of gastric acid, sodium bicarbonate forms carbon dioxide bubbles within the raft, thereby buffering the gastric acid; vitamin B5 enhances the strength and cohesiveness of the raft, and the combination of sodium alginate and dextrose enhances the acid reflux inhibitory effect of AP; and said AP does not contain parabens and is composed entirely of non-synthetic components, said AP.

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