Use of additives (adjuvants, antifreeze, antimicrobials and antioxidants) in natural deep eutectic solvents and their mixtures

Abstract

The present invention relates to NADES (natural deep eutectic solvents) that can be used as additives to products to provide unexpectedly superior or synergistic properties compared to the product alone. The NADES disclosed herein have been shown to perform well in other products as adjuvants, antifreeze agents, antimicrobial agents, or additives to personal care products.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119(e) to U.S. Nonprovisional Patent Application No. 18 / 427,860, filed January 31, 2024, and U.S. Provisional Application No. 63 / 442,122, filed January 31, 2023, the entire contents of which are incorporated herein by reference.

[0002] Technical Field The present invention relates to the use of eutectic solvent systems, i.e., natural deep eutectic solvents (NADES), as additives to products to impart unexpectedly superior or synergistic properties compared to their use alone. The natural deep eutectic solvents of the present invention, as described herein, exhibit superior properties as additives to other products, as adjuvants, antifreeze agents, antimicrobial agents, and / or additives added to personal care products.

[0003] Background technology Deep eutectic solvents, or DESs, are solutions of Lewis or Bronsted acids and bases that form eutectic mixtures. Deep eutectic solvents are highly tunable by varying the structure of their constituent components or the relative ratios of the various components in the mixture. Because they are complex systems with widely differing properties, they have a wide variety of potential applications, including use in catalysis, separation technologies, and electrochemical processes. The parent components of deep eutectic solvents tend to participate in complex hydrogen-bonding networks, and as a result, mixtures tend to exhibit significant freezing point depressions compared to the parent compounds / components in the mixture. In some cases, the individual components in a mixture may be solids at room temperature and atmospheric pressure, but when they are mixed at room temperature and atmospheric pressure, the mixture may become a liquid with a significantly depressed freezing point (e.g., 10°C).

[0004] The term "eutectic" was first coined in 1884 by British chemist and physicist Frederick Guthrie. First-generation eutectic solvents were based on mixtures of hydrogen bond donors, such as amines and / or carboxylic acids, with quaternary ammonium salts. NADES are biologically derived deep eutectic solvents, generally consisting of two or more compounds derived from plant-derived primary metabolites, namely organic acids, sugars, alcohols, amines, and amino acids. Water may also be present as part of the solvent, which can be difficult to remove because it does not readily evaporate.

[0005] Since Frederick Guthrie coined the term "eutectic," much of the research on eutectic solvents has focused on solvent mixtures in which at least one component is a metal-based solvent. However, the release of metals from these solvent systems has presented many drawbacks associated with metal leaching and the associated health, environmental, and safety issues. As a result, interest in non-metal-containing eutectic systems has grown in recent years.

[0006] U.S. Patent No. 10,865,334 relates to a method for extracting substances from biologically derived materials, characterized in that the natural biological material is treated with an extractant consisting of a naturally derived deep eutectic solvent or a naturally derived ionic liquid to produce a naturally derived biological extract dissolved in the solvent or ionic liquid.

[0007] Indian Patent Application No. IN202041012054A relates to a synergistic formulation that can be employed as a vehicle for facile extraction of phytochemicals from natural sources of biomass and herbs, which can be employed in the manufacture of nutritionally fortified livestock feed supplements.

[0008] US Patent No. 10,981,084 relates to the use of coconut water as an extraction solvent, an extraction method using coconut water, and an extract obtained by extraction with coconut water. A description of deep eutectic solvents is given in the Background of the Invention.

[0009] WO 2022 / 101490 relates to the development of NADES using natural products such as sugars, organic bases, and organic acids as starting compounds. These solvents can be used to extract bioactive compounds from natural sources such as cork, agricultural waste including grape seeds and skins, tomatoes, olive oil, and plants (tea, eucalyptus, lavender, etc.) and fish skin and bones. The extracted materials can then be further formulated with topical active cosmetic ingredients to produce cosmetic compositions. WO 2022 / 101490 focuses on the application of NADES in the extraction of chemical compounds from natural sources. This extraction method uses ultrasound-assisted extraction and the "enfleurage" method, a closed-system extraction. The isolated natural extracts can then be directly applied to cosmetic compositions without further purification.

[0010] EP 3971230 A1 relates to a deep eutectic solvent (DES) comprising at least one carboxylic acid having at least two carboxylic acid functional groups and a carbon number ranging from 4 to 10, at least one alcohol having at least two alcohol functional groups and a carbon number ranging from 2 to 12, polyethylene glycol and polypropylene glycol, and water in an amount of 10 to 50 wt % of the total weight of the deep eutectic solvent. This document describes the use of the DES as a solvent system for dissolving lignin from lignin-containing materials or for preparing lignin prepolymers that can be used in the production of films, coatings, thermal insulation foams, adhesives, binders, composites or fiber sizing or for radical curing.

[0011] EP 3693418 A1 relates to solvent compositions, particularly those containing naturally occurring, non-petrochemical components. This document relates to solvent compositions based on plant-derived compounds derived from the fermentation of carbohydrates, such as glucose, fructose, sucrose, starch, cellulose, and mixtures thereof. While this document discloses solvent mixtures, it is believed that it does not relate to deep eutectic solvents.

[0012] EP 4011353 relates to eutectic solvents formed from a mixture of ascorbic acid (vitamin C) and betaine in combination with a third component selected from the group consisting of water, ethanol, glycerol, diols and / or triols containing up to six carbon atoms (in particular 1,3-propanediol, butylene glycol and hexanediol), which allow these active ingredients to be incorporated into cosmetic compositions.

[0013] While some of the above references pertain peripherally to eutectic mixtures and others to the separation / extraction of mixtures, none of the references disclose or suggest the use or addition of NADES with additives in the ratios described herein to provide systems that have unexpectedly superior properties compared to mixtures currently on the market and that can be used for multiple purposes. By using different ratios of these eutectic solvent mixtures with different components or different additives than the prior art, the present invention is able to achieve new and / or unexpectedly superior properties.

[0014] Summary of the Invention In one aspect, the present invention relates to systems, compositions, and methods of using these systems and compositions that include NADES mixtures of solvents as additives. When a eutectic mixture is used as an additive with a product used for a specific purpose, the addition of the eutectic mixture often provides superior and / or synergistic results compared to the product used alone. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 is a diagram showing a comparison of the wetted area on a paper sheet of TX (TritonX-100®) and various eutectic products (NADES). [Figure 2] FIG. 1 is a set of five graphs, each showing a different composition of NADES that can be used as an additive to improve adjuvant performance. [Figure 3] FIG. 1 shows in vitro results of various samples. [Figure 4]FIG. 1 is a bar graph showing the relative wetted area of ​​different solvent systems. [Figure 5] Figure 1 shows a solubility study at a working concentration of 14% w / w (analyte / solvent) first performed at 30°C in a conventional solvent and in a solvent of the invention, where dissolved analyte is indicated as 1 and undissolved analyte is indicated as 0. [Figure 6] FIG. 1 shows IR spectra of NaAcGlH at various temperatures. [Figure 7] FIG. 1 shows IR spectra of LGH at various temperatures. [Figure 8] FIG. 1 shows the viscosity curve of pure LGH. [Figure 9] FIG. 1 shows the viscosity curve of LGH containing 30% water. [Figure 10] FIG. 1 shows the viscosity curve of NaAcGlH in a pure solvent system. [Figure 11] FIG. 1 shows the viscosity curve of NaAcGlH with 50% water.

[0016] Detailed Description of the Invention In one aspect, the present invention relates to the use of a eutectic mixture of solvents as an additive, whereby when the eutectic mixture of the present invention is used as an additive with a product used for a specific purpose, the addition of the eutectic mixture often provides superior and / or synergistic results compared to the use of the product alone.

[0017] In some embodiments, the present invention relates to adding the eutectic mixture as an additive to different products, such as personal care products, antifreeze and / or antimicrobial products (or compositions). In some embodiments, the addition of the eutectic mixture of solvents improves the personal care product, antifreeze and / or antimicrobial product.

[0018] The following examples are presented to illustrate various aspects of the present invention and should not be construed as limiting the invention.

[0019] example Adjuvants Laboratory Testing Product preparation Multiple eutectic systems were prepared by combining eutectic compounds and heating on a magnetic stirrer until a clear liquid was formed. The temperature and time required to produce a clear eutectic solution were optimized for each case. Both hydrophilic and hydrophobic eutectic systems were prepared. The hydrophilic eutectic system used was UL, which is composed of urea (20–40%) and lactic acid (60–80%). The hydrophobic eutectic systems prepared included MT, which is composed of menthol (20–80%) and thymol (20–80%); MOA, which is composed of menthol (10–70%) and oleic acid (30–90%); and BOA, which is composed of borneol (10–30%) and oleic acid (60–90%).

[0020] Wetted area effect (pure system) test A general procedure for evaluating the wetted area of ​​droplets was developed. Test systems were prepared using 1% eutectic product in water with a miscible dye that allowed for visualization of the wetted area of ​​the droplet. To compare the performance of the pure system with a known adjuvant, TX (Triton X-100®: a nonionic surfactant with hydrophilic polyethylene oxide chains with an average of 9.5 ethylene oxide units), TX was prepared under identical conditions and compared to a water / dye blank. Five microliters of each system to be compared was then placed on a paper sheet, as shown in Figure 1.

[0021] Figure 1 shows a comparison of the wetted area of ​​various pure products on a paper sheet, where TX stands for Triton X-100®, the wettability of various liquids starting with HF represents a hydrophilic product, and the wettability of various liquids starting with HB represents a hydrophobic product.

[0022] Comparison on paper sheets The liquid wetting and spreading properties of TX, water, and various hydrophilic and hydrophobic eutectic products of the present invention were quantitatively measured, and the results are shown in Table 1. [Table 1]

[0023] As can be seen from Table 1, the wetted area (mm 2 ) shows that TX alone showed the best results compared to the other systems examined. The products of the present invention (i.e., UL, MT, MOA, and BOA) showed liquid wetting spread with a wetted area of ​​approximately 50% or less compared to the performance of TX.

[0024] Comparison in waxy leaves In the next experiment, the wetted area of ​​the droplet was tested on the waxy leaves of Epipremnum aureum. The quantitative results of these tests are shown in Table 2. In this test, the product of the present invention showed approximately 70% or less efficiency compared to the blank (i.e., performance against TritonX® at the same concentration as the tested NADES). In the case of UL, the wetted area of ​​the droplet did not increase, but penetration was observed in both the paper sheet and the plant leaf. [Table 2]

[0025] Wetted area effect (mixed system) Based on the results of the pure systems on paper and waxy leaves shown in Tables 1 and 2, the next test was conducted to compare mixtures of the product of the present invention with TX on paper sheets. Mixtures containing the product under test and TX were evaluated at 0.9, 0.75, 0.50, 0.25, and 0.10% (1% total concentration). Significant improvements in the wetted area of ​​the droplets were observed in these mixtures compared to TX alone. Quantitative results of these tests are shown in Table 3. Compared to TX / water, the TX / BOA (50 / 50%) mixture increased the wetted area by approximately 190%, the TX / BOA (75 / 25%) and TX / BOA (25 / 75%) systems increased the wetted area by approximately 180%, and TX / BOA (25 / 75%) increased the wetted area by approximately 150% (see Table 3). [Table 3-1] [Table 3-2]

[0026] Figure 2 shows five graphs showing various compositions of wetted area in mixed systems. For example, Figure 2A shows a graph containing TX and water, Figure 2B shows a graph containing TX and UL, Figure 2C shows a graph containing TX and MT, Figure 2D shows a graph containing TX and TOA, and Figure 2E shows a graph containing TX and BOA. Therefore, it is clear that adding the eutectic mixture of the present invention in a relatively appropriate amount and appropriate composition has a synergistic effect on the degree of wettability of the liquid compared to a system containing TX and water.

[0027] Evaporation time measurement Evaporation times were analyzed after applying 5 μL (1 drop) of a 1% solution in water to a glass slide at room temperature. The results of the experiment are shown in Table 4 and indicate that evaporation times were similar in all cases, and that one system did not appear to have a clear advantage over the other in this test. Also, in most cases, a very thin film remained after the droplet evaporated, indicating a wetting effect. Table 4 shows a comparison of wet spread on paper sheets (mixed systems). [Table 4]

[0028] Methylated Seed Oil (MSO) Market trends will continue to move towards more selective, less toxic, less persistent and rapidly biodegradable pesticides. Adjuvants should be considered as management tools that can improve not only the performance level of pesticides but also the consistency of results.

[0029] Adjuvants enhance the action of pesticides by improving or facilitating the control of their physical properties, thereby reducing and minimizing losses and maximizing the effectiveness of the product in which they are used. The properties of an adjuvant determine its functionality, which in turn is determined by the design and properties of the formulation. Functionality depends, among other things, on the chemical composition, the ratio of ingredients, and the dosage (amount used per unit area).

[0030] Newer pesticides tend to use more active molecules that are manufactured in highly concentrated formulations that are more expensive and require much lower dosages than traditional pesticides. In this regard, adjuvants can contribute to effective application, including droplet coating, wetting, adhesion, retention, penetration and transfer, reducing the margin of error.

[0031] The use of adjuvants offers considerable economic and environmental benefits due to their potential to maximize the action of active ingredients. However, it is fundamental to use adjuvants that are derived from renewable resources and are not genetically modified organisms (GMOs). In this context, bioeutectics could be an excellent source of this type of compound. Several natural compounds can be used as adjuvants that act like surfactants / emulsifiers or as humectants to replace current petrochemical-derived adjuvants.

[0032] Therefore, the present invention may be a practical alternative to MSO adjuvants.

[0033] Laboratory Testing Several solvents were mixed with the silicone surfactant Silwet 641 to evaluate their miscibility. The selection criterion was whether the proposed solvent was miscible with Silwet after 1 minute of shaking. Tests were performed on mixtures of 20% Silwet 641 and 80% proposed solvent, adhering to the ratios specified on the formulation's data sheet.

[0034] The preformed mixtures were then evaluated for their emulsifying ability. In this evaluation, the mixtures were added to water at a dosage of 1% (based on the data sheet of the commercial formulation) and their stability was evaluated after 30 minutes, 2 hours, and 24 hours (see Table XX). Fifteen products were stable after 24 hours. The compositions of these solvents are as follows: AT: camphor (30-60%), thymol (40-70%); MBA: menthol (60-80%), borneol (10-30%), camphor (10-30%); TOA: thymol (10-45%), oleic acid (50-90%); GeOA: geraniol (10-40%), oleic acid (30-90%); MOA: menthol (10-70%), oleic acid (30-90%); EucCy: eucalyptol (10-80%), cymene (20-90%); EucA: eucalyptol (10-80%), camphor (20-90%); EucOA: eucalyptol (20-80%), oleic acid (30-80%); OALi: oleic acid (30-80%), limonene (20-90%); OACy: oleic acid (10-80%), cymene (30-70%); OAPi: oleic acid (20-80%), pinene (10-40%); GlBM: glycerol (20-60%), menthol (10-50%), borneol (10-40%); MluA: menthol (10-60%), lauric acid (20-50%); EugEucT: eugenol (10-80%), eucalyptol (10-90%), thymol (20-80%); OctDecLuA: octanoic acid (10-40%), decanoic acid (10-60%), lauric acid (5-70%).

[0035] These 15 solvents were then used as the basis for further testing. A wetting area study was performed by adding 5 μL of dye to 1000 μL of surfactant / product mixture and dropping 5 μL of this mixture onto a piece of paper. The wetting area was then calculated using ImageJ and normalized to the wetted area of ​​the commercial adjuvant as 100%. Both the image and summary table are shown below in Table 5. [Table 5]

[0036] As shown, the five products exhibited wetted areas equal to or greater than that of MSO. Based on this, stability tests of 1% emulsions in water were conducted on these products, confirming that they retained their emulsifying properties. Figure 3 shows the results of these tests. As shown, the emulsions formed with these products were stable and uniform, similar to those formed with MSO.

[0037] conclusion The following products: AT, EucCy, EucA, EucOA and OALi are capable of replacing MSO in adjuvant formulations used in agriculture.

[0038] Alternative to Silwet 641 adjuvant Laboratory Testing Several solvents were mixed with the moisturizer MSO to evaluate their miscibility. The solvent compositions were as follows: CouT: coumarin (20–50%), thymol (50–80%); EucGe: eucalyptol (30–70%), geraniol (30–70%); GeLi: geraniol (30–80%), limonene (30–70%); EucB: eucalyptol (20–80%), borneol (25–75%); ACy: camphor (30–70%), cymene (30–70%).

[0039] The selection criterion was whether the proposed solvent was miscible with MSO after 1 minute of shaking. Tests were carried out on mixtures of 20% Bioeutectics solvent and 80% MSO. In this sense, 86 solvents from our portfolio were tested, 56 of which formed stable mixtures with humectants, and the wetting spread was tested for these products. Figure 4 shows the wetting area of ​​the selected products.

[0040] As shown, no area exceeded the wetted area of ​​Silwet 641. However, several solvents had 50% of the wetted area, suggesting that optimization could improve this.

[0041] conclusion The products CouT, EucGe, GeLi, EucB and ACy are capable of replacing Silwet 641 in adjuvant formulations used in agriculture.

[0042] N-Methylpyrrolidone Substitute N-methylpyrrolidone (NMP) is a polar aprotic solvent used in a variety of industries and applications, including petrochemicals, pesticides, paints, electronics cleaning, and industrial / household cleaning. NMP is used for surface treatment of resins, metal-coated plastics, and textiles, and as a paint stripper. Thus, the demand for this solvent is significant. The global NMP market is estimated to be worth US$950 million in 2022, reaching US$1 billion in 2023 and projected to grow at a compound annual growth rate (CAGR) of 6.8% from 2023 to 2033. Against this backdrop, the demand for this solvent is robust.

[0043] However, NMP is highly toxic and has several known acute effects. It affects the nervous and reproductive systems, liver, and kidneys, and can cause cancer. Based on this, there is a strong need to replace this solvent with a safer alternative. Bioeutectics offers naturally derived solvents derived from renewable resources, produced through more environmentally friendly and efficient processes. These solvents are high-performance, natural, and sustainable solvents applicable to formulation ingredients, carrier solvents, cleaning agents, pesticide formulations, and antimicrobial agents. Our products are primarily based on blends of bio-based ingredients, including natural organic acids, amino acids, alcohols, and sugars. Our technology enables us to obtain liquids even when all the compounds are individually solids.

[0044] Laboratory Testing Initially, products from various natural origin families were selected from the applicant's portfolio. Bioeutectic solvents were selected to evaluate the full range of polarity, considering that the polarities of N-methylpyrrolidone, acetone, and xylene are 0.45, 0.34, and 0.23, respectively. The compositions of these solvents are as follows: TL: lactic acid (20-80%), thymol (20-80%); BT: borneol (15-40%), thymol (60-90%); MOA: menthol (10-70%), oleic acid (30-90%); MAcA: menthol (20-90%), acetic acid (10-80%); LEuc: lactic acid (30-90%), eucalyptol (30-90%); LC: lactic acid (40-80%), citric acid (30-60%); OALi: oleic acid (30-80%), limonene (20-90%); LiT: limonene (30-70%), thymol (40-70%); GeLi: geraniol (30-80%), limonene (30-70%); PiT: pinene (30-80%), thymol (40-70%).

[0045] Solubility tests (for common pesticide active ingredients) were performed at an analyte / solvent working concentration of 14% w / w, first in conventional solvents and then in selected proprietary solvents, at 30°C and with the aid of vortexing and ultrasound. The results are as follows: Analyte A (prometryne): Dissolved in all solvents tested by the applicant. Analyte B (terbutylazine): Dissolved in nine solvents tested by the applicant. Analyte C (atrazine): Dissolved in four of the solvents tested by the applicant.

[0046] The results of these experiments are summarized in Figure 5. The results are shown in Figure 5 and are indicated as 1 if the analyte dissolved and 0 if it did not.

[0047] It was observed that the solvents that were able to dissolve C also dissolved A and B. Therefore, C was considered a problematic analyte with poor solubility, and further testing was performed on C alone.

[0048] Based on this, dissolution tests at different temperatures for C were carried out using selected products. [Table 6]

[0049] As shown in Table 6, TL was found to be the best choice for dissolving C. However, LC could be a good alternative since it is a hydrophilic product.

[0050] Antifreeze products The products of the present invention were also tested for anti-freeze properties. The reactor uses heating and cooling jackets to remove the heat generated by the endothermic / exothermic reactions or to provide the heat required for the reaction to proceed.

[0051] Typically, a jacketed reactor is used for heating and cooling, depending on the operating temperature, using thermal oil or a water / glycol mixture.

[0052] In one aspect, the present invention focuses on NADES products used in cooling jacketed reactors, as these also tend to be suitable for good flow properties at low temperatures.

[0053] The target minimum temperature for antifreeze properties was -20°C.

[0054] The primary objective of the experiments conducted here was to replace glycols such as ethylene glycol and propylene glycol, which are typically used for their antifreeze properties. The NADES products selected are receptive to dilution with water, which reduces the viscosity of the original product.

[0055] Laboratory Testing Several eutectic systems have been tested. For example, systems tested include the hydrophilic eutectic system LGH (lactic acid (20-90%), glucose (10-40%), water (5-15%)) and NaAcGlH (sodium acetate (10-30%), glycerol (30-80%), water (10-60%)). Preferred are LGH: lactic acid (57%), glucose (23%), water (20%), and NaAcGlH: sodium acetate (12%), glycerol (65%), water (23%). (Properties and curve information provided correspond to these ratios.)

[0056] These systems were prepared by heating on a magnetic stirrer at 40° C. for 30 minutes with continuous stirring until a clear liquid was formed.

[0057] Characterization NaAcGlH was found to have the following properties:

[0058] frozen NaAcGlH did not freeze at -80°C. It did not freeze even at dilutions up to 50% with water at -20°C. Viscosity curves for NaAcGlH in pure solvent and at 50% dilution with water were generated using a Myr vr3000 viscometer and are shown in Figures 10 and 11.

[0059] The specific heat was calculated using the Joule calorimeter method and found to be 3.0 kJ / kg°C. Specific heat testing of this product was performed using a Joule calorimeter with an insulated structure and a resistor that heated the liquid under test. Once heating began, the temperature was recorded every 60 seconds, and the heat absorbed per unit time was then calculated, taking into account the power supplied by the calorimeter. From these data, the specific heat value of the solvent was obtained.

[0060] The viscosity at 25°C was determined to be 210 m.Pas (millipascal seconds). The viscosity at 25°C when diluted 50% with water was determined to be 17 m.Pas. The boiling point was determined to be 130°C. The density was 1.267 g / ml, and the conductivity was outside the measurement range and estimated to be greater than +2000 microsiemens. The pH was 8.5, and the Brix value (a measure of solute dissolved in a solvent) was 61.1°.

[0061] Figure 6 shows the IR spectra of the untreated product, after 2 hours at 150° C., after 2 hours at 100° C., and after exposure to temperatures near -80° C. The lack of significant change in the spectrum at these widely varying temperatures indicates that the product is thermally stable to these temperature changes.

[0062] The test was carried out using a Fourier transform infrared spectrometer (FTIR) (IRSpirit (registered trademark) manufactured by Shimadzu Corporation) equipped with a single attenuated total reflection measurement accessory (QATR-S).

[0063] Corrosion analysis of this product on various metals was also conducted, and the results are detailed in Table 7.

[0064] The corrosion analysis was carried out by the Lenor SRL laboratory in Argentina using the following equipment: Thermohygrometer Testo 608-H1 and Sterilizer Dryer FANEM 515. [Table 7] LGH was confirmed to have the following properties:

[0065] frozen LGH did not freeze at -80°C. It did not freeze even at -20°C, even when diluted with water up to 30%. The viscosity curve of pure LGH is shown in Figure 8, and the viscosity curve of LGH containing 30% water is shown in Figure 9.

[0066] The specific heat was calculated by Joule calorimetry to be 2.78 kJ / kg°C, using the same method as above. The viscosity at 25°C was 44 mPa·s, and when diluted 30% with water at 25°C, the viscosity was confirmed to be 17 mPa·s. The density was confirmed to be 1.206 g / mL, and the electrical conductivity was confirmed to be 370 μS / cm. The pH was determined to be 1.07 and the Brix value was determined to be 51.8.

[0067] Conclusions regarding the antifreeze properties of the eutectic products of the present invention The products tested in this study can be used in pure cooling jacket applications and under the proposed dilution conditions for temperatures down to -20°C. Future experiments will more precisely evaluate whether the solvents tested here, and other eutectic solvents, can be used at even lower temperatures. The results of the experiments performed here suggest that in high temperature applications, neither of the systems tested should be exposed to temperatures above 120°C pure or above 100°C after dilution with water. In another embodiment, the eutectic solvent system can be added to a glycol such as ethylene glycol or propylene glycol.

[0068] Figure 7 shows the IR spectra of LGH after exposure to temperatures near -80°C, after 2 hours at 150°C, after 2 hours at 100°C, and after exposure to temperatures near -80°C. It can be seen that the product is thermally stable only up to 100°C, but not at higher temperatures. The test was carried out using a Fourier transform infrared spectrometer (FTIR) (IRSpirit (registered trademark) manufactured by Shimadzu Corporation) equipped with a single attenuated total reflection measurement accessory (QATR-S). Corrosion analysis of this product on various metals was also conducted, and the results are detailed in Table 8.

[0069] The corrosion analysis was carried out by the Lenor SRL laboratory in Argentina using the following equipment: Thermohygrometer Testo 608-H1 and Sterilizer Dryer FANEM 515. [Table 8]

[0070] antibacterial agents The eutectic mixtures of the present invention were evaluated for their antimicrobial preservative effectiveness by a challenge test of selected eutectic systems, also known as the Preservative Effectiveness Test (PET). The products were prepared as described elsewhere herein. Eutectic systems were prepared by heating the eutectic mixture on a magnetic stirrer with continuous stirring until a clear liquid was formed. The temperature and time were optimized for each product prepared.

[0071] Both hydrophilic and hydrophobic systems were prepared using the methods described above. The hydrophilic systems included: LGH: lactic acid (20–90%), glucose (10–40%), water (5–15%); CSH: citric acid (15–50%), sorbitol (15–60%), water (10–60%); UGl: urea and glycerol (1:2 molar ratio); UL: urea (20–40%), lactic acid (60–80%); TAGl: tartaric acid (10–35%), glycerol (5–30%); ArgGl: L-arginine (10–45%), glycerol (50–90%); BeL: betaine (10–30%), lactic acid (20–40%); CGlH: citric acid (25–90%), glycerol. (5-70%), water (1-25%), ArgLH: L-arginine (10-30%), lactic acid (20-50%), water (5-25%), BeUH: betaine (10-40%), urea (10-25%), water (10-40%), BeGH: betaine (10-25%), glucose (5-30%), water (20-60%), LSH: lactic acid (10-60%), sorbitol (5-30%), water (5-25%), MAL: malic acid (10-30%), lactic acid (30-60%), LGlMA: lactic acid (5-30%), glycerol (5-25%), malic acid (10-30%).

[0072] Hydrophobic systems include: AT: camphor (30-60%), thymol (40-70%); AM: camphor (25-45%), menthol (55-75%); ML: menthol (25-65%), lactic acid (35-75%); GeOA: geraniol (10-40%), oleic acid (30-90%); MOA: menthol (10-70%), oleic acid (30-90%); GeM: geraniol (10-40%), menthol (25-70%); EucA: eucalyptol (10-60%), camphor (5-30%); OALuA: oleic acid (20-70%), lauric acid (5-25%). Furthermore, the LGH system was diluted with water to 50%, 25%, 10%, 3% and 0.3% and these systems were also studied for their antibacterial properties.

[0073] Preservative effect The eutectic mixture of the present invention was tested by challenge testing to confirm its supposed antibacterial properties. A challenge test is a method of exposing a product to specific types of bacteria and fungi to determine whether its preservative properties are sufficient. The test microorganisms must be representative of those that may occur as contaminants during use and must consist of gram-positive and gram-negative bacteria, molds, and yeasts. The microorganisms are inoculated into product samples, and aliquots are taken at appropriate intervals to determine the number of surviving bacteria. The initial contamination level tested was 30 x 10 6 CFU / mL.

[0074] The following bacterial, yeast and mold microorganisms were tested: Gram-positive bacteria: Staphylococcus aureus Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa Yeast: Candida sp. Mold: Aspergillus niger

[0075] The inoculated products were kept at room temperature and evaluated at specific intervals over a 28-day period. After 48 hours of incubation, surviving organisms were counted and the reduction of each organism at each interval was reported. In all tested systems, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida sp., and Aspergillus niger were absent after 48 hours. The tests were carried out by the laboratory named Labaratorio Bado.

[0076] The results obtained from preservative effectiveness testing are important to ensure that eutectic mixtures meet the necessary microbial protection standards in various cosmetic and personal care products. This testing helps determine whether a formulation can maintain microbiological stability and safety throughout its intended shelf life. Thus, each system tested demonstrated effectiveness as an antimicrobial system. However, the eutectic systems tested herein for their antimicrobial properties can be substituted or supplemented with one or more preservatives commonly used in cosmetics and pharmaceuticals, such as methylparaben, ethylparaben, propylparaben, butylparaben, and benzyl alcohol.

[0077] It is contemplated that the currently tested system may be further combined with other known antibacterial products to enhance its antibacterial efficacy. In one embodiment, the currently tested system may be combined with one or more antibiotic products selected from the group consisting of penicillin, amoxicillin, doxycycline, cephalexin, ciprofloxacin, clindamycin, metronidazole, azithromycin, sulfamethoxazole, and trimethoprim.

[0078] Personal Care Products The objective of the experiments carried out herein was to evaluate the changes in sensory properties (e.g., odor, color, texture, etc. and combinations thereof) in emulsions after adding NADES as an additive. An additional objective was to analyze the changes in some physicochemical properties in the base cream and observe the variations depending on the properties of NADES. A further objective was to add NADES to the base cream in different ratios and to examine the possibility of using NADES as an additive to obtain different properties. The addition of NADES was expected to provide a superior advantage in preservation performance compared to products containing NADES alone.

[0079] Laboratory Testing The following laboratory tests were conducted. NADES products were prepared to test several different eutectic systems. Both hydrophilic and hydrophobic eutectic systems were prepared. Hydrophilic eutectic systems included: LGH: lactic acid (20-90%), glucose (10-40%), water (5-15%); UGIH: urea (10-55%), glycerol (15-80%), water (0-35%); UL: urea (20-40%), lactic acid (60-80%); BeL: betaine (10-30%), lactic acid (20-40%); ArgCH: L-arginine (5-25%), citric acid (10-30%), water (15-40%); ArgLH: L-arginine (10-30%), lactic acid (20-50%). Water (5-25%), BeUH: Betaine (10-40%), Urea (10-25%), Water (10-40%), BeSH: Betaine (15-35%), Sorbitol (20-40%), Water (5-20%), BeGlG: Betaine (5-25%), Glycerol (5-40%), Glucose (5-30%), BcC: Coconut Betaine (20-60%), Citric Acid (10-30%), LSH: Lactic Acid (10-60%), Sorbitol (5-30%), Water (5-25%).

[0080] Hydrophobic eutectic systems include: MOA: menthol (10-70%), oleic acid (30-90%); OALuA: oleic acid (20-70%), lauric acid (5-25%). The various NADES systems were prepared by heating and stirring on a magnetic stirrer at 40°C for 45 minutes, with continuous stirring until a clear liquid was formed.

[0081] Addition of NADES as an additive to base cream Experiments were conducted to evaluate various NADES systems as additives. They were added to a basic cosmetic cream at concentrations of 1% and 15%, while MOA was used only at a concentration of 1%. These ratios were planned and estimated with reference to the concentrations used in emulsion formulations, taking into account their application as additives (generally, additives are kept to less than about 10%).

[0082] result The following findings were obtained: For the NADES solvent-based LGH, the additive was well incorporated at both ratios, with a decrease in viscosity at 15%. No changes in odor and / or color were observed. After one month of testing, the 15% cream had a slightly sour odor, suggesting a possible change in the formulation; however, the consistency of the formulation was maintained. No observable changes were observed at the 1% concentration.

[0083] For the NADES solvent-based UL, the additive was well incorporated at both ratios, with a decrease in viscosity at 15%. No changes in odor or color were observed. After one month of testing, the 15% cream had a noticeable lactic acid odor; however, the consistency of the formulation was maintained. No observable changes were observed at the 1% concentration. For the NADES solvent-based BeL, the additive was well incorporated at both ratios, with a decrease in viscosity at 15%. The color of the formulation was observed to change to amber, which is closer to the color of the NADES system. After one month of testing, the 15% cream had a noticeable lactic acid odor. The consistency of the formulation was maintained. No observable changes were observed at the 1% concentration. For the NADES solvent system, ArgLH, the high viscosity of NADES made it difficult to incorporate the additive. There was no observable change in odor or color. Furthermore, no observable change was observed one month after the start of the test. For the NADES solvent system, ArgCH, the high viscosity of NADES made it difficult to incorporate additives at a 15% concentration due to the increased viscosity. No changes in odor or color were observed. No observable changes were observed one month after the start of the test. For the NADES solvent-based BeUH, the additive was difficult to incorporate. A color change was observed at the 15% concentration, with the formulation turning a color similar to that of NADES. No observable change in odor was observed. Furthermore, no observable change was observed after one month of testing. No changes were observed with the NADES-solvent-based MOA due to the addition of NADES. However, a menthol-like odor was detected one month after the start of the test.

[0084] pH measurement The pH remained relatively stable over the study period and is shown in Table 9 for each formulation. [Table 9]

[0085] conclusion The NADES systems of the present invention are all believed to be useful for additive purposes in personal care products. In this regard, all additives were stable at the concentrations tested and demonstrated stability over time. All NADES systems of the present invention have demonstrated preservative efficacy, use as preservative systems, and use as additives in functional foods, cosmetics, and personal care products. Of note, LGH maintained its potency at all dilution conditions studied.

[0086] In one aspect, the present invention relates to a NADES system comprising a eutectic solvent that can be added to any of a plurality of products. In one variation, adding the NADES system to a plurality of products makes the product superior to the product in the absence of the NADES system. In one variation, the eutectic solvent comprises two or more of menthol, lactic acid, thymol, oleic acid, urea, glucose, water, L-arginine, tartaric acid, citric acid, sodium acetate, glycerol, borneol, sorbitol, betaine, or camphor. In one variation, the particular solvent system mixture is configured as described herein with the relative amounts described herein. In one variation, the product relates to one or more of an adjuvant, an antifreeze product, an antimicrobial product, or a personal care product. In one variation, the personal care product may be a cream (such as a moisturizing cream), mouthwash, soap, cologne, moisturizer, antiperspirant, hair removal product, body butter, cleanser, conditioner, eye cream, sunscreen, suntan lotion, hand sanitizer, exfoliant, shampoo, toothpaste, skin care product, or other personal care product. In one variation, the antimicrobial product includes, but is not limited to, a disinfectant, bactericide, fungicide, or antibacterial product. The antimicrobial product can be incorporated into the personal care products disclosed herein. In one variation, they can be incorporated into cleaning products, soaps and / or detergents, hand lotions, disinfectants, window cleaners, cleaning cloths, surface sprays, mouthwash, toothpaste, plastic wrap, or fabrics and carpets. In certain embodiments, the NADES systems of the present invention can be added to products used as herbicides, fungicides or bactericides, or to act against plants, fungi or bacteria. In one aspect, the present invention relates to a composition comprising a NADES system as disclosed herein and a product, which can be any of the products disclosed herein.

[0087] Alternatively, the NADES system of the present invention can be added to antifreeze compounds, including, but not limited to, monoethylene glycol, monopropylene glycol, methanol, propylene glycol methyl ether, various organic acids such as 2-ethylhexanoic acid, or other antifreeze compounds. Compositions containing a NADES and an antifreeze compound can further optionally contain sodium silicate, disodium phosphate, sodium molybdate, sodium borate, denatonium benzoate, and / or dextrin, among other additives. Alternatively, the antifreeze may actually be a mixture of two or more of the compounds listed above (or water). Thus, the product is not limited to a single pure compound, but may actually be a mixture of compounds.

[0088] In one embodiment, the NADES system and eutectic solvent mixture of the present invention can be added to an adjuvant. An adjuvant is typically a compound added to a pharmaceutical, vaccine, or drug to enhance the efficacy of the pharmaceutical, vaccine, or drug. Thus, in one embodiment, the present invention relates to a composition mixture comprising a pharmacologically active compound, an adjuvant, and a NADES system of a eutectic solvent. In one variation, the eutectic solvent can increase the solubility of the adjuvant and / or pharmacologically active compound, thereby allowing for the administration of higher doses or improving the efficacy of the administered dose. In one variation, the adjuvant can enhance the delivery system or act as an immunostimulant (something that stimulates the immune system).

[0089] It should be understood that any feature recited above can be combined with any other feature recited above, unless those features are mutually incompatible, and is contemplated as being within the scope of the present invention. When ranges are stated, any actual number included within that range may be considered as an endpoint for defining further ranges that lie within that range. The present invention is then defined by the following claims.

Claims

1. Natural deep eutectic solvent (NADES) systems, including eutectic solvent systems useful as adjuvants, antifreeze agents, antimicrobial agents or additives to personal care products.

2. 10. The NADES system of claim 1, wherein the eutectic solvent system enhances the properties of a product that is an adjuvant, an antifreeze, an antimicrobial, or a personal care product.

3. 2. The NADES system of claim 1, wherein the eutectic solvent system comprises one or more of menthol, lactic acid, thymol, oleic acid, urea, glucose, water, L-arginine, tartaric acid, citric acid, sodium acetate, glycerol, borneol, sorbitol, betaine, and camphor.

4. 10. The NADES system of claim 1, wherein the eutectic solvent system is for an antifreeze, and the eutectic solvent comprises one or more of lactic acid, glucose, sodium acetate, glycerol, and water.

5. 10. The NADES system of claim 1, wherein the eutectic solvent system is for an antibacterial agent and the eutectic solvent comprises one or more of lactic acid, glucose, water, citric acid, sorbitol, urea, glycerol, tartaric acid, L-arginine, camphor, and menthol.

6. 2. The NADES system of claim 1, wherein the eutectic solvent system is for use as an adjuvant and comprises one or more of urea, lactic acid, menthol, thymol, oleic acid, and borneol.

7. 10. The NADES system of claim 1, wherein the eutectic solvent system is for use in personal care products and the eutectic solvent system comprises one or more of lactic acid, glucose, water, urea, betaine, L-arginine, citric acid, water, menthol, and oleic acid.

8. 8. The NADES system of claim 7, wherein the eutectic solvent system is added to a cream product of a cosmetic composition.

9. A composition comprising NADES and a compound used as an adjuvant, antifreeze, antimicrobial, or personal care product.

10. 10. The composition of claim 9, wherein the compound is an adjuvant, and the adjuvant is Triton X-100 (registered trademark).

11. 10. The composition of claim 9, wherein the compound and the NADES are effective against one or more of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida spp. and / or Aspergillus niger.

12. 10. The composition of claim 9, wherein the compound is an antifreeze agent, and the antifreeze agent is a glycol.

13. 13. The composition of claim 12, wherein the glycol is ethylene glycol or propylene glycol.

14. 10. The composition of claim 9, wherein the compound is a personal care product, and the personal care product is a cream cosmetic composition.

15. 12. The composition of claim 11, wherein the composition is effective in treating a bacterial infection caused by Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa.

16. 1. A method of treating an individual suffering from a bacterial infection caused by Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa, comprising administering to the individual the eutectic solvent system and an antimicrobial compound or composition.

17. 17. The method of claim 16, wherein the eutectic solvent system comprises two or more of lactic acid, glucose, water, citric acid, sorbitol, urea, glycerol, tartaric acid, L-arginine, camphor, and menthol.

18. 18. The method of claim 17, wherein the eutectic solvent system comprises a) lactic acid, glucose, and water, b) citric acid, sorbitol, and water, c) urea and glycerol, d) urea and lactic acid, e) tartaric acid and glycerol, f) L-arginine and glycerol, g) camphor and thymol, h) camphor and menthol, or i) menthol and lactic acid.

19. 10. The composition of claim 9, wherein the NADES is one or more compounds selected from the group consisting of menthol, lactic acid, thymol, oleic acid, urea, glucose, water, L-arginine, tartaric acid, citric acid, sodium acetate, glycerol, borneol, sorbitol, betaine, and camphor.

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