Stable glassy material based on histidine, arginine and glutamic acid amino acids

Abstract

The present invention relates to a glassy material comprising at least one compound of formula (I), or a salt thereof, and at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material. The present invention further relates to methods for preparing said glassy material and to its use as a glue, as a cryoprotectant and / or thermal protectant for molecules and / or biological elements when the temperature is below the glass transition temperature of said glassy material, and for molding water-soluble glass structures with a micrometric to nanometric precision. The present invention further relates to a microneedle comprising a glassy material according to the present invention.

Description

STABLE GLASSY MATERIAL BASED ON HISTIDINE, ARGININE ANDGLUTAMIC ACID AMINO ACIDSFIELD OF INVENTION[1] The present invention relates to a glassy material comprising at least one compound of formula (I), or a salt thereof, and at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material. The present invention further relates to methods for preparing said glassy material and to its use as a glue, as a cryoprotectant and / or thermal protectant for molecules and / or biological elements when the temperature is below the glass transition temperature of said glassy material, and for molding water-soluble glass structures with a micrometric to nanometric precision. The present invention further relates to a microneedle comprising a glassy material according to the present invention wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.BACKGROUND OF INVENTION[2] Glassy materials like silica glasses are made of molecular networks joined by covalent bonding. On the opposite, some glassy materials are formed of molecules or polymers joined by non-covalent interactions. They are called supramolecular glasses. Among them, some low molecular weight supramolecular glasses are attractive because they are easier to purify than polymers. Additionally, their structure can be modified more easily to tune the properties of the material. However, they tend to have lower glass stability and therefore they crystallize faster over time. This drawback has hampered their exploitation in the fields that require long-lived amorphous phases such as organic electronics, photonics, and drug delivery.[3] Glassy material made of biological or biocompatible molecules are rare. Among glasses made of biological molecules, the most common molecules are sugars like sucrose or trehalose. These materials have been used for alimentation, pharmaceutical formulation, cryoprotection and also, in a few cases, as an encapsulation media for active principles and to form soluble microneedles for transdermal or intradermal drug administration. Intradermal drug administration may be preferred to subcutaneous drug administration which can be painful and not practical for the patient. In addition, the use of microneedles as drug carrier allows for a controlled release of the bioactive molecule. However, the biocompatibility and solubility of non-biological polymer-based microneedles remains a major drawback for their development. In addition, the inorganic monomers employed often cannot be produced through bioproduction.[4] Xing Ruirui et al. published March 17, 2023 discloses examples of glasses of biological origin fabricated using biologically derived amino acids or peptides through a heating-quenching procedure. However, their glassy material examples are limited to peptides and amino acids modified with specific C-terminal modification using acetyl (Ac-) and 9-fluorenyl-methyloxycarbonyl (Fmoc-) for amino acids, and benzyloxycarbonyl (Cbz-) groups for amino acids and peptides.[5] Therefore, there is a substantial need to develop a new type of glassy material based on natural molecules that displays high biocompatibility, easy customization and has a glass structure that is stable overtime.[6] The inventors of the present invention have surprisingly found a new type of glassy material which is made of amino acids and therefore has an increased biocompatibility. The glassy properties of the material allow precise molding and the fabrication of sharper edges for improved penetration of microneedles. By sharp edges, it is meant edges with tips as low as 300 nm. The glassy material according to the invention is also water-soluble and possesses a supramolecular glass structure that is stable overtime, notably stable for at least a week, or even at least 1 month, or even for at least 6 months, or even more for at least 1 year, even when the molecular weight of said material is low, thereby allowing its use as a long-lived amorphous phase for several applications. Said glassy material according to the invention comprises:a) at least one compound of formula (I):X1-B-X2 (formula (I)), or a salt thereof, whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn) and cysteine (L-Cys or D-Cys), or derivatives thereof and methionine sulfoxide (L-Met-SO or D-Met-SO) ; and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that:the compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present; and the compound of formula (I) is different from a homopolymer of poly-gamma- glutamic acid; and b) at least one polar solvent in a total content ranging from 0.1% to 30 % by weight relative to the total weight of the glassy material.[7] In addition, said glassy material according to the invention is versatile as it can be either viscoelastic or solid, depending on the total content of the at least one polar solvent present in said glassy material. When the total content of the at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, the glassy material is viscoelastic, displaying self-repairing properties. When such viscoelastic glassy material is stretched at low velocity it can form fibers. It can also be used as a water-soluble glue as it dries. When such viscoelastic glassy material is stretched at high velocity, it solidifies and can be used to form microneedles or rods. When the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, the glassy material is solid. In that case, it can be used for molding water-soluble glass structures with a micrometric to nanometric precision such as microneedles, hook needles, spiked microballs, well defined powder and optical lenses or it can be spread through spin coating as thin films with nanometric precision. The material can be used as a cryoprotectant and / or as a thermal protectant for molecules and / or biological elements when the temperature is below the glass transition temperature of said glassy material. The material can be stored at ambient temperature and ambient humidity. Preferably, it can be stored away from light in a dry and cold environment for better preservation and storage.SUMMARY[8] The present invention relates to a glassy material comprising: a) at least one compound of formula (I):X1-B-X2 (formula (I)), or a salt thereof, whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn) and cysteine (L-Cys or D-Cys), or derivatives thereof, and methionine sulfoxide (L-Met-SO or D-Met-SO) ; and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2;optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that: the compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present; and the compound of formula (I) is different from a homopolymer of poly-gamma- glutamic acid; and b) at least one polar solvent in a total content ranging from 0.1% to 30 % by weight relative to the total weight of the glassy material.[9] According to an embodiment, the glassy material comprises: a) at least one compound of formula (I):X1-B-X2 (formula (I)), or a salt thereof, whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof;at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof;B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; with the proviso that: the compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present; and the compound of formula (I) is different from a homopolymer of poly-gamma- glutamic acid; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

[0010] Advantageously, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge. The intramolecular bridge according to the present invention differs from a ring structure.

[0011] Advantageously, the glass transition temperature of the glassy material ranges from 50 °C to 150 °C and preferably from 70 °C to 130 °C.

[0012] Advantageously, the at least one polar solvent is chosen from water, polar organic solvents, and mixtures thereof; preferably from water, acetone, dimethylsulfoxide and mixtures thereof; and more preferably the polar solvent is water.

[0013] In one embodiment, the total content of the at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material.

[0014] In another embodiment, the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

[0015] Advantageously XI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D- Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Om or D-Orn) and cysteine (L-Cys or D-Cys); preferably from histidine (L- His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), ornithine ; and more preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), even more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu).

[0016] In another embodiment,, XI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L- Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys); preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu).

[0017] In one embodiment, B represents a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2, and the number of additional amino acids in the linear sequence of B ranges from 2 to 200; preferably from 2 to 150; and more preferably from 2 to 100.

[0018] In another embodiment, B represents a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2, and the number of additional amino acids in the linear sequence of B ranges from 201 to 700; preferably from 201 to 634.

[0019] In one embodiment, the additional amino acids of B are chosen from alanine (L- Ala or D-Ala), arginine (L-Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp orD-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His) or a derivative thereof, isoleucine (L-Ile or D-Ile), leucine (L-Leu or D-Leu), lysine (L-Lys or D-Lys), methionine (L-Met or D-Met), phenylalanine (L-Phe orD-Phe), proline (L-Pro or D-Pro), pyrrolysine (L-Pyl or D-Pyl), selenocysteine (L-Sec or D-Sec), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), carnitine (L-carnitine or D-carnitine), gamma-aminobutyric acid, hydroxyproline (Hyp), methionine sulfoxide (L-Met-SO or D-Met-SO), selenomethionine (L-SeMet or D-SeMet), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), beta-alanine, alpha-aminoisobutyric acid (Aib), alpha-aminobutyric (L-Abu or D-Abu), 3 -aminomethylbenzoic acid, anthranilic acid, homoarginine (L-Har or D-Har), delta-hydroxy-lysine (Hyl), 3 -mercaptophenylalanine (L-3 -mercaptophenylalanine or D- 3 -mercaptophenylalanine), 2 -hydroxyphenylalanine (L-2-hydroxyphenylalanine or D-2- hydroxyphenylalanine), 3 -hydroxyphenylalanine (L-3 -hydroxyphenylalanine or D-3- hydroxyphenylalanine), phenylglycine (L-Phg or D-Phg), homophenylalanine (L-Hph or D-Hph), beta-(2-pyridyl)-alanine (L-2Pal or D-2Pal), beta-(3-pyridyl)-alanine (L-3Pal or D-3Pal), 4-methyL-phenylalanine (L-4-methyL-phenylalanine or D-4-methyL- phenylalanine), 4-amino-phenylalanine (L-4-amino-phenylalanine or D-4-amino- phenylalanine), 2,3-diaminopropionic acid (L-Dap or D-Dap), 2,4-diaminobutyric acid (L-Dab or D-Dab), 3,4-dihydroproline (L-Dhp or D-Dhp), thiaproline (L-thiaproline or D-thiaproline), alpha-methylproline (L-alpha-methylproline or D-alpha-methylproline), pipecolic acid (L-pipecolic acid or D-pipecolic acid), alpha-aminoadipic acid (L-Aad or D-Aad), 2-aminoheptanedioic acid (L-2-aminoheptanedioic acid or D-2- aminoheptanedioic acid), 2-ami-noheptanedioic acid (L-2-ami-noheptanedioic acid or D- 2-ami-noheptanedioic acid), alpha-aminosuberic acid (L-ASU or D-ASU), and 3,4-dihydroxyphenylalanine (L-DOPA or D-DOPA), 4-(phenylazo)-phenylglycine (L-4- (phenylazo)-phenylglycine or D-4-(phenylazo)-phenylglycine), (4-phenylazo)- phenylalanine (L-(4-phenylazo)-phenylalanine or D-(4-phenylazo)-phenylalanine), (4- (4’-tert-Butoxycarbonyl)phenylazo)phenylalanine (L-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine or D-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine), azobenzyl-lysine (L-azobenzyl-lysine or D- azobenzyl-lysine), or derivatives thereof.

[0020] Advantageously, the additional amino acids of B are chosen from alanine (L-Ala or D-Ala), arginine (L-Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp or D-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His) or a derivative thereof, isoleucine (L-Ile or D-Ile), leucine (L-Leu or D-Leu), lysine (L-Lys or D-Lys), methionine (L-Met or D-Met), phenylalanine (L-Phe orD-Phe), proline (L-Pro or D-Pro), pyrrolysine (L-Pyl or D-Pyl), selenocysteine (L-Sec or D-Sec), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), carnitine (L-carnitine or D-carnitine), gamma-aminobutyric acid, hydroxyproline (Hyp), selenomethionine (L-SeMet or D-SeMet), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), beta-alanine, alpha-aminoisobutyric acid (Aib), alpha-aminobutyric (L-Abu or D-Abu), 3 -aminomethylbenzoic acid, anthranilic acid, homoarginine (L-Har or D-Har), delta-hydroxy -lysine (Hyl), 3 -mercaptophenylalanine (L-3 -mercaptophenylalanine or D-3 -mercaptophenylalanine), 2 -hydroxyphenylalanine (L-2-hydroxyphenylalanine or D-2-hydroxyphenylalanine), 3 -hydroxyphenylalanine (L- 3 -hydroxyphenylalanine or D-3 -hydroxyphenylalanine), phenylglycine (L-Phg or D- Phg), homophenylalanine (L-Hph or D-Hph), beta-(2-pyridyl)-alanine (L-2Pal or D- 2Pal), beta-(3-pyridyl)-alanine (L-3Pal or D-3Pal), 4-methyL-phenylalanine (L-4- methyL-phenylalanine or D-4-methyL-phenylalanine), 4-amino-phenylalanine (L-4- amino-phenylalanine or D-4-amino-phenylalanine), 2,3 -diaminopropionic acid (L-Dap or D-Dap), 2,4-diaminobutyric acid (L-Dab or D-Dab), 3,4-dihydroproline (L-Dhp or D- Dhp), thiaproline (L-thiaproline or D-thiaproline), alpha-methylproline (L-alpha- methylproline or D-alpha-methylproline), pipecolic acid (L-pipecolic acid or D-pipecolic acid), alpha-aminoadipic acid (L-Aad or D-Aad), 2-aminoheptanedioic acid (L-2-aminoheptanedioic acid or D-2-aminoheptanedioic acid), 2-ami-noheptanedioic acid (L- 2-ami-noheptanedioic acid or D-2-ami-noheptanedioic acid), alpha-aminosuberic acid (L-ASU or D-ASU), and 3,4-dihydroxyphenylalanine (L-DOPA or D-DOPA), 4- (phenylazo)-phenylglycine (L-4-(phenylazo)-phenylglycine or D-4-(phenylazo)- phenylglycine), (4-phenylazo)-phenylalanine (L-(4-phenylazo)-phenylalanine or D-(4- phenylazo)-phenylalanine), (4-(4’ -tert-Butoxycarbonyl)phenylazo)phenylalanine (L-(4- (4’-tert-Butoxycarbonyl)phenylazo)phenylalanine or D-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine), azobenzyl-lysine (L-azobenzyl-lysine or D- azobenzyl-lysine), or derivatives thereof.

[0021] Advantageously, the glassy material further comprises at least one additional ingredient, different from the at least one compound of formula (I), or a salt thereof, and from the at least one polar solvent, chosen from active ingredients, pH controlling agents, surfactants, transition metal salts or post-transition metal salts, and mixtures thereof

[0022] The present invention also relates to a method for preparing a glassy material according to the present invention, said method comprising the following steps: i) dissolving the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient in the at least one polar solvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, ii) drying the single-phase solution of step i) to remove partially the at least one polar solvent until the total content of said at least one polar solvent ranges from 0.1 % to 30 % by weight relative to the total weight of the glassy material, to obtain a glassy material according to the present invention, and then iii) optionally, when the glassy material obtained in step ii) has a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, stretching said material to obtain fibers, rods or microneedles.

[0023] Further, the present invention relates to a method for preparing a glassy material according to the invention, where in the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, said method comprises the following steps: i) mixing the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient, ii) heating the mixture of step i) until melting of said mixture to obtain a melted material, the heating temperature being greater than or equal to the glass transition temperature of the at least one compound of formula (I), or of a salt thereof, and then iii) cooling the melted material obtained in step ii) to ambient temperature to obtain a glassy material according to the invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

[0024] The present invention also relates to the use of a glassy material according to the invention, wherein the total content of the at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, as a glue.

[0025] The present invention also relates to the use of a glassy material according to the invention, wherein the total content of the at least one polar solvent ranges from 0.1 % to 30 % by weight relative to the total weight of the glassy material, as a cryoprotectant and / or a thermal protectant for molecules and / or biological elements when the temperature is below the glass transition temperature of said glassy material.

[0026] In addition, the present invention relates to the use of a glassy material according to the present invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, for molding water-soluble glass structures with a micrometric to nanometric precision.

[0027] Finally, the present invention relates to a microneedle comprising the glassy material of the present invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.DEFINITIONS

[0028] In the present invention, the following terms have the following meanings:

[0029] “Ambient temperature” refers to a temperature ranging from 20 °C to 25°C.

[0030] “Ambient humidity” refers to a relative humidity ranging from20 % to 50 %.

[0031] “Acidic amino acid” refers to an amino acid with an acidic side chain. In the present invention, an acidic amino acid is preferably chosen from aspartic acid (L-Asp or D-Asp) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; and more preferably from aspartic acid (L-Asp or D-Asp) and glutamic acid (L-Glu or D-Glu).

[0032] “Active ingredient” refers to photoswitch molecules, pigments, organic compounds having optical effects, cryoprotectants, thermal protectants, molecules or biological elements that needs cryo- or thermal protection, or any ingredient that provides biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of humans or animals.

[0033] “Amino acid” refers to an organic compound containing both a carboxylic acid (COOH) and an amino functional group. The amino acid can be alpha (z'.e., the carboxylic acid group and the amine group are on adjacent carbon atoms) or beta (z'.e., the amine group is attached to the secondary carbon atom from the carboxylic acid group). The amino acid can have a L configuration or a D configuration. In the present invention, an amino acid “AA” with the L configuration will be referred to as “L-AA” or simply as “AA” by default, whereas an amino acid “AA” with the D configuration will always be referred to as “D-AA” or “AAd”. In the present invention, the expression “amino acid”includes standard amino acids such as histidine or glutamic acid and also includes modified versions of said standard amino acids (called “derivatives”).

[0034] “Basic amino acid” refers to an amino acid with a basic side chain. In the present invention, a basic amino acid is preferably chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and lysine (L-Lys or D-Lys), or derivatives thereof; and more preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and lysine (L-Lys or D-Lys).

[0035] “Consisting of’ or “consist” is to be construed in a close, non-inclusive sense, limited to the features following this term.

[0036] “Comprising” or “comprise” is to be construed in an open, inclusive sense, but not limited to.

[0037] “Derivative” refers to a modified version of a standard amino acid. In one embodiment, a derivative of a standard amino acid is N-alkylated, N-acetylation, PEGylated, lipidated, and / or the beta version of said standard amino acid, and / or the a- carbon of the amino acid is attached to a structure selected from the group consisting of(i) H2N-(CH2)-;(ii) H2N-(iii) H(acetyl)N-(CH2)o-i; and(iv) H- or CH3-; and / or the C-terminus has been modified to incorporate a blocking group the type used conventionally in the art of peptide chemistry to protect peptide termini from undesired biochemical attack and degradation in vivo; and / or the N-terminus has been modified to incorporate a blocking group the type used conventionally in the art of peptide chemistry to protect peptide termini from undesired biochemical attack and degradation in vivo. Suitable conventional C-terminus modifications include, for example, groups which form ketones or amides at the carbon atom of the C -terminal carboxyl, or groups which form esters at the oxygen atom of the carboxyl. Suitable conventional N-terminus modifications include, for example, a N-acetylation or a N-alkylation such as a N- methylation. As for histidine (L-His or D-His), its derivatives further include 3,4-dihydroxyphenylalanine (L-DOPA or D-DOPA) and Vinylimidazole, imizadole. The derivatives of histidine (L-His or D-His) can be selected from 3,4- dihydroxyphenylalanine (L-DOPA or D-DOPA), Vinylimidazole, imizadole, 3-methyl- L-histidine, 3-methyl-D-histidine, desamino-histidine, 2-amino-histidine, P-hydroxy- histidine, homohistidine, a-fluoromethyl-histidine and a-methyl- histidine.

[0038] “From X to Y” refers to the range of values between X and Y, the limits X and Y being included in said range.

[0039] “Glass transition temperature” refers to the gradual and reversible transition in amorphous materials from a hard and relatively brittle glassy state into a viscous or rubbery state as the temperature is increased. The glass transition temperature can be measured by means of Differential Scanning Calorimetry (DSC), of Dynamic Mechanical Analysis (DMA), of Dilatometry (DLL) and of Thermomechanical Analysis (TMA) for instance. The temperature is measured inside the instrument.

[0040] “Glassy material” refers to an amorphous non-crystalline material, with no structural order at long range that exhibits a glass transition when heated towards a liquid state.

[0041] “Fatty acid” refers to a carboxylic acid with a linear or branched, saturated, unsaturated or polyunsaturated carbon chain. The number of carbon atom in the fatty acid ranges preferably from 10 to 20 and more preferably from 14 to 18.

[0042] “Lipidation”, in the present invention, refers to the covalent attachment of a fatty acid group to a molecule. The attachment can be performed via a spacer.

[0043] “Microneedle”, in the present invention, refers to a micron-scaled medical device used to administer an active principle, in cosmetics or medicine. For exemple, the microneedle can be used for intraocular, vaginal, cardiac, vascular, gastrointestinal, intracochlear, intradermal and / or transdermal active principle delivery applications.

[0044] “Polar uncharged amino acid” refers to an amino acid with a polar uncharged side chain. In the present invention, a polar uncharged amino acid is preferably chosen from serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln),asparagine (L-Asn or D-Asn), and cysteine (L-Cys or D-Cys), or derivatives thereof; and more preferably from serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L- Gln or D-Gln), asparagine (L-Asn or D-Asn), and cysteine (L-Cys or D-Cys).

[0045] “PEGylation” refers to the covalent attachment of polyethylene glycol (PEG) polymer chains to a molecule. The attachment can be performed via a spacer.

[0046] “Salt” of the compound of formula (I) of the invention refers to said compound of formula (I) combined with a counterion chosen to maintain electric neutrality.

[0047] “Sequence” refers to a series of at least two elements.

[0048] “Side chain”, when referring to an amino acid, designates the chemical group attached to the alpha-carbon atom of the carboxylic acid in the case of an alpha amino acid, or the chemical group attached to the beta-carbon atom of the carboxylic acid backbone in the case of a beta amino acid; said chemical group being different from the amino functional group present on the mentioned above alpha or beta carbon atom.

[0049] “Spacer” refers to a single covalent bond or a moiety comprising series of stable covalent bonds, the moiety often incorporating 1-40 plural valent atoms selected from the group consisting of C, N, O, S and P, that covalently attach two molecules together. The number of plural valent atoms in a spacer may be, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30 or a larger number up to 40 or more. A spacer may be linear or non-linear; some spacers have pendant side chains or pendant functional groups (or both). For instance, spacers may consist of a combination of moieties selected from alkyl, -C(O)NH- , -C(O)O-, -NH-, -S-, -O-, -C(O) -, -S(O)n- where n is 0, 1 or 2; -O-, 5- or 6- membered monocyclic rings and optional pendant functional groups, for example sulfo, hydroxy and carboxy.

[0050] “Stable overtime”, when referring to a glassy material, means that said material retains its amorphous non-crystalline nature preferably for at least 1 month, more preferably for at least 6 months, and even more preferably for at least 1 year, when stored at ambient temperature and ambient humidity.

[0051] “Supramolecular glass” refers to a glassy material whose structuration is made through non covalent interactions, preferably through hydrogen bounds.BRIEF DESCRIPTION OF THE FIGURES

[0052] Figure la displays photos of the self-healing behavior of a fiber obtained after stretching, breaking and sticking together the glassy material obtained in step ii) of the first method for preparing a glassy material according to the present invention, wherein the stretching occurred with a low stretching velocity (z'.e., between 0.01 m / s and 0.3 m / s) and under ambient humidity of 50 % to 90%. Figure lb displays photos of the viscoelastic and self-tensing behavior of a fiber obtained after stretching, obtained in step ii) of the first method for preparing a glassy material according to the present invention, wherein the stretching occurred with a low stretching velocity (z'.e., between 0.01 m / s and 0.3 m / s) and under ambient humidity of 50 % to 90%.

[0053] Figure 2 displays a photo of a borosilicate tube glued to a Teflon block with the glassy material of Example 4.

[0054] Figure 3 displays a photo of tweezers holding a lens shaped glassy material of Example 21.

[0055] Figure 4 displays a graph of the scattering intensity plotted as a function of the wide angle (A-1), obtained by a Wide-Angle X-Ray Scattering analysis, for the glassy material of Example 7 after being stored during 1 year at ambient temperature and ambient humidity.

[0056] Figures 5 A) to C) display respectively photos of the glassy materials of Example 29, Example 15 and Example 34.

[0057] Figure 6 displays a Scanning Electron Microscope (SEM) image of a 300 nm thick slice of the glassy material of Example 21 (scale bar: 1 pm).

[0058] Figures 7 A) to C) display respectively photos of glassy materials of Example23, Example 25 and Example 30, shaped as microneedles with a height of 600 pm.

[0059] Figure 8 displays a graph of the scattering intensity plotted as a function of the wide angle (A-1), obtained by a Wide-Angle X-Ray Scattering analysis, for the material of Comparative Example 6 after being stored during 12 hours at ambient temperature and ambient humidity.

[0060] Figure 9 displays a photo of a three-year-old glassy material (bead) of Example 25.DETAILED DESCRIPTIONGlassy material

[0061] This invention relates to a glassy material comprising: a) at least one compound of formula (I):X1-B-X2 (formula (I)), or a salt thereof, whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), and cysteine (L-Cys or D-Cys), or derivatives thereof and methionine sulfoxide (L-Met-SO or D-Met-SO); and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that: the compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present; and the compound of formula (I) is different from a homopolymer of poly-gamma- glutamic acid; and b) at least one polar solvent in a total content ranging from 0.1% to 30 % by weight relative to the total weight of the glassy material.

[0062] In the present invention, the expression “additional amino acid(s)” always refers to the amino acid(s) of B, when B is present.

[0063] By “linear sequence of at least two identical or different additional amino acids” according to the present invention, it can be understood a short chain of at least two identical or different additional amino acids linked by peptide bonds.

[0064] XI, B and X2 in the sequence X1-B-X2 of the compound of formula (I) are linked by peptide bonds, in that order. If B is absent, XI and X2 in the sequence X1-X2 are linked by peptide bonds.

[0065] Advantageously, the glassy material according to the invention has a glass transition temperature (Tg) ranging from 50 °C to 150°C, and preferably from 70 °C to 130 °C.

[0066] Preferably, the glassy material according to the invention has a maximum absorbance at a wavelength below or equal to 280 nm.

[0067] Advantageously, the glassy material according to the invention is soluble in the at least one polar solvent when the total content of said at least one polar solvent is greater than 30 % by weight relative to the total weight of the glassy material.

[0068] The glassy material according to the present invention is made of amino acids and therefore has an increased biocompatibility. It is also water-soluble.

[0069] Surprisingly, it has been found that a glassy material according to the invention has a supramolecular glass structure that is stable overtime, preferably stable for at least one week, preferably 1 month, more preferably for at least 6 months, and even more preferably for at least 1 year.At least one compound of formula (I)

[0070] The total content of the at least one compound of formula (I), or of a salt thereof, preferably ranges from 40 % to 99.9 % by weight, more preferably ranges from 40 % to 95 % by weight, and even more preferably ranges from 59 % to 88 % by weight relative to the total weight of the glassy material.

[0071] The compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids, notably when B is present. Preferably, the compound of formula (I) comprises at least 39 %, in amino acids, of acidic, basic or polar uncharged amino acids. More preferably, the compound of formula (I) comprises at least 50 %, in amino acids, of acidic, basic or polar uncharged amino acids.

[0072] The compound of formula (I) according to the present invention comprises at least one terminal end (XI or X2) chosen from histidine (L-His or D-His), arginine (L- Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu). It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 1 month.

[0073] Preferably, the additional amino acids of B are chosen from alanine (L-Ala or D- Ala), arginine (L-Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp or D-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His) or a derivative thereof, isoleucine (L-Ile or D-Ile), leucine (L-Leu or D-Leu), lysine (L-Lys or D-Lys), methionine (L-Met or D-Met), phenylalanine (L-Phe orD-Phe), proline (L-Pro or D-Pro), pyrrolysine (L-Pyl or D-Pyl), selenocysteine (L-Sec or D-Sec), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), carnitine (L-carnitine or D-carnitine), gamma-aminobutyric acid, hydroxyproline (Hyp), methionine sulfoxide (L-Met-SO or D-Met-SO), selenomethionine (L-SeMet or D-SeMet), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn), beta-alanine, alpha-aminoisobutyric acid (Aib), alpha-aminobutyric (L-Abu or D-Abu), 3 -aminomethylbenzoic acid, anthranilic acid, homoarginine (L-Har or D-Har), delta-hydroxy-lysine (Hyl), 3 -mercaptophenylalanine (L-3 -mercaptophenylalanine or D- 3 -mercaptophenylalanine), 2 -hydroxyphenylalanine (L-2-hydroxyphenylalanine or D-2- hydroxyphenylalanine), 3 -hydroxyphenylalanine (L-3 -hydroxyphenylalanine or D-3- hydroxyphenylalanine), phenylglycine (L-Phg or D-Phg), homophenylalanine (L-Hph or D-Hph), beta-(2-pyridyl)-alanine (L-2Pal or D-2Pal), beta-(3-pyridyl)-alanine (L-3Pal orD-3Pal), 4-methyL-phenylalanine (L-4-methyL-phenylalanine or D-4-methyL- phenylalanine), 4-amino-phenylalanine (L-4-amino-phenylalanine or D-4-amino- phenylalanine), 2,3-diaminopropionic acid (L-Dap or D-Dap), 2,4-diaminobutyric acid (L-Dab or D-Dab), 3,4-dihydroproline (L-Dhp or D-Dhp), thiaproline (L-thiaproline or D-thiaproline), alpha-methylproline (L-alpha-methylproline or D-alpha-methylproline), pipecolic acid (L-pipecolic acid or D-pipecolic acid), alpha-aminoadipic acid (L-Aad or D-Aad), 2-aminoheptanedioic acid (L-2-aminoheptanedioic acid or D-2- aminoheptanedioic acid), 2-ami-noheptanedioic acid (L-2-ami-noheptanedioic acid or D- 2-ami-noheptanedioic acid), alpha-aminosuberic acid (L-ASU or D-ASU), and 3,4- dihydroxyphenylalanine (L-DOPA or D-DOPA), 4-(phenylazo)-phenylglycine (L-4- (phenylazo)-phenylglycine or D-4-(phenylazo)-phenylglycine), (4-phenylazo)- phenylalanine (L-(4-phenylazo)-phenylalanine or D-(4-phenylazo)-phenylalanine), (4- (4’-tert-Butoxycarbonyl)phenylazo)phenylalanine (L-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine or D-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine), azobenzyl-lysine (L-azobenzyl-lysine or D- azobenzyl-lysine), or derivatives thereof.

[0074] More preferably, the additional amino acids of B are chosen from alanine (L-Ala or D-Ala), arginine (L-Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp or D-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His), isoleucine (L-Ile or D- II e), leucine (L-Leu or D-Leu), lysine (L-Lys or D-Lys), phenylalanine (L-Phe or D-Phe), proline (L-Pro or D-Pro), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), and citrulline (L- Cit or D-Cit), or derivatives thereof

[0075] Even more preferably, the additional amino acids of B are chosen from alanine (L-Ala or D-Ala), arginine (L-Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp or D-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His), isoleucine (L- Ile or D-Ile), leucine (L-Leu or D-Leu), lysine (L-Lys or D-Lys), phenylalanine (L-Phe or D-Phe), proline (L-Pro or D-Pro), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr),tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), and citrulline (L-Cit or D-Cit).

[0076] The compound of formula (I) is preferably chosen from His-His (H2), His-Ser(HS), His-Glu (HE), His-His-His (H3), His-His-Lys (HHK), Hisd-His-Lys (HdHK), Lys- His-His (KHH), His-Lys-His (HKH), Lys-Lys-His (KKH), His-Lys-Lys (HKK), His- His-Cys (HHC), His-His-Arg (HHR), His-His-His-His (H4), His-Gly-His-Lys (HGHK), His-Lys-Lys-His (HKKH), His-His-His-Lys (HHHK), His-His-His-His-His (H5), His- His-Glu-His-His (HHEHH), His-His-Arg-His-His (HHRHH), His-Lys-Lys-Lys-His (HKKKH), His-His-Cit-His-His (HHCitHH), His-His-His-His-His-His (H6), His-His- His-His-His-His-His (H7), His-His-His-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-His- His-His (HHHCYIQNCPLGHHH) Mono Disulfide bridge, His-His-His-His-His-His- His-His-His-His (H10),His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu- Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG), histidine copolymer 2500 g / mol, Glu-Glu (E2), Glu-Glu-Glu-Glu-Glu (E5), glutamic acid copolymer 15000 g / mol, and mixtures thereof, Acetyl-Glu-Glu-Met-Gln-Arg-Arg-NH? (Acetyl-EEMQRR-NH?), Acetyl-Glu-Glu-Met-Gln-Arg-Arg-Ala-Asp-NH? (Acetyl-EEMQRRAD-NH?), Arg-His- His-His (RHHH), Glu-His-His-His (EHHH), Arg-His-His-His-Arg (RHHHR), His-His- His-Ser (HHHS), Glu-Glu-Glu-Asp (EEED), His-His-His-Thr (HHHT), His-His-His-Gln (HHHQ), His-His-His-Orn,His-His-His-Cit,EEAAEAKYKAAKAYKKAAAKKAKYAAKAKAAYKKAKAEKAEE, His-His-His (HHH){N-Me-His).

[0077] The compound of formula (I) is more preferably chosen from His-His (H2), His- Ser (HS), His-Glu (HE), His-His-His (H3), His-His-Lys (HHK), Hisd-His-Lys (HdHK), Lys-His-His (KHH), His-Lys-His (HKH), Lys-Lys-His (KKH), His-Lys-Lys (HKK), His-His-Cys (HHC), His-His-Arg (HHR), His-His-His-His (H4), His-Gly-His-Lys (HGHK), His-Lys-Lys-His (HKKH), His-His-His-Lys (HHHK), His-His-His-His-His (H5), His-His-Glu-His-His (HHEHH), His-His-Arg-His-His (HHRHH), His-Lys-Lys- Lys-His (HKKKH), His-His-Cit-His-His (HHCitHH), His-His-His-His-His-His (H6), His-His-His-His-His-His-His (H7), His-His-His-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-His-His-His (HHHCYIQNCPLGHHH) Mono Disulfide bridge, His-His-His-His- His-His-His-His-His-His (H10),His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser- Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG), histidine copolymer 2500 g / mol, Glu-Glu (E2), Glu-Glu-Glu-Glu-Glu (E5), glutamic acid copolymer 15000 g / mol, and mixtures thereof.

[0078] Optionally, when B represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2, then at least one amino acid comprised in the compound of formula (I) (XI, X2 or an amino acid of B) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably a disulfide bond. Preferably, the compound of formula (I) comprises at least two cysteine (L-Cys or D- Cys) and at least one cysteine (L-Cys or D-Cys) is linked to another cysteine (L-Cys or D-Cys) via a disulfide bond. Preferably, at least two amino acids comprised in the compound of formula (I) are linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, and more preferably, at least three amino acids comprised in the compound of formula (I) are linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge. In other words, there are preferably at least two intramolecular bridges in the compound of formula (I), and more preferably at least three.

[0079] According to one embodiment, the compound of formula (I) is chosen from the compounds of formula (I-a):X1-B-X2 (formula (I-a)), whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D- Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that: the compound of formula (I-a) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; and when XI and / or X2 represents arginine (L-Arg or D-Arg), B is necessarily present; and the compound of formula (I-a) is different from a homopolymer of poly-gamma- glutamic acid.It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 6 months.According to this embodiment, the compound of formula (I-a) is preferably chosen from His-His (H2), His-Glu (HE), His-His-His (H3), His-Lys-His (HKH), His-His-His-His (H4), His-Lys-Lys-His (HKKH), His-His-His-His-His (H5), His-His-Glu-His-His (HHEHH), His-His-Arg-His-His (HHRHH), His-Lys-Lys-Lys-His (HKKKH), His-His- Cit-His-His (HHCitHH), His-His-His-His-His-His (H6), His-His-His-His-His-His-His (H7), His-His-His-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-His-His-His(HHHCYIQNCPLGHHH) Mono Disulfide bridge, His-His-His-His-His-His-His-His- His-His (H10), histidine copolymer 2500 g / mol, Glu-Glu (E2), Glu-Glu-Glu-Glu-Glu (E5), glutamic acid copolymer 15000 g / mol, and mixtures thereof.

[0080] According to one embodiment, the compound of formula (I) is chosen from the compounds of formula (I-b):X1-B-X2 (formula (I-b)),whereinXI and X2 are different and each represents an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys); at least one among XI and X2is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that: the compound of formula (Lb) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; and when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present.In other words, in this embodiment, the two terminal ends XI and X2 are necessarily different from one another. It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 1 month.According to this embodiment, the compound of formula (I-b) is preferably chosen from His-Ser (HS), His-Glu (HE), His-His-Lys (HHK), Hisa-His-Lys (HdHK), Lys-His-His (KHH), Lys-Lys-His (KKH), His-Lys-Lys (HKK), His-His-Cys (HHC), His-His-Arg (HHR), His-Gly-His-Lys (HGHK), His-His-His-Lys (HHHK), His-Ala-Glu-Gly-Thr- Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala- Trp-Leu- Val-Ly s-Gly- Arg-Gly (HAEGTFTSD VS S YLEGQ AAKEFIAWLVKGRG), and mixtures thereof.

[0081] According to a first variant of this embodiment, one among XI and X2 is histidine (L-His or D-His) or a derivative thereof, and preferably histidine(L-His or D- His);and the other among XI and X2 is an amino acid chosen from glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D- Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; preferably from arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), and cysteine (L-Cys or D-Cys), or derivatives thereof; more preferably from arginine (L-Arg or D-Arg) and lysine (L-Lys or D-Lys), or derivatives thereof; and even more preferably from arginine (L-Arg or D-Arg) and lysine (L-Lys or D-Lys).

[0082] According to a second variant of this embodiment, one among XI and X2 is glutamic acid (L-Glu or D-Glu) or a derivative thereof, and preferably glutamic acid (L- Glu or D-Glu); and the other among XI and X2is an amino acid chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L- Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D- Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof;preferably from aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L- Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L- Tyr or D-Tyr), glycine (L-Gly or D-Gly), and cysteine (L-Cys or D-Cys), or derivatives thereof; more preferably the other among XI and X2 is aspartic acid (L-Asp or D-Asp) or a derivative thereof; and even more preferably the other among XI and X2 is aspartic acid (L-Asp or D-Asp).

[0083] According to a third variant of this embodiment, one among XI and X2 is arginine (L-Arg or D-Arg) or a derivative thereof, and preferably arginine (L-Arg or D- Arg); and the other among XI and X2 is an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D- Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; preferably from aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L- Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L- Tyr or D-Tyr), glycine (L-Gly or D-Gly), and cysteine (L-Cys or D-Cys), or derivatives thereof; more preferably the other among XI and X2 is aspartic acid (L-Asp or D-Asp) or a derivative thereof; and even more preferably the other among XI and X2 is aspartic acid (L-Asp or D-Asp).

[0084] According to one embodiment, the compound of formula (I) is chosen from the compounds of formula (I-c):XI -X2 (formula (I-c)), whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; and preferably from histidine (L-His or D-His), glutamic acid(L-Glu or D-Glu), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; and preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu); with the proviso that: the compound of formula (I-c) comprises at least 50 %, in amino acids, of acidic, basic or polar uncharged amino acids; and the compound of formula (Lc) is different from a homopolymer of poly-gamma- glutamic acid.In other words, according to this embodiment, the compound of formula (I-c) consists of two amino acids: XI and X2 as defined previously. Said amino acids XI and X2 are linked by peptide bonds.It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 1 month. Therefore, even low molecular weight supramolecular glassy materials, according to the invention, have good glass stability.According to this embodiment, the compound of formula (I-c) is preferably chosen from His-His (H2), His-Ser (HS), His-Glu (HE), Glu-Glu (E2), and mixtures thereof.

[0085] According to one embodiment, the compound of formula (I) is chosen from the compounds of formula (Ld):X1-B-X2 (formula (I-d)), whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);- B represents an additional amino acid which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that:- the compound of formula (Ld) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; and- the compound of formula (Ld) is different from a homopolymer of poly- gamma-glutamic acid.In other words, according to this embodiment, the compound of formula (Ld) consists of three amino acids: XI, B and X2 as defined previously. Said amino acids XI, B and X2 are linked, in that order, by peptide bonds.It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 1 month. Therefore, even low molecular weight supramolecular glassy materials, according to the invention, have good glass stability.According to this embodiment, the compound of formula (I-d) is preferably chosen from His-His-His (H3), His-His-Lys (HHK), Hisa-His-Lys (HdHK), Lys-His-His (KHH), His- Lys-His (HKH), Lys-Lys-His (KKH), His-Lys-Lys (HKK), His-His-Cys (HHC), His- His-Arg (HHR), and mixtures thereof.

[0086] According to one embodiment, the compound of formula (I) is chosen from the compounds of formula (I-e):X1-B-X2 (formula (I-e)), whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys), or derivatives thereof; and preferably from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D- Asp), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L- Gly or D-Gly), citrulline (L-Cit or D-Cit) and cysteine (L-Cys or D-Cys); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu);- B represents a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; optionally, at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge, preferably via a disulfide bond; with the proviso that:- the compound of formula (I-e) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; and- the compound of formula (I-e) is different from a homopolymer of poly- gamma-glutamic acid.In other words, in this embodiment, the compound of formula (I-e) comprises at least four amino acids in total: the amino acid XI, the at least two identical or different additional amino acids of B and the amino acid X2 as defined previously. The amino acid XI, the linear sequence B of at least two identical or different additional amino acids and the amino acid X2 are linked, in that order, by peptide bonds.It has been found that glassy materials according to this embodiment have a supramolecular glass structure that is stable for at least 1 month.According to this embodiment, the compound of formula (I-e) is preferably chosen from His-His-His-His (H4), His-Gly-His-Lys (HGHK), His-Lys-Lys-His (HKKH), His-His- His-Lys (HHHK), His-His-His-His-His (H5), His-His-Glu-His-His (HHEHH), His-His- Arg-His-His (HHRHH), His-Lys-Lys-Lys-His (HKKKH), His-His-Cit-His-His (HHCitHH), His-His-His-His-His-His (H6), His-His-His-His-His-His-His (H7), His-His- His-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-His-His-His (HHHCYIQNCPLGHHH) Mono Disulfide bridge, His-His-His-His-His-His-His-His-His-His (H10), His-Ala-Glu- Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe- Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG), histidine copolymer (2500 g / mol), Glu-Glu-Glu-Glu-Glu (E5), glutamic acid copolymer (15000 g / mol), and mixtures thereof.Advantageously, the number of additional amino acids in the linear sequence of B, which may be the same or different from XI and X2, ranges from 2 to 700.Advantageously, XI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D- Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L- His or D-His) and glutamic acid (L-Glu or D-Glu).In a first preferred embodiment, the number of additional amino acids in the linear sequence of B, which may be the same or different from XI and X2, ranges from 2 to 200; preferably from 2 to 150; and more preferably from 2 to 100. According to this first preferred embodiment, the compound of formula (Le) is preferably chosen from His-His- His-His (H4), His-Gly-His-Lys (HGHK), His-Lys-Lys-His (HKKH), His-His-His-Lys (HHHK), His-His-His-His-His (H5), His-His-Glu-His-His (HHEHH), His-His-Arg-His- His (HHRHH), His-Lys-Lys-Lys-His (HKKKH), His-His-Cit-His-His (HHCitHH), His- His-His-His-His-His (H6), His-His-His-His-His-His-His (H7), His-His-His-Cys-Tyr-Ile- Gln-Asn-Cys-Pro-Leu-Gly-His-His-His (HHHCYIQNCPLGHHH) Mono Disulfide bridge, His-His-His-His-His-His-His-His-His-His (H10), His-Ala-Glu-Gly-Thr-Phe- Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp- Leu-Val-Lys-Gly-Arg-Gly (HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG), Glu- Glu-Glu-Glu-Glu (E5), histidine copolymer (2500 g / mol), glutamic acid copolymer (15000 g / mol), and mixtures thereof.In a second preferred embodiment, the number of additional amino acids in the linear sequence of B, which may be the same or different from XI and X2, ranges from 201 to 700; preferably from 201 to 634. According to this second preferred embodiment, the compound of formula (Le) is preferably chosen from histidine copolymer, glutamic acid copolymer, and mixtures thereof.

[0087] The compound of formula (I) in the present invention can be under a salt form, which includes at least one counterion. Advantageously, the at least one counterion is chosen from anionic counterions, cationic counterions and mixtures thereof.

[0088] In one embodiment, when the glassy material of the invention comprises a salt of the compound of formula (I), the at least one counterion is an anionic counterion, preferably chosen from acetates, halides, phosphates, nitrates, sulfates or sulfonates, more preferably from acetates, halides, nitrates or sulfates, even more preferably from trifluoroacetate, acetate or chloride, and better still from trifluoroacetate and acetate.

[0089] In another embodiment, when the glassy material of the invention comprises a salt of the compound of formula (I), the at least one counterion is a cationic counterion, preferably chosen from cationic counterions derived from an alkali metal or alkaline-earth metal, an ammonium ion or an ion derived from an organic amine, and more preferably from sodium, potassium or cesium.

[0090] In one embodiment, when the glassy material of the invention comprises a salt of the compound of formula (I), the at least one counterion is a mixture of at least one anionic counterion and at least one cationic counterion, wherein the at least one anionic counterion is preferably chosen from acetates, halides, phosphates, nitrates, sulfates or sulfonates, more preferably from acetates, halides, nitrates or sulfates, even more preferably from trifluoroacetate, acetate or chloride, and better still from trifluoroacetate and acetate; and wherein the at least one cationic counterion is preferably chosen from cationic counterions derived from an alkali metal or alkaline-earth metal, an ammonium ion or an ion derived from an organic amine, and more preferably from sodium, potassium or cesium.

[0091] When the glassy material comprises a salt of the compound of formula (I), the molar ratio R1 between the content of the at least one counterion and the content of the at least one compound of formula (I) is equal to N times the number of polar charged amino acids comprised in said at least one compound of formula (I), wherein N ranges from 1 to 2.At least one polar solvent

[0092] Advantageously, the at least one polar solvent is chosen from water, polar organic solvents and mixtures thereof; preferably from water, acetone, dimethylsulfoxide andmixtures thereof; and more preferably the glassy material according to the invention comprises one polar solvent which is water.

[0093] In one embodiment, the total content of the at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material. According to this embodiment, the glassy material is viscoelastic and displays self-repairing properties.

[0094] In another embodiment, the total content of the at least one polar solvent is greater than or equal to 0.1% and lower than 10 % by weight relative to the total weight of the glassy material. According to this embodiment, the glassy material is preferably a solid.

[0095] Thus, the glassy material according to the invention is versatile as it can be either viscoelastic or solid, depending on the total content of the at least one polar solvent.Additional ingredient

[0096] The glassy material according to the invention may optionally further comprise at least one additional ingredient, different from the compounds previously described (z'.e., the at least one compound of formula (I), or a salt thereof, and the at least one polar solvent), chosen from active ingredients, pH controlling agents, surfactants, transition metal salts or post-transition metal salts, and mixtures thereof.

[0097] The glassy material according to the invention may optionally further comprise at least one active ingredient.

[0098] Advantageously, the optional at least one active ingredient that can be used in the present invention is chosen from painkillers, vaccines, antiwrinkles, dark spot removers, collagen promoters, botulinum toxin, anti-inflammatory drugs, anti-alzheimer drugs, antidote drugs, antibodies, allergens, neurotransmitters, contraceptives, progestin, estrogen, nicotine, mannitol, magnetite, chitosan, morphin, ibuprofen, naproxen, diclofenac, indomethacin, celecoxib, lidocaine, tetracaine, benzocaine, adrenaline, bupivacaine, phenobarbital, amiodarone, digoxin, miltefosine, mycophenolic acid, alendronic acid, zolmitriptan, Hepatitis B surface antigen, Japanese encephalitis virus antigen, adalimumab, ustekinumab, pembroluzimab, casirivimab, imdevimab,lenalidomide, ibrutinib, apixaban, Bis-para-(iodoacetamido)azobenzene, 3,3'-Bis(sulfo)- 4,4'-bis(chloroacetamido)azobenzene, tetra-ortho-methoxy azobenzene, piperazino-tetra- ortho-methoxy-azobenzene, 2-amino-3-(4-((3-vinylphenyl)diazenyl)phenyl) propanoic acid, l-(b-carboxyethyl)-3,3-dimethyl-60-nitrospiro(indoline-2,20[2H-l]benzopyran), ketamine, gentamicin, penicillin V, tranexamic acid, kanamycin, metformin, besifloxacin, sodium nitroprusside, amifostine, doxorubicin, caffeine, donepezil hydrochloride, phenylephrine, diphteria and tetanus toxoid, A-CGRP peptide, dihydroergotamine mesylate, minoxidil, finasteride, triamcinolone acetonide, retinoic acid, methotrexate, rapamycin, buspirone, tacrolimus, vismodegib, aflibercept, nestorone, insulin, naphthalene diimide, water-soluble perylenediimides, benzophenol, pigments, trehalose, sucrose, propanediol, glycerol, ethylene glycol, propylene glycol, and mixtures thereof

[0099] The total content of the at least one active ingredient, when it is present in the glassy material according to the invention, preferably ranges from 0.001% to 60 % by weight, and more preferably ranges from 0.1% to 50 % by weight relative to the total weight of the glassy material.

[0100] The glassy material according to the invention may optionally further comprise at least one surfactant.

[0101] Advantageously, the optional at least one surfactant that can be used in the present invention is chosen from cationic surfactants, anionic surfactants, non-ionic surfactants, and mixtures thereof; preferably the optional at least one surfactant is a nonionic surfactant; and more preferably the optional at least one surfactant is chosen from glyceryl caprylate, polysorbate 20 to 80, polyethylene oxide)-poly(propylene oxide)- block copolymers, and mixtures thereof. As for polysorbate 20 to 80, examples are Tween® 20 to 80. As for polyethylene oxide)-poly(propylene oxide)-block copolymers, examples are Lutrol® F68, Lutrol® F108, Pluronic® F88.

[0102] The glassy material according to the invention may optionally further comprise at least one transition metal salt or post-transition metal salt.

[0103] Advantageously, the cation of the optional at least one transition metal salt or post-transition metal salt is a transition metal or post-transition metal dication; preferably, the transition metal or post-transition metal is chosen from zinc, copper, iron, cobalt, nickel and cadmium; and more preferably, the optional at least one transition metal salt or post-transition metal salt that can be used in the present invention is chosen from zinc sulfate, zinc chloride, zinc nitrate, nickel sulfate, nickel chloride, copper chloride, cobalt chloride, iron chloride, cadmium chloride, and mixtures thereof

[0104] The glassy material according to the invention may optionally further comprise at least one pH controlling agent.

[0105] Advantageously, the optional at least one pH controlling agent that can be used in the present inventionis chosen from organic acids, mineral acids, organic bases, inorganic bases and mixtures thereof; preferably from hydrochloric acid, trifluoroacetic acid, citric acid, malic acid, acetic acid, sodium hydroxide, potassium hydroxide and mixtures thereof; and more preferably from hydrochloric acid, trifluoroacetic acid, acetic acid, sodium hydroxide and mixtures thereof

[0106] The total content of the at least one pH controlling agent, when it is present in the glassy material according to the invention, preferably ranges from 0.001 % to 30 % by weight, and more preferably ranges from 0.01 % to 5 % by weight relative to the total weight of the glassy material.

[0107] If the preparation of the glassy material according to the invention occurs via a step of dissolving the at least one compound of formula (I), or a salt thereof, the optional at least one active ingredient, the optional at least one surfactant and the optional at least one transition metal salt or post-transition metal salt in the at least one polar solvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, then optionally the at least one pH controlling agent is added in the mixture to ensure that: the pH of the single-phase solution is acidic or neutral in the case where the compound of formula (I) is positively charged overall, preferably the pH is below 6.5 and more preferably ranges from 2 to 5,and- the pH of the single-phase solution is basic or neutral in the case where the compound of formula (I) is negatively charged overall, and preferably the pH ranges from 7 to 10.

[0108] In one embodiment, the glassy material according to the invention further comprises at least one active ingredient and at least one surfactant; preferably the at least one active ingredient is chosen from painkillers, vaccines, antiwrinkles, dark spot removers, collagen promoters, botulinum toxin, anti-inflammatory drugs, anti-alzheimer drugs, antidote drugs, antibodies, allergens, neurotransmitters, contraceptives, progestin, estrogen, nicotine, mannitol, magnetite, chitosan, morphin, ibuprofen, naproxen, diclofenac, indomethacin, celecoxib, lidocaine, tetracaine, benzocaine, adrenaline, bupivacaine, phenobarbital, amiodarone, digoxin, miltefosine, mycophenolic acid, alendronic acid, zolmitriptan, Hepatitis B surface antigen, Japanese encephalitis virus antigen, adalimumab, ustekinumab, pembroluzimab, casirivimab, imdevimab, lenalidomide, ibrutinib, apixaban, Bis-para-(iodoacetamido)azobenzene, 3,3'-Bis(sulfo)- 4,4'-bis(chloroacetamido)azobenzene, tetra-ortho-methoxy azobenzene, piperazino-tetra- ortho-methoxy-azobenzene, 2-amino-3-(4-((3-vinylphenyl)diazenyl)phenyl) propanoic acid, l-(b-carboxyethyl)-3,3-dimethyl-60-nitrospiro(indoline-2,20[2H-l]benzopyran), ketamine, gentamicin, penicillin V, tranexamic acid, kanamycin, metformin, besifloxacin, sodium nitroprusside, amifostine, doxorubicin, caffeine, donepezil hydrochloride, phenylephrine, diphteria and tetanus toxoid, A-CGRP peptide, dihydroergotamine mesylate, minoxidil, finasteride, triamcinolone acetonide, retinoic acid, methotrexate, rapamycin, buspirone, tacrolimus, vismodegib, aflibercept, nestorone, insulin, naphthalene diimide, water-soluble perylenediimides, benzophenol, pigments, trehalose, sucrose, propanediol, glycerol, ethylene glycol, propylene glycol, and mixtures thereof; and the at least one surfactant is chosen from glyceryl caprylate, polysorbate 20 to 80, poly(ethylene oxide)-poly(propylene oxide)-block copolymers, and mixtures thereofPreferred glassy materials

[0109] In one embodiment, the glassy material comprises: a) at least one compound of formula (I-a), or a salt thereof, as defined previously, in a total content preferably ranging from 40 % to 99.9 % by weight, more preferably from 40 % to 95 % by weight, and even more preferably from 59 % to 88 % by weight relative to the total weight of the glassy material; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

[0110] In another embodiment, the glassy material comprises: a) at least one compound of formula (I-b),or a salt thereof, as defined previously, in a total content preferably ranging from 40 % to 99.9 % by weight, more preferably from 40 % to 95 % by weight, and even more preferably from 59 % to 88 % by weight relative to the total weight of the glassy material; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

[0111] In one embodiment, the glassy material comprises: a) at least one compound of formula (I-c), or a salt thereof, as defined previously, in a total content preferably ranging from 40 % to 99.9 % by weight, more preferably from 40 % to 95 % by weight, and even more preferably from 59 % to 88 % by weight relative to the total weight of the glassy material; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

[0112] In one embodiment, the glassy material comprises: a) at least one compound of formula (I-d), or a salt thereof, as defined previously, in a total content preferably ranging from 40 % to 99.9 % by weight, morepreferably from 40 % to 95 % by weight, and even more preferably from 59 % to 88 % by weight relative to the total weight of the glassy material; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

[0113] In one embodiment, the glassy material comprises: a) at least one compound of formula (I-e), or a salt thereof, as defined previously, in a total content preferably ranging from 40 % to 99.9 % by weight, more preferably from 40 % to 95 % by weight, and even more preferably from 59 % to 88 % by weight relative to the total weight of the glassy material; and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.First method for preparing a glassy material according to the invention

[0114] The invention also relates to a first method for preparing a glassy material according to the invention that comprises the following steps: i) dissolving the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient in the at least one polar solvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, ii) drying the single-phase solution of step i) to remove partially the at least one polar solvent until the total content of said at least one polar solvent ranges from 0.1 %to 30 % by weight relative to the total weight of the glassy material, to obtain a glassy material according to the invention, and then iii) optionally, when the glassy material obtained in step ii) has a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, stretching said material to obtain fibers, rods or microneedles.

[0115] Steps i) to iii) of the first method for preparing a glassy material according to the invention are performed in that order.

[0116] In a first embodiment, the first method for preparing a glassy material according to the invention comprises the following steps: i) dissolving the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient in the at least one polar solvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, and then ii) drying the single-phase solution of step i) to remove partially the at least one polar solvent until the total content of said at least one polar solvent ranges from 0.1 % to 30 % by weight relative to the total weight of the glassy material, to obtain a glassy material according to the invention.

[0117] In a second embodiment, the first method for preparing a glassy material according to the invention comprises the following steps: i) dissolving the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient in the at least one polar solvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, ii) drying the single-phase solution of step i) to remove partially the at least one polar solvent until the total content of said at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, to obtain a glassy material having a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, and then iii) stretching the material obtained in step ii) to obtain fibers, rods or microneedles.

[0118] When the at least one compound of formula (I) is positively charged overall, optionally the at least one pH controlling agent is added to ensure that the pH of the single-phase solution of step i) is acidic or neutral, preferably the pH is below 6.5 and more preferably ranges from 2 to 5.

[0119] When the at least one compound of formula (I) is negatively charged overall, optionally the at least one pH controlling agent is added to ensure that the pH of the single-phase solution of step i) is basic or neutral, and preferably the pH ranges from 7 to 10.

[0120] The total content of the at least one polar solvent in step i) is chosen so that there is a complete dissolution of the at least one compound of formula (I), or a salt thereof, and of the optional at least one additional ingredient, the complete dissolution being in said at least one polar solvent. A single-phase solution is thus obtained.

[0121] Advantageously, the weight ratio R2 between the content of the at least one polar solvent in step i) and the content of the at least one compound of formula (I), or a salt thereof, is greater than 0.5, and preferably ranges from 1 to 10.

[0122] Step ii) is preferably performed directly after the dissolution of the at least one compound of formula (I), or a salt thereof, and of the optional at least one additional ingredient in the at least one polar solvent (z'.e., directly after step i)), without any intermediate waiting time.

[0123] Advantageously, the drying in step ii) of the single-phase solution of step i) is a desiccation, a heating or another drying technique commonly known by a man skilled in the art. The heating can be performed by microwaves, magnetic induction hyperthermia, for example.

[0124] The drying in step ii) of the single-phase solution of step i) will lead to the formation of a viscous material first (z'.e., according to the present invention, a glassy material having a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material) and after more time drying to the formation of a solid glass (z'.e., according to the present invention, a glassymaterial having a total content of the at least one polar solvent that is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material).

[0125] In an embodiment, the drying in step ii) of the single-phase solution of step i) can be performed into a mold to give a shape to the glassy material thus obtained.

[0126] In an embodiment, a glassy material having a total content of the at least one polar solvent that is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material is obtained in step ii) and it is spread through spin coating as thin films with nanometric precision.

[0127] Optional step iii) is preferably performed directly after the drying in step ii) of the single-phase solution of step i) (z'.e., directly after step ii)), without any intermediate waiting time. Moreover, it is performed only in the case where a glassy material having a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material is obtained in step ii). In other words, optional step iii) is performed only if the drying in step ii) of the single-phase solution of step i) is stopped before the formation of a solid glass (z'.e., according to the present invention, a glassy material having a total content of the at least one polar solvent that is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material).

[0128] Depending on the stretching rate employed in optional step iii) to stretch the material obtained in step ii) and on the humidity conditions ranging from 50 % to 90 %, the properties of the the material obtained can be modified. Indeed, if the stretching velocity is high in step iii), rods or microneedles are obtained in optional step iii), said rods or microneedles being solid and brittle (z'.e., they each have a total content of the at least one polar solvent greater than or equal to 0.1 % and lower than 10 % by weight relative to their total weight). If the stretching velocity is low in step iii), fibers are obtained in optional step iii), said fibers being viscoelastic (z'.e., they each have a total content of the at least one polar solvent ranging from 10 % to 30 % by weight relative to their total weight) and they display self-repairing properties, as shown in the photos of Figure la and Figure lb.

[0129] “High” for stretching velocity means between Im / s and 3m / s.

[0130] “Low” for stretching velocity means between 0.01 m / s and 0.3m / s.

[0131] The stretching velocity can be determined using the particle tracking method or the tensile testing method.Second method for preparing a glassy material according to the invention

[0132] The invention also relates to a second method for preparing a glassy material according to the invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, said method comprises the following steps: i) mixing the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient, ii) heating the mixture of step i) until melting of said mixture to obtain a melted material, the heating temperature being greater than or equal to the glass transition temperature (Tg) of the at least one compound of formula (I), or of a salt thereof, and then iii) cooling the melted material obtained in step ii) to ambient temperature to obtain a glassy material according to the invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1% and lower than 10 % by weight relative to the total weight of the glassy material.

[0133] Steps i) to iii) of the second method for preparing a glassy material according to the invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, are performed in that order.

[0134] Step ii) is preferably performed directly after the mixing of the at least one compound of formula (I), or of a salt thereof, and of the optional at least one additional ingredient (z'.e., directly after step i)), without any intermediate waiting time. Step ii)allows to increase the mixing by reaching the viscoelastic state of the at least one compound of formula (I), or of a salt thereof

[0135] Step iii) is preferably performed directly after the heating of the mixture of step i) until the melting of said mixture (z'.e., directly after step ii)), without any intermediate waiting time.

[0136] Advantageously, the cooling in step iii) consists in letting the melted material of step ii) rest at ambient temperature and atmospheric pressure with or without humidity control.

[0137] The cooling in step iii) of the melted material obtained in step ii) will lead to the formation of a glassy material having a total content of the at least one polar solvent that is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

[0138] In an embodiment, the cooling in step iii) of the melted material of step ii) can be performed into a mold to give a shape to the glassy material thus obtained.

[0139] In an embodiment, cooling in step iii) of the melted material of step ii) can be performed while spreading said melted material through spin coating to obtain a glassy material according to the invention, wherein the total content of the at least one polar solvent is greater than or equal to 0.1% and lower than 10 % by weight relative to the total weight of the glassy material, as thin films with nanometric precision.

[0140] In another embodiment, cooling in step iii) of the melted material of step ii) can be performed while said melted material is deposited on a surface with a 3D printer.

[0141] The at least one polar solvent present in the material may come from the humidity of the air through hygroscopy or is a residue of the synthesis of the peptide.Use of a glassy material according to the invention

[0142] The invention further relates to the use of a glassy material according to the invention, in which the at least one polar solvent is present with a total content rangingfrom 10 % to 30 % by weight relative to the total weight of the glassy material, as a glue. Said material, in which the at least one polar solvent is present with a total content ranging from 10 % to 30 % by weight relative to the total weight of the glassy material, is a viscoelastic substance. As it dries, it can serve as a water-soluble glue with specific biological or chemical properties. Examples of materials that can be glued, in a dry environment, by the above-mentioned viscoelastic material are Teflon and borosilicate glass. A photo of a borosilcate tube glued to a Teflon block with the glassy material of Example 4 can be found in Figure 2.

[0143] The present invention also relates to the use of a glassy material according to the invention, wherein the total content of the at least one polar solvent ranges from 0.1 % to 30 % by weight relative to the total weight of the glassy material, as a cryoprotectant and / or a thermal protectant for molecules and / or biological elements, when the temperature is below the glass transition temperature of said glassy material.

[0144] The invention also relates to the use of a glassy material according to the invention, in which the total content of the at least one polar solvent is greater than 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, for molding water-soluble glass structures with a micrometric (at least 20 pm) to nanometric precision. For example, possible water-soluble glass structures are: microneedles for transdermal or intradermal injection in cosmetics or medicine with rapid or slow release, hook needles, spiked microballs for oral encapsulated absorption and internal injection in the stomach or intestine, powder for intranasal administration, and optical lenses with specific chemical and biological properties as biological optical biomaterials that can be used as an eye medication.A photo of tweezers holding a lens shaped glassy material of Example 21 can be found in Figure 3.The molding can be performed by depositing or spraying the glassy material in viscous or liquid form in a mold. Preferentially, the mold has a hydrophilic surface to allow a better filling. The filled mold can be centrifugated to improve the filling. The liquid form of the glassy material can be degassed beforehand to remove microscopic bubbles.The glassy material according to the invention displays a high biocompatibility which is advantageous when it is used to form microneedles for transdermal or intradermal drug administration. In addition, the glassy material according to the present invention, in which the total content of the at least one polar solvent is greater than 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, can be used for molding microneedles, preferably sharp-edged microneedles, for improved penetration.

[0145] The present invention relates as well to the use of a glassy material according to the invention, in which the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, as a mask in photolithography. Said glassy material, in which the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material, can be spread through spin coating as thin films with nanometric precision.Microneedle

[0146] The present invention also relates to a microneedle comprising the glassy material described above, wherein the total content of the at least one polar solvent is greater than 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

[0147] Preferably, the microneedle is sharp-edged.

[0148] Preferably, the microneedle consists in the glassy material described above, wherein the total content of the at least one polar solvent is greater than 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

[0149] A microneedle according to the present invention displays a high biocompatibility and has improved penetration when used in transdermal or intradermal injection in cosmetics or medicine.EXAMPLES

[0150] The present invention is further illustrated in a non-limitative manner by the following examples.Example 1: Preparation of materialsMaterials and Methods

[0151] Materials were prepared using the following steps: i) dissolving: a compound of formula (I) (invention) or a compound comprising at least one amino acid (comparative), or salts thereof, in water, the total content of water being sufficient for a complete dissolution to form a single-phase solution; ii) drying in a dessicator containing a dessication agent, for instance calcium carbonate, the single-phase solution of step i), at 20 % relative humidity and at ambient temperature, until the total content of water in the material is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.Results

[0152] The compound of formula (I) (invention) or the compound comprising at least one amino acid (comparative), or salts thereof, used are indicated in Table 1.

[0153] Table 1.Example 2: Evaluation of the aging of the materials and measurement of the glass transition temperature (Tg) of the glass materialsMaterials and Methods

[0154] The aspect of the materials prepared in Example 1 was evaluated right after their preparation, after being stored in a closed transparent container during 1 month at ambient temperature and ambient humidity and after being stored during 6 months with the same conditions.

[0155] In addition, the glass transition temperatures (Tg) of the glassy materials prepared in Example 1 have been measured by means of Differential Scanning Calorimetry (DSC). The measurement method is as follow: a peptide sample in liquid, viscous or solid state is inserted in a measurement platinum cup. The sample cup is placed in the calorimeter with an empty cup as reference. The machine is launched to perform 1 to 4 heating / cooling cycles with DSC measurements at temperature between 25°C and 140°C.Results

[0156] The aspect of the above-mentioned materials right after their preparation, after 1 month and after 6 months, as well as the potential glass transition temperatures (Tg) measured, are presented in Table 2.

[0157] Table 2.

[0158] Examples 1-51 correspond to glassy materials according to the invention. The results presented in Table 2 show that said glassy materials according to the invention are solid right after the drying step (z'.e., right after step ii)) and remain solid after a storage in a closed transparent container during 1 month at ambient temperature and ambient humidity. No crystallization was observed. Therefore, this result demonstrates that the glassy materials according to the invention have a supramolecular structure that is stable for at least a month. The glassy material of Example 7 even remains solid for at least 1 year, and its amorphous structure after being stored in a closed transparent container during 1 year at ambient temperature and ambient humidity can be observed in the Wide- Angle X-Ray Scattering graph of Figure 4. Photos of the glassy materials of Examples 29, 15 and 34 can be found respectively in Figures 5 A) to C). A Scanning Electron Microscope (SEM) image of a 300 nm thick slice of the glassy material of Example 21 can be found in Figure 6. Photos of the glassy materials of Example 23, Example 25 and Example 30, which are shaped as microneedles with a height of 600 pm, can be found respectively in Figures 7 A) to C).

[0159] In particular, Examples 1, 3-6, 11, 17, 19, 22-31 and 33-51 correspond to glassy materials according to the invention comprising a compound of formula (La), or a salt thereof, wherein XI and X2, which can be the same or different, represent an amino acid chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L- Glu or D-Glu), or derivatives thereof; preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu); and more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu). The results presented in Table 2 show that said particular glassy materials remain solid for at least 6 months.

[0160] Comparative Examples 1-7 are material comprising a compound that comprises at least one amino acid. However, said compound is different from a compound of formula (I), or a salt thereof, as defined in the present invention. The results presented in Table 2 show that all the materials of Comparative Examples 1-7 were crystalline right after the drying step (z'.e., right after step ii)). The crystalline structure of the material of Comparative Example 6 after being stored during 12 hours at ambient temperature and ambient humidity can be observed in the Wide-Angle X-Ray Scattering graph of Figure8. These results demonstrate the need to have at least one compound of formula (I), or a salt thereof, as defined in the present invention, comprised in the material in order to obtain a solid glassy material. Figure 9 displays a photograph of a three-year-old glassy bead of example 25. This result demonstrates a long stability of the material.

Claims

CLAIMS1. A glassy material comprising: a) at least one compound of formula (I):X1-B-X2 (formula (I)), or a salt thereof, whereinXI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D- Ser), threonine (L-Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L- Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Orn or D-Orn) and cysteine (L-Cys or D-Cys), or derivatives thereof and methionine sulfoxide (L-Met-SO or D-Met-SO); at least one among XI and X2 is chosen from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), or derivatives thereof;B is absent or represents an additional amino acid or a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2; with the proviso that: the compound of formula (I) comprises at least 33 %, in amino acids, of acidic, basic or polar uncharged amino acids; when XI and / or X2 represents lysine (L-Lys or D-Lys) or arginine (L-Arg or D- Arg), B is necessarily present; and the compound of formula (I) is different from a homopolymer of poly-gamma- glutamic acid;and b) at least one polar solvent in a total content ranging from 0.1 % to 30 % by weight relative to the total weight of the glassy material.

2. The glassy material according to claim 1, wherein at least one amino acid of the compound of formula (I) is linked to another non-adjacent amino acid of said compound of formula (I) via an intramolecular bridge.

3. The glassy material according to claim 1 or claim 2, wherein its glass transition temperature ranges from 50 °C to 150°C and preferably from 70 °C to 130°C.

4. The glassy material according to any one of the preceding claims, wherein the at least one polar solvent is chosen from water, polar organic solvents, and mixtures thereof; preferably from water, acetone, methanol, ethanol, dimethylsulfoxide and mixtures thereof; and more preferably the polar solvent is water.

5. The glassy material according to any one of the preceding claims, wherein the total content of the at least one polar solvent ranges from 10 % to 30 % by weight relative to the total weight of the glassy material.

6. The glassy material according to any one of claims 1 to 4, wherein the total content of the at least one polar solvent is greater than or equal to 0.1 % and lower than 10 % by weight relative to the total weight of the glassy material.

7. The glassy material according to any one of the preceding claims, wherein XI and X2, the same or different, represent an amino acid chosen from histidine (L-His or D-His), glutamic acid (L-Glu or D-Glu), arginine (L-Arg or D-Arg), lysine (L-Lys or D-Lys), aspartic acid (L-Asp or D-Asp), serine (L-Ser or D-Ser), threonine (L- Thr or D-Thr), glutamine (L-Gln or D-Gln), asparagine (L-Asn or D-Asn), tyrosine (L-Tyr or D-Tyr), glycine (L-Gly or D-Gly), citrulline (L-Cit or D-Cit), ornithine (L-Om or D-Orn) and cysteine (L-Cys or D-Cys); preferably from histidine (L-His or D-His), arginine (L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), ornithine (L-Om or D-Orn) ; and more preferably from histidine (L-His or D-His), arginine(L-Arg or D-Arg) and glutamic acid (L-Glu or D-Glu), even more preferably from histidine (L-His or D-His) and glutamic acid (L-Glu or D-Glu) .

8. The glassy material according to any one of the preceding claims, wherein B represents a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2, and the number of additional amino acids in the linear sequence of B ranges from 2 to 200; preferably from 2 to 150; and more preferably from 2 to 100.

9. The glassy material according to any one of claims 1 to 7, wherein B represents a linear sequence of at least two identical or different additional amino acids, which may be the same or different from XI and X2, and the number of additional amino acids in the linear sequence of B ranges from 201 to 700; and preferably from 201 to 634.

10. The glassy material according to any one of the preceding claims, wherein the additional amino acids of B are chosen from alanine (L-Ala or D-Ala), arginine (L- Arg or D-Arg), asparagine (L-Asn or D-Asn), aspartic acid (L-Asp or D-Asp), cysteine (L-Cys or D-Cys), glutamic acid (L-Glu or D-Glu), glutamine (L-Gln or D-Gln), glycine (L-Gly or D-Gly), histidine (L-His or D-His) or a derivative thereof, isoleucine (L-Ile or D-Ile), leucine (L-Leu or D-Leu), lysine (L-Lys or D- Lys), methionine (L-Met or D-Met), phenylalanine (L-Phe or D-Phe), proline (L- Pro or D-Pro), pyrrolysine (L-Pyl or D-Pyl), selenocysteine (L-Sec or D-Sec), serine (L-Ser or D-Ser), threonine (L-Thr or D-Thr), tryptophan (L-Trp or D-Trp), tyrosine (L-Tyr or D-Tyr), valine (L-Val or D-Val), carnitine (L-camitine or D- carnitine), gamma-aminobutyric acid, hydroxyproline (Hyp), methionine sulfoxide (L-Met-SO or D-Met-SO), selenomethionine (L-SeMet or D-SeMet), citrulline (L- Cit or D-Cit), ornithine (L-Orn or D-Orn), beta-alanine, alpha-aminoisobutyric acid (Aib), alpha-aminobutyric (L-Abu or D-Abu), 3 -aminomethylbenzoic acid, anthranilic acid, homoarginine (L-Har or D-Har), delta-hydroxy -lysine (Hyl), 3- mercaptophenylalanine (L-3 -mercaptophenylalanine or D-3- mercaptophenylalanine), 2 -hydroxyphenylalanine (L-2-hydroxyphenylalanine orD-2-hydroxyphenylalanine), 3 -hydroxyphenylalanine (L-3 -hydroxyphenylalanine or D-3 -hydroxyphenylalanine), phenylglycine (L-Phg or D-Phg), homophenylalanine (L-Hph or D-Hph), beta-(2-pyridyl)-alanine (L-2Pal or D- 2Pal), beta-(3-pyridyl)-alanine (L-3Pal or D-3Pal), 4-methyL-phenylalanine (L-4- methyL-phenylalanine or D-4-methyL-phenylalanine), 4-amino-phenylalanine (L- 4-amino-phenylalanine or D-4-amino-phenylalanine), 2,3 -diaminopropionic acid (L-Dap or D-Dap), 2,4-diaminobutyric acid (L-Dab or D-Dab), 3,4-dihydroproline (L-Dhp or D-Dhp), thiaproline (L-thiaproline or D-thiaproline), alphamethylproline (L-alpha-methylproline or D-alpha-methylproline), pipecolic acid (L-pipecolic acid or D-pipecolic acid), alpha-aminoadipic acid (L-Aad or D-Aad), 2-aminoheptanedioic acid (L-2-aminoheptanedioic acid or D-2-aminoheptanedioic acid), 2-ami-noheptanedioic acid (L-2-ami-noheptanedioic acid or D-2-ami- noheptanedioic acid), alpha-aminosuberic acid (L-ASU or D-ASU), and 3,4- dihydroxyphenylalanine (L-DOPA or D-DOPA), 4-(phenylazo)-phenylglycine (L- 4-(phenylazo)-phenylglycine or D-4-(phenylazo)-phenylglycine), (4-phenylazo)- phenylalanine (L-(4-phenylazo)-phenylalanine or D-(4-phenylazo)-phenylalanine), (4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine (L-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine or D-(4-(4’-tert-Butoxycarbonyl)phenylazo)phenylalanine), azobenzyl-lysine (L-azobenzyl-lysine or D- azobenzyl-lysine), or derivatives thereof.

11. The glassy material according to any one of the preceding claims, further comprising at least one additional ingredient, different from the at least one compound of formula (I), or a salt thereof, and from the at least one polar solvent, chosen from active ingredients, pH controlling agents, surfactants, transition metal salts or post-transition metal salts, and mixtures thereof12. A method for preparing a glassy material according to any one of claims 1 to 11 comprising the following steps: i) dissolving the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient in the at least one polarsolvent, the total content of said at least one polar solvent being sufficient for a complete dissolution to form a single-phase solution, ii) drying the single-phase solution of step i) to remove partially the at least one polar solvent until the total content of said at least one polar solvent ranges from 0.1 % to 30 % by weight relative to the total weight of the glassy material, to obtain a glassy material according to any one of claims 1 to 11, and then iii) optionally, when the glassy material obtained in step ii) has a total content of the at least one polar solvent that ranges from 10 % to 30 % by weight relative to the total weight of the glassy material, stretching said material to obtain fibers, rods or microneedles.

13. A method for preparing a glassy material according to any one of claims 1 to 4 and 6 to 11 comprising the following steps: i) mixing the at least one compound of formula (I), or a salt thereof, and the optional at least one additional ingredient, ii) heating the mixture of step i) until melting of said mixture to obtain a melted material, the heating temperature being greater than or equal to the glass transition temperature of the at least one compound of formula (I), or of a salt thereof, and then iii) cooling the melted material obtained in step ii) to ambient temperature to obtain a glassy material according to any one of claims 1 to 4 and 6 to 11.

14. Use of a glassy material according to any one of claims 1 to 5 and 7 to 11 as a glue.

15. Use of a glassy material according to any one of claims 1 to 11 as a cryoprotectant and / or a thermal protectant for molecules and / or biological elements when the temperature is below the glass transition temperature of said glassy material.

16. Use of a glassy material according to any one of claims 1 to 4 and 6 to 11, for molding water-soluble glass structures with a micrometric to nanometric precision.

17. A microneedle comprising the glassy material according to any one of claims 1 to 4 and 6 to 11.

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