Novel complex derived from natural extract having ph adjusted by acid-base reaction and method for synthesizing same

Abstract

The present invention relates to a novel complex derived from a natural extract having pH adjusted by an acid-base reaction, and a method for synthesizing same. The present invention provides a novel complex synthesized by chemical reaction formula 1. [Chemical reaction formula 1] Acid + (base + polyphenol-containing natural extract) → novel complex + by-product

Description

A novel complex from a natural extract whose pH is controlled by acid-base and a method for its synthesis

[0001] The present invention relates to a novel complex from a natural extract whose pH is controlled by an acid-base and a method for synthesizing the same.

[0002]

[0003] In order to substitute or exchange salts such as organic or inorganic acids in natural extracts containing polyphenol components, many process difficulties and economic / non-economic losses were involved.

[0004] In particular, polyphenols undergo structural changes depending on pH, resulting in different physicochemical and physiological activities. Therefore, pH-dependent reactions and their corresponding effects must be considered. However, specific details regarding this have not been disclosed.

[0005] For example, Korean Patent Publication No. 10-2022-0022425 (“Desalting and crystallization purification method of a basic amino acid-based cationic surfactant”) discloses a method for stably desalting an ester compound without structural change by maintaining a constant pH based on a basic amino acid-based cationic surfactant and its derivatives, and performing a single crystallization purification operation by treating it with an organic or inorganic acid suitable for the purpose.

[0006]

[0007] However, as in the present invention, the process of first adjusting the pH by adding a base or alkaline substance to a natural extract and then reacting it with an acid substance is not specifically disclosed. Therefore, the present invention discloses an improved reaction / process compared to the above-mentioned prior art.

[0008]

[0009] The present invention aims to provide a novel complex from a natural extract whose pH is controlled by an acid-base and a method for synthesizing the same.

[0010]

[0011] As a means for solving the above problem, the present invention provides a novel complex synthesized by the following chemical reaction formula 1.

[0012]

[0013] [Chemical Reaction Formula 1]

[0014] Acid + (base + natural extract containing polyphenol components) → new complex + byproduct

[0015]

[0016] In the above [chemical reaction formula 1], a natural extract containing a base and polyphenol components first becomes a mixed solution, and then the mixed solution reacts with an acid.

[0017]

[0018] The above acid is an organic acid, inorganic acid or salt thereof having a pH range of 0 to 6.

[0019]

[0020] The above base includes a basic substance or an alkaline substance.

[0021]

[0022] The above natural extract is a natural extract containing polyphenol, which is adjusted to pH 8 to 10 using a basic substance and then reacted with an acid.

[0023]

[0024] The above chemical reaction formula 1 is carried out in a solvent, and the solvent is capable of dissolving both organic and inorganic acids, while being insoluble in water.

[0025]

[0026] In addition, the present invention provides a novel method for synthesizing a complex from a natural extract, comprising: (S1) a first step of mixing a natural extract containing a polyphenol component with a base to adjust the pH to 8 to 10; (S2) a step of reacting the mixture of the natural extract containing the polyphenol component and the base with an acid in the pH range of 0 to 6, thereby adjusting the pH to 5 to 8; and (S3) a step of generating a novel complex and by-products.

[0027]

[0028] The present invention provides a novel complex from a natural extract whose pH is controlled by an acid-base and a method for synthesizing the same, which has several advantages in terms of stability and activation, reaction efficiency and yield, reaction range, environmental stability, etc., as described below.

[0029]

[0030] Hereinafter, embodiments of the present invention will be described in detail. However, these embodiments are intended to illustrate the present invention and not represent the only embodiments. These embodiments are provided to ensure a complete disclosure of the present invention and to fully convey the scope of the invention to those skilled in the art.

[0031] Those skilled in the art will appreciate that variations and modifications can be made to the embodiments of the present invention without departing from the essential characteristics of the disclosed technology. Therefore, the disclosed methods should be considered illustrative rather than restrictive.

[0032] Hereinafter, the present invention will be described in detail.

[0033]

[0034] According to the present invention, a novel complex synthesized by the following chemical reaction formula 1 is disclosed.

[0035]

[0036] [Chemical Reaction Formula 1]

[0037] Acid + (base + natural extract containing polyphenol components) → new complex + byproduct

[0038]

[0039] In the above [chemical reaction formula 1], the base and natural extract first form a mixed solution, and then the mixed solution reacts with an acid.

[0040]

[0041] The acid is an organic acid, an inorganic acid or a salt thereof having a pH range of 0 to 6. It may be composed of an organic acid based on a cationic amino acid such as arginine, histidine or lysine, or a salt thereof, and may be, for example, ethyl lauroyl arginate [or ethyl lauroyl arginate hydrochloride (Ethyl Lauroyl Arginate HCl)].

[0042]

[0043] More specifically, Arginine, Histidine, Lysine, Ornithine, Piperidinecarboxylic Acid, Guanidinoacetic Acid, Ethyl Lauroyl Arginate, Ammonium Salt (NH₄ + ), hydrazinium (H₂N-NH₃ + ), hydroxyl ammonium (NH₃OH +), protonated amines, etc., organic and inorganic acids that can be cationic, gallic acid, butyl paraben, l-(+)-ascorbic acid, salicylic acid, gabapentin, cocrystal, ketoconazole, tannic acid, fatty acids, citric acid, lactic acid, hydrochloric acid (HCl), acetic acid, malic acid, citric acid, formic acid, butyric acid, oxalic acid, propionic acid, fumaric acid, adipic acid, succinic acid, tartaric acid, malic acid Substances based on, but not limited to, Acid, Gluconic Acid, Galactonic Acid, Mannonic Acid, Glutaric Acid, Pyruvic Acid, Fluorosilicic Acid, Isobutyric Acid, Isovaleric Acid, Palmitic Acid, and Gluconic Acid, as well as Sulfonic Acid, Nitric Acid, and Phosphoric Acid.

[0044]

[0045] The base includes a basic substance or an alkaline substance. For example, the base may include at least one selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonia, calcium hydroxide, magnesium hydroxide, piperidine, triethylamine, diethylethylenediamine, methylamine, sodium carbonate, potassium carbonate, sodium acetate, phosphate salt, barium hydroxide, lithium hydroxide, and sodium bicarbonate, but is not limited thereto.

[0046]

[0047] The above natural extract is a natural extract containing polyphenol, and is characterized in that it reacts with an acid by adjusting the pH to 8 to 10 by mixing with a base. The above natural extracts are hydroxycinnamic acid, chicoric acid, monocaffeyltartaric acid, chlorogenic acid, silymarin, curcumin, catechin, kaempferol, resveratrol, luteolin, quercetin, rutin, gallic acid, tannin, hesperetin, hesperidin, flavonoid, anthocyanidin, anthocyanin, naringenin, naringin, baicalein, baicalin, caffeic acid, It may be one or more selected from the group consisting of, but is not limited to, Rosmarinic Acid, Carnosic Acid, Capsaicin, Flavanols, Theobromine, Quercetin, Epigallocatechin Gallate (EGCG).

[0048] At this time, natural extracts can be relatively stable even in acidic environments as long as they contain polyphenol components. However, if the pH is excessively low, the chemical structure of the polyphenols can change, and they can easily decompose or be deformed. For example, when polyphenol components react with acidic substances, various reactions such as oxidation-reduction reactions, oxidation reactions, and complex formation can occur. During oxidation-reduction or oxidation reactions, color changes, reactive oxygen species generation, or structural changes can occur.

[0049]

[0050] The above solvent is characterized in that it can simultaneously dissolve organic acids and inorganic acids, while being insoluble in water.

[0051] The solvent is at least one solvent selected from the group consisting of, but not limited to, ethyl acetate, acetone, dichloromethane, chloroform, toluene, hexane, diethylether, solvent naphtha, xylene, butanol, isopropyl alcohol, acetonitrile, tetrahydrofuran (THF), methyl isobutyl ketone (MIBK), etc.

[0052]

[0053] Next, the by-products include metal ion salts and carbonates, and may be water-soluble sodium salts of sodium carbonate, sodium fatty acid, sodium citrate, sodium lactate, sodium acetate, sodium malate, sodium citrate, sodium formate, sodium oxalate, sodium propionate, sodium fumarate, sodium adipate, sodium succinate, sodium tartrate, sodium malate, sodium gluconate, sodium mannonic acid, sodium glutarate, sodium pyruvate, sodium fluorosilicate, and sodium isobutyrate, but are not limited thereto. These by-products are harmless to the environment and can be naturally biodegraded, so that no or minimal impact on the environment can be had.

[0054]

[0055] In the present invention, according to the above [chemical reaction formula 1], a natural extract is substituted with a salt of an acid to form a new complex.

[0056]

[0057] Now, as an example, let us examine the reaction (solvent: ethyl acetate) using Taraxacum officinale extract as a natural extract containing polyphenol components, sodium bicarbonate as a base, and ethyl lauroyl arginate hydrochloride as an acid salt.

[0058] Ethyl lauroyl alginate hydrochloride is a cationic substance that contains a positively charged functional group such as a guanidinium group, and thus can generally induce electrostatic interaction or complex formation with anionic substances (e.g., organic acids, anionic polymers, natural extracts, etc.).

[0059] First, ethyl lauroyl alginate hydrochloride is dissolved in ethyl acetate. Meanwhile, sodium bicarbonate is added to the ethanol-extracted dandelion extract to raise the pH, thereby anionizing the organic acidic components in the dandelion extract. The aqueous stirred solution prepared in this manner (hereinafter referred to as the "anionized dandelion extract solution") is added dropwise or by stirring to the ethyl acetate solution in which ethyl lauroyl alginate hydrochloride has been dissolved, prepared previously.

[0060] During this process, the hydrochloric acid (HCl) contained in ethyl lauroyl alginate hydrochloride undergoes a neutralization reaction with sodium bicarbonate, producing salt (NaCl) and water (H₂O), which are discharged as byproducts during the reaction. Consequently, the ethyl lauroyl alginate (desalted form) from which HCl has been removed forms a novel complex by forming electrostatic or non-covalent complex bonds with the anionic components present in the dandelion extract.

[0061]

[0062] Here, the content of the natural extract is preferably 1 / 8 to 1 / 5 of the acid input amount (based on g), and more preferably 1 / 8 to 1 / 4. As the ratio approaches 1 / 1, the color of the product becomes cloudy (turning to a deep dark green), and as it approaches 1 / 8, it becomes distinctly white, resulting in relatively higher marketability. Therefore, for example, if the ratio exceeds 1 / 1, it is unsuitable for use as a commercial product.

[0063] The table below summarizes the color, turbidity, etc. when the reactants are ethyl lauroyl alginate, sodium bicarbonate, and dandelion extract, and the solvent is ethyl acetate, and the ratios are changed.

[0064]

[0065] Natural extract: Acid ratio Product color Turbidity Marketability Note 1 / 8 White Low High High marketability with optimal ratio 1 / 6 Off-white Low Medium to high Somewhat high marketability 1 / 4 Light green Medium Medium Medium Medium marketability 1 / 2 Green Medium to high Low Low marketability 1 / 1 Dark green High Very low High turbidity, not suitable for marketability

[0066]

[0067] Next, the aqueous solution containing the natural extract and the base is added in a ratio of 5:40 to 16:40, preferably 8:40 to 12:40, and more preferably 9:40 (based on g) to the acid (aqueous solution).

[0068]

[0069] Mixed solution: acid ratio Complex formation rate (%) Natural extract activity Reactivity Note 5:40 65 Low Low Low reactivity, low natural extract activity 8:40 78 Medium Moderate Moderate reactivity, but not optimal 9:40 85 High High Optimal reactivity and natural extract activity 12:40 80 High Medium Reactivity is still high, but efficiency is less than optimal 16:40 70 Medium Low Low reactivity, low natural extract activity

[0070]

[0071] At this time, considering the activity of the natural extract, the aqueous solution containing the natural extract and the base should preferably have a pH of 8 to 10. If the pH is below 8, it is close to neutrality, making it difficult to obtain the activity of the natural extract. If the pH exceeds 10, it is a strong base, making it difficult to handle. In addition, the natural extract may be denatured / destroyed by the strong base, which may actually inhibit the reaction. In addition, since an excessive amount of acid must be added when reacting with an acid substance in the future, it is even more dangerous and results in economic waste.

[0072]

[0073] pH Natural extract activity (%) Reactivity (complex formation rate %) Denaturation Amount of acid used (mL) Economic efficiency Notes 88580 None 80 High Optimal reactivity and appropriate acid usage 98885 None 75 High Optimal activity and reactivity, lowest acid usage 107060 Partial denaturation 110 Somewhat high Denaturation reduces reactivity and increases acid usage 115040 Denaturation 180 Very low Denaturation reduces reactivity and highest acid usage

[0074]

[0075] The reaction according to the present invention must be performed at the highest temperature below the melting point of the acid substance. At temperatures above or below the melting point, the acid will melt and be discharged as a filtrate. In this case, the acid substance used in the desired reaction will not react properly, resulting in the reaction / bonding not occurring as intended. In some cases, problems may arise, such as changes in the physical / chemical structure of the natural extract or denaturation / destruction of the active ingredient due to the high temperature.

[0076] Accordingly, a temperature of 50 to 75 degrees Celsius, preferably 60 to 70 degrees Celsius, is recommended. However, since the melting point may vary depending on the reactant, it is best to select the highest temperature below the melting point while still maintaining a temperature that does not denature or destroy the structure of the natural extract.

[0077]

[0078] Temperature (°C)Natural extract activity (%)Reactivity (complex formation rate %)Product quality (purity %)Denaturation Notes50757085NoneLow reactivity, moderate activity55807888NoneModerate activity and reactivity60858592NoneGood activity and reactivity65908895NoneOptimal reactivity and quality, no denaturation70888594NoneHigh activity and reactivity, excellent product quality75726580Partial denaturationLower activity and reactivity, some denaturation occurs80605070DenaturationSignificantly reduced activity and reactivity due to denaturation

[0079]

[0080] Meanwhile, when making a mixed solution (aqueous solution) of a base and a natural extract, the structural stability of the natural extract can be strengthened and its reactivity can be increased by using a catalyst or auxiliary agent.

[0081] For example, the addition of catalysts or adjuvants, including polyvinylpyrrolidine (PVP), polyethylene glycol (PG), polyglycerol esters, and silane coupling agents, can protect the active ingredients of natural extracts from oxidation. However, such catalysts or adjuvants should not alter the physical / chemical properties of bases or natural extracts, and preferably, they should not affect reactions with acidic substances.

[0082] In particular, these adjuvants may be included in an amount of 0.1 to 0.5% (w / v) relative to the mixture of base and natural extract. When adding the adjuvants, ensure that they are uniformly dissolved by stirring at low speed. The mixing time is set to 5 to 10 minutes to prevent excessive heat generation and ensure uniform mixing.

[0083]

[0084] Meanwhile, according to the present invention, two or more solvents can be used to facilitate solvent exchange. For example, when preparing a mixed aqueous solution of a base and a natural extract, solvent A can be used, and then solvent B can be used to react with an acid substance. This can enhance reaction efficiency or reactivity.

[0085] For example, solvent A is a hydrophilic solvent such as ethanol or methanol, which dissolves the base and natural extract well and plays a role in stabilizing the active ingredients of the natural extract. At this time, the ratio of solvent A to the mixed solution is set to 10 to 20% (v / v) to maximize the solubility while maintaining an appropriate viscosity. In addition, solvent B is a lipophilic solvent such as dichloromethane (DCM) or ethyl acetate, which is suitable for reaction with an acid and can promote complex formation. At this time, solvent B can be diluted to a ratio of 1:2 to 1:5% (v / v) compared to the mixed aqueous solution of the base and natural extract and then reacted with an acid.

[0086] Additionally, a mixture of solvents A and B may be used. For example, a mixture of ethanol and dichloromethane may be utilized throughout the entire process. In this case, the ethanol and dichloromethane may be mixed in a ratio of 3:7 to 7:3, or even in a ratio of 4:6 to 6:4.

[0087] When the ratio of ethanol and dichloromethane is changed, the solubility and reactivity, product purity and yield are calculated as follows.

[0088]

[0089] Solvent ratio (ethanol:dichloromethane)Solubility (mg / mL)Reactivity (% complex formation)Product purity (%)Yield (%)2:81.26588703:71.57291764:628594825:51.87889756:41.4608568

[0090]

[0091] Meanwhile, when reacting an acid with a mixed aqueous solution of a base and a natural extract, the acid can be added gradually in a dropwise manner to maintain a stable pH of the reaction solution, thereby preventing denaturation of the natural extract due to sudden pH changes. In addition, in conjunction with this, it can be combined with a pH monitoring system to allow real-time pH measurement and control of the acid addition speed.

[0092] For example, when controlling the acid drop rate, setting it to 1-2 ml / min minimizes pH changes and maintains the activity of natural extracts. Furthermore, a pH monitoring system precisely measures pH and adjusts the acid injection rate based on this measurement.

[0093]

[0094] After the reaction with the acid is completed, a cooling crystallization method can be used to increase the crystallinity of the complex, and a centrifugation or ultrafiltration process can be additionally applied to increase the purity and separate it.

[0095] Here, using the cooling crystallization method, after the reaction is completed, the final solution is slowly cooled at a rate of 0.5 to 1 degree Celsius per minute to induce crystallization. The cooling temperature is set to -5 to 5 degrees Celsius to prevent uneven crystallization due to excessive temperature changes. In some cases, a trace amount of a crystallization promoter (e.g., zinc acetate) or a spray dryer may be used.

[0096] Meanwhile, further recrystallization and drying can be performed. This can yield a high-purity complex material. For example, the complex is dissolved in a high-purity B solvent at low temperature, then slowly cooled to crystallize, and then dried in a low-temperature vacuum dryer at 40 degrees Celsius or lower to prevent denaturation of the active ingredient and maintain a constant crystallinity.

[0097]

[0098] Additional background information regarding the present invention is provided.

[0099]

[0100] When polyphenols and organic acids combine to form water-soluble complexes, this affects the polyphenol's functions and physicochemical properties. A simple example is the reaction between tannins (polyphenols containing tannic acid) and strong acids, forming complexes. For example, tannins combine with iron (Fe) ions to form pigments in acidic environments. Another example is flavonoids, which undergo structural changes in acidic environments to form new compounds, and curcumin (a polyphenol component of turmeric) undergoes a color change in an acidic environment.

[0101]

[0102] However, when pH is controlled through a base as in the present invention, there may be advantages in many aspects, such as stability and activation, reaction efficiency, reaction range, and environmental stability.

[0103] First, as described above, since polyphenol components are decomposed or undergo structural changes in a strongly acidic environment, the stability of polyphenols can be maintained by adjusting the pH using a base, thereby preserving the desired physicochemical or physiological properties of polyphenols.

[0104] Furthermore, since polyphenols' functional groups are activated or deactivated depending on pH, adjusting pH can induce structural changes in polyphenols, leading to new chemical reactions or activations. Furthermore, some polyphenol components exhibit varying solubility across specific pH ranges, so adjusting pH using a base can alter the solubility of polyphenols, allowing the desired chemical reaction to occur.

[0105] Additionally, the speed of chemical reactions can vary depending on pH control. For example, when the optimal pH for polyphenol reaction is achieved, the efficiency can be greatly increased, and in some cases, a neutralization reaction can occur, which can help form a complex or enhance the function of polyphenol.

[0106] In addition, it can promote alkylation, esterification, or other chemical transformations or form complexes by interacting with basic substances, and can enjoy environmentally friendly effects by adjusting pH using bases in chemical process steps.

[0107]

[0108] To summarize the technical gist of the present invention, (1) a mixture aqueous solution containing a natural extract containing polyphenols and a base adjusted to a pH of 8 to 10 is mixed, and (2) a (weak) acidic organic acid or inorganic acid (or its salt) having a pH of 0 to 6 is added so that the pH becomes 5 to 8, and at the same time, polyphenol dissolved in the mixture aqueous solution of the natural extract and the base is bonded to the salt site of the (weak) acid substance, and the salt of the (weak) acid is desalted, and at the same time, a reaction occurs in which the natural extract (the pH of which is adjusted to 8 to 10 due to the base and the reaction efficiency is increased) is substituted for the salt site of the (weak) acid that has been desalted, thereby forming a new complex.

[0109] This overcomes the drawback of conventional (weak) acids, such as organic or inorganic acids, which is their lack of reactivity or low reactivity due to ionic differences with specific excipients. In other words, by utilizing natural extracts and alkaline substances to adjust pH, thereby altering the properties of organic compounds, compatibility issues are addressed. This process suggests a method for improving the properties of organic or inorganic acids and enabling their effective utilization.

[0110] As described above, in the present invention, rather than sequentially adding a base and a natural extract to a (weak) acid, a reaction is carried out by adding an aqueous solution of a base and a natural extract to a (weak) acid. Therefore, the natural extract containing a polyphenol component under basic conditions may be in a state in which the polyphenol is relatively stabilized or modified so that the intended type of reaction can occur. In addition, as the aqueous solution of the base and the natural extract reacts with the (weak) acid, the initial pH (0 to 6) of the acid substance becomes pH 5 to 8 during the reaction process, so that the salt of the acid and one component of the natural extract are exchanged or substituted.

[0111] In other words, by adjusting the pH to a basic state (pH 8-10) and increasing the activity of the natural extract, the acid-base neutralization reaction occurs while reacting with the acid substance, and at the same time, the reaction with the natural extract is performed to obtain the desired product. If the acid, base, and natural extract are added all at once instead of in a mixed state with the base, the acid-base neutralization reaction occurs more quickly, which slows down the reaction to the natural extract, reduces the yield, or causes unwanted reactions to take precedence due to rapid changes in pH and changes in the activity of the natural extract.

[0112] In the past, a lot of time and money had to be invested to exchange or replace the salt of an acid with a component of the desired natural extract, and a large number of chemicals that inevitably affect the environment were used. However, according to the present invention, the production time can be reduced (at least about 1 hour), structural stability is strengthened, and a low-carbon, non-heat-resistant simultaneous substitution process (the temperature during the process is 40 to 55 degrees Celsius) is performed [for example, when ethyl lauroyl alginate hydrochloride is used as a (weak) acid and sodium bicarbonate (NaHCO3) is used as a base, the process of NaHCO3 + HCl → NaCl(aq) + H2O + CO2(↑) is performed through this technology], and depending on the substance used, by-products can be discharged as environmentally harmless domestic wastewater.

[0113] In addition, through simultaneous exchange or substitution of natural extracts and salts, the physicochemical stability can be maintained / preserved, such as maintaining the antioxidant activity of natural extracts, promoting interaction with acid components, and securing high yields due to increased crystallinity. For example, if simultaneous exchange / substitution is not performed, the bonding between the acid component and the natural extract does not proceed smoothly, which may result in defects in the quality of the product, and unreacted (unbound) substances are disposed of as waste liquid as a filtrate, resulting in a loss in yield (yield of approximately 60% if simultaneous substitution is not performed).

[0114] Through the above contents, the advantages of the present invention can be confirmed.

Claims

1. A novel complex synthesized by the following chemical reaction formula 1. [Chemical Reaction Formula 1] Acid + (base + natural extract containing polyphenol components) → new complex + byproduct However, in the above [chemical reaction formula 1], the natural extract containing the base and polyphenol components first becomes a mixed solution, and then the mixed solution reacts with the acid.

2. In paragraph 1, The above acid is an organic acid, inorganic acid or salt thereof having a pH range of 0 to 6, The above base includes a basic substance or an alkaline substance, A novel complex characterized in that the natural extract containing the polyphenol component is adjusted to pH 8 to 10 by the base and reacts with an acid.

3. In paragraph 1 or 2, The above chemical reaction formula 1 proceeds in a solvent. A novel complex characterized in that the solvent is a solvent capable of dissolving both organic and inorganic acids simultaneously, while being insoluble in water. 4.(S1) Step 1: Mixing a natural extract containing polyphenol components with a base to adjust the pH to 8 to 10; (S2) a step of reacting a mixture of a natural extract containing the polyphenol component and a base with an acid having a pH range of 0 to 6, while adjusting the pH to 5 to 8 through the process; and (S3) A method for synthesizing a novel complex from a natural extract, comprising a step of generating a novel complex and a by-product.