Euclide matrix for nutritional supplement compositions

Abstract

The present disclosure describes a composition comprising a eutectic matrix containing methylsulfonylmethane and a sugar alcohol, and particles of a dietary supplement within the eutectic matrix. In some embodiments, the sugar alcohol:methylsulfonylmethane ratio can be 95:5 to 20:80. Methods for producing the composition and for increasing the solubility and bioavailability of the dietary supplement are also provided herein.

Description

[Background technology]

[0001] (background) Flavonoids, or bioflavonoids, are polyphenolic compounds found in plants and fungi. Many flavonoids are hydrophobic and have poor water solubility. As a result, they have poor bioavailability.

[0002] For example, flavonols are a subclass of flavonoids that have a molecular structure based on a 3-hydroxyflavone skeleton. They are widely distributed in nature and are most commonly found in fruits and vegetables. Some examples of common flavonols include fisetin, galangin, gossipetin, kaemperia, kaemperool, isorhamnetin, morin, myricetin, pachypodol, quercetin, rhamnadin, and ramnetin. Flavonols have limited water solubility, although flavonol glycosides have somewhat better solubility.

[0003] As another example, quercetin is one of the most commonly consumed flavonoid compounds derived from everyday foods. It has been reported to be found in foods such as capers, dill, cilantro, onions, kale, chokeberries, cranberries, and plums. Quercetin commonly exists in nature as quercetin glycosides and contains quercetin aglycones, which are conjugated to sugar moieties such as glucose or rutinose. Quercetin has been reported to exhibit antioxidant, anti-cancer, anti-inflammatory, anti-aggregating, and vasodilatory effects. Unfortunately, the bioavailability of quercetin is generally poor, and several factors affect its bioavailability.

[0004] Other examples of poorly water-soluble compounds with limited bioavailability include quercetin glycosides (such as rutin) (e.g., rutinose glycoside of quercetin, found in capers, raspberries, buckwheat, and asparagus) and curcuminoids, which are generally hydrophobic compounds thought to possess various therapeutic benefits, such as anti-inflammatory, antioxidant, and / or anticancer activity. Further examples include fat-soluble vitamins (such as vitamin A, vitamin D2, vitamin D3, vitamin E, or vitamin K), isolated food compounds containing nonpolar moieties (such as sterols, stanols, omega-3 fatty acids, or omega-3 fatty acid esters, supplied from fish, krill, plants, or algae), or carotenoids (such as astaxanthin, lutein, and zeaxanthin).

[0005] However, their therapeutic use has been limited by their hydrophobicity, which results in poor solubility and rapid elimination from the body (i.e., low bioavailability). [Overview of the project] [Problems that the invention aims to solve]

[0006] There is a need for a solubilizing matrix that enhances the solubilization and bioavailability of flavonoids or bioflavonoids. This disclosure attempts to meet these needs and provides further relevant benefits. [Means for solving the problem]

[0007] (overview) This summary is provided to introduce, in a simplified form, the selected concepts that are further described below in the detailed explanation. This summary is not intended to identify the essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

[0008] In one aspect, the present disclosure features a composition comprising a eutectic matrix containing methylsulfonylmethane and sugar alcohols; and particles of a nutritional supplement contained within the eutectic matrix.

[0009] In one embodiment, the ratio of sugar alcohol to methylsulfonylmethane is 95:5 to 20:80. In one embodiment, the sugar alcohol is a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecose alcohol, or any combination thereof. In one embodiment, the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof. In one embodiment, the sugar alcohol is xylitol.

[0010] In one embodiment, the eutectic matrix has a melting point lower than that of methylsulfonylmethane and the sugar alcohol, respectively. In one embodiment, the eutectic matrix is ​​methylsulfonylmethane and the sugar alcohol. In one embodiment, the methylsulfonylmethane and the sugar alcohol form an organized structure or repeating pattern. In one embodiment, the dietary supplement forms hydrogen bonds and / or ionic bonds with the eutectic matrix.

[0011] In one embodiment, the dietary supplement is quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, shizandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof. In one embodiment, the dietary supplement is quercetin.

[0012] In one embodiment, the composition further comprises lipids. In one embodiment, the lipids are edible oils or mixtures of oils. In one embodiment, the lipids are medium-chain triglycerides. In one embodiment, the lipids form a lipid-soluble matrix with methylsulfonylmethane, sugar alcohols, or nutritional supplements. In one embodiment, the composition further comprises saponins, cocoa, or any combination thereof.

[0013] In one embodiment, the composition has a larger AUC than a 250 ng / ml nutritional supplement when administered to a subject. 0~8時間 It has the following characteristics. In one embodiment, the composition is in the form of a tablet, capsule, softgel, gummy, or liquid.

[0014] In one embodiment, the nutritional supplement has a water solubility at least 4% greater than the water solubility of the nutritional supplement in the individual matrix components. In one embodiment, the nutritional supplement has a water solubility that is not linearly correlated with the diameter of its particles and is not linearly correlated with the percentage of methylsulfonylmethane in the composition. In one embodiment, the nutritional supplement has a peak water solubility at a methylsulfonylmethane concentration of 20% to 50% by weight. In one embodiment, the nutritional supplement has a water solubility greater than the sum of the water solubility of the nutritional supplement in methylsulfonylmethane and sugar alcohols, respectively. In one embodiment, the composition has an enteric coating.

[0015] In one aspect, the present disclosure provides a method for producing a composition comprising the steps of: mixing methylsulfonylmethane and a sugar alcohol to form a mixture; heating the mixture to melt the methylsulfonylmethane and the sugar alcohol; adding a nutritional supplement composition; and cooling the mixture to form a eutectic matrix containing particles of the nutritional supplement.

[0016] In one aspect, the present disclosure provides a method for producing a composition comprising the steps of: dissolving methylsulfonylmethane and a sugar alcohol in water, ethanol, acetone, or a polar solvent to form a solution; adding a nutritional supplement to the solution; and recrystallizing the solution to obtain a eutectic matrix containing particles of the nutritional supplement.

[0017] In one aspect, the present disclosure provides a method for enhancing the solubility of a dietary supplement by adding it to a lipid-soluble matrix. In one embodiment, the lipid-soluble matrix comprises methylsulfonylmethane, a sugar alcohol, and a lipid. In one embodiment, the methylsulfonylmethane and the sugar alcohol form a eutectic matrix. In one embodiment, the ratio of sugar alcohol to methylsulfonylmethane is 95:5 to 20:80.

[0018] In one embodiment, the sugar alcohol is a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecase alcohol, or any combination thereof. In one embodiment, the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof. In one embodiment, the sugar alcohol is xylitol.

[0019] In one embodiment, the lipid is edible oil or a mixture of oils. In another embodiment, the lipid is a medium-chain triglyceride.

[0020] In one embodiment, the dietary supplement is quercetin, epimedium extract, curcuminoid, echinacea alkylamide, soybean isoflavone, hesperidin, grape seed extract, giant thistle extract, procyanidin, schizandra fruit extract, lemon balm extract, ginger root extract, saxifrage extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterol, stanol, or any combination thereof. In one embodiment, the dietary supplement is quercetin. In one embodiment, the fat-soluble matrix further comprises saponin, cocoa, or any combination thereof.

[0021] In one aspect, the present disclosure provides a method for enhancing the bioavailability of a dietary supplement by adding the dietary supplement to a fat-soluble matrix.

[0022] In one embodiment, the fat-soluble matrix comprises methylsulfonylmethane, sugar alcohol, and lipid. In one embodiment, methylsulfonylmethane and sugar alcohol form a eutectic matrix. In one embodiment, the ratio of sugar alcohol to methylsulfonylmethane is from 95:5 to 20:80. In one embodiment, the sugar alcohol is a tetrose alcohol, pentose alcohol, hexose alcohol, dodecose alcohol, or any combination thereof. In one embodiment, the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, maltitol, and any combination thereof. In one embodiment, the sugar alcohol is xylitol.

[0023] In one embodiment, the lipid is edible oil or a mixture of oils. In one embodiment, the lipid is medium-chain triglyceride.

[0024] In one embodiment, the dietary supplement is quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof. In one embodiment, the dietary supplement is quercetin. In one embodiment, the lipid-soluble matrix further comprises saponins, cocoa, or any combination thereof.

[0025] Many of the aspects of this disclosure and the associated advantages described above will be better understood by referring to the following detailed description in conjunction with the attached drawings, and will therefore be easier to grasp. [Brief explanation of the drawing]

[0026] [Figure 1] Figure 1 is a graph showing the mean quercetin concentration in whole blood over time for embodiments of the compositions of this disclosure and for comparative compositions.

[0027] [Figure 2A] Figure 2A is a table showing the average quercetin concentration in whole blood over time for comparative compositions containing quercetin as micronized powder.

[0028] [Figure 2B] Figure 2B is a table showing the mean whole blood quercetin concentration over time for comparative compositions containing quercetin solubilized in a micelle matrix.

[0029] [Figure 2C] Figure 2C is a table showing the average whole blood quercetin concentration over time for comparative compositions containing quercetin as granular powder.

[0030] [Figure 2D]Figure 2D is a table showing the mean whole blood quercetin concentration over time for comparative compositions containing quercetin solubilized in a micelle matrix containing peppermint oil.

[0031] [Figure 2E] Figure 2E is a table showing the mean quercetin concentration in whole blood over time for comparative compositions contained in hard gelatin capsules.

[0032] [Figure 2F] Figure 2F is a table showing the mean quercetin concentration in whole blood over time for comparative compositions contained in hard gelatin capsules.

[0033] [Figure 2G] Figure 2G is a table showing the mean quercetin concentration in whole blood over time for comparative compositions contained in hard gelatin capsules.

[0034] [Figure 2H] Figure 2H is a table showing the mean quercetin concentration in whole blood over time for embodiments of the compositions of this disclosure.

[0035] [Figure 2I] Figure 2I is a table showing the mean whole blood quercetin concentration over time for comparative compositions containing enzyme-modified sugar quercetin.

[0036] [Figure 2J] Figure 2J is a table showing the mean whole blood quercetin concentration over time for comparative compositions containing quercetin formulated with cyclodextrin.

[0037] [Figure 3] Figure 3 is a high-pressure liquid chromatogram of the water solubility of Epimedium extract. Black line: MSM without xylitol matrix. Blue line: MSM with xylitol matrix.

[0038] [Figure 4]Figure 4 shows the high-pressure liquid chromatogram of the water solubility of curcuminoids. Black line: MSM: without xylitol matrix. Blue line: MSM: with xylitol matrix.

[0039] [Figure 5] Figure 5 shows the high-pressure liquid chromatogram of the water solubility of echinacea alkylamide. Black line: MSM: without xylitol matrix. Blue line: MSM: with xylitol matrix.

[0040] [Figure 6] Figure 6 is a high-pressure liquid chromatogram of the water solubility of soy isoflavones. Black line: MSM: without xylitol matrix. Blue line: MSM: with xylitol matrix.

[0041] [Figure 7] Figure 7 shows the high-pressure liquid chromatogram of the water solubility of hesperidin. Black line: MSM: without xylitol matrix. Blue line: MSM: with xylitol matrix.

[0042] [Figure 8] Figure 8 shows a high-pressure liquid chromatogram of the water solubility of grape seed extract. Black line: MSM without xylitol matrix. Blue line: MSM with xylitol matrix.

[0043] [Figure 9] Figure 9 shows the high-pressure liquid chromatogram of the water solubility of milk thistle extract. Black line: MSM: results without xylitol matrix. Blue line: MSM: with xylitol matrix.

[0044] [Figure 10] Figure 10 is a graph showing the nonlinear behavior of quercetin solubility and hydrodynamic particle volume (particle size) as a function of MSM ratio. Solubility of dietary supplements does not correlate with smaller particle sizes.

[0045] [Figure 11A] Figure 11A is a table of melting points for embodiments of the matrix of this disclosure, with measured melting points of MSM:xylitol in various ratios.

[0046] [Figure 11B] Figure 11B is a graph of the melting points of an embodiment of the matrix of the present disclosure.

[0047] [Figure 12-1] Figure 12 shows a table of water solubility of embodiments of the compositions of this disclosure. [Figure 12-2] Figure 12 shows a table of water solubility of embodiments of the compositions of this disclosure. [Figure 12-3] Figure 12 shows a table of water solubility of embodiments of the compositions of this disclosure.

[0048] [Figure 13] Figure 13 is a bar graph showing the solubility of the nutritional supplements in the compositions of this disclosure.

[0049] [Figure 14] Figure 14 is a graph of the solubility of embodiments of the compositions of this disclosure as a function of the MSM ratio.

[0050] [Figure 15A] Figure 15A is a table showing the solubility of embodiments of the composition of this disclosure, in which the active ingredient is grape seed extract, as a function of the MSM ratio.

[0051] [Figure 15B] Figure 15B is a graph of the solubility of grape seed extract catechins as a function of the MSM ratio.

[0052] [Figure 16] Figure 16 shows embodiments of quercetin compositions and a table of their corrected water solubility.

[0053] [Figure 17A] Figure 17A shows embodiments of Epimedium compositions and a table of their water solubility.

[0054] [Figure 17B] Figure 17B shows embodiments of Epimedium compositions and graphs of their water solubility.

[0055] [Figure 18A] Figure 18A shows embodiments of hesperidin compositions and a table of their water solubility.

[0056] [Figure 18B] Figure 18B shows embodiments of hesperidin compositions and graphs of their water solubility.

[0057] [Figure 19A] Figure 19A shows embodiments of curcumin compositions and a table of their water solubility.

[0058] [Figure 19B] Figure 19B shows embodiments of curcumin compositions and graphs of their water solubility.

[0059] [Figure 20A] Figure 20A is a table showing the pharmacokinetic properties of the comparative quercetin compositions.

[0060] [Figure 20B] Figure 20B is a table showing the pharmacokinetic properties of the compositions of this disclosure.

[0061] [Figure 20C] Figure 20C is a graph of blood quercetin concentrations for the compositions of this disclosure and comparative compositions.

[0062] [Figure 21A] Figure 21A is a table comparing the solubility of milk thistle extract in its unmodified form, in a eutectic matrix, and in a lipid-soluble matrix.

[0063] [Figure 21B] Figure 21B is a table comparing the solubility and bioavailability of berberine extract in its unmodified form, with ascorbic acid, in a eutectic matrix with ascorbic acid, and in a eutectic matrix without ascorbic acid.

[0064] [Figure 21C] Figure 21C is a table comparing the solubility and permeability of vitamin D3 in its unmodified form and in its lipid-soluble matrix form.

[0065] [Figure 21D] Figure 21D is a table comparing the bioavailability of Boswellia extract in its unmodified form and in its lipid-soluble matrix form with saponins.

[0066] [Figure 21E] Figure 21E is a table comparing the solubility of coenzyme Q10 (CoQ10) in its unmodified form and in a lipid-soluble matrix form with cocoa.

[0067] [Figure 21F] Figure 21F is a table comparing the solubility of ubiquinol in its unmodified form, in a lipid-soluble matrix form with cocoa, and in a lipid-soluble matrix form without cocoa. [Modes for carrying out the invention]

[0068] (Detailed explanation) This disclosure features a composition comprising a eutectic matrix containing methylsulfonylmethane and sugar alcohols; and a nutritional supplement contained within the eutectic matrix. The nutritional supplement may be in the form of particles. In some embodiments, the composition does not contain phospholipids, sugars, oils, enzymes, caffeine, green tea, green tea extract, and / or vitamins.

[0069] (definition) For clarity, it is understood that certain features of the Disclosure described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features of the Disclosure described in the context of a single embodiment for brevity may also be provided separately or in any suitable partial combination.

[0070] It will be readily apparent that the aspects of this disclosure, as generally described and illustrated in the drawings herein, can be arranged, substituted, combined, separated, and designed in a wide variety of configurations, all of which are expressly intended herein.

[0071] The grouping of alternative elements or embodiments of the disclosures disclosed herein should not be construed as limitation. Each member of a group may be referred to and claimed individually or in any combination with other members of that group or other elements found herein. It is anticipated that one or more members of a group may be included in or omitted from a group for reasons of convenience and / or patentability. Where such any inclusion or omission occurs, this specification shall be considered to include that group as a modified version and thus satisfy the description requirements of all Markush groups used in the appended claims.

[0072] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art. Methods and materials similar to or equivalent to those described herein may be used in the practice or testing of this disclosure, but suitable methods and materials are described below. All publications, patent applications, patents and other references referenced herein are invoked by reference in their entirety. In case of any conflict, this specification, including definitions, shall prevail. Furthermore, those materials, methods and examples are illustrative only and are not intended to be limiting.

[0073] Furthermore, the specific arrangements shown in the drawings should not be considered limiting. It should be understood that other embodiments may include, to some extent, each of the elements shown in the given drawings. Moreover, some of the exemplary elements may be combined or omitted. Furthermore, exemplary embodiments may include elements not illustrated in the drawings. As used herein, "approximately" means + / - 5% with respect to measurements. As used herein, the range described includes both endpoints, and consequently, 0.5 mol percent to 99.5 mol percent includes both 0.5 mol percent and 99.5 mol percent.

[0074] As used herein, the term “curcuminoid” is intended to include a variety of linear diarylheptanoide compounds of natural and synthetic origin, or naturally occurring compounds of the same origin that are later synthetically modified. Diarylheptanoides consist of a seven-carbon chain (heptane) or two aromatic rings (aryl groups) linked by seven carbon atoms to form one ring and a linear linker (see, for example, cyclocurcumin), allowing for various substituents. Common curcuminoids may include one or more of the following: curcumin; demethoxycurcumin; bisdemethoxycurcumin; cyclocurcumin; tetrahydrocurcumin; dihydrocurcumin; curcumin-glucuronoside; dihydrocurcumin-glucuronoside; tetrahydrocurcumin-glucuronoside; curcumin sulfate; and hexahydrocurcumin.

[0075] As used herein, the term “green tea extract” is intended to include tea extracts derived from Camellia sinensis. For example, decaffeinated powdered green tea extract is available from Millipore Sigma® in many forms and purities (i.e., CAS Number: 84650-60-2). Its main component is epigallocatechin gallate (EGCG), the most abundant catechin in tea (i.e., CAS Number 989-51-5).

[0076] As used herein, the terms "rutin" or "rutoside" refer to a glycoside (α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose) formed by combining the flavonol quercetin with the disaccharide rutinose. It is a citrus flavonoid found in a wide variety of plants, including citrus fruits. [ka]

[0077] As used herein, the term "methylsulfonylmethane" (MSM) refers to an organosulfur compound having the formula (CH3)2SO2. 。 MSM is also known by several other names, including DMSO2, methylsulfone, and dimethylsulfone. The structure of MSM is: [ka] That is the case.

[0078] The term "sugar alcohol," also known as polyhydric alcohol, polyalcohol, alditol, or glycitol, refers to organic compounds that are typically derived from sugars and contain one hydroxyl group (-OH) bonded to each carbon atom. Sugar alcohols generally have the formula HOCH2(CHOH). n It contains CH2OH.

[0079] As used herein, the terms “solubilizing matrix” or “matrix” are intended to include a specific subset of a solubilizing agent or a single solubilizing agent.

[0080] The term "eutectic" refers to a homogeneous mixture of substances that melts or solidifies at a single temperature lower than the melting point of any of its constituent components. The "eutectic temperature" is the lowest possible melting temperature for all mixing ratios of the constituent species.

[0081] As used herein, the term "solubilizer" refers to a substance that improves the solubility of bioflavonoids in water.

[0082] As used herein, the term "solubility" refers to the property of a solid, liquid, or gaseous chemical substance ("solute") to dissolve in a solid, liquid, or gaseous solvent. The solubility of a substance depends fundamentally on the physical and chemical properties of its solute and solvent, as well as the temperature, pressure, and pH of the solution. Solubility tests of the compositions of this disclosure may be carried out as follows: A 25 mg to 500 mg composition containing approximately 25 mg of the nutritional supplement is added to 10 mL of distilled water in a screw-cap test tube. The test tube is vortexed for 2 minutes and then sonicated for 1 hour in a water bath set to a specified temperature. The sample is then filtered through a 0.45 μm syringe filter and subsequently analyzed by high-pressure liquid chromatography (HPLC). The filtrate after the filtration step contains water-soluble particles smaller than 450 nm. If the concentration determined by HPLC is not within the calibration curve, the sample is further diluted to the appropriate concentration and re-analyzed.

[0083] As used herein, the term “organic solvent” refers to any solvent having at least one carbon atom and one hydrogen atom, low molecular weight, lipophilicity, and volatility, and existing in liquid form at room temperature. Organic solvents can be further classified as aliphatic or aromatic. Organic solvents are useful because they can dissolve oils, fats, resins, rubber, and plastics. Organic solvents may be selected from methanol, ethanol, propanol, butanol, acetonitrile, and acetone.

[0084] As used herein, interchangeable terms “individual,” “subject,” or “patient” refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, most preferably humans.

[0085] As used herein, the term “bioavailability” means the proportion of a drug or other substance (e.g., a dietary supplement) that, when introduced into a subject, can enter circulation and exert an active effect. Bioavailability testing of the compositions of this disclosure may proceed as follows: After fasting overnight, blood samples may be collected from each volunteer before ingesting the composition to be tested. Blood may be collected again at 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours. After all blood samples have been collected, they may be processed as follows: (1) Pipette a fixed amount of blood (e.g., 50 μL to 100 μL) into a microcentrifuge vial; (2) Add a sufficient amount of enzyme (e.g., 100 μL) to the vial; (3) Incubate the vial at 37°C for 1 hour to hydrolyze the nutritional supplement conjugate; (4) Add 10 μl of internal standard (IS) working solution and 400 μl of a suitable solvent (typically ethanol, methanol, acetone, or isopropanol) to the vial; (5) The mixture is sonicated at 25°C to 50°C for 10 minutes to 1.5 hours to extract the analyte; (6) Centrifuge at 3000 g or more for 5 minutes, then place the supernatant in a suitable container for later analysis; (7) Analyze the blood concentration of the nutritional supplement by performing liquid chromatography-mass spectrometry (LC-MS). The AUC value is calculated by integrating the area under the curve for the mean blood concentration over time for the product being tested.

[0086] As used herein, the phrase “therapeutic dose” means the amount of a therapeutic agent (i.e., a drug, dietary supplement, or therapeutic composition) that elicits a biological or pharmacokinetic response in a tissue, system, animal, individual, or human being sought by a researcher, veterinarian, physician, or other clinician, and such response includes one or more of the following: (1) To prevent disease; for example, to prevent a disease, condition, or disability in an individual who may have a predisposition to that disease, condition, or disability but has not yet experienced or exhibited the pathology or overall symptoms of that disease; (2) inhibiting a disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or exhibiting the pathology or overall symptoms of that disease, condition or disorder; and (3) To alleviate a disease; for example, to reduce a disease, condition or disability in an individual who is experiencing or exhibiting the pathology or overall symptoms of the disease, condition or disability (i.e., to reverse the pathology and / or overall symptoms), for example, to reduce the severity of the disease.

[0087] "Approximately" includes all values ​​that have substantially the same effect or provide substantially the same result as the reference value. Therefore, the range included by the term "approximately" varies depending on the context in which the term is used, for example, the parameter to which the reference value relates. Thus, depending on the context, "approximately" could mean, for example, ±15%, ±10%, ±5%, ±4%, ±3%, ±2%, ±1%, or less than ±1%. Importantly, any enumeration of reference values ​​preceded by the term "approximately" is also intended to be a listing of that reference value only. Notwithstanding the foregoing, in this specification, the term "approximately" means Area under the curve (AUC, AUC) t , and AUC ∞ (Examples include), C max , T max It has a specific meaning with respect to pharmacokinetic parameters such as those mentioned above. When used in relation to values ​​of pharmacokinetic parameters, the term "approximately" means 80% to 125% of that reference parameter.

[0088] "Nutritional supplement" or "nutritional supplement composition" means a formulation of the compounds of the Disclosure, for example, a plant extract containing one or more phytochemicals (such as flavonoids), an isolated food compound containing a nonpolar portion (such as sterols, stanols, quinones, carotenoids, terpenes, or fatty acids, or vitamins), and a matrix that is generally accepted in the art for the delivery of nutritional supplements to mammals (e.g., humans). Such media include all pharmaceutically acceptable carriers, diluents, or excipients for that purpose.

[0089] "Pharmacologically acceptable" means that a substance is suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, etc., has a reasonable benefit-risk ratio, and is effective for its intended use within the bounds of sound medical judgment.

[0090] Enteric-coated polymers are polymers that have poor solubility in aqueous media at a pH of approximately 4.5 or lower, but become soluble in aqueous media at a pH greater than approximately 5. For example, enteric-coated polymers have poor solubility in gastric juice, but are soluble in the lower gastrointestinal environment.

[0091] (composition) As described above, the composition of this disclosure comprises a eutectic solubilization matrix containing methylsulfonylmethane (MSM) and sugar alcohols; and a nutritional supplement contained within the eutectic matrix.

[0092] In some embodiments, the sugar alcohol:methylsulfonylmethane ratio is 95:5 by weight (e.g., 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70) to 20:80 by weight (e.g., 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10). In certain embodiments, the sugar alcohol:methylsulfonylmethane ratio is 25:75 to 70:30 by weight. In preferred embodiments, the sugar alcohol:methylsulfonylmethane ratio is 40:60 to 65:35 by weight.

[0093] Sugar alcohols may include tetrasaccharide alcohols, pentose alcohols, hexose alcohols, dodecose alcohols, or any combination thereof. In some embodiments, the sugar alcohol is erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, and / or maltitol. In certain embodiments, the sugar alcohol is xylitol.

[0094] A eutectic matrix (i.e., a eutectic solubilization matrix) has a melting point lower than the melting points of methylsulfonylmethane and sugar alcohols in that matrix. In some embodiments, the eutectic matrix consists of methylsulfonylmethane and sugar alcohols. In some embodiments, the eutectic matrix consists of methylsulfonylmethane and xylitol. The range of the ratio of methylsulfonylmethane to sugar alcohols in the eutectic matrix can be determined by determining the melting point of the combined mixture. Briefly, MSM and sugar alcohols can be mechanically mixed together. The mixture can then be heated by gradually increasing the temperature until melting is observed, and heating is stopped when the mixture is completely melted. Alternatively, the mixture of MSM and sugar alcohols can be dissolved in water, ethanol, acetone, or a suitable polar solvent or combination of polar solvents. The solution can then be recrystallized or dried by spray drying, vacuum drying, freeze-drying, or other drying techniques to obtain a homogeneous mixture of MSM and sugar alcohols in solid form. It is also possible to melt MSM or sugar alcohols so that one of the components becomes liquid. The still-unmelted solid component is then dissolved into the liquid component and mixed as a homogeneous mixture. This mixture solidifies upon cooling to provide a solid mixture. This solid mixture can then be subjected to melting point determination. If the determined melting point of the solid mixture is lower than the melting point of the lower molten component, or lower than the theoretical melting point calculated from a proportional arithmetic combination of their melting points, then the mixture is a eutectic matrix. In some embodiments, the ratio of methylsulfonylmethane to xylitol in the eutectic matrix ranges from 5:95 to 80:20 by weight.

[0095] Methylsulfonylmethane and sugar alcohols can form organized structures (such as repeating patterns). In some embodiments, the dietary supplement forms hydrogen bonds and / or ionic bonds with a eutectic matrix. In some embodiments, the dietary supplement, methylsulfonylmethane, and sugar alcohols together form organized structures (such as repeating patterns). For example, these repeating patterns may exist in a crystalline solid. In some embodiments, the organized structures of the dietary supplement, methylsulfonylmethane, and sugar alcohols can be suspended in a liquid.

[0096] In some embodiments, the dietary supplement contains flavonoids and / or bioflavonoids, e.g., quercetin, epimedium extract (e.g., epimedium extract obtained by extracting epimedium with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), curcuminoids, echinacea alkylamides (e.g., isolated as described in U.S. Patent No. 6,511,683, which is incorporated herein by reference in its entirety), soy isoflavones (e.g., genistein, genistin, malonylgenistin, acetylgenistin, daidzein, daidzin, malonyl Daidjin, acetyldaidjin, glycitein, glycinin, malonylglycinin, and / or acetylglycinin), hesperidin, grape seed extract (e.g., grape seed extract obtained by extracting grape seeds with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water, or by extracting with hot water or steam), milk thistle extract (e.g., milk thistle obtained by extracting milk thistle with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), procyanidin (e.g., obtained from cocoa liquor), schisandra berry (schisandra berry) The formula includes extracts of berries (e.g., obtained by extracting Schisandra chinensis berries with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), lemon balm extract (e.g., obtained by extracting lemon balm with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), ginger root extract (e.g., obtained by extracting ginger root with supercritical carbon dioxide or an organic solvent), Rhodiola rosea extract (e.g., obtained by extracting Rhodiola rosea with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), berberine extract (e.g., obtained by extracting Berberis vulgaris with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water), and / or Boswellia extract (e.g., obtained by extracting Boswellia with an organic solvent (such as alcohol or ketone) or a mixture of an organic solvent and water).In some embodiments, the dietary supplement contains quercetin.

[0097] In some embodiments, the dietary supplement contains quinones, such as pyrroloquinoline quinone, CoQ10, and / or ubiquinol. In some embodiments, the dietary supplement contains fat-soluble vitamins, such as vitamin A, vitamin D2, vitamin D3, vitamin E, or vitamin K. In some embodiments, the dietary supplement contains isolated food compounds including nonpolar moieties, such as sterols, stanols, omega-3 fatty acids or omega-3 fatty acid esters, or carotenoids (such as astaxanthin, lutein, and zeaxanthin) supplied from fish, krill, plants, or algae.

[0098] In some embodiments, the particles of the nutritional supplement are mixed with lipids to form a lipid-soluble matrix. In some embodiments, the lipids include fats selected from the group consisting of dairy fat (e.g., milk fat, butter fat), animal fat (e.g., lard), or vegetable fat (e.g., coconut oil, cocoa butter, or palm oil).

[0099] In some embodiments, the lipids include edible oils or mixtures of oils. Such oils include vegetable oils (e.g., canola oil, soybean oil, palm kernel oil, olive oil, safflower oil, sunflower seed oil, linseed oil, corn oil, cottonseed oil, peanut oil, walnut oil, almond oil, grape seed oil, evening primrose oil, coconut oil, borage oil, and blackcurrant oil); marine oils (e.g., fish oil and fish liver oil), or mixtures thereof.

[0100] In some embodiments, the lipids include medium-chain triglycerides ("MCTs"), such as oils (coconut oil, palm kernel oil, and butter) or refined forms of MCTs. The lipid-soluble matrix further enhances the solubility of the dietary supplement.

[0101] The nutritional supplement may be present in the composition in an amount of 1% to 80% by weight (e.g., 5% to 80% by weight, 5% to 50% by weight, 5% to 40% by weight, 10% to 50% by weight, 10% to 40% by weight, or 10% to 30% by weight). In some embodiments, more preferably, the nutritional supplement may be present in the composition in an amount of 5% to 50% by weight, or most preferably 10% to 30% by weight. In some embodiments, the nutritional supplement does not exceed 25% by weight in the composition.

[0102] In some embodiments, when administered to a subject, the composition comprising the nutritional supplement and the co-fusion matrix provides an AUC 0~8時間 that is 2 to 25 times (e.g., 4 to 25 times, 6 to 25 times, 8 to 25 times, 10 to 25 times, 10 to 20 times, 15 to 25 times, or 15 to 20 times) that measured from the same nutritional supplement without the solubilization matrix (e.g., comparing the AUC from FIG. 2H to the AUC from FIG. 2G). In certain embodiments, the composition comprising the nutritional supplement and the co-fusion matrix provides an increase in AUC of at least 100% (e.g., at least 150%, at least 200%, at least 250%, at least 300%, at least 350%, or at least 425%) when compared to the nutritional supplement without the solubilization matrix. 0~8時間 In a preferred embodiment, the composition comprising the nutritional supplement and the co-fusion matrix provides an increase in AUC of at least 425% when compared to the nutritional supplement without the solubilization matrix (e.g., comparing the AUC from FIG. 2H to the AUC from FIG. 2A). 0~8時間 In some embodiments, when administered to a subject, the composition provides the nutritional supplement at a peak plasma level (C max ) that is higher (e.g., up to 26 times higher) than that of the nutritional supplement without the solubilization matrix (e.g., dividing C max from FIG. 2H by C max from FIG. 2G).

[0103] The dietary supplement has a water solubility at least 4% by weight (at least 8% by weight, at least 10% by weight, or at least 20% by weight) higher than the water solubility of the dietary supplement in the individual matrix components (e.g., MSM, or sugar alcohols). While we do not wish to be constrained by theory, it is considered that water solubility correlates with bioavailability, with higher water solubility providing higher bioavailability. In some embodiments, the dietary supplement has a water solubility that is not linearly correlated with the diameter of its particles. In certain embodiments, the dietary supplement has a water solubility that is not linearly correlated with the percentage of methylsulfonylmethane in the composition.

[0104] In some embodiments, the dietary supplement has peak water solubility at methylsulfonylmethane concentrations of 20% to 50% by weight of the composition and sugar alcohol concentrations of 25% to 55% by weight of the composition. In some embodiments, the dietary supplement in the eutectic matrix has a higher water solubility than the sum of the water solubility of the dietary supplement in each of the components of the eutectic matrix (i.e., in each of the methylsulfonylmethane and sugar alcohols).

[0105] The composition may be in the form of tablets, pills, capsules, softgels, gummies, powders, or liquids. Tablets or pills may be coated. In some embodiments, tablets or pills are coated with an enteric layer or enteric coating. Various materials may be used for the enteric layer or enteric coating, such as numerous polymer acids, as well as mixtures of polymer acids with materials such as shellac, cetyl alcohol, and cellulose acetate. Liquid compositions may be produced by first formulating the composition into a powder, and then dissolving or suspending the powder in a liquid vehicle.

[0106] (Method for producing the composition) (Method for generating a eutectic matrix) The eutectic matrix of this disclosure can be produced, for example, by mechanically mixing MSM and a sugar alcohol together. The mixture can then be heated to a temperature at which the components of the eutectic matrix are completely melted. Depending on the sugar alcohol, the heating temperature can be between 70°C and 125°C.

[0107] In some embodiments, one component of the eutectic mixture may first melt at or above its melting point, and then other components may dissolve into the melted component. The eutectic matrix solidifies upon cooling.

[0108] In some embodiments, a mixture of MSM and sugar alcohol is dissolved in water, ethanol, acetone, or a suitable polar solvent, or a combination of polar solvents. Alternatively, the MSM and sugar alcohol may be dissolved separately in the same polar solvent or different polar solvents and then combined. The eutectic matrix is ​​then recrystallized from its solution, or the solution is evaporated via spray drying, vacuum drying, freeze-drying, or other drying techniques to obtain the eutectic matrix in solid form.

[0109] (Method for producing nutritional supplement compositions) In some embodiments, the nutritional supplement is added directly to the liquefied eutectic matrix, with or without an additional solvent, in one of the processes described above, before the eutectic matrix is ​​obtained in a solid form. The composition may be obtained when the eutectic matrix solidifies, or when the solvent evaporates and the eutectic matrix is ​​obtained in a solid form.

[0110] Methods for generating a eutectic matrix and methods for generating a nutritional supplement composition are described in the above and below examples, but it is understood that these methods can be readily adapted and modified as are known to those skilled in the art.

[0111] (Methods for characterizing a composition) (Bioavailability) Four to eight volunteers aged between 25 and 55 years may be selected as subjects for a study comparing the various nutritional supplement compositions of this disclosure. After fasting overnight, blood samples may be collected from each volunteer before they ingest the composition to be tested. Blood may be collected again at 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, and 8 hours. After all blood samples have been collected, they may be processed as follows: (1) Pipette a fixed amount of blood (e.g., 50 μL to 100 μL) into a microcentrifuge vial; (2) Add a sufficient amount of enzyme (e.g., 100 μL) to the vial; (3) Incubate the vial at 37°C for 1 hour to hydrolyze the nutritional supplement conjugate; (4) Add 10 μl of internal standard (IS) working solution and 400 μl of a suitable solvent (typically ethanol, methanol, acetone, or isopropanol) to the vial; (5) The mixture is sonicated at 25°C to 50°C for 10 minutes to 1.5 hours to extract the analyte; (6) Centrifuge at 3000 g or more for 5 minutes, then place the supernatant in a suitable container for later analysis; (7) Analyze the blood concentration of the nutritional supplement by performing liquid chromatography-mass spectrometry (LC-MS). The AUC value is calculated by integrating the area under the curve for the mean blood concentration over time for the product being tested.

[0112] (Water solubility) A composition ranging from 25 mg to 500 mg, containing approximately 25 mg of the nutritional supplement, may be added to 10 mL of distilled water in a screw-cap test tube. The test tube may be vortexed for 2 minutes and then sonicated for 1 hour in a water bath set to a specified temperature. The sample may then be filtered through a 0.45 μm syringe filter and subsequently analyzed by high-pressure liquid chromatography (HPLC). The filtrate after the filtration step will contain water-soluble particles smaller than 450 nm. If the concentration determined by HPLC is not within the calibration curve, the sample may be further diluted to the appropriate concentration and re-analyzed.

[0113] The following embodiments are included for illustrative purposes only, and not to limit the embodiments described. [Examples]

[0114] (Examples) (Example 1. Evaluation of quercetin's bioavailability) Participants received a standardized breakfast and lunch: Breakfast: Cheese-filled egg and ham mac muffin, or sausage egg and mac muffin. Lunch: Fried chicken (2-3 pieces), french fries, gravy, coleslaw; or beef noodle soup.

[0115] (treatment) Treatment A: Untreated quercetin powder, 500 mg divided into 3 capsules Treatment B: 500 mg softgel formulation containing ethanol, divided into 3 capsules. Treatment C: Granulated quercetin (40-60 mesh filled in hard gel capsules) Treatment D: Contains peppermint oil (mixed and filled into hard gel capsules) Treatment E: Naka Extra Strength Quercetin 500mg - 1 capsule Treatment F: New Roots Herbal Quercetin Bioflavonoid 500mg - 1 Capsule Treatment G: Amazing Nutrition Amazing Formulas Quercetin 500MG - 1 Capsule Treatment H: MSM + quercetin and rutin in xylitol, 3g dose Treatment I: Quercetin EMIQ capsules, 10 capsules per person Treatment J: SunActive Quercetin (Cyclodextran) Treatment K: MSM + quercetin and rutin in xylitol, 2g dose Treatment L: MSM xylitol containing MCT, 2g (660mg quercetin) dosage Treatment M: Quercetin EMIQ capsules, 2 capsules per person [Table 2]

[0116] Figure 1 shows that when treatment H, a composition containing a eutectic matrix, was administered to subjects, quercetin reached higher blood concentrations compared to all other treatments. Treatment H also showed a higher AUC compared to the other treatments. 0~8時間 Bioavailability measured through [method / tool] is provided. Figures 2A–2J contain the data used to create Figure 1. AUC was calculated numerically to facilitate comparison. max This could be determined from these tables by looking at column 3.

[0117] (Example 2. Water solubility measurement value) [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4]

[0118] The water solubility of various compositions was tested by HPLC to obtain mg of soluble component / ml of water solubility. One of these combinations was MSM with choline. Although choline is commonly used in other known eutectic systems, its solubility increases considerably less than that of sugar alcohols (such as xylitol). This demonstrates the unexpected effectiveness of MSM with sugar alcohols (e.g., xylitol) in improving solubility.

[0119] Other dietary supplements were also tested as eutectic mixtures containing other ingredients, but they did not function as well as MSM with sugar alcohols (e.g., xylitol). Vitamin C with choline and water is a known eutectic system, but it did not solubilize quercetin as well as MSM with xylitol. Other combinations tested were MSM with choline, MSM alone, xylitol alone, and MSM with sorbitol. While we do not wish to be constrained by theory, AUC is thought to correlate with the dose. Figure 1 shows that the MSM-sugar alcohol eutectic matrix unparalleled in increasing bioavailability, since all administered treatments contained the same dose of quercetin.

[0120] (Example 3. Nonlinear solubility behavior in MSM: xylitol matrix) A composition containing approximately 25 mg of the active ingredient, ranging from 25 mg to 500 mg, was added to 10 mL of distilled water in a screw-cap test tube. The test tube was vortexed for 2 minutes and then sonicated for 1 hour in a water bath set to a specified temperature. The sample was then filtered through a 0.45 μm syringe filter and analyzed by HPLC. The filtrate after filtration contained only water-soluble particles smaller than 450 nm in size. If the concentration determined by HPLC was not within the calibration curve, the sample was further diluted to the appropriate concentration and re-analyzed.

[0121] Figure 12 shows that many low-solubility dietary supplements exhibit improved solubility when incorporated into an MSM-xylitol eutectic matrix.

[0122] (Example 4. Solubility study) Figure 13 shows that the water solubility was improved for many of the dietary supplement components in the compositions of this disclosure. Figure 14 compares the solubility as a function of the MSM ratio in the MSM-sugar alcohol eutectic matrix and shows that the optimal ratio was around 38% (corresponding to 50:50 MSM:xylitol). Figures 15A, 15B, 16, 17A, 17B, 18A, 18B-19 show the raw data for Figure 14.

[0123] Figures 20A–20C show a comparison of the bioavailability of quercetin with 42.5% MSM compared to quercetin without a solubilizing matrix. Compared to the data in Figure 14, the MSM-to-xylitol ratio in this treatment was the point of lowest water solubility. However, this treatment still showed unexpectedly high bioavailability when administered. This indicates that the increase in bioavailability in the MSM-sugar alcohol eutectic matrix cannot be explained solely by the increase in water solubility.

[0124] (Example 5. Lipid-soluble matrix study) A eutectic matrix containing methylsulfonylmethane and sugar alcohols can be combined with oil to form a lipid-soluble matrix that further enhances the solubility of dietary supplements. Figure 21A shows that a eutectic matrix containing only methylsulfonylmethane and sugar alcohols (MSM / xylitol) can increase the solubility of plain, unmodified milk thistle extract by 279%. When the eutectic matrix and milk thistle extract are combined with oil (e.g., MCT), the solubility of the milk thistle extract increases to 1119%. Combining the lipid-soluble matrix with saponins or cocoa further increases the solubility of the milk thistle extract in the lipid-soluble matrix form compared to the plain, unmodified form, but not to the same extent as the lipid-soluble matrix without saponins or cocoa.

[0125] Figure 21B shows that a eutectic matrix containing methylsulfonylmethane and sugar alcohols can enhance bioavailability independently of solubility. As shown in Figure 21B, the addition of ascorbic acid to berberine extract increased its solubility by 665%, which is greater than the 162% increase in solubility of berberine extract in MSM / xylitol form and greater than the 519% increase in solubility of berberine extract in MSM / xylitol form with ascorbic acid. However, the bioavailability of the MSM / xylitol form with ascorbic acid is higher than that of the berberine extract form with ascorbic acid, even though the former has lower solubility than the latter.

[0126] These results further demonstrate that the addition of auxiliary components can increase the bioavailability provided by the eutectic matrix containing methylsulfonylmethane and sugar alcohols. Both ascorbic acid and bergamot extract have been shown to be useful auxiliary components for increasing bioavailability.

[0127] Figure 21C shows the increased permeability of fat-soluble vitamins and dietary supplement components. As shown in Figure 21C, the permeability of vitamin D3 through the Caco-2 cell layer is enhanced by a eutectic matrix containing methylsulfonylmethane and sugar alcohols, combined with oil to form a fat-soluble matrix. The addition of cocoa further increases the permeability of vitamin D3 to 456%. On the other hand, the addition of saponins decreases the permeability of vitamin D3 compared to the fat-soluble matrix and compared to the fat-soluble matrix with cocoa.

[0128] Figure 21D shows that a eutectic matrix containing methylsulfonylmethane and sugar alcohols, combined with oil to form a lipid-soluble matrix, significantly increases the bioavailability and maximum blood concentration of Boswellia upon addition of saponins.

[0129] Figure 21E shows that a eutectic matrix containing methylsulfonylmethane and sugar alcohols, combined with oil to form a lipid-soluble matrix, significantly increases the water solubility of CoQ10 upon the addition of cocoa. Regarding Figure 21E, MSM, xylitol, and cocoa powder were added to a base of CoQ10 and MCT at 50°C. The mixture was heated in a water bath to approximately 80°C and then cooled. These results show an increase in the water solubility of CoQ10 compared to the water solubility of unmodified CoQ10 without any additions.

[0130] Figure 21F shows that a eutectic matrix containing methylsulfonylmethane and sugar alcohols, combined with oil to form a lipid-soluble matrix, exhibits a significant increase in the solubility of ubiquinol in water, either with or without the addition of cocoa. A lipid-soluble matrix form of ubiquinol was prepared by mixing ubiquinol and MCT and vortexing the mixture at room temperature. A lipid-soluble matrix with cocoa was prepared by adding MSM, xylitol, and cocoa powder to the ubiquinol and MCT base at 50°C. The mixture was heated in a water bath at approximately 80°C and then cooled. These results demonstrate an increase in water solubility for the lipid-soluble matrix form of ubiquinol compared to unmodified ubiquinol without additions, and compared to the lipid-soluble matrix with cocoa.

[0131] While exemplary embodiments have been illustrated and described, it will be understood that various modifications can be made to those exemplary embodiments without departing from the spirit and scope of this disclosure. The embodiments of this disclosure that claim exclusive ownership or exclusive rights are defined as follows: In embodiments of the present invention, for example, the following items are provided. (Item 1) A eutectic matrix containing methylsulfonylmethane and sugar alcohols; Particles of the nutritional supplement in the eutectic matrix and A composition containing the following: (Item 2) The composition according to item 1, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:80. (Item 3) The composition according to item 1, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecose alcohol, or any combination thereof. (Item 4) The composition according to item 3, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof. (Item 5) The composition according to item 4, wherein the sugar alcohol contains xylitol. (Item 6) The composition according to item 1, wherein the eutectic matrix has a melting point lower than that of the methylsulfonylmethane and the sugar alcohol, respectively. (Item 7) The composition according to item 1, wherein the eutectic matrix consists of methylsulfonylmethane and the sugar alcohol. (Item 8) The composition according to item 1, wherein the methylsulfonylmethane and the sugar alcohol form an organized structure or repeating pattern. (Item 9) The composition according to item 1, wherein the nutritional supplement forms hydrogen bonds and / or ionic bonds with the eutectic matrix. (Item 10) The composition according to item 1, wherein the nutritional supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof. (Item 11) The composition according to item 10, wherein the nutritional supplement contains quercetin. (Item 12) The composition described in item 1, further comprising lipids. (Item 13) The composition according to item 12, wherein the lipid comprises edible oil or a mixture of oils. (Item 14) The composition according to item 13, wherein the lipid comprises a medium-chain triglyceride. (Item 15) The composition according to item 12, wherein the lipid forms a lipid-soluble matrix with the methylsulfonylmethane, the sugar alcohol, and the nutritional supplement. (Item 16) A composition according to either item 1 or item 12, further comprising saponins, cocoa, or any combination thereof. (Item 17) When administered to the target population, it has a larger AUC than the aforementioned nutritional supplement at 250 ng / ml. 0~8時間 The composition described in item 1, having the following characteristics. (Item 18) The composition described in item 1, which is in the form of a tablet, capsule, softgel, gummy, or liquid. (Item 19) The composition according to item 1, wherein the nutritional supplement has a water solubility at least 4% greater than the water solubility of the nutritional supplement in each individual matrix component. (Item 20) The composition according to item 1, wherein the nutritional supplement has a water solubility that does not linearly correlate with the diameter of the particles and does not linearly correlate with the percentage of methylsulfonylmethane in the composition. (Item 21) The composition according to item 1, wherein the nutritional supplement has a peak water solubility at a methylsulfonylmethane concentration of 20% to 50% by weight. (Item 22) The composition according to item 1, wherein the nutritional supplement has a water solubility greater than the sum of the water solubility of methylsulfonylmethane and sugar alcohol in each of the nutritional supplements. (Item 23) The composition according to item 1, further comprising an enteric coating. (Item 24) A method for producing the composition described in item 1, A step of mixing methylsulfonylmethane and sugar alcohol to form a mixture; A step of heating the mixture to melt the methylsulfonylmethane and sugar alcohol; The step of adding a nutritional supplement composition; and The process involves cooling the mixture to form a eutectic matrix containing particles of the nutritional supplement. Methods that include... (Item 25) A method for producing the composition described in item 1, A step of dissolving methylsulfonylmethane and a sugar alcohol in water, ethanol, acetone, or a polar solvent to form a solution; The step of adding a nutritional supplement to the solution; and The process involves recrystallizing the solution to obtain a eutectic matrix containing particles of the nutritional supplement. Methods that include... (Item 26) Process of adding nutritional supplements to a lipid-soluble matrix A method for increasing the solubility of nutritional supplements, including [specific ingredient / method]. (Item 27) The method according to item 26, wherein the lipid-soluble matrix comprises methylsulfonylmethane, sugar alcohols, and lipids. (Item 28) The method according to item 27, wherein the methylsulfonylmethane and the sugar alcohol form a eutectic matrix. (Item 29) The method according to item 27, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:80. (Item 30) The method according to item 27, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecase alcohol, or any combination thereof. (Item 31) The method according to item 30, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof. (Item 32) The method according to item 31, wherein the sugar alcohol contains xylitol. (Item 33) The method according to item 27, wherein the lipid comprises edible oil or a mixture of oils. (Item 34) The method according to item 33, wherein the lipid comprises a medium-chain triglyceride. (Item 35) The method according to item 26, wherein the dietary supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof. (Item 36) The method according to item 35, wherein the nutritional supplement contains quercetin. (Item 37) The method according to item 27, wherein the lipid-soluble matrix further comprises saponin, cocoa, or any combination thereof. (Item 38) Process of adding nutritional supplements to a lipid-soluble matrix Methods for enhancing the bioavailability of dietary supplements, including [specific examples of methods]. (Item 39) The method according to item 38, wherein the lipid-soluble matrix comprises methylsulfonylmethane, sugar alcohols, and lipids. (Item 40) The method according to item 39, wherein the methylsulfonylmethane and the sugar alcohol form a eutectic matrix. (Item 41) The method according to item 39, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:80. (Item 42) The method according to item 39, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecase alcohol, or any combination thereof. (Item 43) The method according to item 42, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof. (Item 44) The method according to item 43, wherein the sugar alcohol comprises xylitol. (Item 45) The method according to item 39, wherein the lipid comprises edible oil or a mixture of oils. (Item 46) The method according to item 45, wherein the lipid comprises a medium-chain triglyceride. (Item 47) The method according to item 38, wherein the dietary supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof. (Item 48) The method according to item 47, wherein the nutritional supplement contains quercetin. (Item 49) The method according to item 38, wherein the lipid-soluble matrix further comprises saponin, cocoa, or any combination thereof.

Claims

1. A eutectic matrix containing methylsulfonylmethane and sugar alcohols; Particles of the nutritional supplement in the eutectic matrix and A composition containing the following:

2. The composition according to claim 1, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:

80.

3. The composition according to claim 1, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecose alcohol, or any combination thereof.

4. The composition according to claim 3, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof.

5. The composition according to claim 4, wherein the sugar alcohol comprises xylitol.

6. The composition according to claim 1, wherein the eutectic matrix has a melting point lower than that of the methylsulfonylmethane and the sugar alcohol, respectively.

7. The composition according to claim 1, wherein the eutectic matrix comprises methylsulfonylmethane and the sugar alcohol.

8. The composition according to claim 1, wherein the methylsulfonylmethane and the sugar alcohol form an organized structure or a repeating pattern.

9. The composition according to claim 1, wherein the nutritional supplement forms hydrogen bonds and / or ionic bonds with the eutectic matrix.

10. The composition according to claim 1, wherein the nutritional supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof.

11. The composition according to claim 10, wherein the nutritional supplement contains quercetin.

12. The composition according to claim 1, further comprising lipids.

13. The composition according to claim 12, wherein the lipid comprises edible oil or a mixture of oils.

14. The composition according to claim 13, wherein the lipid comprises a medium-chain triglyceride.

15. The composition according to claim 12, wherein the eutectic matrix combined with the lipids forms a lipid-soluble matrix, and the nutritional supplement is at least partially solubilized in the resulting matrix.

16. The composition according to any one of claim 1 or 12, further comprising saponins, cocoa, or any combination thereof.

17. When administered to the subject, the AUC is greater than that of the aforementioned nutritional supplement at 250 ng / ml. ０～８時間 The composition according to claim 1, having the following characteristics.

18. The composition according to claim 1, which is in the form of a tablet, capsule, softgel, gummy, or liquid.

19. The composition according to claim 1, wherein the nutritional supplement has a water solubility at least 4% greater than the water solubility of the nutritional supplement in each individual matrix component.

20. The composition according to claim 1, wherein the nutritional supplement has a water solubility that does not linearly correlate with the diameter of the particles and does not linearly correlate with the percentage of methylsulfonylmethane in the composition.

21. The composition according to claim 1, wherein the nutritional supplement has a peak water solubility at a methylsulfonylmethane concentration of 20% to 50% by weight.

22. The composition according to claim 1, wherein the nutritional supplement has a water solubility greater than the sum of the water solubility of methylsulfonylmethane and sugar alcohol in each of the nutritional supplements.

23. The composition according to claim 1, further comprising an enteric coating.

24. A method for producing the composition described in claim 1, A step of mixing methylsulfonylmethane and sugar alcohol to form a mixture; A step of heating the mixture to melt the methylsulfonylmethane and sugar alcohol; The step of adding a nutritional supplement composition; and The process involves cooling the mixture to form a eutectic matrix containing particles of the nutritional supplement. Methods that include...

25. A method for producing the composition described in claim 1, A step of dissolving methylsulfonylmethane and a sugar alcohol in water, ethanol, acetone, or a polar solvent to form a solution; The step of adding a nutritional supplement to the solution; and The process involves recrystallizing the solution to obtain a eutectic matrix containing particles of the nutritional supplement. Methods that include...

26. A method for increasing the solubility of a nutritional supplement, Process of adding nutritional supplements to a lipid-soluble matrix The lipid-soluble matrix includes, (i) A eutectic matrix containing methylsulfonylmethane and sugar alcohols, (ii) Lipids and Obtained by combining, A method in which a nutritional supplement is at least partially solubilized in the resulting matrix.

27. The method according to claim 26, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:

80.

28. The method according to claim 26, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecase alcohol, or any combination thereof.

29. The method according to claim 28, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof.

30. The method according to claim 29, wherein the sugar alcohol comprises xylitol.

31. The method according to claim 26, wherein the lipid comprises edible oil or a mixture of oils.

32. The method according to claim 31, wherein the lipid comprises a medium-chain triglyceride.

33. The method according to claim 26, wherein the nutritional supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof.

34. The method according to claim 33, wherein the nutritional supplement contains quercetin.

35. The method according to claim 26, wherein the lipid-soluble matrix further comprises saponin, cocoa, or any combination thereof.

36. A method for enhancing the bioavailability of a nutritional supplement, Process of adding nutritional supplements to a lipid-soluble matrix The lipid-soluble matrix includes, (i) A eutectic matrix containing methylsulfonylmethane and sugar alcohols, (ii) Lipids and Obtained by combining, A method in which a nutritional supplement is at least partially solubilized in the resulting matrix.

37. The method according to claim 36, wherein the ratio of the sugar alcohol to methylsulfonylmethane is 95:5 to 20:

80.

38. The method according to claim 36, wherein the sugar alcohol comprises a tetrasaccharide alcohol, a pentose alcohol, a hexose alcohol, a dodecase alcohol, or any combination thereof.

39. The method according to claim 38, wherein the sugar alcohol is selected from erythritol, xylitol, arabitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, maltitol, and any combination thereof.

40. The method according to claim 39, wherein the sugar alcohol comprises xylitol.

41. The method according to claim 36, wherein the lipid comprises edible oil or a mixture of oils.

42. The method according to claim 41, wherein the lipid comprises a medium-chain triglyceride.

43. The method according to claim 36, wherein the nutritional supplement comprises quercetin, epimedium extract, curcuminoids, echinacea alkylamide, soy isoflavones, hesperidin, grape seed extract, milk thistle extract, procyanidin, schisandra berry extract, lemon balm extract, ginger root extract, rhodiola extract, berberine extract, boswellia extract, CoQ10, ubiquinol, vitamin D3, sterols, stanols, or any combination thereof.

44. The method according to claim 43, wherein the nutritional supplement contains quercetin.

45. The method according to claim 36, wherein the lipid-soluble matrix further comprises saponin, cocoa, or any combination thereof.

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