Glycosyl ionic liquids, methods of making and using the same, and antioxidant formulations

Abstract

The present application relates to the technical field of ionic liquid and biological medicine, in particular to a glycosyl ionic liquid, a preparation method and application thereof and an antioxidant preparation. The glycosyl ionic liquid is named [O]X, wherein [O] represents a hydrogen bond acceptor part, and X represents a hydrogen bond donor part; the hydrogen bond acceptor part is derived from furanose and analogues thereof or pyranose and analogues thereof; the hydrogen bond donor part is derived from a compound shown in the following structural formula: the ionic liquid can be used as a solvent and stabilizer of API, and can completely replace traditional volatile organic solvents, thereby reducing the double harm to environment and health.

Description

[0001] This invention claims priority to Chinese Patent Application No. 2025105137066, entitled "Glycosyl Ionic Liquids, Preparation Methods Thereof, Applications Thereof and Antioxidant Agents Thereof," the contents of which are incorporated herein by reference in their entirety and are part of the original description of this invention. Technical Field

[0002] This invention relates to the fields of ionic liquids and biomedicine, and more specifically, to glycosyl ionic liquids, their preparation methods, their applications, and antioxidant agents. Background Technology

[0003] Throughout the processes of disease, health, and aging, the metabolism of organisms is always accompanied by the generation of free radicals, leading to oxidative stress, lipid peroxidation damage, and the production of inflammatory factors. Although many chronic inflammatory diseases are considered to be caused by oxidative stress, and therefore, antioxidants such as ascorbic acid are often used for treatment, the treatment of oxidative stress with antioxidants such as ascorbic acid has historically been largely unsuccessful, with the prognosis of the antioxidant treatment group often being worse than that of the placebo group. This is because nominally antioxidant molecules such as ascorbic acid have complex multi-electron redox chemistry and can actually act as pro-oxidants (Borodina I, et al. The biology of ergothioneine, an antioxidant nutraceutical. Nutr Res Rev. 2020 Dec; 33(2):190-217.). For example, the antioxidant carotenoid may also act as a pro-oxidant under certain conditions, as confirmed by the ATBC trial organized by the National Cancer Institute (NIH). In the trial, a large cohort of participants supplemented with 20 mg of β-carotene daily for 5-8 years. Compared with the control group, people who took beta-carotene supplements had an 18% increased risk of lung cancer (Jomova K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023 Oct; 97(10):2499-2574.).

[0004] In fact, similar to ascorbic acid, many active pharmaceutical ingredients (APIs) suffer from similar instability issues, including the inactivation of antioxidants and biodegradation. Therefore, the solubility and stability of APIs have always been a major challenge in the biopharmaceutical field.

[0005] Ionic liquids, as non-volatile, thermally stable, non-flammable, and tunable designable green solvents, hold promise for replacing volatile organic solvents in drug synthesis. The application of ionic liquids in drug delivery formulations is not limited to solubilization; their use in localized systems can also enhance drug therapeutic effects. Through rational design of ionic liquid structures, it is possible to control drug solubility, stability, absorption, and bioavailability (Zhang Suojiang, Zhou Qing, and Lü Xingmei, eds., *Green Technology of Ionic Liquids*, China Railway Publishing House, 1st edition, 2024).

[0006] Therefore, the object of this invention is to develop a bio-ionic liquid solvent and stabilizer for dissolving and stabilizing APIs.

[0007] In view of this, the present invention is proposed. Summary of the Invention

[0008] The purpose of this invention is to provide glycosyl ionic liquids, their preparation methods, applications, and antioxidant agents. Embodiments of this invention provide a glycosyl ionic liquid for use as a solvent and stabilizer for APIs. It can completely replace traditional volatile organic solvents as a solvent, and when used as a stabilizer, it eliminates the need for additional chelating agents, thus reducing environmental, water, and soil pollution.

[0009] This invention is implemented as follows:

[0010] In a first aspect, the present invention provides a glycosyl ionic liquid, the glycosyl ionic liquid being named [O]X, wherein [O] represents the hydrogen bond acceptor portion and X represents the hydrogen bond donor portion;

[0011] The hydrogen bond acceptor is derived from furanose and its analogues or pyranose and its analogues;

[0012] The hydrogen bond donor portion is derived from the compound shown in the following structural formula:

[0013]

[0014] In an optional embodiment, the hydrogen bond acceptor portion is derived from any one of furan, hydrogenated furan, hydrogenated furanol, carbonyl-containing furan, furanose compounds, pyran, hydrogenated pyran, hydrogenated pyranol, carbonyl-containing pyran, pyranose compounds, and pyranoside compounds.

[0015] In an optional embodiment, the hydrogen bond acceptor portion is derived from any one of deoxyribose, ribose, fructose, furan, tetrahydrofuran, tetrahydrofurfuran, furfural, ascorbic acid, and glucose, mannose, galactose, xylose, rhamnose, lactose, maltose, trehalose, sucrose, gluconolactone, maltitol, maltol, ethyl maltol, glucosamine, N-acetylglucosamine, methyl β-xylanoside, methyl galactopyranoside, pyran, pyranonium, tetrahydropyran, 2,3-dihydropyran, tetrahydropyranol, isobutylmethyltetrahydropyranol, hydroxypropyltetrahydropyrantriol, and pyranone.

[0016] In an optional embodiment, the glycosyl ionic liquid is a hydrated glycosyl ionic liquid solvent.

[0017] In an optional embodiment, the molar ratio of the hydrogen bond acceptor portion to the hydrogen bond donor portion is 5:1 to 1:5.

[0018] Secondly, the present invention provides a method for preparing the glycosyl ionic liquid described in the foregoing embodiments, comprising: mixing and dissolving a raw material forming a hydrogen bond acceptor portion [O] with a raw material forming a hydrogen bond donor portion X.

[0019] In an optional embodiment, preparation is carried out under non-vacuum conditions;

[0020] Preferably, the mixing and dissolving temperature is 25-45℃, and the time is 10-30 minutes;

[0021] Preferably, water is used to dissolve the raw materials that form the hydrogen bond acceptor portion [O] and the raw materials that form the hydrogen bond donor portion X.

[0022] Thirdly, the present invention provides the use of the glycosyl ionic liquid described in the foregoing embodiments as a stabilizer to enhance the stability of antioxidant preparations;

[0023] Preferably, the antioxidant includes ascorbic acid.

[0024] Fourthly, the present invention provides an application of the glycosyl ionic liquid described in the foregoing embodiments as a solvent and / or stabilizer for APIs.

[0025] In an optional embodiment, the API includes at least one of vanillin, gallic acid, melatonin, and ascorbic acid;

[0026] Preferably, when the glycosyl ionic liquid is used as a solvent for API, it no longer contains volatile organic solvents. In other words, the glycosyl ionic liquid can completely replace traditional volatile organic solvents for the preparation of API formulations that do not contain any organic solvents, thereby reducing the dual harm to the environment and health caused by traditional volatile organic solvents.

[0027] Preferably, when the glycosyl ionic liquid is used as a stabilizer for APIs, no chelating agent is added. That is, the glycosyl ionic liquid can replace chelating agents such as EDTA, reducing water and soil pollution caused by chelating agents.

[0028] Fifthly, the present invention provides an antioxidant preparation comprising a glycosyl ionic liquid and an antioxidant active ingredient, wherein the antioxidant active ingredient comprises ascorbic acid. The antioxidant preparation does not contain any volatile organic solvents or does not contain chelating agents.

[0029] This hydrated glycosyl ionic liquid is a water-soluble, biocompatible glycosyl ionic liquid that can be mixed with water in any proportion to prepare pure aqueous solutions of corresponding poorly soluble and unstable APIs.

[0030] The present invention has the following beneficial effects: The embodiments of the present invention combine cationic and anionic compounds with specific structures as hydrogen bond acceptors and hydrogen bond donors to form glycosylated hydrated ionic liquids. These ionic liquids have the dual properties of being both solvents and stabilizers for APIs, and can completely replace traditional volatile organic solvents, including chelating agents such as EDTA. They can be mixed with water in any proportion to prepare corresponding API pure aqueous solutions, thereby improving the bioavailability of APIs and reducing the dual harm to the environment and health. Attached Figure Description

[0031] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 A comparison diagram of the thermodynamic properties of ascorbic acid in aqueous solution, gas phase and aqueous solution of glycosyl ionic liquid provided in the embodiments of the present invention;

[0033] Figure 2 This is a comparison chart showing the color changes of ascorbic acid glycosyl ionic liquid aqueous solution, ascorbic acid aqueous solution, and commercially available ascorbic acid solution after being stored at room temperature under non-light-protected conditions for more than 3 months. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0035] In a first aspect, the present invention provides a glycosyl ionic liquid, the name of which is [O]X, wherein [O] represents the hydrogen bond acceptor portion, i.e., the cation portion, and X represents the hydrogen bond donor portion, i.e., the anion portion.

[0036] The hydrogen bond acceptor is derived from furanose and its analogues or pyranose and its analogues;

[0037] The hydrogen bond donor portion is derived from the compound shown in the following structural formula:

[0038]

[0039] Specifically, carbohydrates are the primary source of energy for all living organisms to maintain life activities, essential components of biological tissues and cells, and crucial raw materials for the synthesis of fats, proteins, and nucleic acids in the human body. Carbohydrates can be used to modify other drugs; the modified hybrid molecules exhibit increased activity and reduced side effects compared to the parent drug. Therefore, naturally derived carbohydrates are ideal building blocks for biofunctionalized ionic liquids. Carbohydrates are also major low-molecular-weight compatible solutes in organisms, playing a vital protective role against various external pressures on cells, such as high temperature, high osmotic pressure, dryness, and radiation.

[0040] From a molecular structure perspective, carbohydrates are polyhydroxy aldehydes or ketones and their dehydration condensation products. Structurally, they are polyhydroxy aldehydes or ketones, thus exhibiting varying degrees of reducing and antioxidant properties. Naturally derived carbohydrate compounds include six-membered heterocyclic pyranoses and five-membered heterocyclic furans, containing multiple chiral centers. These multifunctional compounds readily undergo chemical reactions and can act as cationic moieties or hydrogen bond acceptors, binding with suitable anionic moieties or hydrogen bond donors via hydrogen bonding forces. This allows them to self-assemble into task-specific, cationic chiral, functional glycosyl ionic liquid solvents and stabilizers.

[0041] Therefore, in the embodiments of the present invention, the hydrogen bond acceptor portion is derived from furanose and its analogues or pyranose and its analogues. Specifically, the cation or hydrogen bond acceptor portion is derived from any one of furan, hydrogenated furan, hydrogenated furanol, carbonyl-containing furan, furanose compounds, pyran, hydrogenated pyran, hydrogenated pyranol, carbonyl-containing pyran, pyranose compounds, and pyranoside compounds. Examples include, but are not limited to, deoxyribose, ribose, fructose, furan, tetrahydrofuran, tetrahydrofurfuran, furfural, ascorbic acid, and any one of glucose, mannose, galactose, xylose, rhamnose, lactose, maltose, trehalose, sucrose, gluconolactone, maltitol, maltol, ethyl maltol, glucosamine, N-acetylglucosamine, methyl β-xylopyranoside, methyl galactopyranoside, pyran, pyranonium, tetrahydropyran, 2,3-dihydropyran, tetrahydropyranol, isobutylmethyltetrahydropyranol, hydroxypropyltetrahydropyrantriol, and pyranone.

[0042] The hydrogen bond donor of this glycosyl bioionic liquid is derived from 2-mercapto-histidine-trimethyl inner salt, and its structural formula is shown below:

[0043] 2-Mercapto-histidine-trimethyl inner salt is a natural product synthesized by many bacteria and most fungi, and is non-toxic to humans. The hydrogen at position 2 of the 2-mercapto-histidine-trimethyl inner salt ring is replaced by a thiol group, and it exists as two tautomers: thione and thiol. The thione isomer is dominant at physiological pH.

[0044]

[0045] It is understood that the hydrogen bond donor portion provided in the embodiments of the present invention also includes two forms of tautomers: thioketones and thiols.

[0046] Therefore, the phenolic hydroxyl, ketone, thiol, and thione functional groups widely present in the glycosyl ionic liquid structure provided by the embodiments of the present invention, as well as the strong hydrogen bonding between ions, endow the glycosyl ionic liquid with dual properties as a solvent and stabilizer. It not only serves as a good solvent for poorly soluble APIs, especially antioxidants, but also as a stabilizer for API antioxidants.

[0047] Based on the electronegativity theory, structural The 2-mercapto-histidine-trimethyl inner salt molecule represented by this design has a relatively high electronegativity of the central atom O, which carries a partial negative charge. This enhances the stability and acidity of the carboxylate anion, making it more favorable for dissociation into R-COO. - As an anionic ion, it can therefore serve as an anionic moiety or hydrogen bond donor in the [O]X structure in the glycosyl ionic liquid;

[0048] Carbohydrates have oxygen-containing furan and pyran heterocyclic structures. Under acidic conditions, the oxygen atoms on the ring are protonated to form typical oxonium ions. Alternatively, under the induction of polar molecules, it can protonate to form a stable cation, such as the furanose cation. In the embodiments, all products were acidic (pH < 7.4), tending to accept protons to form oxocations. Deprotonation of the glycohydroxyl groups to form oxocations was only possible under alkaline conditions. Therefore, the carbohydrate compounds could act as the cation moiety or hydrogen bond acceptor in the [O]X structure of the glycosyl ionic liquid.

[0049] The following embodiments of the present invention will be specifically described using ascorbic acid as an example.

[0050] Ascorbic acid is a water-soluble antioxidant whose antioxidant activity is mainly achieved by scavenging free radicals. It is converted into hemidehydroascorbic acid through a stepwise electron donation process, thus achieving the purpose of free radical scavenging. Ascorbic acid is extremely unstable and readily oxidized in aqueous solution to form dehydroascorbic acid, resulting in browning and exhibiting pro-oxidative properties. Structurally, ascorbic acid is an oxide of trihydroxyfuran, existing as a tautomer of an unsaturated lactone.

[0051]

[0052] Ascorbic acid exhibits significant thermochromic and photochromic properties, leading to browning. The thermochromic mechanism may be related to the delocalized π bonds on the furan ring in the ascorbic acid molecule, resulting in changes in crystal or molecular structure. Photochromism may occur simultaneously with many photochemical reactions, leading to alterations in molecular structure; these reactions primarily involve valence isomerization and oxidation. Ascorbic acid is not only sensitive to heat but also highly responsive to other external stimuli, such as acid-induced and solvent-induced color changes.

[0053] The mechanism by which the glycosyl ionic liquid provided in this invention eliminates the discoloration of ascorbic acid may be related to the delocalized electrons on the furan and pyran rings. This electrostatic interaction and interionic hydrogen bonding contribute to the stability of the large π bond, thus making the molecular configuration of ascorbic acid more stable. When the ionic liquid can replace the organic solvent, the solvent-induced discoloration of ascorbic acid can be further reduced.

[0054] Ascorbic acid, as a five-membered heterocyclic furanose derivative, like other sugar derivatives, can also self-assemble with the 2-mercapto-histidine-trimethyl inner salt anion via hydrogen bonding to form the glycosyl ionic liquid of this invention, and also has a certain stabilizing effect.

[0055] Molecular simulation data show that, compared with their conformations in aqueous solution and the gas phase, the ascorbic acid molecule exhibits a more stable molecular conformation and lower thermodynamic energy in the aqueous solution of the glycosyl ionic liquid (see [link to data]). Figure 1 The molecular simulation experimental data are consistent with the experimental results of Application Example 6-13.

[0056] Experimental verification shows that the glycosyl ionic liquid provided in this embodiment of the invention also has the same effect of improving the solubility and stability of other API model compounds.

[0057] Furthermore, the glycosyl ionic liquid is a glycosyl hydrated ionic liquid solvent, and the molar ratio of the hydrogen bond acceptor portion to the hydrogen bond donor portion is 5:1 to 1:5, that is, the molar ratio of [O] to X is (5:1) to (1:5); for example, any value between (5:1) and (1:5) such as 2:1, 3:1, 4:1, 5:1, 1:1, 1:2, 1:3 and 1:4.

[0058] Secondly, the present invention provides a method for preparing the glycosyl ionic liquid described in the foregoing embodiments, comprising: mixing and dissolving a raw material forming a hydrogen bond acceptor portion [O] with a raw material forming a hydrogen bond donor portion X.

[0059] The entire preparation process is carried out under non-vacuum conditions (e.g., ambient temperature and pressure). The raw materials for forming the hydrogen bond acceptor [O] and the raw materials for forming the hydrogen bond donor X are dissolved in water. The mixing and dissolution temperature is 25-45℃, and the time is 10-30 min. Alternatively, no solvent is added during the preparation of the glycosyl ionic liquid; the two raw materials are directly mixed to form the desired ionic liquid.

[0060] Thirdly, the present invention provides the use of the glycosyl ionic liquid described in the foregoing embodiments as a stabilizer to enhance the stability of antioxidant preparations; wherein the antioxidant includes ascorbic acid.

[0061] Fourthly, the present invention provides the use of the glycosyl ionic liquid described in the foregoing embodiments as a solvent and / or stabilizer for APIs.

[0062] In an optional embodiment, the API model compound includes at least one of vanillin, gallic acid, melatonin, and ascorbic acid.

[0063] The application of this glycosyl ionic liquid as a solvent, wherein the solvent contains only the glycosyl ionic liquid and no other solvents or organic solvents, and can completely replace traditional volatile organic solvents for the preparation of API formulations that do not contain any organic solvents, thereby reducing the dual harm to the environment and health caused by traditional volatile organic solvents.

[0064] Meanwhile, this hydrated glycosyl ionic liquid is water-soluble, biocompatible, and can be mixed with water in any proportion to prepare corresponding API pure aqueous solutions. It can replace chelating agents such as EDTA, reducing water and soil pollution.

[0065] Fifthly, the present invention provides an antioxidant preparation comprising a glycosyl ionic liquid and an antioxidant active ingredient, wherein the antioxidant active ingredient comprises ascorbic acid. The antioxidant preparation contains no volatile organic solvents or contains no chelating agents.

[0066] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0067] Methods for determining the physical properties of the glycosyl ionic liquid:

[0068] pH testing method: pH is determined by direct measurement with a pH meter. The actual test temperature is 25–30℃.

[0069] Thermal stability test methods: (1) Cold resistance: Pre-adjust the refrigerator to 0℃ (temperature control accuracy ±1℃) or (0℃±1℃), and place one sample bottle in the refrigerator. After 24 hours, take it out, restore it to room temperature, and visually observe it. If there is no obvious difference in appearance compared with before the test, it is considered stable. (2) Heat resistance: Pre-adjust the constant temperature incubator to 40℃ (temperature control accuracy ±1℃), and place one sample bottle in the constant temperature incubator. After 24 hours, take it out, restore it to room temperature, and visually observe it. If there is no obvious difference in appearance compared with before the test, it is considered stable.

[0070] Methods for determining color change: (1) Photochromic change: at room temperature (18-20℃), 10m 2 (1) In a dark room, a sample bottle was placed under a 100W ultraviolet lamp for direct irradiation. After 24 hours, it was taken out and visually observed, and there was no obvious difference in color compared with before the test. (2) Thermal color change: The constant temperature incubator was pre-adjusted to 40℃ (temperature control accuracy ±1℃), and a sample bottle was placed in the constant temperature incubator. After 24 hours, it was taken out, restored to room temperature, and visually observed, and there was no obvious difference in appearance compared with before the test.

[0071] The sources and abbreviations of the raw materials provided in the embodiments of the present invention are as follows:

[0072] 2-Mercapto-histidine-trimethylammonium salt (99%, Nanjing Letao), histidine, deoxyribose, ribose, maltol, ethyl maltol, glucosamine, gallic acid (95-99%, Aladdin), fructose, mannose, galactose, xylose, maltose (BR, Sinopharm), N-acetylglucosamine, hydroxypropyl tetrahydropyranotriol (98%, Bloomage), tetrahydrofuran (AR, 97%, Maclean), tetrahydrofurfural (AR, Lin's), ascorbic acid, glucose (AR, 99.5%, Xiyu), rhamnose (100%, Taidong), trehalose (100%, Linyuan), gluconolactone (99%, Xinhuanghai), melatonin (99%, Leibu).

[0073] Deoxyribose, ribose, fructose, furan, thf, thk, fal, ascorbic acid, glu, man, gal, xylose, rha, gdl, lactone, lac, maltose, trehalose, suc, mat, maltitol, m et (maltol), ema (ethyl maltol), gla (glucosamine), nag (N-acetylglucosamine), xym (methyl β-xylanoside), mga (methyl galactopyranoside), pyr (pyran), pyl (pyranonium), thp (tetrahydropyran), dhp (2,3-dihydropyran), thl (tetrahydropyranol), imt (isobutylmethyltetrahydropyranol), pro (hydroxypropyltetrahydropyrantriol), apy (pyranone), H (histidine).

[0074] Examples 1-19

[0075] Examples 1-19 each provide a glycosyl ionic liquid, the composition of which is shown in Table 1 below.

[0076] Examples 1-19 all provide a method for preparing a glycosyl ionic liquid, comprising: adding the glycosyl raw material forming the hydrogen bond acceptor [O] and the raw material forming the hydrogen bond donor X, 2-mercapto-histidine-trimethyl inner salt, sequentially to a small amount of water according to the molar ratio in Table 1, stirring at 25-45°C for 10-30 min until completely dissolved, and adding water to bring the total amount to 100%, thereby obtaining the glycosyl ionic liquid [O]X of Examples 1-19.

[0077] Among them, the glycosyl ionic liquid provided in Example 1 is a slightly yellow transparent solution due to the influence of the color of the deoxyribose raw material itself, while the other glycosyl ionic liquids are all colorless and transparent solutions.

[0078] Table 1. Composition and physicochemical properties of glycosyl ionic liquids

[0079]

[0080]

[0081] Note: Molar ratios are rounded to the nearest integer.

[0082] As shown in Table 1, the glycosyl hydrated ionic liquid provided in this embodiment exhibits good thermal stability. No separation, crystallization, precipitation, or pH shift was observed after standing at room temperature for more than 3 months.

[0083] Application Examples 1-5

[0084] The glycosyl ionic liquid from Example 1 was used to dissolve API model compounds, such as vanillin, gallic acid, and melatonin, to verify the solubility and stability of the glycosyl ionic liquid for poorly soluble and unstable API model compounds. Specific results are shown in Table 2.

[0085] Specifically, the preparation method includes mixing the glycosyl ionic liquid of the example with API, and the specific amounts of each substance are shown in Table 2.

[0086] Table 2 Composition and physicochemical properties of application examples 1-5

[0087]

[0088]

[0089] Note: Molar ratios are rounded to the nearest integer.

[0090] As shown in Table 2, the glycosyl ionic liquid provided in the embodiments of the present invention can dissolve and stabilize poorly soluble and unstable API model compounds, such as vanillin, gallic acid, and melatonin, and the resulting API solution is a colorless and transparent aqueous solution.

[0091] Furthermore, the glycosyl ionic liquid provided in this embodiment of the invention can dissolve poorly soluble API compounds even without the addition of any organic solvent. For example, it can dissolve 0.1-1.0 wt% of vanillin, 1 wt% of gallic acid, and 1 wt% of melatonin. Therefore, the glycosyl ionic liquid provided in this embodiment of the invention can effectively dissolve and stabilize poorly soluble and unstable API model compounds, and can be used as a solvent and stabilizer for poorly soluble and unstable APIs.

[0092] Application Example 6-13

[0093] Application Example 6-13 verified the stabilizing effect of the glycosyl ionic liquid on the unstable API model compound ascorbic acid, see Table 3.

[0094] Table 3 Composition and physicochemical properties of application examples 6-13

[0095]

[0096]

[0097] Note: Molar ratios are rounded to the nearest integer.

[0098] The results showed that ascorbic acid exhibited good stability in the aqueous solution of the glycosyl ionic liquid, meaning that the glycosyl ionic liquid provided in the embodiments of the present invention can be used as a stabilizer to improve the stability of antioxidant preparations.

[0099] Specifically, according to Table 3, the results of the color change test showed that: (1) Photochromic color change test results: the aqueous solution of ascorbic acid glycosyl ionic liquid obtained in Example 6-13 did not show any visible color change after 24 hours of direct UV 100W exposure; (2) Thermochromic color change test results: the aqueous solution of ascorbic acid glycosyl ionic liquid obtained in Example 6-13 did not show any visible color change after 24 hours of continuous heating in a constant temperature incubator at 40°C.

[0100] Furthermore, the API solution obtained in corresponding use case 6-13 was subjected to cold and heat resistance tests, which showed that it had good thermal stability and no separation, crystallization, precipitation or pH shift was observed after standing at room temperature for more than 3 months.

[0101] Furthermore, the ascorbic acid glycosyl ionic liquid aqueous solution obtained in Example 6-13 was left to stand at room temperature and under non-light-protected conditions for more than 3 months, and the color change of the solution was visually observed. The results are shown in […]. Figure 2 .

[0102] according to Figure 2 It can be seen that Example 6 (10% ascorbic acid glycosyl ionic liquid aqueous solution) is light yellow (I); Example 10 (20% ascorbic acid glycosyl ionic liquid aqueous solution) is light yellow (II); the control group (10% ascorbic acid aqueous solution) is distinctly yellow (III); the control group (20% ascorbic acid aqueous solution) is brownish-yellow (IV); and the control group (15% ascorbic acid CE commercial skin care product, packaged in a brown light-proof glass bottle) is brownish-yellow (V).

[0103] This demonstrates that glycosylated ionic liquid aqueous solutions have a significant stabilizing effect on API model compounds that are unstable when exposed to heat and light, such as ascorbic acid. Even at high concentrations of up to 20%, it still exhibits good stabilizing properties, making the stability of ascorbic acid in aqueous solutions significantly better than that of API under existing technical conditions.

[0104] Furthermore, when the glycosyl ionic liquid is used to prepare API formulations or antioxidant formulations, the glycosyl ionic liquid may be selected from any one or a combination of two or more of Examples 1-19 as a solvent or stabilizer for the antioxidant.

[0105] Furthermore, when the ascorbic acid glycosyl ionic liquid aqueous solution is used directly as an API formulation or an antioxidant, other pharmaceutical excipients can be easily added, such as cellulose, sodium hyaluronate, sodium alginate, carrageenan, xanthan gum, agar, carbomer, etc., to form transparent gels, emulsions or creams, or to form topical skin dosage forms such as sprays.

[0106] Molecular simulation experiment

[0107] Molecular simulation experiments were conducted using density functional theory (DFT) at the B3LYP / 6-31G(d,p) level for molecular structure optimization and frequency calculations. Furthermore, the thermodynamic energy of ascorbic acid molecules in hydrated glycosyl ionic liquids was calculated using the SCRF method. The reaction conditions were set at 298.150 Kelvin and 1 atm.

[0108] In the tested glycosyl compounds, most reactions exhibited Gibbs free energies (ΔG≤0) and formed stable hydrogen bonds, predicting that the reaction could proceed towards the product side and form a stable ionic liquid. This is consistent with laboratory test results. Molecular simulation experimental data are shown in Table 4.

[0109] Furthermore, solvation simulation experiments showed that the molecular conformation of ascorbic acid in aqueous glycosyl ionic liquids is lower and more stable than that in the gas phase, significantly lower than that in aqueous solution, consistent with laboratory test results. Among these, ascorbic acid exhibits the lowest thermodynamic energy in aqueous tetrahydrofurfuryl alcohol and furfural ionic liquids, followed by deoxyribose, galactose, trehalose, fructose, glucose, rhamnose, lactose, and other glycosyl ionic liquids (not all are shown in the table). Figure 1 The thermodynamic energy of ascorbic acid molecules is as follows: Figure 1 As shown.

[0110] Furthermore, molecular simulation results show that when the anionic or hydrogen bond donor component of the glycosyl ionic liquid is replaced with histidine, the Gibbs free energy (ΔG≥0) of most reactions predicts that an ionic liquid cannot be formed. Even if the Gibbs free energy (ΔG≤0) of the reaction is low, the hydrogen bond energy is low, making it difficult to form a stable ionic liquid. Molecular simulation data are shown in Table 5.

[0111] Table 4. Molecular simulation experimental data of glycosyl ionic liquids

[0112]

[0113]

[0114]

[0115]

[0116] Table 5. Simulation data of histidine glycosyl ionic liquid molecules

[0117]

[0118]

[0119]

[0120]

[0121] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A glycosyl ionic liquid, characterized in that, The name of the glycosyl ionic liquid is [O]X, where [O] represents the hydrogen bond acceptor portion and X represents the hydrogen bond donor portion; The hydrogen bond acceptor portion is composed of furanose, pyranose, and trehalose; The hydrogen bond donor portion is a compound with the following structural formula: 。 2. The glycosyl ionic liquid according to claim 1, characterized in that, The hydrogen bond acceptor portion is any one of fructose, glucose, galactose, rhamnose, and trehalose.

3. The glycosyl ionic liquid according to claim 1, characterized in that, The glycosyl ionic liquid is a hydrated glycosyl ionic liquid solvent.

4. The glycosyl ionic liquid according to claim 1, characterized in that, The molar ratio of the hydrogen bond acceptor portion to the hydrogen bond donor portion is 5:1 to 1:

5.

5. A method for preparing the glycosyl ionic liquid according to claim 1, characterized in that, include: The hydrogen bond acceptor portion [O] is mixed and dissolved with the hydrogen bond donor portion X.

6. The preparation method according to claim 5, characterized in that, Preparation was carried out under non-vacuum conditions; The mixing and dissolving temperature is 25-45℃, and the time is 10-30 minutes.

7. The preparation method according to claim 5 or 6, characterized in that, The hydrogen bond acceptor portion [O] and the hydrogen bond donor portion X are dissolved in water.

8. Use of the glycosyl ionic liquid of claim 1 as a stabilizer to enhance the stability of antioxidant preparations.

9. The use according to claim 8, characterized in that, The antioxidants include ascorbic acid.

10. The application of the glycosyl ionic liquid of claim 1 as a solvent and / or stabilizer for APIs, characterized in that, The API includes at least one of vanillin, gallic acid, melatonin, and ascorbic acid.

11. The application according to claim 10, characterized in that, When the glycosyl ionic liquid is used as a solvent for API, it no longer contains volatile organic solvents.

12. The application according to claim 10, characterized in that, When the glycosylated ionic liquid is used as a stabilizer for API, no chelating agent is added.

13. An antioxidant preparation, characterized in that, It includes the glycosyl ionic liquid of claim 1 and an antioxidant active ingredient, wherein the antioxidant active ingredient includes ascorbic acid.

14. The antioxidant preparation according to claim 13, characterized in that, The antioxidant preparation does not contain any volatile organic solvents or chelating agents.

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