[go: up one dir, main page]

WO2024180161A1 - Multicomponent deep eutectic solvents, their preparation and use - Google Patents

Multicomponent deep eutectic solvents, their preparation and use Download PDF

Info

Publication number
WO2024180161A1
WO2024180161A1 PCT/EP2024/055165 EP2024055165W WO2024180161A1 WO 2024180161 A1 WO2024180161 A1 WO 2024180161A1 EP 2024055165 W EP2024055165 W EP 2024055165W WO 2024180161 A1 WO2024180161 A1 WO 2024180161A1
Authority
WO
WIPO (PCT)
Prior art keywords
yes
glycerol
tmao
urea
dess
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2024/055165
Other languages
French (fr)
Inventor
Thanos Andreou
Marina CVJETKO BUBALO
Dimitrios KALIAS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vio Invent Private Co
Original Assignee
Vio Invent Private Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vio Invent Private Co filed Critical Vio Invent Private Co
Publication of WO2024180161A1 publication Critical patent/WO2024180161A1/en
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Definitions

  • the present invention belongs to the fields of chemistry and biotechnology, more precisely to the field of deep eutectic solvents for various uses.
  • the invention relates to multicomponent deep eutectic solvents (DESs), methods for their preparation and use of said multicomponent DESs.
  • Neoteric systems that effectively mimic the natural environment of various biological systems and of the biomolecules they consist of, i.e., any organic molecule that includes carbohydrates, protein, lipids, and/or nucleic acids, the so-called Deep Eutectic Solvents (DESs), have been in the past years intensively studied as nontoxic and highly tunable solvents in food, agrochemicals, cosmetics, and pharmaceuticals production (Vanda et al; 2019: Natural deep eutectic solvents: From their discovery to their applications. in Deep Eutectic Solvents: Synthesis, Properties, and Applications 61–81).
  • DESs Deep Eutectic Solvents
  • a DES is a mixture of two or more, usually solid compounds combined in a suitable molar ratio to form a liquid at ambient temperature (Hansen et al., 2021: Chem. Rev.121, 1232–1285).
  • Natural DESs NADESs
  • DESs only consist of compounds that occur in nature (Dai et al., 2013: Anal. Chim. Acta 766, 61–68).
  • DESs usually have negligible volatility, are non-flammable, water-tolerant, and are easy to prepare with high purity at low price.
  • DESs are usually considered green solvents due to their typical biodegradability and biocompatibility.
  • DESs are highly tunable through varying the components or relative ratio of components and thus have a wide variety of potential applications.
  • novel DESs systems with novel and/or even more diverse properties are required.
  • the present invention aims to address this need.
  • Most notably, currently known DESs are mostly used for extraction, but are thereafter discarded or need to be recycled.
  • Choline chloride (ChCl) is often used due to its low price. ChCl is manufactured from ethylene oxide, which comes from ethylene, made from fossil fuels (petroleum or natural gas). For reasons of sustainability, elimination of ChCl is preferred.
  • patent EP3870227 relates to a deep eutectic solvent (DES) composition, comprising a combination of a glycol with a polymer solubilizer component, which polymer solubilizer component is selected from the group consisting of esters and lactones of organic acids; dicarboxylic acids; esters of dicarboxylic acids; esters, ethers and carbonates of diols and triols; and mixtures thereof, in a molar ratio of a glycol to the polymer solubilizer component in the range of between 12 to 1 and 1 to 10, preferably in a range of between 8 to 1 and 1 to 2, and more preferably in a range of between 4 to 1 and 1 to 1; the composition further comprising at least one DES constituent.
  • DES deep eutectic solvent
  • Patent application EP3971230 discloses a DES comprising: ⁇ at least one carboxylic acid which comprises at least two carboxylic acid functional groups and has a number of carbon atoms in the range of from 4 to 10; ⁇ at least one alcohol which comprises at least two alcohol functional groups, and which is selected from the group consisting of: o alcohols having several carbon atoms in the range of from 2 to 12 carbon atoms, o polyethylene glycol and o polypropylene glycol; and ⁇ water in an amount of from 10 to 50 wt.% of the total weight of the DES.
  • Patent application EP3485874 describes a method of preparing or optimizing a system comprising a NADESs and one or more active ingredients, comprising the following steps: a) analysing an active ingredient or target compound; b) matching the active ingredient to at least one potential NADES starting composition; c) synthesizing a stable, liquid NADESs-active ingredient system; and d) optimizing the system prepared in step (c).
  • Patent application WO2017134190 discloses a DES consisting of (2-hydroxyethyl) trimethyl ammonium chloride and dithiothreitol in a molar ratio of from 1:2 to 1:3 and from 0% to 10% co-solvent, and methods of enzymatic production of polypeptides using the DES.
  • Esquieri et al. (2013; Phys. Chem. Chem. Phys., 15, 11248 – 11256) studied the stability of hen's egg white lysozyme in different choline chloride-based pseudo-concentrated and neat DESs has been studied by means of intrinsic fluorescence and CD spectroscopy.
  • Thermal unfolding experiments carried out in non-diluted urea:choline chloride and glycerol:choline chloride eutectic solvents (UChCl-DES and GChCl-DES, respectively) showed the accumulation at certain temperatures of discrete, partially folded intermediates that displayed a high content of secondary structure and a disrupted tertiary structure.
  • betaine:urea, choline chloride: urea, glycerol:betaine, , glycerol:choline chloride, malic acid:choloride, lactic acid:betaine, levulinic acid:betaine, pyruvic acid:betaine, urea:betaine HCl, betaine:sorbitol, proline:levulinic acid, betaine:proline, proline:glucose, betaine:glucose, lysine:levulinic acid, sorbitol:levulinic acid, xylitol:levulinic acid, glucose:levulinic acid, glucose:levulinic acid, glycerol:sorbitol, glycerol:lactic acid, sorbitol: lactic acid, and glycerol:levulinic acid are disclosed.
  • the multicomponent DESs according to the first aspect of the invention comprises at least 2 components, wherein at least one of the components is selected in the group consisting of ectoine, trimethylamine N-oxide (TMAO), sarcosine, glycerophosphocholine (GPC), dimethylsulfonopropionate (DMSP), guanidine, arginine, and taurine.
  • TMAO trimethylamine N-oxide
  • GPC glycerophosphocholine
  • DMSP dimethylsulfonopropionate
  • guanidine arginine
  • taurine guanidine
  • the multicomponent DESs has 3, more preferably 4 components.
  • the DESs also comprises water. It has been observed that these multicomponent DESs improve biomolecule stability, as well as stability and viability of cells stored at lower temperatures, while maintaining the biomolecule function or even improving it. Consequently, a possible embodiment of the invention is also a medium for stabilization of biomolecules or cryoprotection of cells/tissues comprising the DESs comprising at least two components, wherein at least one of the components is selected in the group consisting of ectoine, TMAO, sarcosine, GPC, DMSP, guanidine, arginine and taurine.
  • a method for stabilization of biomolecules or for of biological systems, such as organisms, organs, organelles, cells or tissues comprises at least a step in which the biomolecule or biological systems, cells or tissues or artifical engineered constructs are exposed to the above-mentioned medium.
  • the medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner.
  • preservation relates to any kind of processes for storing biological systems or biomolecules that aims to maintain usual biological, chemical and/or physical properties of the biological system or biomolecules, respectively.
  • preservation may relate to storage at any given temperature, including cryopreservation at low temperatures, typically in the range from -80 °C to -196 °C, or preservation at temperatures above -80 °C.
  • a second aspect of the present invention showing the same technical effect as the DESs described above is a multicomponent DESs comprising at least 4 components.
  • at least one of the components of the DESs are selected in the group comprising naturally occurring osmolytes. Therefore, another possible embodiment of the invention is also a medium for stabilization of biomolecules or preservation, for example cryoprotection, of biological systems, cells or tissues comprising the DESs comprising at least four components.
  • a method for stabilization of biomolecules or for preservation/cryoprotection of biological systems, cells or tissues comprises at least a step in which the biomolecule or cells/tissue are exposed to the above-mentioned medium.
  • the medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner.
  • the naturally occurring osmolytes are preferably selected in the group comprising: (i) polyols and sugar polyols, for example glycerol, sorbitol, xylitol; (ii) sugars and their derivatives, for example glucose, sucrose, trehalose; (iii) amino acids and their derivatives, for example glycine, proline, ectoine, taurine; (iv) methylamines, for example trimethylamine N-oxide (TMAO), sarcosine, betaine, glycerophosphocholine (GPC); (v) methylsulfonium compounds, for example dimethylsulfoniopropionate (DMSP); (vi) Y-conjugated compounds, for example urea, guanidine and arginine.
  • polyols and sugar polyols for example glycerol, sorbitol, xylitol
  • sugars and their derivatives for example glucose, suc
  • the naturally occurring osmolytes are selected in the group consisting of ectoine, TMAO, sarcosine, GPC, DMSP, guanidine, arginine, and taurine.
  • the DESs may optionally comprise water.
  • the other remaining components of the multicomponent DESs can be selected among common DES/IL compounds, such as methylamines, methylsulfonium compounds, organic acids, sugars, polyols, amino acids and Y-conjugated compounds.
  • the DES may be formulated with or without water, such as solution comprising a DES essentially free of water.
  • Methylamines may be selected from trimethylamine N-oxide (TMAO), betaine, glycerophosphocholine (GPC), carnitine, homarine, and derivatives thereof, for example, their halide forms, such as betaine halides (betaine HCl).
  • Methyl sulfonium compounds may be selected from dimethylsulfonopropionate (DMSP) and other compounds containing a methylsulfonium moiety.
  • Organic acids may be selected from levulinic acid, lactic acid, malic acid, maleic acid, pyruvic acid, fumaric acid, succinic acid, citric acid, citraconic acid, glutaric acid, glycolic acid, acetic acid, aconitic acid, tartaric acid, ascorbic acid, malonic acid, oxalic acid, glucuronic add, neuraminic acid, sialic acid, shikimic acid, phytic acid, galacturonic acid, iduronic acid, hyaluronic acid, hydroxycitric acid, lactone derivatives and derivatives thereof.
  • Sugars may be selected from trehalose, glucose, sucrose, lactose, ribose, galactose, fructose, etc. and derivatives thereof.
  • Polyols may be selected from glycerol, erythritol, mannitol, sorbitol, xylitol, ethylene glycol, propylene glycol, ribitol, aldonitol, propanediol, inositol, pentylene glycol, and derivatives thereof (such as o-methyl-inositol).
  • Amino acids may be selected from glycine, proline, taurine, lysine, etc. and derivatives thereof (e.g.
  • Y-conjugated compounds may be selected from urea, guanidine, arginine and compounds that incorporate the guanidino moiety (such as creatine, glycocyamine, agmatine, 4- guanidinobutanoic acid etc.) and derivatives thereof, such as guanidinium halides (for example guanidine HCl).
  • the molar ratio of each DES component with respect to the total moles of the DES may range from 0.001 to 0.9.
  • Molar ratio is defined as unit of the amount of a component (expressed in moles), n i , divided by the total amount of all components in a mixture (also expressed in moles), n tot .
  • the molar ratio of each DES component with respect to the total moles of the DES may be between 0.003 and 0.7.
  • the molar ratio of each DES component with respect to the total moles of the DES may be between 0.005 and 0.6.
  • the preferred ratios may also depend on the combination of components in the DES as well as on the targetted use of the DES.
  • the DES may be formulated with or without water (such as solution comprising a DES wherein said solution is essentially free of water).
  • the water used in the DESs may be from 0% to 90%, as from about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.5, 1, 5, 10, 15, 20, 30 or about 40% to about 90, 80, 70, 60 or about 50%. In a preferred embodiment, the water used in from about 5% to about 30%, such as about 10%, 20% 25% or about 30%.
  • the DESs as prepared may also be further diluted. In the most preferred embodiments of the invention the multicomponent DESs comprise the components in combinations as given in the Tables 2 and 3 below. Table 2.
  • Preferred embodiments of the multi-component deep eutectic solvents comprising naturally occurring osmolytes Components
  • ⁇ stabilization of biomolecules ⁇ preservation of biological systems, including cryoprotection, ⁇ pharmaceutical preparations, such as pharmaceutical excipients and similar components, ⁇ cosmetics, ⁇ food, and ⁇ preparation of extracts, wherein the DESs is optionally a component of the final extract.
  • DES systems are possible for the extraction, stabilization, analysis, formulation, preservation and/or any form of culture, monitoring, handling, treatment and use of organisms, organs, tissues, organelles, biological systems, cells, biomolecules and bioactive compounds, including but not limited to plants, animals, algae, bacteria, fungi and other microorganisms, whole cells, membranes and other cell components, proteins, enzymes, antibodies, peptides and other molecules consisting of aminoacids or aminoacid derivatives, polysaccharides and biopolymers of any composition, lipids and supramolecular structures containing lipids, nucleotides, nucleosides and their precursors and derivatives, polynucleotides of any length, sense and molecular weight and composition, including but not limited to all types of DNA and RNA, all types of gels, emulsions, dispersions, liquid and/or solid compositions comprising the DESs according to the present invention and/or biomolecules and/or other payloads, including
  • the invention or preparations comprising the DESs according to the invention may be used as pharmaceutical excipients, cosmetic compositions, nutritional compositions, feed compositions, biomass extracts, nutritional products, etc.
  • An aspect of the invention is thus a stabilizing composition comprising any of the DESs described above for use in stabilization of biomolecules, particularly proteins, most preferably enzymes.
  • Another aspect of the invention is a composition or medium for preservation, for example cryoprotection of biological systems, cells, tissues and molecules comprising any of the DESs described above.
  • the medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner.
  • An additional aspect of the invention is also the method for stabilization of biomolecules or for preservation/cryoprotection of biological systems, cells or tissues, said method comprising at least a step in which the biomolecule, biological systems, cells or tissue are exposed to the above-mentioned medium.
  • the multicomponent DESs comprise the components in combinations and ratios as given in the Table 4 below. Table 4.
  • Exemplary embodiments of the multi-component deep eutectic solvents comprising naturally occurring osmolytes Water Components Components content molar ratio (wt.
  • Table 6 Multiple-component DESs Water Components DES Components content molar ratio (wt. %) 20 ChCl:Gly ChCl:Glycerol 1:2 40 Bet:U Betaine:Urea 1:1 20 TMAO:Gly TMAO:Glycerol 1:2 40 20 Sar:Gly Sarcosine:Glycerol 1:2 40 20 DMPS:Gly DMSP:Glycerol 1:2 40 20 Ect:Gly Ectoine:Glycerol 1:2 40 Bet:Sor:Tau:GPC:U Betaine:Sorbitol:Taurine:GPC:Urea 1:3.1:0.1:2.8:7.1 20 TMAO:Bet:Tau:U TMAO:Betaine:Taurine:Urea 1:0.1:0.1:1.5 20 Bet:Gly:Sor Betaine:Glycerol:Sorbitol 1:1:2 20 Bet:Gly:Sor:Ect Betaine:Glycerol:Sorbitol:Ectoine 1:4:2:1 20
  • Example 2 Lysozyme stabilization at 25 °C by selected DESs prepared in example 1 Lysozyme activity was determined according to the method of Shugar et al. (1952, Biochim Biophys Acta 8: 302–9), which is based on the decrease in turbidity of the substrate, Micrococcus lysodeikticus, in a suspension. Lysozyme solutions at a concentration of 0.1 mg ml -1 were prepared in different DESs and in 10 mM sodium phosphate buffer solution (pH 7). The solutions were incubated at different temperatures (25, 45, 70°C) for 1, 3, 5 and 7 days (Examples 2 and 3) or 15, 60 and 120 min (Example 4).
  • Table 7 Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 25°C for 1, 3, 5 and 7 days. Results are presented as residual activity - relative to the enzyme activity prior incubation (%).
  • Example 3 Lysozyme stabilization at 45 °C by selected DESs prepared in example 1 The experiment was performed in the same manner as described for Example 2, except that the incubation temperature was 45 °C.
  • Table 8 Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 45°C for 1, 3, 5 and 7 days. Results are presented as residual activity - relative to the enzyme activity prior incubation (%).
  • Example 4 Lysozyme stabilization at 70 °C by selected DESs prepared in example 1 The experiment was performed in the same manner as described for Example 2, except that the incubation temperature was 70 °C and incubation times were 15, 60 and 120 minutes, respectively.
  • Table 9 Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 70°C (heat shock) for 15-, 60- or 120-min. Results are presented as residual activity - relative to the enzyme activity prior incubation (%).
  • YADH solutions at a concentration of 0.4 mg ml -1 were prepared in different DESs and in glycine-pyrophosphate buffer (pH 9). The solutions were incubated at different temperatures (25 and 45°C) for 2, 5, 8, 24 and 48 h (at 25°C) or 1, 2, 4, 8 and 24 h (at 45°C). Briefly, to 975 ⁇ l of glycine-pyrophosphate buffer (pH 9) in a plastic disposable cuvette 5 ⁇ l of NAD + in PBS buffer (50 mg ml -1 ), 10 ⁇ l of ethanol (96%) and 10 ⁇ l of the YADH solution were added.
  • Results are presented as residual activity - relative to the enzyme activity prior incubation (%).
  • R esidual activity (%) after incubation at 45°C for DESs Water 1 h 2 h 4 h 8 h 24 h content
  • Control 1 (phosphate buffer) 0 0 0 0 0 0
  • Control 2 (ChCl:Gly 1:2) 20 2.1 0 0 0 0 40 1.7 Sar:Gly 20 136.9 138.6 66.9 34.4 11.3
  • Bet:Sor:Tau:GPC:U 20 25.0 2.6 0 0 0
  • the results shown in tables 10 and 11 show that some DESs according to the invention can stabilize YADH to a higher degree than conventionally used buffers or stabilizing media.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention belongs to the fields of chemistry and biotechnology, more precisely to the field of deep eutectic solvents for various uses. The invention relates to multicomponent deep eutectic solvents (DESs), methods for their preparation and use of said multicomponent DESs. The multicomponent DESs according to the first aspect of the invention comprises at least 2 components, wherein at least one of the components is selected in the group consisting of ectoine, trimethylamine N-oxide (TMAO), sarcosine, glycerophosphocholine (GPC), dimethylsulfonopropionate (DMSP), guanidine, arginine, and taurine. A second aspect of the present invention is a multicomponent DESs comprising at least 4 components. In a preferred embodiment, at least one of the components of the DESs are selected in the group comprising naturally occurring osmolytes.

Description

MULTICOMPONENT DEEP EUTECTIC SOLVENTS, THEIR PREPARATION AND USE Field of the invention The present invention belongs to the fields of chemistry and biotechnology, more precisely to the field of deep eutectic solvents for various uses. The invention relates to multicomponent deep eutectic solvents (DESs), methods for their preparation and use of said multicomponent DESs. Background and the technical problem Neoteric systems that effectively mimic the natural environment of various biological systems and of the biomolecules they consist of, i.e., any organic molecule that includes carbohydrates, protein, lipids, and/or nucleic acids, the so-called Deep Eutectic Solvents (DESs), have been in the past years intensively studied as nontoxic and highly tunable solvents in food, agrochemicals, cosmetics, and pharmaceuticals production (Vanda et al; 2019: Natural deep eutectic solvents: From their discovery to their applications. in Deep Eutectic Solvents: Synthesis, Properties, and Applications 61–81). Unlike conventional molecular solvents, a DES is a mixture of two or more, usually solid compounds combined in a suitable molar ratio to form a liquid at ambient temperature (Hansen et al., 2021: Chem. Rev.121, 1232–1285). A particular subgroup of these systems, Natural DESs (NADESs), only consist of compounds that occur in nature (Dai et al., 2013: Anal. Chim. Acta 766, 61–68). DESs usually have negligible volatility, are non-flammable, water-tolerant, and are easy to prepare with high purity at low price. Besides, DESs are usually considered green solvents due to their typical biodegradability and biocompatibility. Furthermore, DESs are highly tunable through varying the components or relative ratio of components and thus have a wide variety of potential applications. In order to satisfy emergent needs for green solvents, pharmaceutical industry, biochemistry, material science and biotechnology, novel DESs systems with novel and/or even more diverse properties are required. The present invention aims to address this need. Most notably, currently known DESs are mostly used for extraction, but are thereafter discarded or need to be recycled. Choline chloride (ChCl) is often used due to its low price. ChCl is manufactured from ethylene oxide, which comes from ethylene, made from fossil fuels (petroleum or natural gas). For reasons of sustainability, elimination of ChCl is preferred. It is an aim of the invention to provide novel DESs without ChCl that could also be used in final products and would exhibit novel properties and functions. Prior art Several DESs are known and reported in scientific articles and patent applications. To mention a few, patent EP3870227 relates to a deep eutectic solvent (DES) composition, comprising a combination of a glycol with a polymer solubilizer component, which polymer solubilizer component is selected from the group consisting of esters and lactones of organic acids; dicarboxylic acids; esters of dicarboxylic acids; esters, ethers and carbonates of diols and triols; and mixtures thereof, in a molar ratio of a glycol to the polymer solubilizer component in the range of between 12 to 1 and 1 to 10, preferably in a range of between 8 to 1 and 1 to 2, and more preferably in a range of between 4 to 1 and 1 to 1; the composition further comprising at least one DES constituent. Patent application EP3971230 discloses a DES comprising: − at least one carboxylic acid which comprises at least two carboxylic acid functional groups and has a number of carbon atoms in the range of from 4 to 10; − at least one alcohol which comprises at least two alcohol functional groups, and which is selected from the group consisting of: o alcohols having several carbon atoms in the range of from 2 to 12 carbon atoms, o polyethylene glycol and o polypropylene glycol; and − water in an amount of from 10 to 50 wt.% of the total weight of the DES. Patent application EP3485874 describes a method of preparing or optimizing a system comprising a NADESs and one or more active ingredients, comprising the following steps: a) analysing an active ingredient or target compound; b) matching the active ingredient to at least one potential NADES starting composition; c) synthesizing a stable, liquid NADESs-active ingredient system; and d) optimizing the system prepared in step (c). Patent application WO2017134190 discloses a DES consisting of (2-hydroxyethyl) trimethyl ammonium chloride and dithiothreitol in a molar ratio of from 1:2 to 1:3 and from 0% to 10% co-solvent, and methods of enzymatic production of polypeptides using the DES. Esquembre et al. (2013; Phys. Chem. Chem. Phys., 15, 11248 – 11256) studied the stability of hen's egg white lysozyme in different choline chloride-based pseudo-concentrated and neat DESs has been studied by means of intrinsic fluorescence and CD spectroscopy. Thermal unfolding experiments carried out in non-diluted urea:choline chloride and glycerol:choline chloride eutectic solvents (UChCl-DES and GChCl-DES, respectively) showed the accumulation at certain temperatures of discrete, partially folded intermediates that displayed a high content of secondary structure and a disrupted tertiary structure. Reversibility of the unfolding process was incomplete in these circumstances, with the urea-based DES showing higher protein structure destabilization upon thermal treatment. On the other hand, aqueous dilution of the eutectic mixtures allowed the recovery of a reversible, two-state denaturation process. Lysozyme activity was also affected in neat and pseudo-concentrated GChCl-DES, with an increasing recovery of activity upon aqueous dilution, and full restoration after DES removal through extensive dialysis. The results of Esquembre et al. suggest that protein interactions at room temperature are reversible and depend on the DES components and on the aqueous content of the original DES dilution. Similarly, Banerjee et al. (Adv. Healthcare Mater., 2017, 6, 1601411) observed that a DES consisting of choline:geranate solution in 1:2 ratio preserved the physical integrity of insulin while retaining its activity. Analogously, Lee et al. (J. Ind. Eng. Chem., 2018, 65, 343-348) improved human interferon stability by using sugar-based DESs. Improved stability of some other proteins, namely chemotrypsin and Trp-cage protein, at high temperatures was ensured by a choline-based DES (Yadav et al. (ACS Sustainable Chem. Eng., 2020, 8, 10151-10160; Pal et al. (J. Phys. Chem. B, 2020, 124, 7598-7610)). Sanchez-Fernandez et al. (2022; Green Chem., 24, 4437-4442), by using lysozyme as a valuable model protein, showed the potential of choline chloride:glycerol DES (molar ratio 1:2) as synthetically accessible media for the storage and preservation of proteins in a concentrated regime without the requirement of other excipients. The behaviour of lysozyme in choline chloride:glycerol was studied over a wide range of concentrations, ranging from dilute (1.4 mg ml−1, 0.100 mM) to concentrated (142 mg ml−1, 9.9 mM) conditions and compared to that in aqueous buffer. It has been shown that lysozyme retained its globularity in the DES with an overall structure similar to that in aqueous phosphate buffer, which potentially enabled the protein to remain physically stable even after long periods of storage (40 days at room temperature) in the DES. Importantly, the enzymatic activity of the reconstituted and hydrated lysozyme solutions was totally retained after storage in DES. Nardecchia et al. (2012; Biomacromolecules 13, 7, 2029–2036) report that UChCl-DES, which was obtained by heating urea and choline chloride in a 2:1 molar ratio at 80 °C and stirring until a homogeneous liquid was formed, promoted the stabilization of the collapsed state of elastin-like recombinamers – and the subsequent formation of aggregates – upon the loss of the structural water molecules involved in hydrophobic hydration. Cryo-etch scanning electron microscopy allowed the observation of these aggregates in neat DES. The suppression of the lower critical solution temperature transition, observed by differential scanning calorimetry and dynamic light scattering, confirmed the presence of the elastin-like recombinamers in their collapsed state. The transition from the collapsed to the expanded state was suppressed even after moderate aqueous dilution – for water contents ranging from 0 to ca.45 wt % – and it was only recovered upon further addition of water – above 50 wt %. These features revealed the preferred stabilization of the collapsed state in not only neat deep eutectic solvents but also partially hydrated DES. Patent application US2022305401 discloses various combinations of two-component DESs and also suggests use of three components, albeit not specifically disclosing any combination of three components. According to this solution combinations of betaine:urea, choline chloride: urea, glycerol:betaine, , glycerol:choline chloride, malic acid:choloride, lactic acid:betaine, levulinic acid:betaine, pyruvic acid:betaine, urea:betaine HCl, betaine:sorbitol, proline:levulinic acid, betaine:proline, proline:glucose, betaine:glucose, lysine:levulinic acid, sorbitol:levulinic acid, xylitol:levulinic acid, glucose:levulinic acid, glucose:levulinic acid, glycerol:sorbitol, glycerol:lactic acid, sorbitol: lactic acid, and glycerol:levulinic acid are disclosed. In table below several disclosures of NADESs in scientific articles are compiled. The cited articles are: 1. Yancey and Somero; Biochem. J.183, 317–323 (1979), 2. Liang, Y. et al. Bioresour. Technol.310, 123389 (2020) 3. Zeng et al. J. Mol. Liq.219, 74–78 (2016). 4. Benlebna, M. et al. Journal of Agricultural and Food Chemistry vol.66 (2018). 5. Syakfanaya et al. Pharmacogn. J.11, 267–271 (2019). 6. Jesus et al. Cryobiology 101, 95–104 (2021). 7. Panić, M. et al. Waste Manag.120, 340–350 (2021). 8. Simeonov and Afonso, RSC Adv.6, 5485–5490 (2016). 9. Zhong, L. et al. Bioresour. Technol.343, 126022 (2022). 10. Pedro, S. N. et al. Pharmaceutics 14, 827 (2022). 11. Karadendrou, et al. Catalysts 12, (2022). 12. Sut, S. et al. Molecules 22, 1–11 (2017). 13. Faggian, M. et al. Molecules 21, 1–11 (2016). 14. Ilgen and König Green Chem.11, 848–85 (2009). 15. Zdanowicz Int. J. Biol. Macromol.176, 387–393 (2021). 16. Wang, T. et al. J. Pharm. Biomed. Anal.145, 339–345 (2017) Table 1. Reported deep eutectic solvents comprising naturally occurring osmolytes Water Components Components content Reference molar ratio (wt. %) 1 2 3 betaine urea - 1:1:2(H2O) 17 3 betaine glycerol - 1:2:2(H2O) 10 4 betaine sorbitol - 1:1.2:6(H2O) 25 5 betaine trehalose - 4:1 unk. 1 betaine xylose - 2:1:3(H2O) 12 6 betaine glucose - 5:2 - 1 betaine mannose - 5:2 unk. 1 betaine lysine - 1:1:27-180(H2O) 65-93 2 betaine histidine - 1:1:28-190(H2O) 65-93 2 betaine arginine - 1:1:30-200(H2O) 65-93 2 glucose fructose - 1:1:8(H2O) 30 7 glucose glycerol - 1:4 - 6 glucose trehalose - 1:2:13(H2O) 21 6 fructose trehalose - 1:2:13(H2O) 20 6 glycerol trehalose - 30:1 - 6 glycerol urea - 5:2 unk. 8 guanidine glycerol - 5:2 - 9 HCl glycerol arginine - 4:1 - 10 proline glucose - 5:3 unk. 1 proline glycerol - 1:2 - 11 proline sorbitol - 1:1 unk. 1 proline sucrose - 2:1, 3:1 unk. 1 proline urea - 2:1 unk. 12 glutamic proline - 2:1 unk. 13 acid serine glucose - 5:4 unk. 1 carnitine urea - 2:3 - 14 betaine sorbitol urea 1:1.2:1:7(H2O) 25 5 betaine trehalose raffinose 9:1:1:35(H2O) 25 1 betaine sucrose proline 5:2:2:21(H2O) 20 6 betaine glycerol sucrose 2:3:1:5(H2O) 10 6 betaine glycerol trehalose 2:3:1:5(H2O) 13 6 betaine sucrose proline 5:2:2:21(H2O) 20 6 sucrose glucose fructose 1:1:1:11(H2O) 22 6 fructose glucose trehalose 1:1:1:11(H2O) 21 6 fructose glucose urea 1:1:2 unk. 15 fructose glycerol urea 2:1:1 - 15 glucose glycerol urea 2:1:1 - 15 glycerol sucrose sorbitol 2:1:2:10(H2O) 16 6 glycerol trehalose sorbitol 2:1:2:10(H2O) 16 6 glycerol glucose sorbitol 1:1:1:3(H2O) 12 6 sorbitol glycerol urea 1:1:2 - 16 trehalose glucose sorbitol 1:2:1:13(H2O) 17 6 proline fructose glycerol 1:1:1:5(H2O) 20 16 proline glucose glycerol 5:3:3:20(H2O) 21 6 Unk. = unknown. Description of the solution to the technical problem The invention aims to provide alternative DESs that will extend the use of these systems in various fields and will eliminate choline chloride. The technical problem is solved as defined in the independent claims, wherein preferred embodiments of the invention are defined in the dependent claims. The multicomponent DESs according to the first aspect of the invention comprises at least 2 components, wherein at least one of the components is selected in the group consisting of ectoine, trimethylamine N-oxide (TMAO), sarcosine, glycerophosphocholine (GPC), dimethylsulfonopropionate (DMSP), guanidine, arginine, and taurine. Preferably, the multicomponent DESs has 3, more preferably 4 components. Optionally, the DESs also comprises water. It has been observed that these multicomponent DESs improve biomolecule stability, as well as stability and viability of cells stored at lower temperatures, while maintaining the biomolecule function or even improving it. Consequently, a possible embodiment of the invention is also a medium for stabilization of biomolecules or cryoprotection of cells/tissues comprising the DESs comprising at least two components, wherein at least one of the components is selected in the group consisting of ectoine, TMAO, sarcosine, GPC, DMSP, guanidine, arginine and taurine. A method for stabilization of biomolecules or for of biological systems, such as organisms, organs, organelles, cells or tissues comprises at least a step in which the biomolecule or biological systems, cells or tissues or artifical engineered constructs are exposed to the above-mentioned medium. The medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner. The term preservation relates to any kind of processes for storing biological systems or biomolecules that aims to maintain usual biological, chemical and/or physical properties of the biological system or biomolecules, respectively. The term preservation may relate to storage at any given temperature, including cryopreservation at low temperatures, typically in the range from -80 °C to -196 °C, or preservation at temperatures above -80 °C. A second aspect of the present invention showing the same technical effect as the DESs described above is a multicomponent DESs comprising at least 4 components. In a preferred embodiment of the multicomponent DESs comprising at least 4 components, at least one of the components of the DESs are selected in the group comprising naturally occurring osmolytes. Therefore, another possible embodiment of the invention is also a medium for stabilization of biomolecules or preservation, for example cryoprotection, of biological systems, cells or tissues comprising the DESs comprising at least four components. A method for stabilization of biomolecules or for preservation/cryoprotection of biological systems, cells or tissues comprises at least a step in which the biomolecule or cells/tissue are exposed to the above-mentioned medium. The medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner. In a preferred embodiment of the invention the naturally occurring osmolytes are preferably selected in the group comprising: (i) polyols and sugar polyols, for example glycerol, sorbitol, xylitol; (ii) sugars and their derivatives, for example glucose, sucrose, trehalose; (iii) amino acids and their derivatives, for example glycine, proline, ectoine, taurine; (iv) methylamines, for example trimethylamine N-oxide (TMAO), sarcosine, betaine, glycerophosphocholine (GPC); (v) methylsulfonium compounds, for example dimethylsulfoniopropionate (DMSP); (vi) Y-conjugated compounds, for example urea, guanidine and arginine. Preferably, the naturally occurring osmolytes are selected in the group consisting of ectoine, TMAO, sarcosine, GPC, DMSP, guanidine, arginine, and taurine. The DESs may optionally comprise water. The other remaining components of the multicomponent DESs can be selected among common DES/IL compounds, such as methylamines, methylsulfonium compounds, organic acids, sugars, polyols, amino acids and Y-conjugated compounds. As mentioned before, in the method or used defined herein, the DES may be formulated with or without water, such as solution comprising a DES essentially free of water. Methylamines may be selected from trimethylamine N-oxide (TMAO), betaine, glycerophosphocholine (GPC), carnitine, homarine, and derivatives thereof, for example, their halide forms, such as betaine halides (betaine HCl). Methyl sulfonium compounds may be selected from dimethylsulfonopropionate (DMSP) and other compounds containing a methylsulfonium moiety. Organic acids may be selected from levulinic acid, lactic acid, malic acid, maleic acid, pyruvic acid, fumaric acid, succinic acid, citric acid, citraconic acid, glutaric acid, glycolic acid, acetic acid, aconitic acid, tartaric acid, ascorbic acid, malonic acid, oxalic acid, glucuronic add, neuraminic acid, sialic acid, shikimic acid, phytic acid, galacturonic acid, iduronic acid, hyaluronic acid, hydroxycitric acid, lactone derivatives and derivatives thereof. Sugars may be selected from trehalose, glucose, sucrose, lactose, ribose, galactose, fructose, etc. and derivatives thereof. Polyols may be selected from glycerol, erythritol, mannitol, sorbitol, xylitol, ethylene glycol, propylene glycol, ribitol, aldonitol, propanediol, inositol, pentylene glycol, and derivatives thereof (such as o-methyl-inositol). Amino acids may be selected from glycine, proline, taurine, lysine, etc. and derivatives thereof (e.g. ectoine, sarcosine, theanine, dimethyglycine, etc.). Y-conjugated compounds may be selected from urea, guanidine, arginine and compounds that incorporate the guanidino moiety (such as creatine, glycocyamine, agmatine, 4- guanidinobutanoic acid etc.) and derivatives thereof, such as guanidinium halides (for example guanidine HCl). According to the invention, the molar ratio of each DES component with respect to the total moles of the DES may range from 0.001 to 0.9. Molar ratio is defined as unit of the amount of a component (expressed in moles), ni, divided by the total amount of all components in a mixture (also expressed in moles), ntot.In a preferred embodiment, the molar ratio of each DES component with respect to the total moles of the DES may be between 0.003 and 0.7. In a further preferred embodiment, the molar ratio of each DES component with respect to the total moles of the DES may be between 0.005 and 0.6. The preferred ratios may also depend on the combination of components in the DES as well as on the targetted use of the DES. As mentioned before, the DES may be formulated with or without water (such as solution comprising a DES wherein said solution is essentially free of water). The water used in the DESs may be from 0% to 90%, as from about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.5, 1, 5, 10, 15, 20, 30 or about 40% to about 90, 80, 70, 60 or about 50%. In a preferred embodiment, the water used in from about 5% to about 30%, such as about 10%, 20% 25% or about 30%. The DESs as prepared may also be further diluted. In the most preferred embodiments of the invention the multicomponent DESs comprise the components in combinations as given in the Tables 2 and 3 below. Table 2. Preferred embodiments of the multi-component deep eutectic solvents comprising naturally occurring osmolytes Components Water 1 2 3 betaine arginine - yes betaine guanidine HCl - yes TMAO urea - yes TMAO glycerol - yes TMAO sorbitol - yes TMAO glucose - yes TMAO trehalose - yes TMAO xylitol - yes TMAO guanidine HCl - yes TMAO arginine - yes sarcosine urea - yes sarcosine guanidine HCl - yes sarcosine arginine yes sarcosine glycerol - yes GPC urea - yes GPC guanidine HCl - yes GPC arginine - yes DMSP HCl urea - yes DMSP HCl guanidine HCl - yes DMSP HCl arginine - yes DMSP HCl glycerol - yes glycerol sorbitol - no proline guanidine HCl - yes proline arginine - yes ectoine urea - yes ectoine guanidine HCl - yes ectoine arginine - yes ectoine glycerol - yes sorbitol urea - yes sorbitol guanidine HCl - yes sucrose urea - yes sucrose guanidine HCl - yes sucrose arginine - yes betaine sorbitol guanidine HCl yes betaine taurine glycerol no betaine ectoine glycerol no betaine ectoine sorbitol yes TMAO urea glycerol yes TMAO guanidine HCl glycerol yes TMAO urea sorbitol yes TMAO guanidine HCl sorbitol yes TMAO betaine urea yes TMAO betaine guanidine HCl yes fructose glucose guanidine HCl yes fructose glycerol guanidine HCl yes glucose glycerol guanidine HCl yes glucose trehalose urea yes glucose trehalose guanidine HCl yes sorbitol glycerol guanidine HCl no trehalose glucose glycerol no trehalose glucose sorbitol yes trehalose proline glycerol yes trehalose ectoine glycerol yes proline glycerol sorbitol yes Table 3: Preferred embodiments of the multi-component deep eutectic solvents comprising 4 or more components Water Components Components molar ratio content 1 2 3 4 5 6 (wt. %) Betaine GPC Sorbitol Taurine Urea - 1:2.8:3.1:0.1:7.1:1(H2O) 7 Betaine GPC Sorbitol Inositol Urea - 1:0.7:0.7:0.9:7.1:3.5H2O) 38 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.2:0.6:8.1:3(H2O) 30 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.5:0.4:8.3:2.5(H2O) 21 Betaine Glycerol Sorbitol Ectoine - - 1:4:2:1:14(H2O) 20 TMAO Betaine Taurine Urea - - 1:0.1:0.1:1.5:5(H2O) 34 TMAO Betaine Taurine Urea - - 1:6:0.5:15:9(H2O) 9 TMAO Betaine Sorbitol α-alanine Taurine Urea 1:0.1:0.05:0.1:0.05:2:2(H2O 14 TMAO Betaine Inositol α-alanine Urea - 1:0.1:0.05:0.2:1:5 (H2O) 37 TMAO Inositol Urea α-alanine - - 1:0.05:1:0.2:5(H2O) 37 Trehalose Proline Glycerol Sorbitol - - 1:1:4:1:14(H2O) 20 DESs according to the invention are prepared with a method comprising the following steps: a) mixing components in required molar ratios, and b) stirring and heating the mixtures up to 60°C until a colourless and homogeneous liquid is formed. Use of the multi-component DESs according to the invention is multi-faceted, wherein at least the following uses are preferred: − stabilization of biomolecules, − preservation of biological systems, including cryoprotection, − pharmaceutical preparations, such as pharmaceutical excipients and similar components, − cosmetics, − food, and − preparation of extracts, wherein the DESs is optionally a component of the final extract. Use of DES systems according to the invention is possible for the extraction, stabilization, analysis, formulation, preservation and/or any form of culture, monitoring, handling, treatment and use of organisms, organs, tissues, organelles, biological systems, cells, biomolecules and bioactive compounds, including but not limited to plants, animals, algae, bacteria, fungi and other microorganisms, whole cells, membranes and other cell components, proteins, enzymes, antibodies, peptides and other molecules consisting of aminoacids or aminoacid derivatives, polysaccharides and biopolymers of any composition, lipids and supramolecular structures containing lipids, nucleotides, nucleosides and their precursors and derivatives, polynucleotides of any length, sense and molecular weight and composition, including but not limited to all types of DNA and RNA, all types of gels, emulsions, dispersions, liquid and/or solid compositions comprising the DESs according to the present invention and/or biomolecules and/or other payloads, including all types of bioactive compounds. The invention or preparations comprising the DESs according to the invention may be used as pharmaceutical excipients, cosmetic compositions, nutritional compositions, feed compositions, biomass extracts, nutritional products, etc. An aspect of the invention is thus a stabilizing composition comprising any of the DESs described above for use in stabilization of biomolecules, particularly proteins, most preferably enzymes. Another aspect of the invention is a composition or medium for preservation, for example cryoprotection of biological systems, cells, tissues and molecules comprising any of the DESs described above. The medium may be supplemented with any other components and storage of the mixture of medium and biomolecules, biological systems, cells or tissues is performed in any suitable manner. An additional aspect of the invention is also the method for stabilization of biomolecules or for preservation/cryoprotection of biological systems, cells or tissues, said method comprising at least a step in which the biomolecule, biological systems, cells or tissue are exposed to the above-mentioned medium. Detailed description of the invention The invention will be described in further detail based on exemplary embodiments and examples. In the most preferred embodiments of the invention the multicomponent DESs comprise the components in combinations and ratios as given in the Table 4 below. Table 4. Exemplary embodiments of the multi-component deep eutectic solvents comprising naturally occurring osmolytes Water Components Components content molar ratio (wt. %) 1 2 3 Betaine arginine - 5:1:28(H2O) 40 Betaine guanidine HCl - 1:2:3(H2O) 17 TMAO urea - 1:1:3.5(H2O) 33 TMAO glycerol - 1:1:2(H2O) 17 TMAO sorbitol - 1:1:2(H2O) 12 TMAO glucose - 5:2:12(H2O) 23 TMAO trehalose - 4:1:8(H2O) 18 TMAO xylitol - 1:1:4(H2O) 24 TMAO guanidine HCl - 1:1:2(H2O) 18 TMAO arginine - 15:4:56(H2O) 37 sarcosine urea - 2:5:9(H2O) 25 sarcosine guanidine HCl - 2:5:11(H2O) 23 sarcosine arginine 3:2:19(H2O) 36 sarcosine glycerol - 1:2:4(H2O) 20 GPC urea - 1:2:1.5(H2O) 7 GPC guanidine HCl - 1:2:1(H2O) 4 GPC arginine - 11:4:80(H2O) 30 DMSP HCl urea - 1:2:2(H2O) 11 DMSP HCl guanidine HCl - 1:1:3(H2O) 17 DMSP HCl arginine - 5:4:45(H2O) 37 DMSP HCl glycerol 1:2:5(H2O) 20 glycerol sorbitol - 2:1 - proline guanidine HCl - 2:1:8(H2O) 30 proline arginine - 2:1:11(H2O) 33 ectoine urea - 1:2:2(H2O) 12 ectoine guanidine HCl - 1:2:3(H2O) 14 ectoine arginine - 2:1:10(H2O) 30 ectoine glycerol - 1:2:4.5(H2O) 20 sorbitol urea - 2:3:1(H2O) 3 sorbitol guanidine HCl - 2:3:1(H2O) 3 sucrose urea - 4:1:8(H2O) 9 sucrose guanidine HCl - 2:1:12 (H2O) 23 sucrose arginine - 5:2:16(H2O) 12 betaine sorbitol guanidine HCl 1:1.2:1:7(H2O) 23 betaine sorbitol glycerol 1:1:2 - betaine taurine glycerol 1:1:3 - betaine ectoine glycerol 1:2:3 - betaine ectoine sorbitol 1:2:3:5(H2O) 9 TMAO urea glycerol 1:2:2:2(H2O) 8 TMAO guanidine HCl glycerol 1:1:2:2(H2O) 9 TMAO urea sorbitol 1:2:2:2(H2O) 6 TMAO guanidine HCl sorbitol 1:1:2:2 (H2O) 6 TMAO betaine urea 1:1:2:2(H2O) 10 TMAO betaine guanidine HCl 1:1:2:6(H2O) 21 fructose glucose guanidine HCl 1:1:2:1 4 fructose glycerol guanidine HCl 2:1:1:1(H2O) 4 glucose glycerol guanidine HCl 2:1:1:6(H2O) 16 glucose trehalose urea 1:1:2:3(H2O) 7 glucose trehalose guanidine HCl 1:1:1:3(H2O) 8 sorbitol glycerol guanidine HCl 1:1:2 - trehalose glucose glycerol 1:1:5 - trehalose glucose sorbitol 1:1:4:13(H2O) 20 trehalose proline glycerol 1:1:4:8 (H2O) 15 trehalose ectoine glycerol 1:1:4:6 (H2O) 11 proline glycerol sorbitol 1:1:1:3(H2O) 12 In the most preferred embodiments of the invention the multicomponent DESs that comprise at least four components comprise the components in combinations and ratios as given in the Table 5 below. Table 5. Exemplary embodiments of the multi-component deep eutectic solvents comprising naturally occurring osmolytes Water Components Components molar ratio content 1 2 3 4 5 6 (wt. %) Betaine GPC Sorbitol Taurine Urea - 1:2.8:3.1:0.1:7.1:1(H2O) 7 Betaine GPC Sorbitol Inositol Urea - 1:0.7:0.7:0.9:7.1:3.5H2O) 38 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.2:0.6:8.1:3(H2O) 30 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.5:0.4:8.3:2.5(H2O) 21 Betaine Glycerol Sorbitol Ectoine - - 1:4:2:1:14(H2O) 20 TMAO Betaine Taurine Urea - - 1:0.1:0.1:1.5:5(H2O) 34 TMAO Betaine Taurine Urea - - 1:6:0.5:15:9(H2O) 9 TMAO Betaine Sorbitol α-alanine Taurine Urea 1:0.1:0.05:0.1:0.05:2:2(H2O 14 TMAO Betaine Inositol α-alanine Urea - 1:0.1:0.05:0.2:1:5 (H2O) 37 TMAO Inositol Urea α-alanine - - 1:0.05:1:0.2:5(H2O) 37 Trehalose Proline Glycerol Sorbitol - - 1:1:4:1:14(H2O) 20 Examples Example 1: Preparation of exemplary DESs according to the invention In order to test the prepared DESs according to the invention and preferred embodiments as well as to show their capacity to stabilize biomolecules, a group of multi-component DESs was prepared according to the combinations and ratios given in the table 6 below. Table 6: Multiple-component DESs Water Components DES Components content molar ratio (wt. %) 20 ChCl:Gly ChCl:Glycerol 1:2 40 Bet:U Betaine:Urea 1:1 20 TMAO:Gly TMAO:Glycerol 1:2 40 20 Sar:Gly Sarcosine:Glycerol 1:2 40 20 DMPS:Gly DMSP:Glycerol 1:2 40 20 Ect:Gly Ectoine:Glycerol 1:2 40 Bet:Sor:Tau:GPC:U Betaine:Sorbitol:Taurine:GPC:Urea 1:3.1:0.1:2.8:7.1 20 TMAO:Bet:Tau:U TMAO:Betaine:Taurine:Urea 1:0.1:0.1:1.5 20 Bet:Gly:Sor Betaine:Glycerol:Sorbitol 1:1:2 20 Bet:Gly:Sor:Ect Betaine:Glycerol:Sorbitol:Ectoine 1:4:2:1 20 Treh:Pro:Gly:Sor Trehalose:Proline:Glycerol:Sorbitol 1:1:4:1 20 Treh:Pro:Gly:Sor Trehalose:Proline:Glycerol:Sorbitol 1:1:4:1 40 The DESs were prepared by calculating the appropriate amount of each component, adding it to a mixture and heating at a temperature up to 60 °C to obtain a liquid solution that was used in further experiments. Example 2: Lysozyme stabilization at 25 °C by selected DESs prepared in example 1 Lysozyme activity was determined according to the method of Shugar et al. (1952, Biochim Biophys Acta 8: 302–9), which is based on the decrease in turbidity of the substrate, Micrococcus lysodeikticus, in a suspension. Lysozyme solutions at a concentration of 0.1 mg ml-1 were prepared in different DESs and in 10 mM sodium phosphate buffer solution (pH 7). The solutions were incubated at different temperatures (25, 45, 70°C) for 1, 3, 5 and 7 days (Examples 2 and 3) or 15, 60 and 120 min (Example 4). Briefly, to 525µl of 10 mM sodium phosphate buffer solution (pH 7) in a plastic disposable cuvette 30 µl of Micrococcus lysodeikticus bacteria suspension in sterile PBS buffer (7 mg ml- 1) and 30 µl of the lysozyme solution were added. Immediately after mixing, the cuvette was placed in a UV/VIS spectrophotometer and the absorbance was measured at a wavelength of 450 nm over a period of linear turbidity decline. The relative activity (%) was calculated from the initial reaction rate obtained by the enzyme (calculated from ∆A450 min-1) after incubation, compared to the one obtained without previous exposure. Table 7: Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 25°C for 1, 3, 5 and 7 days. Results are presented as residual activity - relative to the enzyme activity prior incubation (%). Residual activity (%) after incubation for DESs Water 1 day 3 days 5 days 7 days content Control 1 (phosphate buffer) 89.4 78.4 77.2 75.4 Control 2: Stabilizing 20 95.3 86.6 85.3 81.6 medium for lysozyme (ChCl:Gly 1:2) Sar:Gly 1:2 20 97.3 84.1 90.3 95.8 Sar:Gly 1:2 40 102.9 93.3 100.2 108.8 DMSP:Gly 1:2 20 92.2 95.4 100.0 95.3 Ectoine: Gly 1:2 40 99.2 102.9 103.6 109.8 Bet : Sor : Tau : GPC : U 20 NA 94.9 95.3 96.2 Bet : Gly : Sor 20 NA 91.8 92.4 93.2 Bet : Gly : Sor : Ect 20 NA 110.0 105.4 101.5 NA= not analyzed As can be seen from the table, DESs comprising sarcosine and glycerol in any water content enabled higher residual lysozyme activity in comparison to both controls, especially after 5 and 7 days. The effect was more pronounced in the composition with higher water content. Similar values as for Sar:Gly 40 were observed for the DESs containing DMSP and glycerol, the DESs containing betaine, sorbitol, GPC, urea and taurine, and the DESs containing betaine, sorbitol and glycerol. Presence of ectoine is, however, the most preferred for lysozyme stabilization, as all analysed DESs comprising ectoine showed more than 100% residual activity, even after one week. These results suggest that the prepared DESs in all their variability stabilize lysozyme stored at 25 °C in a significantly better and longer-lasting manner than the currently known best stabilizing medium containing ChCl and glycerol. Example 3: Lysozyme stabilization at 45 °C by selected DESs prepared in example 1 The experiment was performed in the same manner as described for Example 2, except that the incubation temperature was 45 °C. Table 8: Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 45°C for 1, 3, 5 and 7 days. Results are presented as residual activity - relative to the enzyme activity prior incubation (%). Residual activity (%) after incubation for DESs Water 1 day 3 days 5 days 7 days content Control 1 (phosphate buffer) 66.3 55.9 50.3 50.2 Control 2 (ChCl:Gly 1:2) 20 85.4 79.7 81.2 79.3 Sar:Gly 20 99.5 102.4 99.4 103.3 Sar:Gly 40 102.7 115.4 114.3 106.7 DMSP:Gly 20 93.3 100.3 102.4 106.7 Ectoine: Gly 40 99.2 99.7 102.4 105.0 Bet : Sor : Tau : GPC : U 20 NA 89.7 88.3 86.2 Bet : Gly : Sor 20 NA 130.8 110.3 108.2 Bet : Gly : Sor : Ect 20 NA 99.5 96.3 86.7 The results presented in table 8 indicate that all DESs enabled significantly higher residual lysozyme activity in comparison to both controls, even after 1 day, but especially after 5 and 7 days. Many of residual activities were higher than 100%, in accordance with previous observations (Delorme et al., 2020: doi: 10.1016/j.ijbiomac.2020.07.022; Kaar et al., 2022; J. AM. CHEM. SOC. 2003, 125, 4125-4131; Varriale et al., 2022: 10.1021/acssuschemeng.1c07104) Overall, these results suggest that the prepared DESs in all their variability stabilize lysozyme stored at 45 °C in a significantly better and longer-lasting manner than the currently known best stabilizing medium containing ChCl and glycerol. Example 4: Lysozyme stabilization at 70 °C by selected DESs prepared in example 1 The experiment was performed in the same manner as described for Example 2, except that the incubation temperature was 70 °C and incubation times were 15, 60 and 120 minutes, respectively. Table 9: Incubation of lysozyme in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 70°C (heat shock) for 15-, 60- or 120-min. Results are presented as residual activity - relative to the enzyme activity prior incubation (%). Residual activity (%) after incubation for DESs Water 15 minutes 60 minutes 120 minutes content Control 1 (phosphate buffer) 83.9 69.2 59.8 Control 2 (ChCl:Gly 1:2) 20 87.2 79.7 69.6 TMAO:Gly 40 109.2 105.5 78.9 Sar:Gly 20 84.4 83.0 80.3 Sar:Gly 40 103.8 102.9 100.3 DMSP:Gly 20 106.8 103.3 103.4 Ectoine: Gly 40 112.7 110.6 96.4 Bet : Sor : Tau : GPC : U 20 94.2 87.9 85.2 Bet : Gly : Sor 20 110.1 115.0 105.6 Bet : Gly : Sor : Ect 20 84.6 77.1 77.1 The results presented in table 9 suggest that all DESs enabled significantly higher resistance of lysozyme to heat shock in comparison to both controls. Many of residual activities were higher than 100%. The pronounced stabilization effect was least significant for the DESs containing sarcosine and glycerol as well as for the DESs consisting of betaine, glycerol, sorbitol and ectoine. These results suggest that the prepared DESs in all their variability stabilize lysozyme treated at 70 °C in a significantly better manner than the currently known media, whereas some of DESs exhibit better function at lower temperatures, while some are better for protection against heat shock. Example 5: Yeast alcohol dehydrogenase (YADH) stability by selected DESs prepared in example 1 YADH activity was determined according to the method of Walker et al. (Doi: 10.1016/0307- 4412(92)90021-D). YADH solutions at a concentration of 0.4 mg ml-1 were prepared in different DESs and in glycine-pyrophosphate buffer (pH 9). The solutions were incubated at different temperatures (25 and 45°C) for 2, 5, 8, 24 and 48 h (at 25°C) or 1, 2, 4, 8 and 24 h (at 45°C). Briefly, to 975 µl of glycine-pyrophosphate buffer (pH 9) in a plastic disposable cuvette 5 µl of NAD+ in PBS buffer (50 mg ml-1), 10 µl of ethanol (96%) and 10 µl of the YADH solution were added. Immediately after mixing, the cuvette was placed in a UV/VIS spectrophotometer and the absorbance was measured at a wavelength of 340 nm for 2 minutes. The relative activity (%) was calculated from the initial reaction rate obtained by the enzyme (calculated from ∆A340 min-1) after incubation, compared to the one obtained without previous exposure. Table 10: Incubation of YADH in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 25°C for 2, 5, 8, 24 and 48 hours, respectively. Results are presented as residual activity - relative to the enzyme activity prior incubation (%). Residual activity (%) after incubation at 25°C for DESs Water 2 h 5 h 8 h 24 h 48 h content Control 1 (phosphate buffer) 95.5 51.5 34.0 8.4 0 Control 2 (ChCl:Gly 1:2) 40 55.0 50.8 2.17 0 0 Sar:Gly 20 112,6 123,9 110.2 50.7 95.2 Sar:Gly 40 76.6 96.7 105.5 98.2 95.2 Treh:Ect:Gly 20 80.9 90.5 82.8 26.8 0 Treh:Ect:Gly 40 135.0 123.2 78.6 13.6 17.2 Treh:Pro:Gly:Sor 20 77.6 71.4 62.1 51.1 57.8 Treh:Pro:Gly:Sor 40 83.3 78.5 63.3 47.6 0 Table 11: Incubation of YADH in different DES and 10 mM sodium phosphate buffer solution (pH 7) at 45°C for 1, 2, 4, 8, and 24 hours, respectively. Results are presented as residual activity - relative to the enzyme activity prior incubation (%). Residual activity (%) after incubation at 45°C for DESs Water 1 h 2 h 4 h 8 h 24 h content Control 1 (phosphate buffer) 0 0 0 0 0 Control 2 (ChCl:Gly 1:2) 20 2.1 0 0 0 0 40 1.7 Sar:Gly 20 136.9 138.6 66.9 34.4 11.3 Sar:Gly 40 93.8 88.8 72.7 40.6 4.2 Treh:Ect:Gly 40 39.8 3.5 0 0 0 Bet:Sor:Tau:GPC:U 20 25.0 2.6 0 0 0 The results shown in tables 10 and 11 show that some DESs according to the invention can stabilize YADH to a higher degree than conventionally used buffers or stabilizing media. Among tested DES, exceptional stabilisation properties of Sar:Gly have been observed. Based on known results of other DES stabilization of other proteins as well as DNA and other biomolecules is expected. Due to presence of osmolytes in the DESs according to the invention, cryoprotection of cells and tissues is enabled with the invention.

Claims

Patent claims 1. A multicomponent deep eutectic solvent (DESs) comprising at least four components. 2. The multicomponent DESs according to claim 1, wherein at least one of the components of the DESs are selected in the group comprising naturally occurring osmolytes. 3. The multicomponent DESs according to claim 1 or 2, wherein the naturally occurring osmolytes are selected in the group comprising: − polyols and sugar polyols, for example glycerol, sorbitol, xylitol; − sugars and their derivatives, for example glucose, sucrose, trehalose; − amino acids and their derivatives, for example glycine, proline, ectoine, taurine; − methylamines, for example trimethylamine N-oxide (TMAO), sarcosine, betaine, glycerophosphocholine (GPC); − methylsulfonium compounds, for example dimethylsulfoniopropionate (DMSP); − Y-conjugated compounds, for example urea, guanidine and arginine. 4. A multicomponent deep eutectic solvent comprising at least two components, wherein at least one of the components is selected in the group consisting of ectoine, trimethylamine N-oxide (TMAO), sarcosine, glycerophosphocholine (GPC), dimethylsulfonopropionate (DMSP), guanidine, arginine, and taurine. 5. The multicomponent DESs according to claim 4, wherein the multicomponent DESs has at least three, preferably at least four components. 6. The multicomponent DESs according to any of the preceding claims, wherein remaining components of the multicomponent DESs are selected among common DES/IL compounds, such as methylamines, methylsulfonium compounds, organic acids, sugars, polyols, amino acids and Y-conjugated compounds. 7. The multicomponent DESs according to claim 6, wherein methylamines are selected from N-trimethylamine oxide (TMAO), betaine, glycerophosphocholine (GPC), carnitine, homarine, and derivatives thereof, for example, their halide forms, such as betaine halides (betaine HCl).
8. The multicomponent DESs according to claim 6, wherein methyl sulfonium compound is dimethylsulfonopropionate (DMSP). 9. The multicomponent DESs according to claim 6, wherein organic acids are selected in the group comprising: levulinic acid, lactic acid, malic acid, maleic acid, pyruvic acid, fumaric acid, succinic acid, citric acid, citraconic acid, glutaric acid, glycolic acid, acetic acid, aconitic acid, tartaric acid, ascorbic acid, malonic acid, oxalic acid, glucuronic add, neuraminic acid, sialic acid, shikimic acid, phytic acid, galacturonic acid, iduronic acid, hyaluronic acid, hydroxycitric acid, lactone derivatives and derivatives thereof. 10. The multicomponent DESs according to claim 6, wherein sugars are selected in the group comprising: trehalose, glucose, sucrose, lactose, ribose, galactose, fructose, etc. and derivatives thereof. 11. The multicomponent DESs according to claim 6, wherein polyols are selected in the group comprising: glycerol, erythritol, mannitol, sorbitol, xylitol, ethylene glycol, propylene glycol, ribitol, aldonitol, propanediol, inositol, pentylene glycol, and derivatives thereof, such as o- methyl-inositol. 12. The multicomponent DESs according to claim 6, wherein amino acids are selected in the group comprising: glycine, proline, taurine, lysine, etc. and derivatives thereof, such as ectoine, sarcosine, theanine, dimethyglycine and similar. 13. The multicomponent DESs according to claim 6, wherein Y-conjugated compounds are selected in the group comprising: urea, guanidine, arginine and compounds that incorporate the guanidino moiety, such as creatine, glycocyamine, agmatine, 4- guanidinobutanoic acid, and derivatives thereof, such as guanidinium halides, for example guanidine HCl. 14. The multicomponent DESs according to any of the preceding claims, wherein the molar ratio of each DES component with respect to the total moles of the DES may range from 0.001 to 0.9. 15. The multicomponent DESs according to any of the preceding claims, wherein the DESs also comprises water. 16. The multicomponent DESs according to claim 15, wherein the amount of water used in the DESs is from 0% to 90%, as from about 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.5, 1, 5, 10, 15, 20, 30 or about 40% to about 90, 80, 70, 60 or about 50%. 17. The multicomponent DESs according to claim 16, wherein the amount of water used in from about 5% to about 30%, such as about 10%, 20% 25% or about 30%. 18. The multicomponent DESs according to any of the preceding claims, wherein the DESs as prepared is diluted. 19. The multicomponent DESs according to any of the preceding claims, wherein the multicomponent DESs is selected in the group consisting of: Components Water 1 2 3 betaine arginine - yes betaine guanidine HCl - yes TMAO urea - yes TMAO glycerol - yes TMAO sorbitol - yes TMAO glucose - yes TMAO trehalose - yes TMAO xylitol - yes TMAO guanidine HCl - yes TMAO arginine - yes sarcosine urea - yes sarcosine guanidine HCl - yes sarcosine arginine yes sarcosine glycerol - yes GPC urea - yes GPC guanidine HCl - yes GPC arginine - yes DMSP HCl urea - yes DMSP HCl guanidine HCl - yes DMSP HCl arginine - yes DMPS HCl glycerol - yes glycerol sorbitol - no proline guanidine HCl - yes proline arginine - yes ectoine urea - yes ectoine guanidine HCl - yes ectoine arginine - yes ectoine glycerol - yes sorbitol urea - yes sorbitol guanidine HCl - yes sucrose urea - yes sucrose guanidine HCl - yes sucrose arginine - yes betaine sorbitol guanidine HCl yes betaine taurine glycerol no betaine ectoine glycerol no betaine ectoine sorbitol yes TMAO urea glycerol yes TMAO guanidine HCl glycerol yes TMAO urea sorbitol yes TMAO guanidine HCl sorbitol yes TMAO betaine urea yes TMAO betaine guanidine HCl yes fructose glucose guanidine HCl yes fructose glycerol guanidine HCl yes glucose glycerol guanidine HCl yes glucose trehalose urea yes glucose trehalose guanidine HCl yes sorbitol glycerol guanidine HCl no trehalose glucose glycerol no trehalose glucose sorbitol yes trehalose proline glycerol yes trehalose ectoine glycerol yes proline glycerol sorbitol yes 20. The multicomponent DESs according to any of the preceding claims, wherein the multicomponent DESs is selected in the group consisting of: Water Components Components content molar ratio (wt. %) 1 2 3 betaine arginine - 5:1:28(H2O) 40 betaine guanidine HCl - 1:2:3(H2O) 17 TMAO urea - 1:1:3.5(H2O) 33 TMAO glycerol - 1:1:2(H2O) 17 TMAO sorbitol - 1:1:2(H2O) 12 TMAO glucose - 5:2:12(H2O) 23 TMAO trehalose - 4:1:8(H2O) 18 TMAO xylitol - 1:1:4(H2O) 24 TMAO guanidine HCl - 1:1:2(H2O) 18 TMAO arginine - 15:4:56(H2O) 37 sarcosine urea - 2:5:9(H2O) 25 sarcosine guanidine HCl - 2:5:11(H2O) 23 sarcosine arginine 3:2:19(H2O) 36 sarcosine glycerol - 1:2:4(H2O) 20 GPC urea - 1:2:1.5(H2O) 7 GPC guanidine HCl - 1:2:1(H2O) 4 GPC arginine - 11:4:80(H2O) 30 DMSP HCl urea - 1:2:2(H2O) 11 DMSP HCl guanidine HCl - 1:1:3(H2O) 17 DMSP HCl arginine - 5:4:45(H2O) 37 DMSP HCl glycerol 1:2:5(H2O) 20 glycerol sorbitol - 2:1 - proline guanidine HCl - 2:1:8(H2O) 30 proline arginine - 2:1:11(H2O) 33 ectoine urea - 1:2:2(H2O) 12 ectoine guanidine HCl - 1:2:3(H2O) 14 ectoine arginine - 2:1:10(H2O) 30 ectoine glycerol - 1:2:4.5(H2O) 20 sorbitol urea - 2:3:1(H2O) 3 sorbitol guanidine HCl - 2:3:1(H2O) 3 sucrose urea - 4:1:8(H2O) 9 sucrose guanidine HCl - 2:1:12 (H2O) 23 sucrose arginine - 5:2:16(H2O) 12 betaine sorbitol guanidine HCl 1:1.2:1:7(H2O) 23 betaine sorbitol glycerol 1:1:2 - betaine taurine glycerol 1:1:3 - betaine ectoine glycerol 1:2:3 - betaine ectoine sorbitol 1:2:3:5(H2O) 9 TMAO urea glycerol 1:2:2:2(H2O) 8 TMAO guanidine HCl glycerol 1:1:2:2(H2O) 9 TMAO urea sorbitol 1:2:2:2(H2O) 6 TMAO guanidine HCl sorbitol 1:1:2:2 (H2O) 6 TMAO betaine urea 1:1:2:2(H2O) 10 TMAO betaine guanidine HCl 1:1:2:6(H2O) 21 fructose glucose guanidine HCl 1:1:2:1 4 fructose glycerol guanidine HCl 2:1:1:1(H2O) 4 glucose glycerol guanidine HCl 2:1:1:6(H2O) 16 glucose trehalose urea 1:1:2:3(H2O) 7 glucose trehalose guanidine HCl 1:1:1:3(H2O) 8 sorbitol glycerol guanidine HCl 1:1:2 - trehalose glucose glycerol 1:1:5 - trehalose glucose sorbitol 1:1:4:13(H2O) 20 trehalose proline glycerol 1:1:4:8 (H2O) 15 trehalose ectoine glycerol 1:1:4:6 (H2O) 11 proline glycerol sorbitol 1:1:1:3(H2O) 12 21. The multicomponent DESs according to any of the preceding claims, wherein the multicomponent DESs is selected in the group consisting of: Water Components Components molar ratio content 1 2 3 4 5 6 (wt. %) Betaine GPC Sorbitol Taurine Urea - 1:2.8:3.1:0.1:7.1:1(H2O) 7 Betaine GPC Sorbitol Inositol Urea - 1:0.7:0.7:0.9:7.1:3.5H2O) 38 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.2:0.6:8.1:3(H2O) 30 Betaine GPC Sorbitol Inositol Urea - 1:0.9:1.5:0.4:8.3:2.5(H2O) 21 Betaine Glycerol Sorbitol Ectoine - - 1:4:2:1:14(H2O) 20 TMAO Betaine Taurine Urea - - 1:0.1:0.1:1.5:5(H2O) 34 TMAO Betaine Taurine Urea - - 1:6:0.5:15:9(H2O) 9 TMAO Betaine Sorbitol α-alanine Taurine Urea 1:0.1:0.05:0.1:0.05:2:2(H2O 14 TMAO Betaine Inositol α-alanine Urea - 1:0.1:0.05:0.2:1:5(H2O) 37 TMAO Inositol Urea α-alanine - - 1:0.05:1:0.2:5(H2O) 37 Trehalose Proline Glycerol Sorbitol - - 1:1:4:1:14(H2O) 20 22. A method for preparation of DESs according to any of the preceding claims, said method comprising the following steps: a) mixing components in required molar ratios, and b) stirring and heating the mixtures up to 60°C until a colourless and homogeneous liquid is formed. 23. Use of the multi-component DESs according to any of the preceding claims in: − stabilization of biomolecules, − preservation of biological systems, − pharmaceutical preparations, such as pharmaceutical excipients and similar components, − cosmetics, − food industry, and − preparation of extracts, wherein the DESs is optionally a component of the final extract. 24. A medium for stabilization of biomolecules or preservation biological systems comprising the DESs according to any of the preceding claims.
25. The method according to claim 24, wherein the biological system is an organism, an organ, an organelle, a cell or a tissue or an engineered construct. 26. The method according to claim 24, wherein the biomolecule is selected in the group comprising. cell components, proteins, enzymes, antibodies, peptides and other molecules consisting of aminoacids or aminoacid derivatives, polysaccharides, biopolymers, lipids, supramolecular structures containing lipids, nucleotides, nucleosides and their precursors and derivatives, polynucleotides of any length, sense and molecular weight and composition, DNA and RNA. 27. A method for stabilization of biomolecules or for preservation of biological systems comprises at least a step in which the biomolecule or the biological system are exposed to the above-mentioned medium. 28. The method according to claim 27, wherein the biological system is an organism, an organ, an organelle, a cell or a tissue or an engineered construct. 29. The method according to claim 27, wherein the biomolecule is selected in the group comprising. cell components, proteins, enzymes, antibodies, peptides and other molecules consisting of amino acids or amino acid derivatives, polysaccharides, biopolymers, lipids, supramolecular structures containing lipids, nucleotides, nucleosides and their precursors and derivatives, polynucleotides of any length, sense and molecular weight and composition, DNA and RNA.
PCT/EP2024/055165 2023-03-01 2024-02-28 Multicomponent deep eutectic solvents, their preparation and use Pending WO2024180161A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EPPCT/EP2023/055248 2023-03-01
EP2023055248 2023-03-01

Publications (1)

Publication Number Publication Date
WO2024180161A1 true WO2024180161A1 (en) 2024-09-06

Family

ID=90368117

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/055165 Pending WO2024180161A1 (en) 2023-03-01 2024-02-28 Multicomponent deep eutectic solvents, their preparation and use

Country Status (1)

Country Link
WO (1) WO2024180161A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119367269A (en) * 2024-10-16 2025-01-28 四川大学 A self-assembled eutectoid gel with cell permeability and multiple anti-inflammatory effects, and its preparation method and application
KR102827958B1 (en) * 2025-04-09 2025-07-03 주식회사 로우맵 Hyaluronic acid nanocapsules for promoting skin absorption, method for producing the same, and cosmetic composition containing the same

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017134190A1 (en) 2016-02-05 2017-08-10 F. Hoffmann-La Roche Ag Thiol-based deep eutectic solvent
EP3485874A1 (en) 2017-11-17 2019-05-22 SeraNovo B.V. Method of preparing a natural deep eutectic solvent (nades)-active ingredient system; a nades-, and preferably a polymeric precipitation inhibitor containing nades-, based drug formulation technology and development method
EP3870227A2 (en) 2018-10-24 2021-09-01 SeraNovo B.V. Deep eutectic solvent platform for oral pharmaceutical formulations
EP3971230A1 (en) 2020-09-16 2022-03-23 Fundación Tecnalia Research & Innovation Deep eutectic solvents, uses thereof, and method for preparing a lignin prepolymer based on the deep eutectic solvents
US20220305401A1 (en) 2019-06-20 2022-09-29 Givaudan Sa Eutectic extraction of solids

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017134190A1 (en) 2016-02-05 2017-08-10 F. Hoffmann-La Roche Ag Thiol-based deep eutectic solvent
EP3485874A1 (en) 2017-11-17 2019-05-22 SeraNovo B.V. Method of preparing a natural deep eutectic solvent (nades)-active ingredient system; a nades-, and preferably a polymeric precipitation inhibitor containing nades-, based drug formulation technology and development method
EP3870227A2 (en) 2018-10-24 2021-09-01 SeraNovo B.V. Deep eutectic solvent platform for oral pharmaceutical formulations
US20220305401A1 (en) 2019-06-20 2022-09-29 Givaudan Sa Eutectic extraction of solids
EP3971230A1 (en) 2020-09-16 2022-03-23 Fundación Tecnalia Research & Innovation Deep eutectic solvents, uses thereof, and method for preparing a lignin prepolymer based on the deep eutectic solvents

Non-Patent Citations (33)

* Cited by examiner, † Cited by third party
Title
BENLEBNA, M ET AL., JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 66, 2018
DAI ET AL., ANAL. CHIM. ACTA, vol. 766, 2013, pages 61 - 68
ESQUEMBRE ET AL., PHYS. CHEM. CHEM. PHYS., vol. 15, 2013, pages 11248 - 11256
FAGGIAN, M ET AL., MOLECULES, vol. 21, 2016, pages 1 - 11
FAREEDA CHEMAT: "Thermal and physical properties of (Choline chloride + urea +l-arginine) deep eutectic solvents", JOURNAL OF MOLECULAR LIQUIDS, vol. 218, 1 June 2016 (2016-06-01), NL, pages 301 - 308, XP093168003, ISSN: 0167-7322, DOI: 10.1016/j.molliq.2016.02.062 *
HANSEN ET AL., CHEM. REV., vol. 121, 2021, pages 1232 - 1285
ILGENKONIG, GREEN CHEM, vol. 11, 2009, pages 848 - 85
JELINSKI TOMASZ ET AL: "Application of a computational model of natural deep eutectic solvents utilizing the COSMO-RS approach for screening of solvents with high solubility of rutin", JOURNAL OF MOLECULAR MODELING, SPRINGER BERLIN HEIDELBERG, BERLIN/HEIDELBERG, vol. 24, no. 7, 27 June 2018 (2018-06-27), pages 1 - 17, XP036545630, ISSN: 1610-2940, [retrieved on 20180627], DOI: 10.1007/S00894-018-3700-1 *
JESUS ET AL., CRYOBIOLOGY, vol. 101, 2021, pages 95 - 104
KAAR ET AL., J. AM. CHEM. SOC., vol. 125, 2003, pages 4125 - 4131
KARADENDROU ET AL., CATALYSTS, vol. 12, 2022
LEE ET AL., J. IND. ENG. CHEM., vol. 65, 2018, pages 343 - 348
LIANG, Y ET AL., BIORESOUR. TECHNOL, vol. 310, 2020, pages 123389
MA CHUNYAN ET AL: "Development of Low-Cost Deep Eutectic Solvents for CO2Capture", ENERGY PROCEDIA, ELSEVIER, NL, vol. 142, 31 January 2018 (2018-01-31), pages 3320 - 3325, XP085334990, ISSN: 1876-6102, DOI: 10.1016/J.EGYPRO.2017.12.464 *
NARDECCHIA ET AL., BIOMACROMOLECULES, vol. 13, no. 7, 2012, pages 2029 - 2036
PAL ET AL., J. PHYS. CHEM. B, vol. 124, 2020, pages 7598 - 7610
PANIC, M ET AL., WASTE MANAG, vol. 120, 2021, pages 340 - 350
PEDRO, S. N ET AL., PHARMACEUTICS, vol. 14, 2022, pages 827
PENGFEI LIU: "Ternary deep eutectic solvents catalyzed d-glucosamine self-condensation to deoxyfructosazine: NMR study", GREEN ENERGY & ENVIRONMENT, vol. 6, no. 2, 1 April 2021 (2021-04-01), pages 261 - 270, XP093168161, ISSN: 2468-0257, DOI: 10.1016/j.gee.2020.04.010 *
RAHMAN MD SAJJADUR ET AL: "Formulation, structure, and applications of therapeutic and amino acid-based deep eutectic solvents: An overview", JOURNAL OF MOLECULAR LIQUIDS, ELSEVIER, AMSTERDAM, NL, vol. 321, 10 November 2020 (2020-11-10), XP086425066, ISSN: 0167-7322, [retrieved on 20201110], DOI: 10.1016/J.MOLLIQ.2020.114745 *
SANCHEZ-FERNANDEZ ET AL., GREEN CHEM., vol. 24, 2022, pages 4437 - 4442
SHUGAR ET AL., BIOCHIM BIOPHYS ACTA, vol. 8, 1952, pages 302 - 9
SHU-XIAN ZHU: "Equimolar CO Capture by Cuprous-Based Quaternary Deep Eutectic Solvents", INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, vol. 62, no. 6, 1 February 2023 (2023-02-01), pages 2937 - 2943, XP093168250, ISSN: 0888-5885, Retrieved from the Internet <URL:https://pubs.acs.org/doi/pdf/10.1021/acs.iecr.2c04620> DOI: 10.1021/acs.iecr.2c04620 *
SIMEONOVAFONSO, RSC ADV, vol. 6, 2016, pages 5485 - 5490
SIMILARLYBANERJEE ET AL., ADV. HEALTHCARE MATER, vol. 6, 2017, pages 1601411
SUT, S ET AL., MOLECULES, vol. 22, 2017, pages 1 - 11
SYAKFANAYA ET AL., PHARMACOGN. J, vol. 11, 2019, pages 267 - 271
VANDA ET AL.: "Natural deep eutectic solvents: From their discovery to their applications", IN DEEP EUTECTIC SOLVENTS: SYNTHESIS, PROPERTIES, AND APPLICATIONS, vol. 61, 2019, pages 81
YADAV ET AL., ACS SUSTAINABLE CHEM. ENG., vol. 8, 2020, pages 10151 - 10160
YANCEYSOMERO, BIOCHEM. J., vol. 183, 1979, pages 317 - 323
ZDANOWICZ, INT. J. BIOL. MACROMOL, vol. 176, 2021, pages 387 - 393
ZENG ET AL., J. MOL. LIQ, vol. 219, 2016, pages 74 - 78
ZHONG, L ET AL., BIORESOUR. TECHNOL, vol. 343, 2022, pages 126022

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119367269A (en) * 2024-10-16 2025-01-28 四川大学 A self-assembled eutectoid gel with cell permeability and multiple anti-inflammatory effects, and its preparation method and application
KR102827958B1 (en) * 2025-04-09 2025-07-03 주식회사 로우맵 Hyaluronic acid nanocapsules for promoting skin absorption, method for producing the same, and cosmetic composition containing the same

Similar Documents

Publication Publication Date Title
WO2024180161A1 (en) Multicomponent deep eutectic solvents, their preparation and use
US12274739B2 (en) Pharmaceutical liquid composition of botulinum toxin with improved stability
RU2640922C1 (en) Lyophilised preparation of botulinum toxin
Reslan et al. Ionic liquids as biocompatible stabilizers of proteins
Wlodarczyk et al. Influence and effect of osmolytes in biopharmaceutical formulations
JP5599778B2 (en) Liquid buffered GDF-5 formulation
FR2719479A1 (en) Lyophilized stable formulation comprising a protein: assay kit.
Bubalo et al. Natural multi-osmolyte cocktails form deep eutectic systems of unprecedented complexity: discovery, affordances and perspectives
JP2006182750A (en) Freeze-dried cosmetic and method for producing the same
CN110200899A (en) A kind of preservative and its preparation method and application
CN101602799A (en) A rapid preparation method of native antibacterial polypeptide in chickpea
WO2007097652A2 (en) Synthetic mannosylglycerate derivatives for the stabilisation and preservation of biomaterials
CA2288649A1 (en) Stable pharmaceutical administration forms of peptides, proteins and nucleic acids
CN121218976A (en) Multicomponent eutectic solvents, their preparation and uses
US11110176B2 (en) Composition and method for the protection of proteins, cell components and cells during temperature stress
US8911790B2 (en) Solid composition containing a hypothiocyanite salt
JPH03168075A (en) Ethanol preparation for food preservation
Madsen et al. The use of surfactants to solubilise a glucagon analogue
Attanasio et al. Trehalose effects on α-crystallin aggregates
Guncheva Role of ionic liquids on stabilization of therapeutic proteins and model proteins
CN111329862B (en) Tetrahydropyrimidine and ethanol compound disinfectant and preparation method and application thereof
JP2009203223A (en) Protectant for freeze drying and production method of physiologically active substance
JP4707811B2 (en) Dehydration stress protective agent
CN101450205A (en) Pig fusion protein preparation
Kumar et al. Effect of concentration and temperature variations on interactions in (L-serine/L-valine+ aqueous glucose/sucrose/lactose) systems: Viscometric and activation parametric study

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24712775

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2024712775

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2024712775

Country of ref document: EP

Effective date: 20251001

ENP Entry into the national phase

Ref document number: 2024712775

Country of ref document: EP

Effective date: 20251001

ENP Entry into the national phase

Ref document number: 2024712775

Country of ref document: EP

Effective date: 20251001

ENP Entry into the national phase

Ref document number: 2024712775

Country of ref document: EP

Effective date: 20251001

ENP Entry into the national phase

Ref document number: 2024712775

Country of ref document: EP

Effective date: 20251001