Compositions, pharamceuticals, and methods of using resveratrol in food and beverage products

Abstract

Disclosed herein are methods, pharmaceuticals, and compositions for preserving food and beverage products and preventing oxidation and bacterial growth related to food and beverage spoilage and food and beverage taste.

Description

Docket No. AMR-101-PCTTITLECOMPOSITIONS, PHARAMCEUTICALS, AND METHODS OF USING RESVERATROL IN FOOD AND BEVERAGE PRODUCTSBACKGROUND

[0001] The invention generally relates to food and beverage products, and more particularly, to the storage or preservation of food and beverage products, food and beverage taste, food and beverage shelf life, or preserving or extending the shelf-life of a pharmaceutical composition.

[0002] Coffee is a popular liquid beverage that is brewed from roasted coffee beans. It is consumed in nearly all parts of the world. Coffee also includes ‘instant coffee’ or ‘soluble coffee’ which is a powder prepared from dried or freeze-dried coffee. Instant coffee is largely or entirely soluble in water and is typically dissolved in water prior to consumption. Coffee and instant coffee may be served at any temperature, hot or cold. Coffee is thought by some to have health benefits. The popularity of coffee makes it an ideal vehicle for providing further health benefits to the coffee drinking public.

[0003] Fruits and vegetables are consumed as food in all parts of the world. They include apples, pears, bananas, avocados, potatoes, carrots, tomatoes, onions, mangos, watermelon and peppers, to name a few.

[0004] In 2023, over 100 million tons of poultry meat were consumed globally, making it the most consumed type of meat in the world. The average global consumption of fish and other seafood per person was 19 kilograms per capita in 2021. The average daily consumption of unprocessed red meat worldwide in 2018 was 51 grams per person per day.

[0005] According to experts at the University of California Davis, food spoilage, or food loss and waste is a global issue that affects the environment, the economy, and human health. Approximately one-third of the world's food is lost or wasted, which is equivalent to 24% of the world's food supply. This amounts to more than 1 billion tons of food, or 30 million tons per year in the United States alone. This costs the global economy more than $1 trillion annually, contributes to climate change by accounting for 8-10% of global greenhouse gas emissions, wastes valuable resources like land, energy and water. If current trends continue, food loss or wasted is expected to double by 2050.

[0006] Food products, including but not limited to coffee, fruits and vegetables, poultry, fish and meat, spoil due to air oxidation, bacterial growth and other issues. Degradation due to bacterialDocket No. AMR-101-PCT growth and air oxidation lead to food spoilage by breaking down the food, producing carboxylic acids or other waste products, and changing some combination of the texture, smell, composition and taste of the food.

[0007] The present invention attempts to solve these problems, as well as others.SUMMARY OF THE INVENTION

[0008] Provided herein are methods and compositions for food, pharmaceutical, and beverage products and preventing oxidation and bacterial growth related to food and beverage spoilage and food and beverage taste. In one embodiment, the food and beverage products

[0009] The methods and compositions are set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practice of the methods and compositions. The advantages of the methods and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the methods and compositions, as claimed.

[0010] Accordingly, it is an object of the invention not to encompass within the invention any previously known product, process of making the product, or method of using the product such that Applicants reserve the right and hereby disclose a disclaimer of any previously known product, process, or method. It is further noted that the invention does not intend to encompass within the scope of the invention any product, process, or making of the product or method of using the product, which does not meet the written description and enablement requirements of the USPTO (35 U.S.C. § 112, first paragraph) or the EPO (Article 83 of the EPC), such that Applicants reserve the right and hereby disclose a disclaimer of any previously described product, process of making the product, or method of using the product. It may be advantageous in the practice of the invention to be in compliance with Art. 53(c) EPC and Rule 28(b) and (c) EPC. All rights to explicitly disclaim any embodiments that are the subject of any granted patent(s) of applicant in the lineage of this application or in any other lineage or in any prior filed application of any third party is explicitly reserved. Nothing herein is to be construed as a promise.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In the accompanying figures, like elements are identified by like reference numerals among the several preferred embodiments of the present invention.Docket No. AMR-101-PCT

[0012] FTG. 1A is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 30 seconds.

[0013] FIG. IB is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 5 minutes.

[0014] FIG. 1C is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 470 minutes.

[0015] FIG. ID is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 1300 minutes.

[0016] FIG. 2 is a Specialty Coffee Association Cupping Form used when evaluating brewed coffee With and Without the resveratrol composition.

[0017] FIGS. 3A-3C are photographs of the control, solutions #l-#3 treated apple slices over a period of 10 minutes, 60 minutes, and 240 minutes, respectively.

[0018] FIG. 4A are photographs of the raw picture and average color taken of the control apple slice from 0, 10, 30, 60, 120, and 240 minutes.

[0019] FIG. 4B are photographs of the raw picture and average color taken of the apple slice treated with ascorbic acid in water from 0, 10, 30, 60, 120, and 240 minutes.

[0020] FIG. 4C are photographs of the raw picture and average color taken of the apple slice treated with ascorbic acid and Resveratrol in water-Ethanol from 0, 10, 30, 60, 120, and 240 minutes.

[0021] FIG. 4D are photographs of the raw picture and average color taken of the apple slice treated with ascorbic acid and Resveratrol in Ethanol from 0, 10, 30, 60, 120, and 240 minutes.

[0022] FIG. 4E are the average color taken of the control apple slice, apple slice treated with ascorbic acid in water, apple slice treated with ascorbic acid and Resveratrol in water-Ethanol, and apple slice treated with ascorbic acid and Resveratrol in Ethanol from 0, 10, 30, 60, 120, and 240 minutes.DETAILED DESCRIPTION OF THE INVENTION

[0023] The foregoing and other features and advantages of the invention are apparent from the following detailed description of exemplary embodiments, read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative of the invention rather than limiting, the scope of the invention being defined by the appended claims and equivalents thereof.Docket No. AMR-101-PCTEmbodiments of the invention will now be described with reference to the Figures, wherein like numerals reflect like elements throughout. The terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive way, simply because it is being utilized in conjunction with detailed description of certain specific embodiments of the invention. Furthermore, embodiments of the invention may include several novel features, no single one of which is solely responsible for its desirable attributes, or which is essential to practicing the invention described herein.

[0024] The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. It will be further understood that the terms “comprises,” “comprising,” “includes,” and / or “including,” when used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0025] Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. The word “about,” when accompanying a numerical value, is to be construed as indicating a deviation of up to and inclusive of 10% from the stated numerical value. The use of any and all examples, or exemplary language (“e g.” or “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any nonclaimed element as essential to the practice of the invention.

[0026] References to “one embodiment,” “an embodiment,” “example embodiment,” “various embodiments,” etc., may indicate that the embodiment(s) of the invention so described may include a particular feature, structure, or characteristic, but not every embodiment necessarily includes the particular feature, structure, or characteristic. Further, repeated use of the phrase “in one embodiment,” or “in an exemplary embodiment,” do not necessarily refer to the same embodiment, although they may.

[0027] As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques andDocket No. AMR-101-PCT procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, biological, biochemical, and food arts. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification.

[0028] Description of Embodiments

[0029] Just as free radicals are associated with the early onset of many diseases, they are also associated with the oxidation and spoilage of food. Free radicals can be quenched using antioxidants like resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid. Bacterial growth on foods also results in spoilage. Ascorbic acid and resveratrol are well known antioxidants that quench free radicals. Resveratrol is associated with anti-bacterial behavior, even against foodborne pathogens. The present invention comprises a method of using novel compositions of resveratrol, glycosylated resveratrol and ascorbic acid that slow oxidation, bacterial growth and food spoilage when present in coffee and other food products. Combinations of resveratrol, glycosylated resveratrol and ascorbic acid work synergistically to be soluble in food products and preserve food and prevent spoilage. While glycosylated resveratrol and ascorbic acid are water soluble, resveratrol is fat soluble. Thus, the combination of resveratrol, glycosylated resveratrol and ascorbic acid enables a greater scope of food preservation options than any single component. Moreover, the combination of resveratrol, glycosylated resveratrol and ascorbic acid acts as a preservation agent by slowing both free radical-driven and bacteria-driven food spoilage. Finally, resveratrol, glycosylated resveratrol and ascorbic acid are all-natural compounds, each with their own set of reported health benefits as described in the scientific literature. Thus, the present invention describes a novel, all-natural food preservative prepared and delivered either in food grade solutions or in solid form that simultaneously slows food spoilage while delivering recognized health benefits.

[0030] Coffee includes brewed coffee of all types including green coffee beans and roasted coffee beans. Food products include foods of many types including apples and other fruits, potatoes andDocket No. AMR-101-PCT other starches, bread, milk, cooking, vegetable and olive oils, fish, poultry, red meat, beverages of all types and many others. The combination of resveratrol, glycosylated resveratrol and ascorbic acid compositions act as a preservative in these foods, slowing their oxidation and food spoilage.

[0031] Generally speaking, the composition comprises either a solution composed of varying concentrations of resveratrol, glycosylated resveratrol and ascorbic acid in a food grade liquid, oil, or a solid composed of varying concentrations of resveratrol, glycosylated resveratrol and ascorbic acid, alone or in the presence of an additional solid. Solutions are prepared in food grade liquids including but not limited to water, ethanol and glycerin, applied to a food product in various manners including dipping, spraying, misting and rubbing. Solid compositions are applied directly to the food in manners including rubs and dry sprays. In one embodiment, a solution comprised of resveratrol, glycosylated resveratrol and ascorbic acid in a food grade liquid in varying concentrations is applied to coffee. In one embodiment, a food grade solution of resveratrol, glycosylated resveratrol and ascorbic acid in varying concentrations possess the recognized health benefits associated with these natural antioxidants.

[0032] In another embodiment, the composition comprises an antioxidant solution including a combination of resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid present in varying concentrations in one or more of several food grade solutions. In one embodiment, resveratrol, glycosylated resveratrol and ascorbic acid are prepared in an ethanol- rich solution. In one embodiment, resveratrol, glycosylated resveratrol and ascorbic acid are prepared in a water-rich solution. In one embodiment, the concentrations of resveratrol, glycosylated resveratrol and ascorbic acid in a food grade solution ranges from about 0.1 ppm to about 1 mole / liter (Molar). In one embodiment, a solid composition containing varying concentrations of resveratrol, glycosylated resveratrol and ascorbic acid ranging from 0% to 100% by weight is applied to a food in the form of a dry spray.

[0001] In one embodiment, resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid may be in a solvent including, but not limited to food grade solvents, organic solvents, polar solvents, non-polar solvents, GRAS (“generally recognized as safe”) certified solvents, acceptable solvents, stabilizers, suspending agents, emulsifiers, release modifying, targeting and viscosity agents, diluents, excipients, and combinations thereof. Other food grade solvents include GRAS oils.Docket No. AMR-101-PCT

[0033] Other food grade solvents may be used, including, but not limited to a high purity solvent that is free of additives and is safe for a variety of food production applications. Some other common high purity solvents include heptane, acetate, hexane, aliphatic and aromatic hydrocarbons, alcohols, ethers, ester, ketones, halogenated hydrocarbons, nitrogen compounds, and sulfur compounds.

[0034] In one embodiment, the method of preserving a food product comprises applying some combination of resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid to a food product to delay the onset and progression of oxidation. Oxidation in food has many negative effects, including but not limited to taste degradation, discoloration, and a loss of vibrant appearance.

[0035] In another embodiment, a method of preserving or extending the shelf-life a pharmaceutical composition, comprising: applying a resveratrol, glycosylated resveratrol and ascorbic acid solution to a pharmaceutical composition.

[0036] In another embodiment, the method comprises limiting oxidation in brewed coffee by applying a combination of resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid to the coffee before brewing. The rate of coffee oxidation can be related to the rate of oxidation of key compounds present in the coffee including but not limited to furfuryl thiol and certain aldehydes. The rate of thiol oxidation in the presence and absence of resveratrol was measured in a laboratory. A second study utilized certified Q graders to assess the impact of coffee oxidation on taste over time. This study was similarly conducted utilizing brewed coffee both with and without Resveratrol.

[0037] In one embodiment, the method comprises using a combination of resveratrol, glycosylated resveratrol (also known as piceid) and ascorbic acid as a preservative across a number of food products.

[0038] In one embodiment, the formulation comprises resveratrol and glycerin and a method to infuse this formulation into or spray onto roasted coffee beans. The resveratrol / glycerin formulation leads to an increased solubility and bioavailability of resveratrol. In other embodiments, the formulation comprises glycosylated resveratrol (also known as piceid) and ascorbic acid in a food grade solvent.

[0039] In one embodiment, the method comprises using resveratrol, glycosylated resveratrol (also known as piceid) as a preservative for a pharmaceutical composition and treating a subject. TheDocket No. AMR-101-PCT method further comprises providing cognitive support by increasing blood flow and cellular connectivity; and enhancing memory, alertness, and concentration of a subject. The method further comprises protecting the skin from oxidative stress and inflammation; and improving skin elasticity and hydration as to reduce age spots and wrinkles. The method further comprises promoting normal blood flow and oxygen delivery to an eye of a subject; and protecting retinal cells from aging and environmental stressors. The method further comprises increasing bone mineralization and formation; and complementing at least one bone supporting supplement. The method further comprises increasing cellular blood glucose uptake; and supporting post-meal blood glucose level. The method further comprises preserving healthy gut bacteria with selective anti-bacterial activity; and supporting anti-inflammation of intestine of a subject. The method further comprises promoting gum and oral health; and preventing chronic bad breath based on selective anti-bacterial activity. The method further comprises supporting blood circulation and healthy blood pressure; improving vascular system; and maintaining healthy cholesterol and lipid levels.

[0040] Resveratrol

[0041] Resveratrol is a stilbenoid, a type of natural polyphenol, produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria or fungi. Food sources of resveratrol include the skin of grapes, blueberries, raspberries and mulberries. Resveratrol has antioxidant properties. Antioxidants protect the body from damage caused by harmful molecules called free radicals. Many experts believe free radical damage is a factor in the development of blood vessel disease (atherosclerosis), cancer and many other conditions. Red wine has been shown to have health benefits that are believed to be related to the relatively high concentration of resveratrol in it. Thus, the present invention helps coffee drinkers obtain the health benefits available from resveratrol.

[0042] Resveratrol is a chemical compound that is found in numerous natural products including peanuts, Japanese knotweed and red grapes. Both cis-resveratrol and trans-resveratrol are included in the present invention.

[0043] Resveratrol has the proper (i.e., scientific) name 3,5,4'-trihydroxystilbene. The compound can exist in two diastereomeric forms: either cis-3,5,4'-trihydroxystilbene or trans-3,5,4'- trihydroxystilbene. The trans-3,5,4'-trihydroxystilbene is known to isomerize to cis-3,5,4'- trihydroxystilbene in the presence of UV light.Docket No. AMR-101-PCT

[0044] As discussed above, resveratrol has antioxidant properties and the inclusion of resveratrol into coffee may provide or is thought to provide health benefits for coffee drinkers.

[0045] Resveratrol has a very low solubility in water. Thus, the addition of resveratrol to coffee may have little impact on coffee drinkers as it is unlikely to be fully dissolved and absorbed by the body in sufficient quantities. In order to aid in the absorption of resveratrol into the body, i.e., increase its solubility and bioavailability, the resveratrol on the present invention is part of a formulation that includes glycerin. Resveratrol is at least 48 times more soluble in glycerin than in water. Resveratrol solubilized in glycerin has greatly enhanced bioavailability over resveratrol solubilized in water.

[0046] Resveratrol includes a molecular function through three main mechanisms 1) Antioxidant capacity; 2) Activating SIRT1; and 3) Activating AMPK. Antioxidant capacity scavenges reactive oxygen species and free radicals, reducing damage caused by oxidative stress. Activating SIRT1 is a regulator to stressors, longevity, and healthy aging. Activating AMPK regulates cellular energy homeostasis, regulates glucose (energy) uptake, may help boost fat burning and weight loss. As a vaso-activator it Increases blood flow, delivering more oxygen and nutrients

[0047] Cognitive Support

[0048] Resveratrol boosts blood flow and cellular connectivity and enhances the ability to maintain memory, alertness and concentration. Resveratrol can act through multiple pathways including adenosine monophosphate protein kinase, Sirtuin-1 and via estrogen receptors to increase endothelial nitric oxide production and bioavailability. Regular supplementation with resveratrol can improve both systemic and cerebral endothelium-dependent vasodilatation, as measured by flow-mediated dilatation of the brachial artery and cerebrovascular responsiveness (CVR) to hypercapnic and cognitive challenges. In a 14-week pilot study in postmenopausal women, compared to placebo, supplementing with 2 times 75 mg of resveratrol per day resulted in a sustained enhancement of neurovascular coupling which was accompanied by improved cognitive performance. In a larger, longer term (24- month) crossover-design trial, which included an interim 12-month parallel comparison individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance. Women >65 years of age showedDocket No. AMR-101-PCT a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV, CVR to hypercapnia, CVR to cognitive stimuli, fasting insulin and insulin resistance index. Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women by improving resting cerebral blood flow, cerebrovascular resistance, neurovascular coupling and cognition.

[0049] Skin Care

[0050] Resveratrol protects skin from oxidative stress and inflammation and improves skin elasticity and hydration, reduces age spots and wrinkles. Resveratrol boost collagen production to improve the appearance of fine lines, wrinkles, and sagging, and also has anti-inflammatory properties that can help soothe redness and acne

[0051] Eye Health

[0052] Resveratrol promotes normal blood flow and oxygen delivery and helps protect retinal cells from aging and environmental stressors such as UV-light. Resveratrol shows potential for eye health due to its antioxidant and anti-inflammatory properties, which may help with age-related conditions like glaucoma, cataracts, and age-related macular degeneration (AMD). It may protect against oxidative stress, reduce inflammation, and inhibit abnormal blood vessel growth. While promising results are seen in lab and animal studies, more human research is needed, as resveratrol has challenges with low bioavailability and delivery to the eye.

[0053] Resveratrol may combat oxidative stress, a major factor in many eye diseases, and reduce inflammation associated with them. Studies suggest resveratrol, especially when combined with other treatments like selective laser trabeculoplasty (SLT), resveratrol lowers intraocular pressure (IOP) and promote optic nerve regeneration to treat glaucoma.

[0054] Resveratrol’s antioxidant properties could help prevent or treat cataracts, which are linked to oxidative stress. Resveratrol has been shown to protect against cataract development in animal models. Resveratrol may help prevent and treat this condition by suppressing oxidative damage, inflammation, and abnormal blood vessel growth caused by high glucose levels, for Diabetic retinopathy.

[0055] Resveratrol helps protect against oxidative stress and inhibit abnormal blood vessel formation, a key feature of wet age-related macular degeneration (AMD). A study indicated thatDocket No. AMR-101-PCT taking a resveratrol supplement was associated with a lower need for anti-VEGF injections in patients with wet AMD.

[0056] Preliminary studies suggest resveratrol could help with Dry eye disease (DED), a condition also driven by oxidative stress, but more research is needed.

[0057] Bone Strength

[0058] Resveratrol supports bone mineralization and formation and complements other bone supporting supplements. In an acute dose-response study in adults with type 2 diabetes, we found that 75 mg resveratrol was equally or more efficacious than 150 mg and 300 mg doses for enhancing cerebral vasodilatation and improving sustained attention. In a study, reseveratrol improved of cerebrovascular function in postmenopausal women after 14 weeks of resveratrol supplementation. The benefits of resveratrol for cerebrovascular function might also be partially mediated by the activation of estrogen receptors on endothelial cells to facilitate vasodilatation It is plausible that the ability of resveratrol to enhance microvascular perfusion may also benefit bone health, especially in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine and neck of femur, which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in ' / '-score and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck ' / ’-score with resveratrol correlated with improvement in perfusion. The bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily can slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis.

[0059] Inflammation independent effects of resveratrol in relation to bone, resveratrol stimulates osteoblast differentiation, inhibits osteoclast activity, and protects against bone loss in ovariectomized rats, immobilized rats, and aged mice. The effect of resveratrol on biochemical markers of bone turnover in a randomized placebo-controlled trial designed to investigate potential effects of high-dose RSV supplementation on substrate metabolism, insulin sensitivity, and body composition. Obese men were randomly assigned to either placebo or 1500 mg RSV daily for 4Docket No. AMR-101-PCT weeks. A highly significant increase in bone alkaline phosphatase (BAP), without changes in other biochemical markers of bone turnover or calcium homeostasis.

[0060] A larger randomized placebo-controlled trial of longer duration and using two doses of resveratrol showed the effects of resveratrol treatment on bone turnover markers, bone mass, and bone structure in obese men with Metabolic syndrome (MetS). The study population comprised 74 middle-aged obese men with MetS were orally treated with 1000 mg resveratrol, 150mg RSV, or placebo daily for 16 weeks. Prespecified primary endpoint was change in bone alkalinephosphatase (BAP) was measured. BAP increased dose dependently with resveratrol, resulting in a significantly greater increase in BAP in the lOOOmg resveratrol group compared with placebo at all time-points. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol, with a significant increase in the lOOOmg resveratrol group compared with placebo. In addition, changes in BAP and Lumbar spine trabecular volumetric bone mineral density were positively correlated. lOOOmg resveratrol supplementation positively affects bone, primarily by stimulating formation or mineralization.

[0061] In a randomized, placebo-controlled, double-blinded and parallel -group design, 24 obese non-diabetic men were randomly assigned to 500 mg resveratrol or placebo treatment three times daily for four weeks. Biomarkers of bone metabolism, inflammatory parameters and circulating hormones were measured before and after the intervention period. Plasma levels of bone-specific alkaline phosphatase increased significantly in the resveratrol group as compared to placebo. This was paralleled by a tendency of total alkaline phosphatase to rise within the resveratrol group, whereas no changes were detected in other biomarkers of bone and calcium metabolism, including PINP, osteocalcin, CTx, or PTH.

[0062] Blood Glucose Regulation

[0063] Resveratrol triggers cellular blood glucose uptake and supports healthy fasting and postmeal blood glucose level. Resveratrol may help regulate blood glucose by improving insulin sensitivity and lowering blood glucose levels, particularly in individuals with type 2 diabetes. Its mechanisms may include activating SIRT1, which influences key proteins involved in glucose metabolism, and potentially protecting pancreatic beta cells.

[0064] Resveratrol has been shown to improve insulin sensitivity (measured by the Matsuda index) in some studies. Resveratrol achieves this by deactivating proteins that inhibit the insulin signaling pathway, such as PTP1B.Docket No. AMR-101-PCT

[0065] Resveratrol activates the protein SIRT1 , which is crucial for regulating metabolism. STRT1 influences key proteins that impact glucose metabolism, such as FOXO1.

[0066] In some models, resveratrol has been shown to increase the number of pancreatic beta cells and improve insulin secretion, which could help the body manage high blood glucose levels.

[0067] Some meta-analyses show that resveratrol can significantly decrease blood glucose and insulin levels, especially in adults aged 45-59. Other studies found a decrease in postmeal glucose and insulin levels with resveratrol. Some studies show improvement with higher doses or longer intervention periods for effect on HbAlc (a measure of long-term blood glucose control).

[0068] Gut Microbiota

[0069] Resveratrol preserves healthy gut bacteria with selective anti-bacterial activity and supports anti-inflammation of intestine. Resveratrol positively impacts the gut microbiota by modulating its composition, increasing diversity, and enhancing the integrity of the gut barrier. It can decrease harmful bacteria and increase beneficial bacteria that produce short-chain fatty acids (SCFAs). The gut microbiota also metabolizes resveratrol into active compounds that have further health benefits, highlighting a synergistic relationship where each influences the other.

[0070] Resveratrol can shift the balance of gut bacteria, such as reversing the negative effects of a high-fat diet on the ratio of Bacteroidetes to Firmicutes. Resveratrol can decrease the abundance of certain "bad" bacteria like Desulfovibrio and Lachnospiraceae_NK4A316_group. Resveratrol can increase the presence of beneficial SCFA-producing bacteria like Bacteroides and Blautia.

[0071] Resveratrol can enhance the overall diversity of the gut microbiota. Resveratrol improves gut barrier integrity by upregulating genes involved in creating tight junctions between intestinal cells. By improving the gut barrier and modulating the microbiota, resveratrol can help reduce intestinal inflammation. The positive changes in gut microbiota are linked to resveratrol's antiobesity and metabolic benefits. Microbiota from resveratrol-treated mice can decrease weight gain and improve insulin sensitivity in the recipients.

[0072] Oral Health

[0073] Resveratrol promotes gum and oral health and prevents chronic bad breath based on selective anti-bacterial activity. Resveratrol shows potential benefits for oral health by strengthening enamel, reducing inflammation, and inhibiting harmful bacteria. Resveratrol helps prevent cavities and erosion, act as an anti-inflammatory agent for conditions like gingivitis andDocket No. AMR-101-PCT periodontitis and inhibit the bacteria responsible for dental plaque. Resveratrol may protect tooth enamel from erosion and support remineralization, making teeth more resistant to acid and decay. Resveratrol can inhibit the growth of bacteria linked to dental plaque, such as S. mutans, and can reduce their acid production and biofilm formation. Resveratrol can reduce inflammation associated with gum disease like periodontitis and gingivitis. It may also help protect the surrounding bone tissue. By inhibiting the virulence of cavity-causing bacteria and reducing plaque, resveratrol helps prevent dental caries. Resveratrol may have a role in preventing oral cancer by reducing inflammation and proliferation of cancer cells.

[0074] Cardiovascular Health

[0075] Resveratrol supports blood circulation and healthy blood pressure and improves vascular system and maintains healthy cholesterol and lipid levels. Resveratrol may benefit cardiovascular health by reducing oxidative stress and inflammation, improving blood pressure, and lowering "bad" cholesterol while raising "good" cholesterol. It appears to work by enhancing nitric oxide production for vasodilation and potentially through its antioxidant effects on LDL cholesterol. Resveratrol has shown potential in lowering blood pressure, particularly in animal models. Resveratrol may help lower total, LDL, and VLDL cholesterol, as well as triglycerides. Resveratrol can also help increase HDL cholesterol levels. Resveratrol helps blood vessels relax by increasing the production of nitric oxide, a potent vasodilator. Resveratrol may offer protection against stroke by preserving blood-brain barrier function and reducing inflammation and damage in the brain. Resveratrol helps combat oxidative stress and inflammation, which are key factors in the development of cardiovascular diseases. Resveratrol shows promise in reducing the risk of atherosclerosis, including improving plaque stability in animal studies.

[0076] Anti-Fungal, herbicide properties

[0077] Resveratrol has antifungal properties, especially in its oligomeric forms, which are produced by plants as a defense mechanism against fungi. While research shows some direct antifungal activity, especially against certain bacteria and fungi, resveratrol also has a role as a plant-based "antiviral" agent.

[0078] Resveratrol is a phytoalexin produced by plants in response to fungal attacks. Resveratrol is synthesized at the site of infection and its concentration increases in resistant plants. While resveratrol monomers show limited antifungal activity, the oligomeric forms (chains of resveratrol) have more potent antifungal properties. Studies have shown that resveratrol oligomersDocket No. AMR-101-PCT can inhibit fungal growth and have antifungal activity against various species. Resveratrol can also work synergistically with other antifungal compounds to increase their effectiveness

[0079] Resveratrol has been shown to help with wound healing in plants.

[0080] Taste modifiers and neutralizers

[0081] Taste modifiers are compounds that alter the human perception of taste in food and beverages, influencing flavors such as sweet, sour, salty, bitter, and umami without changing the food's inherent chemical makeup. They are used in the food industry to create healthier products with reduced sugar or sodium while maintaining palatability and can also be used to mask off- flavors, enhance existing tastes, or act as salt or sweetness replacers.

[0082] Taste modifiers interact with taste receptors on the tongue to change how humans perceive basic tastes. Taste modifiers can block bitter tastes, reduce the amount of sugar needed for sweetness, or enhance the perception of saltiness. Taste modifiers are used to cover or reduce undesirable off-flavors, such as those from plant-based proteins or mineral content, according to Ingredion.

[0083] Taste modifiers can reduce bitterness, often used when reducing sugar or adding ingredients that can have a bitter taste. Taste modifiers reduce sodium content while maintaining a perception of saltiness or enhance existing saltiness. Taste modifiers increase the perception of sweetness, allowing for less sugar to be used in products. Taste modifiers can intensify existing flavors, particularly umami (savory), without adding their own distinct flavor, notes McCormick Flavor Solutions. Taste modifiers can cover or hide unpleasant flavors by tricking the brain with strong tastants or phantom aromas.

[0084] Examples

[0085] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and / or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

[0086] Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc ), but some errors and deviations should be accounted for. Unless indicatedDocket No. AMR-101-PCT otherwise, parts are parts by weight, temperature is in ° C or is at ambient temperature, and pressure is at or near atmospheric.

[0087] Example 1. Slowing Oxidation in Potatoes

[0088] A resveratrol composition was sprayed onto freshly cut Idaho potato slices and compared over time to slices that had not been treated with resveratrol. The results are shown in the FIGS. 1A-1D. FIG. 1A is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 30 seconds. FIG. IB is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 5 minutes. FIG. 1C is a photograph of the top view of potato slices treated with the resveratrol composition 100 and without the resveratrol composition 120 after 470 minutes. FIG. ID is a photograph of the top view of potato slices treated with the resveratrol composition and without the resveratrol composition after 1300 minutes. In FIGS. 1A-1D, the potato slices that were treated with resveratrol 100 are shown on the right while the untreated potato slices 110 are shown on the left. The ‘yellowing’ or ‘browning’ of potatoes is associated with oxidation, aging and eventual spoilage. The untreated potato slices are observed to age more significantly and faster than the treated slices.

[0089] Example 2. Slowing Oxidation in Coffee

[0090] In one example, thin-layer chromatography and 1H NMR spectroscopy were used to monitor the rate of oxidation of a thiol in the presence and absence of resveratrol. Several aldehydes and thiols were dissolved in either water or water / ethanol solutions and heated in open air with magnetic stirring. To understand the impact of resveratrol on air oxidation, reactions were run with and without added resveratrol. This initial study shows that oxidation occurs about 1.5 times to about 2 times faster in the absence of resveratrol, as judged by the onset of 1H NMR signals associated with oxidation products and the diminishment of signals associated with the starting thiol.

[0091] In a second coffee study, four coffee Q graders tested brewed coffee samples prepared from identical beans except that some beans had been treated with resveratrol prior to brewing. Brewed coffee is known to oxidize rapidly leading to coffee that tastes less agreeable. A biting or acidic taste is often associated with brewed coffee that has oxidized significantly. The Q graders performed two tests: ‘Off-Brew’ and ‘On Burner’ tests. For the ‘off-brew’ testing, they brewed coffee of both types (with and without resveratrol) and taste tested both types immediately afterDocket No. AMR-101-PCT brewing. They placed the freshly brewed samples in separate thermos’ and performed separate taste-tests after 2 hours ‘off-brew’ and finally after 4 hours ‘off-brew’ . For the ’on-burner’ testing, the Q graders taste tested freshly brewed coffee of both types and left the coffees on the burner / heat source. They subsequently performed additional taste tests after 30 and 60 minutes ‘on-burner’.

[0092] During the ‘off-brew’ testing, the Q graders described the coffee treated with resveratrol as tasting better with a more pronounced body. During the ‘on-burner’ testing, the Q graders described the coffee treated with resveratrol as tasting better, not tasting burnt, as holding up better, and as having more soul.

[0093] Thus, the method comprises preserving taste qualities in coffee treated with resveratrol and includes preserving the taste qualities of other foods and beverages in addition to coffee.

[0094] Example 3: Coffee Cupping with Resveratrol composition

[0095] Coffee cupping, or coffee tasting, is the practice of observing the tastes and aromas of brewed coffee. It is considered a professional practice when performed by certified experts known as "Q Graders". Q Graders must pass a series of rigorous tests to become licensed professionals who are capable of scoring the quality of roasted coffees. On June 12, 2024, a panel of experts participated in a formal coffee cupping that included coffee infused with the resveratrol composition and without the resveratrol composition.

[0096] Cupping method

[0097] Panel of Experts including a certified Q Grader. The cupping methodology included the following: Off brew coffee with samples of with the resveratrol composition and without the resveratrol composition; brewed coffee with the resveratrol composition and without the resveratrol composition and immediately tasted; brewed coffee in a thermos for about 2 hours with the resveratrol composition and without the resveratrol composition and tasted; and brewed coffee in thermos for 4 hours with the resveratrol composition and without the resveratrol composition and tasted.

[0098] On burner coffee included samples of with the resveratrol composition and without the resveratrol composition; brewed coffee with the resveratrol composition and without the resveratrol composition and immediately tasted; brewed coffee that sits on the burner for 30 min with the resveratrol composition and without the resveratrol composition and tasted; and brewed coffee that sits on the burner for about 60 min with the resveratrol composition and without the resveratrol composition and tasted.Docket No. AMR-101-PCT

[0099] Coffee experts utilized the official Specialty Coffee Association Cupping Form when evaluating brewed coffee with and without the resveratrol composition, as shown in FIG. 2. The results of the tasting are shown in Table 1.

[0100] Table 1 : Panel of Experts Cupping Results

[0101] Example 4; Fruit Oxidation Study

[0102] The Resveratrol-based formulation has demonstrated that it decreases the rate of oxidation in brewed coffee, and the effects on additional food categories, beginning with fruits were tested.

[0103] For this example, a Honeycrisp apple from Chile (supermarket code 3283) was utilized.

[0104] Antioxidant Solutions:

[0105] 1. Ascorbic Acid in water (no ethanol, no resveratrol as resveratrol only shows very low — likely ppm — solubility in pure water).

[0106] 2. Ascorbic Acid and Resveratrol in 151 proof grain alcohol (75.5% ethanol). In the pictures provided, this solution is labelled “EtOH”. Ascorbic acid shows reduced solubility inDocket No. AMR-101-PCT alcohol compared to water. Thus, this solution contains an excess of resveratrol compared to ascorbic acid.

[0107] 3. Ascorbic Acid and Resveratrol in 151 proof with water added (-45% ethanol in the solution). In the pictures provided, this solution is labelled “EtOH / H2O”. As the concentration of water increases, the solubility of ascorbic acid increases while the solubility of resveratrol decreases. Thus, this solution contains an excess of ascorbic acid compared to resveratrol.

[0108] Honeycrisp Apple Example

[0109] The apple was cut into thin slices using a sharp steel knife. Each of three separate slices was treated with a different antioxidant solution (see description of antioxidant solutions 1-3 above). A fourth slice was left untreated, as a control. The apple slices were left on a white paper plate, exposed to ambient air with an air temperature of 70 °F and a relative humidity of 55%. The remaining apple was eaten. Its tart flavor with modest sweetness suggested that it was ripe or very nearly so.

[0110] For treatment with antioxidants, the corresponding antioxidant solution was sprayed onto the apple slices using a small, plastic spray bottle purchased at Walmart. The nozzle of the spray bottle was adjusted such that the spray was a fine mist. The amount of antioxidant added to each slice was not controlled for these experiments, but generally 2-3 squirts of a fine mist were added to each slice. Average colors were determined using the on-line average color tool at https : / / mat kl , github . i o / aver age- col or / . The tool coverts each picture to a single pixel, and the average color of this pixel is generated.[OHl] As shown in FIGS. 3A-3D, the untreated ‘control’ apple slice 200 oxidizes the fastest as judged by its relatively fast discoloration / browning. Significant brown patches were observed on the control slice 200 within approximately 10 minutes, as shown in FIG. 3A. Browning continued for the control slice 200 over the duration of the experiment, as shown in FIGS. 3B. After 120 minutes, a relatively large brown patch was observed toward the middle of the slice with brown “veins” traversing elsewhere, as shown in FIG. 3C. FIG. 4A shows the control slice getting darker with the green and blue values getting higher.

[0112] The second fastest oxidation was observed with the apple slice treated with antioxidant solution #1 (ascorbic acid in water, no ethanol, no resveratrol 210), as shown in FIGS. 3A-3C. While this apple slice 210 oxidizes considerably slower than the untreated control, it started showing some small patches of brown discoloration after approximately 30 minutes, as shown inDocket No. AMR-101-PCTFIG. 3A, and continued to brown (at a relatively slow pace) throughout the course of the experiment, as shown in FIG. 3C. FIG. 4B shows the slice with solution #1 not getting darker.

[0113] The apple slices treated with antioxidant solutions 2 (220) and 3 (230) performed the best. As shown in FIG. 3B, neither slice 220, 230 showed significant brown discoloration after 60 minutes in ambient air and light. As shown in FIG. 3C, even after 120 minutes of exposure to ambient light and air, only faint brown discoloration was observed for the slice 220 treated with antioxidant solution 2 while no discoloration whatsoever was observed for the slice 230 treated with antioxidant solution 3. As shown in FIG. 3C, even after 4 hours of exposure to ambient light and air, the apple slice 230 treated with antioxidant solution 3 showed no signs of browning. It maintained excellent appearance, looking like a freshly cut slice. FIG. 4C shows the slice not getting darker getting darker.

[0114] FIG. 4D shows the slice treated with solution #3 no color change. FIG. 4E are the average color taken of the control apple slice, apple slice treated with ascorbic acid in water, apple slice treated with ascorbic acid and Resveratrol in water-Ethanol, and apple slice treated with ascorbic acid and Resveratrol in Ethanol from 0, 10, 30, 60, 120, and 240 minutes.

[0115] Conclusion:

[0116] Antioxidant Solutions 2 and 3 (ethanol-based solutions containing both resveratrol and ascorbic acid) effectively preserve apple slices for long durations at least 10, 30, 60, 120, and 240 minutes.

[0117] A water-based antioxidant solution containing ascorbic acid and no resveratrol (antioxidant solution 1) performed better than the control (i.e., an untreated apple slice), but not nearly as efficient as antioxidant solutions 2 and 3.

[0118] No significant browning of apple slices treated with antioxidant solutions 2 and 3 was observed after 4 hours.

[0119] Based upon the rates of browning observed, it is fair to state that apple slices 220, 230 treated with either antioxidant solution 2 or 3 oxidize at least 40 times slower than untreated apple slices, and at least 5 times slower than apple slices treated with an aqueous solution of ascorbic acid (i.e., antioxidant solution 1).

[0120] Potential Additional Testing:

[0121] Additional preparations and testing an entirely water-based antioxidant solution containing a water-soluble form of resveratrol and ascorbic acid. While resveratrol itself is not water solubleDocket No. AMR-101-PCT to an appreciable extent, glycosylated resveratrol or piceid is water soluble. Piceid is a naturally occurring glycosylated form of resveratrol that is commercially available. In plants, piceid is formed naturally as a precursor to resveratrol. It has been tested and shown to possess positive health effects, albeit less so than resveratrol itself. It has never been tested (to our knowledge) as a water-soluble preservative.

[0122] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0123] While the invention has been described in connection with various embodiments, it will be understood that the invention is capable of further modifications. This application is intended to cover any variations, uses or adaptations of the invention following, in general, the principles of the invention, and including such departures from the present disclosure as, within the known and customary practice within the art to which the invention pertains.

Claims

Docket No. AMR-101-PCTCLAIMSWhat is claimed is:

1. A composition comprising: a resveratrol, glycosylated resveratrol and ascorbic acid solution applied to a food product or a beverage product; the resveratrol, glycosylated resveratrol and ascorbic acid solution are present in amounts effective to synergistically enhance aqueous solubility of the resveratrol and glycosylated resveratrol and to inhibit oxidation of a food product, preserve taste or flavor, or prevent spoilage.

2. The composition of Claim 1, wherein the concentration of resveratrol, glycosylated resveratrol or ascorbic acid is between about 0 and about 10 mole / liter (Molar).

3. The composition of Claim 2, wherein the resveratrol, glycosylated resveratrol and ascorbic acid are dissolved in a food grade solvent.

4. The composition of Claim 3, wherein the food grade solvent is ethanol.

5. The composition of Claim 4, wherein the beverage product is coffee.

6. The composition of Claim 2, wherein at least one of resveratrol, glycosylated resveratrol and ascorbic acid.

7. The composition of Claim 6, wherein some combination of resveratrol, glycosylated resveratrol and ascorbic acid are dissolved in water.

8. The composition of Claim 7, wherein the food product is selected from the group consisting of: fruits, potatoes and other starches, bread, milk, cooking, vegetable, oils, fish, poultry, drinks, and meat.

9. A method of preserving a food product or a beverage product, comprising: applying a resveratrol, glycosylated resveratrol and ascorbic acid solution to a food product or beverage product in synergistically effective amounts to form a preservative composition to delay the onset and progression of oxidation and food spoilage.Docket No. AMR-101-PCT10. The method of Claim 9, wherein the concentration of resveratrol, glycosylated resveratrol and ascorbic acid in solution is between about 0 and about 10 mole / liter (Molar).

11. The method of Claim 10, wherein the resveratrol, glycosylated resveratrol and ascorbic acid is dissolved in a food grade solvent.

12. The method of Claim 11, wherein the food grade solvent is ethanol.

13. The method of Claim 12, wherein the beverage product is coffee.

14. The method of Claim 1, wherein the resveratrol, glycosylated resveratrol and ascorbic acid are applied to a food product in solid form.

15. The method of Claim 14, wherein the individual compositions of resveratrol, glycosylated resveratrol and ascorbic acid are between about 0% and about 100% by weight.

16. The composition of Claim 15, wherein the food product is selected from the group consisting of: coffee, fruits, potatoes and other starches, bread, milk, cooking, vegetable and olive oils, fish, poultry, and red meat.

17. A method of preserving a food product or a beverage product, comprising: applying a resveratrol, glycosylated resveratrol and ascorbic acid mixture in solid form in synergistically effective amounts to a food product or a beverage product to delay the onset and progression of oxidation and food spoilage.

18. The method of Claim 17, wherein the individual compositions of resveratrol, glycosylated resveratrol and ascorbic acid are between 0% and 100% by weight.

19. A method of preserving or extending the shelf-life of a pharmaceutical composition, comprising: applying a resveratrol, glycosylated resveratrol and ascorbic acid solution to a pharmaceutical composition.Docket No. AMR-101-PCT20. The method of Claim 19, further comprising providing cognitive support by increasing blood flow and cellular connectivity; and enhancing memory, alertness, and concentration of a subject.

21. The method of Claim 19, further comprising protecting the skin from oxidative stress and inflammation; and improving skin elasticity and hydration as to reduce age spots and wrinkles.

22. The method of Claim 19, further comprising promoting normal blood flow and oxygen delivery to an eye of a subject; and protecting retinal cells from aging and environmental stressors.

23. The method of Claim 19, further comprising increasing bone mineralization and formation; and complementing at least one bone supporting supplement.

24. The method of Claim 19, further comprising increasing cellular blood glucose uptake; and supporting post-meal blood glucose level.

25. The method of Claim 19, further comprising preserving healthy gut bacteria with selective anti-bacterial activity; and supporting anti-inflammation of intestine of a subject.

26. The method of Claim 19, further comprising promoting gum and oral health; and preventing chronic bad breath based on selective anti-bacterial activity.

27. The method of Claim 19, further comprising supporting blood circulation and healthy blood pressure; improving vascular system; and maintaining healthy cholesterol and lipid levels.

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