Method for producing tetrahydrocurcumin free of oxalates and heavy metals using food-grade vinegar (acetic acid and water), heat and pressure, from curcumin without the presence of metallic catalysts

Abstract

The present invention relates to a method for converting the curcuminoid curcumin into tetrahydrocurcumin free of oxalates and heavy metals. The method uses food-grade vinegar (mixture of acetic acid and water) as a reducing medium, applying controlled heat and pressure for an extended period, without the use of metallic catalysts. The method enables efficient, safe and natural conversion, improving the bioavailability of the curcuminoids converted into tetrahydrocurcumin. The obtained product exhibits greater absorption in the human body and is suitable for applications in the pharmaceutical, nutraceutical, cosmetic and food industries, owing to its antioxidant, anti-inflammatory and neuroprotective properties.

Description

[0001] METHOD FOR PREPARING OXALATE- AND HEAVY METAL-FREE TETRAHYDROCURCUMIN USING FOOD GRADE VINEGAR (ACETIC ACID AND WATER), HEAT AND PRESSURE, FROM CURCUMIN WITHOUT THE PRESENCE OF METALLIC CATALYSTS

[0002] METHOD FOR PRODUCING TETRAHYDROCURCUMIN FREE OF OXALATES AND HEAVY METALS USING FOOD-GRADE VINEGAR (ACETIC ACID AND WATER), HEAT, AND PRESSURE, FROM CURCUMIN WITHOUT THE PRESENCE OF METALLIC CATALYSTS

[0003] DESCRIPTION

[0004] OBJECT OF THE INVENTION

[0005] The object of the present invention is to provide a natural, economical and heavy metal-free method for the conversion of curcumin (C2IH 20 O6) present in the root of Turmeric (Curcuma longa), in tetrahydrocurcumin (C2IH 24O6), using only acetic acid, water, heat, and pressure, without the need for metal catalysts. Furthermore, this method allows for the transformation of oxalates present in the root of Curcuma longa, resulting in a final product free of these substances. The invention aims to offer a healthier, more environmentally friendly solution that improves the bioavailability of curcumin (C2IH). 20 O6) present in Turmeric, transforming it into tetrahydrocurcumin (C2IH 24 O6) while eliminating unwanted compounds such as the oxalate family, thus maximizing the benefits for human health by consuming truly activated curcuminoids that are more easily metabolized in the body, reducing the risk of side effects such as kidney stone formation in people sensitive to calcium oxalates. TECHNICAL FIELD

[0006] The invention falls within the field of food chemical engineering and environmental chemical engineering, specifically in the molecular transformation processes of bioactive compounds present in functional foods such as turmeric to enhance the health benefits of curcumin (C2IH 20 O6) transforming it into tetrahydrocurcumin (C2IH 24 O6) and that it is free of oxalates as well as heavy metals, so that it can be used in applications in the nutraceutical, food, cosmetic and pharmaceutical industries.

[0007] BACKGROUND

[0008] In the current state of the art, the conversion of curcumin to tetrahydrocurcumin has been achieved primarily through catalytic hydrogenation processes that require the use of heavy metals as catalysts, such as palladium, platinum, nickel, manganese, copper, and zinc, among others, as well as the direct use of molecular hydrogen and solvents such as acetone, methanol, ethanol, ethyl acetate, and other chemical compounds like ammonium formate and monosodium phosphite. While these methods have proven efficient in the laboratory, they also involve toxicological risks, especially due to the potential for heavy metal residues. Furthermore, the chemical reaction conditions are costly and, in some cases, hazardous to operating personnel, thus limiting their applicability in completely clean formulations for human consumption.

[0009] The following describes some of the most representative state-of-the-art patents: US Patent No. 5266344A describes a method for producing tetrahydrocurcumin by reducing curcumin using a metallic catalyst in the presence of hydrogen within an organic solvent. The catalysts mentioned include Raney nickel, as well as manganese, copper, and zinc catalysts. Suitable organic solvents for this process include acetone, methanol, and ethanol.

[0010] Furthermore, this patent number US5266344A details a method for producing hydrogenated oils containing tetrahydrocurcumin. This process involves adding curcumin to a fat or oil and then performing hydrogenation in the presence of a metal catalyst, which allows the curcumin to be simultaneously transformed into tetrahydrocurcumin during the hydrogenation of the oil or fat.

[0011] Similarly, patent number CN104496779A presents a method for synthesizing tetrahydrocurcumin from curcumin using platinum-iron-nickel hydroxide nanoparticles as a catalyst. The process is carried out at room temperature and consists of the following three steps:

[0012] 1. Reaction: Curcumin, ethanol and the catalyst are mixed in a reaction flask, keeping the mixture stirred for 1 to 2 hours at room temperature.

[0013] 2. Solvent removal: After the reaction, the ethanol is removed by evaporation under reduced pressure, obtaining a concentrate.

[0014] 3. Crystallization: The concentrate is dissolved in hot ethanol, concentrated, cooled, and left to stand to induce the crystallization of tetrahydrocurcumin. We also found another patent, EP1328263B1, which describes a method for producing tetrahydrocurcumin from curcumin extracted from the root of Curcuma longa. The process uses a catalytic hydrogen transfer reaction, known as a hydride transfer reaction, to saturate the olefinic double bonds present in the curcuminoids. In this method, the natural curcuminoids are dissolved in an organic solvent of ethyl acetate and mixed with a hydrogen transfer agent, such as ammonium formate or monosodium phosphite, in the presence of a palladium-on-carbon (Pd / C) catalyst and acetic acid. The mixture is heated to a temperature between 100 and 110 degrees Celsius for 20 to 30 minutes, completing the reduction and obtaining tetrahydrocurcumin.

[0015] There is another patent, number EP2813145A1, which discloses tetrahydrocurcumin derivatives obtained by hydrogenation for use in cosmetics. This patent presents novel curcumin derivatives, such as tetrahydrocurcumin, modified in one of their phenolic groups to incorporate more reactive groups. These derivatives are presented in the form of monomers, dimers, and polymers, and are designed to improve the water solubility and bioavailability of curcumin, while maintaining or enhancing its biological properties.

[0016] Specific modifications include the addition of acrylate, methacrylate, carboxylic acid, alkyne, N-hydroxysuccinimide, and azide groups. These modifications allow curcumin to be conjugated with biopolymers such as dextrans, proteins (e.g., collagen and elastin), and synthetic polymers.

[0017] We also found patent number US12115138B2, which describes a method for synthesizing tetrahydrocurcumin from curcumin via a catalytic hydrogenation process. In this process, curcumin undergoes a hydrogenation reaction in the presence of a catalyst, such as palladium on carbon (Pd / C), in a suitable organic solvent, such as ethyl acetate, and a hydrogen transfer agent, such as ammonium formate or monosodium phosphite. The mixture is heated to a temperature between 100 and 110 degrees Celsius for 20 to 30 minutes, which allows the saturation of the olefinic double bonds of curcumin, resulting in the formation of tetrahydrocurcumin.

[0018] We also located patent number WO2019022991 A1, which describes a process for isolating bioactive components from spent turmeric (Curcuma longa), referring to the insoluble residue remaining after solvent extraction of turmeric powder. This process involves aqueous extraction of the spent turmeric, followed by the removal of residual curcuminoids and oxalic acid by washing with acetone and methanol.

[0019] The resulting material is dried, pulverized, and sieved to obtain a turmeric starch containing polysaccharides and hydrophobic glycoproteins.

[0020] Although patent number WO2019022991 A1 does not focus exclusively on the removal of oxalates from turmeric, the process described in this patent includes steps that reduce the oxalic acid content in spent turmeric material, which could be beneficial in decreasing the risk of kidney stone formation associated with oxalate consumption.

[0021] Regarding oxalate removal, we identified patent number US4264463A, which describes a process for removing calcium oxalate scale using aqueous solutions containing aluminum and / or ferric iron ions and acid anions such as acetic acid. However, this method is intended exclusively for cleaning industrial equipment pipes and not for decomposing oxalates present in natural compounds such as turmeric.

[0022] It is important to note that none of the prior patents describe a process that uses only vinegar (food-grade acetic acid and water), along with controlled heat and pressure, without the use of metal catalysts or hydrogen, to convert curcumin to tetrahydrocurcumin and simultaneously transform the oxalates present. Therefore, the present invention completely eliminates metal catalysts and potential toxic residues such as heavy metals, as well as the removal of oxalates, making it a very safe, environmentally friendly, economical process compatible with food, pharmaceutical, nutraceutical, and cosmetic applications.

[0023] Although independent thermal reactions for the decomposition of oxalic acid and formic acid have been described in the scientific literature, there is no previous report that integrates them into a single natural, continuous, and non-catalytic process that allows the conversion of curcumin into tetrahydrocurcumin and, at the same time, the decomposition of oxalates present in plant matrices such as turmeric.

[0024] The present invention satisfies this technical need through the exclusive use of food-grade vinegar (acetic acid and water), combined with controlled heat and pressure, without requiring metallic catalysts, organic solvents, or molecular hydrogen. This process enables a clean, efficient, economical, and safe transformation, with high compatibility for food, pharmaceutical, nutraceutical, and cosmetic applications.

[0025] BRIEF DESCRIPTION OF THE FIGURES

[0026] Figure 1. Flowchart of the general process of transforming curcumin and oxalates present in turmeric using vinegar, heat and pressure.

[0027] Figure 2. Schematic representation of the chemical conversion of curcumin (C2IH 20 O6) to tetrahydrocurcumin (C2IH 24 O6) under conditions of heat and pressure in an acidic medium.

[0028] Figure 3. Schematic representation of the decomposition of calcium oxalate (CaC2O4) under heat and pressure in an acidic medium, generating carbon dioxide (CO2), carbon monoxide (CO), and water (H2O).

[0029] Note: These figures represent simplified overall reactions to illustrate the proposed mechanisms. They do not imply detailed intermediate mechanisms or exact stoichiometric balances.

[0030] DETAILED DESCRIPTION OF THE INVENTION

[0031] The present invention is characterized by being entirely novel, not obvious to a person skilled in the art, and of immediate industrial applicability. Its clean, environmentally friendly approach, based on natural ingredients, represents a significant advance over prior art methods that utilize metallic catalysts, molecular hydrogen, and solvents.

[0032] In addition to its technical simplicity and low cost, this invention offers a functional solution to the low bioavailability of curcumin (C2IH 20 O6), by transforming it naturally, cleanly and economically into tetrahydrocurcumin (C2IH 24 O6), which is a molecule from the curcuminoid family with substantially higher bioavailability.

[0033] This improvement allows the human body to more efficiently utilize the antioxidant, anti-inflammatory, and neuroprotective properties of this other curcuminoid compound.

[0034] The relevant aspect of this invention is that tetrahydrocurcumin (C2IH 24 The resulting O6) is completely free of heavy metals and solvents, making it ideal for nutraceutical, food, and cosmetic applications.

[0035] Another key aspect of this invention is the transformation of the oxalates present in turmeric during the process. The root of Curcuma longa contains oxalates, primarily in the form of calcium oxalate. Although these levels are low in turmeric compared to spinach and other vegetables, calcium oxalate is a water-insoluble compound and can form crystals with implications for human health, particularly in the formation of kidney stones, especially in people predisposed to developing them.

[0036] Under the specific conditions of this method using acetic acid, heat and pressure, oxalates decompose into carbon dioxide (CO2), carbon monoxide (CO) and water (H2O), thus eliminating their presence in the final product where tetrahydrocurcumin (C2IH) is desired. 24 O6) of high quality and purity for human consumption for different applications in the nutraceutical, food, cosmetic and pharmaceutical industries.

[0037] The following details the elements that make up the process for the production of tetrahydrocurcumin (C2IH 24 O6) free of oxalates and heavy metals:

[0038] Main reagents:

[0039] - Curcumin (C2IH) 20 O6) pure powder, pulp or standardized extract.

[0040] - Food grade vinegar suitable for human consumption (2% to 6% acetic acid) and purified water.

[0041] It can be apple cider vinegar, cane vinegar, rice vinegar, among other types of vinegar for human consumption.

[0042] Process conditions:

[0043] - Temperature: 150°C to 180°C

[0044] - Pressure: Approximately 15 psi

[0045] - Time: 30 to 45 minutes. Process stages according to Figure 1:

[0046] 100. Preparation of the mixture: A homogeneous mixture is made between turmeric root powder, which contains curcumin (C2IH 20 O6) and calcium oxalate (CaC2O4), with food vinegar, composed of acetic acid (CH3COOH) and water (H2O).

[0047] 200. Transfer to reactor: The mixture is introduced into a hermetically sealed reactor, which may be an autoclave or equivalent equipment that can withstand high temperature and pressure conditions.

[0048] 300. Application of heat and pressure: The mixture is subjected to temperatures between 150 °C and 180 °C and an approximate pressure of 15 psi for a time of 30 minutes, the reactor reaching these temperature and pressure conditions, thus allowing the reduction and decomposition reactions to occur.

[0049] 400. Controlled cooling: Once the heating stage is complete, the temperature is reduced until ambient conditions are reached.

[0050] 500. Obtaining the final product: A solution composed of tetrahydrocurcumin (C2IH) is recovered 24 O6), residual acetic acid, water, carbon dioxide (CO2), and carbon monoxide (CO), with effective removal of oxalates and no metallic residues or organic solvents. Summary of the curcumin conversion mechanism (C2IH 20 O6) to tetrahydrocurcumin (C2IH 24 O6):

[0051] The conversion of curcumin to tetrahydrocurcumin is carried out by a non-catalytic hydrogenation reaction, where the presence of vinegar (aqueous mixture of acetic acid and water), plus heat and pressure is required.

[0052] This reaction does not occur spontaneously at room temperature, as it requires external energy to break the TT bonds of curcumin and allow its reduction.

[0053] The overall chemical reaction can be expressed as:

[0054] Curcumin (C2IH) 20 O6) + 2[H] Tetrahydrocurcumin (C2IH 24 O6)

[0055] Proposed mechanism:

[0056] 1. Ionization of the acidic medium: Under high thermal conditions (-150-180 °C) and pressure (-15 psi), the acetic acid (CH3COOH) and water (H2O) present in vinegar undergo partial ionization:

[0057] CH3COOH CH3COO- + H H2O H + + OH'

[0058] This ionization generates an acidic medium with redox capacity, favoring the formation of protons (H + ) and hydrogen radicals (H), which act as reducing agents. Electronic activation of curcumin: In this acidic environment (pKa of acetic acid ~ 4.76), protons interact with the conjugated double bonds of curcumin, facilitating its electronic activation by protonation:

[0059] C 21 H 20 O6+ 2H + C 21 H 20 O6 2+

[0060] This protonated form is more susceptible to chemical reduction.

[0061] Reduction to tetrahydrocurcumin: The protons and hydrogen radicals generated in the medium react with the TT (double) bonds of the activated curcumin, saturating the bonds and reducing the compound:

[0062] C 21 H 20 O6 2+ +2[H] C 21 H 24 O6

[0063] This process does not use metallic catalysts or organic solvents, which is a relevant technical advantage for applications in the food, nutraceutical, cosmetic and pharmaceutical industries.

[0064] Furthermore, this is an endothermic reaction, meaning it requires an external energy source (heat) and a pressurized environment to occur. At room temperature and atmospheric pressure, the curcumin molecule remains stable and does not spontaneously transform into tetrahydrocurcumin. Summary of the transformation mechanism of calcium oxalate (CaC2O4) into carbon dioxide (CO2), carbon monoxide (CO), and water (H2O) in the presence of acetic acid (CH3COOH) under conditions of heat and pressure:

[0065] 1. Initial chemical formula of calcium oxalate: CaC2O4

[0066] 2. Acid-base stage (at room temperature):

[0067] When calcium oxalate is mixed with vinegar (acetic acid and water), a weak acid-base reaction occurs:

[0068] CaC2O4(s) + 2CH3COOH (aq) Ca 2+ (aq) + H2C2O4(oxalic acid) + 2CH3COO“ (aq)

[0069] Here acetic acid releases protons (H + ) that protonate oxalate to generate oxalic acid (H2C2O4).

[0070] This reaction stops here if no heat is applied.

[0071] 3. Thermal decomposition stage of oxalic acid (requires heat and pressure):

[0072] a) First step (decomposition of oxalic acid in the presence of heat and pressure):

[0073] H2C2O4CO2+ HCOOH (farmic acid)

[0074] b) Second step (decomposition of formic acid in the presence of heat and pressure):

[0075] HCOOH → CO + H2O

[0076] Both steps require heat and pressure. Overall reaction of the calcium oxalate decomposition process under conditions with applied heat and pressure:

[0077] CaC2O4+ 2CH3COOH Ca 2+ + 2CH3COO- + CO2+ CO + H2O

[0078] Technical description and novelty of the process:

[0079] This reaction summarizes the transformation of calcium oxalate (CaC2O4) in an acidic medium using vinegar, which is formulated from acetic acid (CH3COOH) and water (H2O), under controlled conditions of heat (between 150 and 180 °C) and pressure (-15 psi), where the following occurs:

[0080] CaC2O4 (Calcium Oxalate): It is a poorly soluble salt that is found naturally in turmeric and other plant matrices.

[0081] CH3COOH (Acetic Acid): Acts as a weak acid that protonates and facilitates the release of the oxalate ion (C2O4 2- ), which allows its subsequent transformation through thermal reactions.

[0082] AC 2+ (Calcium Cation): It is released as a stable product in solution. Although it does not directly modify the pH, its presence helps to buffer the acidity of the medium (mild buffering effect), improving the stability and safety of the final product for food or cosmetic applications.

[0083] CH3COO (Acetate): This is an anion formed by the dissociation of acetic acid. It is a naturally occurring compound in human metabolism, approved for food use by international organizations such as the FDA, EFSA, and COFEPRIS. Its presence in the solution does not represent any toxicity, reinforcing the harmless nature of the process.

[0084] CO2 and CO (Carbon Dioxide and Carbon Monoxide respectively): These are gaseous products generated by the thermal decomposition of intermediate oxalic acid (H2C2O4) and secondary formic acid (HCOOH). These byproducts are naturally removed from the system when the reactor is opened.

[0085] H2O (Water): It is another product generated by the thermal decomposition of the intermediate oxalic acid (H2C2O4) and the secondary formic acid (HCOOH), which remains in the final aqueous medium when the water vapor condenses as the reactor cools down.

[0086] Technical innovation:

[0087] Although the decomposition stages of oxalic and formic acids have been previously described in certain academic contexts, the present invention represents the first integration of these reactions into a natural and unified protocol, where food-grade vinegar, under controlled heat and pressure, simultaneously allows:

[0088] The conversion of curcumin to tetrahydrocurcumin by reduction without metal catalysts, and

[0089] The decomposition of calcium oxalate into harmless products, eliminating compounds potentially harmful to the human body. The entire process occurs in an aqueous environment, within a reactor that withstands high temperatures and pressure, without the use of organic solvents or toxic additives, making it unique, safe, environmentally friendly, economical, and highly applicable in the food, nutraceutical, cosmetic, and pharmaceutical industries. EXAMPLE OF IMPLEMENTATION

[0090] Example 1:

[0091] Reagents:

[0092] Apple cider vinegar: 1 liter (5% acetic acid concentration) Turmeric powder: 60 grams

[0093] Apple cider vinegar is mixed with turmeric powder until a homogeneous solution is obtained (100). The mixture is introduced into a reactor and hermetically sealed (200), and heat is applied (300) until an internal pressure of 15 psi is reached, stabilizing the temperature in a range of 150°C to 180°C.

[0094] Once these conditions are reached, a constant isotemperature and isopressure are maintained for 30 minutes, counted from the moment the pressure of 15 psi is reached.

[0095] After 30 minutes, the heat source of the sealed reactor is turned off and it is left to cool until it is completely depressurized.

[0096] Next, when the reactor is at room temperature, the reactor is opened and the process of separating the tetrahydrocurcumin (500) precipitated in the liquid mixture is carried out. If it is desired to obtain the tetrahydrocurcumin in a dry solid state and free of residual vinegar, it must be subjected to a filtration process to obtain the precipitate and subsequently subjected to a drying process by evaporation so that the precipitated tetrahydrocurcumin in a dry solid state can be used as a raw material in different applications in the nutraceutical, food, cosmetic and pharmaceutical industries.

[0097] The resulting substance can also be homogenized to formulate tetrahydrocurcumin (500) in liquid solution where the precipitate remains mixed with the residual vinegar post-reaction (mixture of acetic acid and water). INDUSTRIAL APPLICATION

[0098] The process is reproducible under laboratory conditions and scalable for industrial applications.

[0099] Its clean, ecological nature, with the absence of oxalates and without toxic residues of heavy metals, makes the present process ideal for producing tetrahydrocurcumin for food, cosmetic and pharmaceutical applications.

[0100] Furthermore, by improving the bioavailability of curcuminoids in the human body through the transformation of curcumin into tetrahydrocurcumin without oxalates and without heavy metal residues, it allows the development of more effective formulations for the utilization of their antioxidant, anti-inflammatory and neuroprotective properties.

Claims

CLAIMS Having sufficiently described my invention, I consider it novel and therefore claim as my exclusive property the content contained in the following claims:

1. Process for the conversion of curcumin (C2IH 20 O6) in tetrahydrocurcumin (C2IH 24 O6), characterized by comprising the stages of: a) Mix turmeric (Curcuma longa) powder, pulp or extract with food grade vinegar containing between 2% and 6% acetic acid (CH3COOH), until a homogeneous mixture is obtained; b) introduce said mixture into a sealed reactor, preferably an autoclave or equivalent equipment; c) apply heat until an internal temperature between 150 °C and 180 °C is reached, and an approximate pressure of 15 psi; d) maintain these conditions for a period of 30 to 45 minutes; e) cease applying heat and allow the system to cool; and f) recover tetrahydrocurcumin (C2IH 24 O6) as a resulting product.

2. The process according to claim 1, wherein the vinegar used is selected from the group consisting of apple cider vinegar, cane vinegar, rice vinegar, or any food-grade vinegar suitable for human consumption.

3. The process according to any of the preceding claims, characterized in that it is carried out without the use of metallic catalysts, without metallic salts, without molecular hydrogen, and without organic solvents.

4. The process according to any of the preceding claims, wherein the acidic medium generated by the vinegar favors the in situ formation of protons (H + ) and hydrogen radicals (H ), which act as reducing agents for the saturation of the double bonds of curcumin.

5. The process according to any of the preceding claims, further characterized by causing the thermal decomposition of the calcium oxalate (CaC2O4) present in turmeric, transforming it into carbon dioxide (CO2), carbon monoxide (CO) and water (H2O).

6. The process according to claim 5, wherein said transformation comprises the intermediate conversion of calcium oxalate (CaC2O4) into oxalic acid (H2C2O4), followed by its thermal decomposition into carbon dioxide (CO2), carbon monoxide (CO) and water (H2O) under conditions of heat and pressure.

7. A composition resulting from the process of any of the preceding claims, comprising tetrahydrocurcumin (C2IH 24 O6) in solid or dissolved state, in an aqueous medium containing residual acetic acid (CH3COOH) and water (H2O), where the composition is substantially free of oxalates and heavy metals.

Images