Soluble biomolecular glass and its use

Abstract

The present invention provides biomolecular glass and its use. The biomolecular glass is obtained by volatilizing a solvent from a solution of biomolecular raw materials, the solution of biomolecular raw materials comprising biomolecular raw materials, a modifier, and a solvent. The biomolecular raw materials include natural amino acids, peptides, amino acid derivatives, peptide derivatives, or mixtures of two or more of the above. The soluble biomolecular glass of the present invention has excellent biocompatibility, high light transmittance, good mechanical strength, flexible processability, and biodegradability, and can be processed into implantable or non-implantable medical materials and / or devices, fillers and stent materials, electronic sensing materials and / or devices, temporary electronic materials and / or devices, etc., and can be decomposed by living organisms or nature, with decomposition products being non-contaminating.

Description

[Technical Field]

[0001] This invention relates to soluble biomolecular glass, a method for producing it, and its use, and belongs to the technical field of materials and methods for producing the same. This invention discloses soluble biomolecular glass based on amino acids and peptides, and a method for producing glass by evaporating a solvent from a biomolecular solution. Such soluble biomolecular glass can be processed into implantable or non-implantable medical materials and / or devices, fillers and stent materials, electronic sensing materials and / or devices, temporary electronic materials and / or devices, and can be applied in the fields of healthcare, health monitoring, security encryption, information transmission, and storage. [Background technology]

[0002] Glass is an amorphous solid with properties such as transparency, high hardness, and corrosion resistance, and its applications are diverse. For example, 1) as an important building material, glass is widely used in building facades, roofs, partitions, doors and windows, stair railings, and skylights. 2) Because glass has excellent electrical properties, it is widely used in electronic devices such as display screens, touchscreens, and fiber optic transmission chips. Glass has special physical, chemical, and mechanical properties, and with the continuous progress and innovation of science and technology, the application fields of glass continue to expand.

[0003] The chemical properties of glass are extremely stable, and glass products do not decompose in nature, remaining in the natural environment for long periods, thus placing a serious burden on the ecological environment. Biomolecules, especially amino acids and peptides, possess excellent biocompatibility and biodegradability. Currently, researchers are using biomolecules to produce biodegradable glass.

[0004] Currently, the production of biomolecular glass based on conventional melt-quenching methods has been disclosed. For example, biodegradable glass based on amino acids, peptides, and derivatives (CN113754556B), cyclic peptide glass, and pharmaceutical composition glass containing cyclic peptides (CN114014908A) have been disclosed. However, conventional melt-quenching methods for producing amino acid / peptide glass have significant limitations. Firstly, amino acid / peptide molecules have high melting points and are prone to thermal decomposition before high-temperature melting. Secondly, the high-temperature melting and low-temperature quenching processes are complex and environmentally unfriendly. Thirdly, amino acid / peptide molecules are easily oxidized under high-temperature conditions, affecting the light transmittance and transparency of the glass. Furthermore, heating alters the structure and conformation of amino acid / peptide molecules, significantly reducing their biological activity. Therefore, there are limitations to the production of biomolecular glass by melt-quenching methods.

[0005] Currently, no method for producing amino acid / peptide glass other than the "melt-quenching" method has been disclosed. Surprisingly, the present invention has discovered that amino acid / peptide molecules can form glass in an aqueous solution by adding a modifier and then evaporating the solvent. Such amino acid / peptide biomolecular glass is water-soluble, biodegradable by organisms or nature, and the degradation products are completely environmentally friendly. Compared to the conventional melt-quenching method, the method of the present invention is simpler, gentler, more controllable, and more environmentally friendly.

[0006] This invention is based on this discovery. The soluble biomolecular glass and biomolecular glass materials and / or devices developed based on this invention are expected to have applications in fields such as implantable and non-implantable medical materials and / or devices, fillers and stents, electronic sensing materials and / or devices, the manufacture of temporary electronic materials and / or devices, healthcare, health monitoring, security encryption, information transmission and storage. [Overview of the project] [Problems that the invention aims to solve]

[0007] The main object of the present invention is to provide a soluble biomolecular glass mainly composed of natural amino acids, peptides, amino acid derivatives, peptide derivatives, or mixtures of two or more of the above, modifiers, and aqueous solvents, and a method for producing the same. Unlike the previously disclosed "melt quenching" (CN113754556B, CN114014908A) for producing amino acid / peptide glass, the present invention discloses a method for producing glass by heating and / or pressurizing an aqueous biomolecular solution to achieve solvent volatilization. [Means for solving the problem]

[0008] The soluble biomolecular glass of the present invention possesses excellent biocompatibility, high light transmittance, good mechanical strength, and flexible processability. The soluble glass produced by this method can be processed into implantable or non-implantable medical materials and / or devices, fillers and stent materials, electronic sensing materials and / or devices, temporary electronic materials and / or devices, and can be decomposed by the biological or ecological environment, with the decomposition products being completely environmentally friendly.

[0009] The soluble biomolecular glass and its manufacturing method of the present invention can be applied to fields such as healthcare, health monitoring, security encryption, information transmission, and storage.

[0010] In the first embodiment, a biomolecular glass is obtained by volatilizing a solvent from a solution of biomolecular raw materials, the solution of biomolecular raw materials comprises biomolecular raw materials, a modifier, and a solvent, and the biomolecular raw materials comprise natural amino acids, peptides, amino acid derivatives, peptide derivatives, or a mixture of two or more of the above.

[0011] In the second embodiment, in the soluble biomolecular glass described above, the biomolecular raw material comprises a natural amino acid, a peptide, an amino acid derivative, a peptide derivative, or a mixture of two or more of the above. in particular, A natural amino acid molecule represented by formula (1), or a derivative of an amino acid, or a pharmaceutically acceptable salt thereof, or a mixture of any one or more of the above. [Chemical formula] The amino acids include glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, and pyrrolysine. Or a peptide molecule formed by condensing formula (1) via a peptide bond, or a derivative of a peptide, or a pharmaceutically acceptable salt thereof, or a mixture of any one or more of the above. The peptide is a molecule formed by condensing n of the above amino acids via a peptide bond, where n ≥ 2, preferably 2 ≤ n ≤ 10. In the derivatives of the above amino acids or peptides, the protecting groups include, but are not limited to, Trt, Boc, Fmoc, Cbz / Z, Allyl, C2-C18 acyl, benzoyl, naphthoyl, OFm, Otbu, OBzl, OAll, OMe, OEt.

[0012] In the third aspect, in the above soluble biomolecule glass, the regulator is selected from nucleotides, nucleotide polymers, RNA, DNA and / or other regulators, or a mixture of two or more of the above. Exemplarily, The nucleotides include, but are not limited to, adenosine-5'-monophosphate (AMP), nicotinamide mononucleotide (NMN), guanosine-5'-monophosphate (GMP), uridine-5'-monophosphate (UMP), cytidine-5'-monophosphate (CMP), and adenosine-3'-monophosphate (3-AMP). Other regulators include, but are not limited to, D / L-tartaric acid, hydrochloric acid, sulfuric acid, phosphoric acid, lactic acid, polylactic acid, hyaluronic acid, alginic acid, lactobionic acid, citric acid, tartaric acid, oxalic acid, D / L-malic acid, maleic acid, pseudolaric acid, acamprosate, quinic acid, adipic acid, fumaric acid, hexanoic acid, heptanoic acid, caprylic acid, valeric acid, butyric acid, propionic acid, and glacial acetic acid. Preferably, they are hydrochloric acid, nucleotide, citric acid, glacial acetic acid, and malic acid.

[0013] In the fourth aspect, in the above soluble biomolecule glass, the solvent is water or its salt solution.

[0014] In the fifth aspect, the method for producing soluble biomolecule glass is as follows. Step (1): Weigh, mix, and uniformly pulverize the biomolecule raw materials. Step (2): Dissolve the raw material powder from step (1) in a solvent to obtain a biomolecule solution. Step (3): Add a regulator to the biomolecule solution from step (2) and adjust the final pH of the solution by controlling the amount of the regulator. When the regulator is a mixed solution, it needs to be uniformly premixed. Step (4): Put the aqueous solution from step (3) into a container and volatilize the solvent by adjusting the temperature and / or applying pressure and / or vacuum to the solution to produce soluble biomolecule glass.

[0015] In the sixth aspect, in the above soluble biomolecule glass and production method, the pH of the biomolecule solution to which the regulator is added is 1 to 8, preferably 4 to 7.

[0016] In the seventh aspect, in the above soluble biomolecule glass and production method, the volatilization of the solvent can be achieved by air flow, spraying, fluidized bed, rotary flash, infrared rays, microwaves, freezing / vacuum freezing.

[0017] In the eighth aspect, in the above soluble biomolecule glass and manufacturing method, the volatilization time of the solvent is 20 min to 7 h, preferably 40 min to 4 h, which is characterized by this.

[0018] In the ninth aspect, in the above soluble biomolecule glass and manufacturing method, the mass fraction of the biomolecule raw material in the glass is 50 to 99.5 wt%, preferably 85 to 99 wt%, the mass fraction of the modifier in the glass is 0 to 50 wt%, preferably 0 to 15 wt%, more preferably greater than 0 wt%, and the mass fraction of the solvent in the glass is 0.05 to 5 wt%, preferably 0.1 to 2 wt%, which is characterized by this.

[0019] In the tenth aspect, in the above soluble biomolecule glass and manufacturing method, there is a strong hydrogen bonding action between the biomolecule and the modifier and / or solvent, and the hydrogen bond network is richly contained in the biomolecule glass, which is characterized by this.

[0020] In the eleventh aspect, the above soluble biomolecule glass is a glassy amorphous body, that is, an amorphous solid, showing isotropy, having no fixed melting point, and being reversible, which is characterized by this.

[0021] In the twelfth aspect, in the above soluble biomolecule glass, there is a glass transition temperature (Tg), and Tg can be adjusted within 0 to 200 °C. Preferably, the Tg of the soluble biomolecule glass is 20 °C < Tg < 200 °C, which is characterized by this.

[0022] More preferably, the range of Tg of the soluble biomolecule glass is 20 °C < Tg < 160 °C.

[0023] In the thirteenth aspect, the above soluble biomolecule glass has a relatively good glass-forming ability (GFA), that is, the ratio of Tg (glass transition temperature) / Tm (melting point temperature) is distributed between 0.55 and 0.75, preferably 0.66 to 0.75, which is characterized by this.

[0024] In the 14th embodiment, the performance indicators for the soluble biomolecular glass described above are as follows: If its thickness is 1 mm, at a wavelength of 500 nm, The light transmittance is 40-99%, preferably 80-99%. It is characterized by having a hardness greater than 20 MPa, and preferably greater than 50 MPa.

[0025] In the 15th embodiment, the soluble biomolecular glass described above can be processed into implantable or non-implantable medical materials and / or devices, fillers and stent materials, electronic sensing materials and / or devices, temporary electronic materials and / or devices, and the processing method may be spin coating, casting, electrospinning, or 3D printing.

[0026] In the sixteenth embodiment, the above-mentioned soluble biomolecular glass and biomolecular glass material and / or device can be decomposed by a biological or ecological environment, preferably at room temperature and / or human body temperature, in a compost environment, and more preferably temporarily decomposed in an aqueous solution, blood, tissue fluid, or bodily fluid environment.

[0027] In the 17th aspect, the above-mentioned soluble biomolecular glass and biomolecular glass material and / or device is characterized in that the dissolution time can be controlled according to the glass raw material, size, and structure, with a range of 0.5 minutes to 3.5 months, and the dissolution rate can be adjusted and / or controlled by controlling the dissolution time according to the glass raw material, size, and structure.

[0028] In the 18th embodiment, the soluble biomolecular glass and biomolecular glass material and / or device described above are characterized by being completely decomposed and / or temporarily dissolved.

[0029] In the 19th aspect, the above-mentioned soluble biomolecular glass and biomolecular glass materials and / or devices can be applied in fields such as healthcare, health monitoring, security encryption, information transmission and storage. Preferably, it can be used for processing and manufacturing soluble glass microneedles for puncturing the skin and / or mucous membranes, the blood-eye barrier, the blood-brain barrier, etc., for pharmaceutical purposes. And / or, it can be used in soluble supercapacitors, chips, glass electrodes, temporary circuits / memories, etc. for pharmaceutical, sensing, or electronic applications. It is characterized in that it can be used for pharmaceutical or medical purposes as a soluble stent, preferably a bone stent, and / or a cardiac stent, and / or a vascular stent, etc. [Brief explanation of the drawing]

[0030] [Figure 1] This is a photograph of the actual arginine glass produced in Example 1. [Figure 2] This is the mass spectrum of the arginine glass produced in Example 1, demonstrating the stability of the molecular structure of the produced amino acids. [Figure 3] This shows the decomposition curve of the arginine glass produced in Example 1 in industrial wastewater and industrial soil, demonstrating its decomposition properties. [Figure 4] This is a real-world image of the phenylalanine solid glass produced in Example 2 at room temperature. It can be processed into glass blocks or glass wires as needed, demonstrating its high processability. [Figure 5] These are bright-field and polarized-field microscopic images of the phenylalanine glass and phenylalanine crystals produced in Example 2, demonstrating that the formed amino acid glass has an amorphous structure. [Figure 6]The infrared spectra of the phenylalanine glass and phenylalanine crystals produced in Example 2 show that the peaks in the infrared spectrum of the glass are significantly broadened, indicating that the molecules within the phenylalanine glass are disordered. [Figure 7] These are the DSC and TG spectra of the histidine solid glass produced in Example 3. [Figure 8] These are the XRD patterns of tyrosine crystal powder and glass in Example 4. [Figure 9] This is the transmittance of the aspartate solid glass in Example 5. [Figure 10] This is the sustained release curve of the exenatide glass produced in Example 5. [Figure 11] These are the emission curves for the aspartate glass and crystals produced in Example 5. [Figure 12] This is a photograph of the actual glass sample of thymopentine in Example 8. [Figure 13] This is a photograph of glass formed using a mold with thymopentine glass in Example 9. [Figure 14] This is a photograph of the actual glass sample of exenatide used in Example 10. [Figure 15] This is a curve showing the blood glucose control of spontaneously developing type II diabetes mice using aspartate glass produced in Example 5. [Figure 16] This shows the XRD patterns of Boc-Val glass and crystalline powder in Example 6. [Figure 17] This is a polarized light microscope image of the solid glass containing the N-acetyl-L-threonine and L-arginine composition in Example 7. [Figure 18] This is an in vivo pharmacodynamic evaluation of thymopentin solid glass in rats in Example 8. [Figure 19] This is the neurological function score in experimental autoimmune encephalomyelitis (EAE) mice using tuftsin glass in Example 9. [Figure 20]This is an actual image of the microneedle manufactured in Example 29. [Figure 21] This is a photograph of a laser conduction waveguide made of phenylalanine glass optical fiber manufactured in Example 31. [Figure 22] This is the process of disappearance due to water exposure of the simulated circuit in Example 32. [Figure 23] This is the process of the interdigital electrode disappearing upon exposure to water in Example 33. [Modes for carrying out the invention]

[0031] The technical solutions of the present invention will be described in detail below through examples, but the scope of protection of the present invention is not limited thereto. Example 1

[0032] A method for producing bioglass based on arginine includes the following steps. A 250 ml solution of 0.01 M citric acid was prepared and ready for use. 500 mg of L-arginine powder was weighed out and ground uniformly in a mortar. The arginine powder from step (2) was placed in a 500 ml round-bottom flask, 20 ml of ultrapure water was added, and the arginine powder was completely dissolved to obtain an arginine solution. 20 ml of the citric acid solution from step (1) was added to the arginine solution from step (3) to adjust the pH of the arginine solution to 6.0. Heat the arginine solution from step (4) for 10K min. -1 The round-bottom flask was heated to 373K at the specified heating rate, and the solvent was evaporated by constant temperature treatment at this temperature for 2 hours to obtain arginine (Arg) based glass. Figure 1 shows an image of the arginine glass produced in Example 1. As shown in Figure 1, this glass was found to have good optical properties. Furthermore, the transmittance at 500 nm (sample thickness 1 mm) measured with a UV spectrometer is shown in Table 1. The mass spectrum of the produced arginine glass is shown in Figure 2. The results showed that the produced amino acid had a stable molecular structure and did not oxidize or decompose. The produced glass has a glass transition temperature Tg=337K, a melting point Tm=495K, and a Tg / Tm ratio of 0.68. It was shown to have relatively good glass-forming ability. Figure 3 shows the decomposition curves of the arginine glass (mass 32.2 mg) produced in Example 1 in industrial soil and industrial wastewater, demonstrating that the arginine glass can decompose in the environment. Example 2

[0033] A method for producing biological glass based on phenylalanine includes the following steps: 250 ml of 0.2 M citric acid aqueous solution was prepared and ready for use. 1 g of L-phenylalanine powder was weighed and placed in a mortar and ground uniformly. The phenylalanine powder from step (2) was placed in a 500 ml round-bottom flask, 20 ml of ultrapure water was added, and the phenylalanine powder was completely dissolved to obtain a phenylalanine solution. 20 ml of the citric acid solution from step (1) was added to the phenylalanine solution from step (3) to adjust the pH of the phenylalanine solution to 5.0. The phenylalanine solution from step (4) is heated at a constant temperature for 40K min. -1 The round-bottom flask was heated to 363K at the following heating rate, and the temperature was maintained at 363K for 2.5 hours. Once the solution in the round-bottom flask in step (5) becomes a viscous fluid, keep it warm for another 30 minutes, then cool the apparatus for 40K min. -1 The temperature was lowered to 273K at the specified rate. After incubation for 30 minutes, phenylalanine (Phe) biomolecular glass was obtained. Figure 4 shows a real-world image of the manufactured phenylalanine solid glass at room temperature. This glass can be processed into glass blocks or glass wires as needed, demonstrating its strong processability. Figure 5 shows bright-field and polarized-field micrographs of the phenylalanine glass and phenylalanine crystals manufactured in Example 2, demonstrating that the formed amino acid glass has an amorphous structure. Figure 6 shows the infrared spectra of the phenylalanine glass and phenylalanine crystals manufactured in Example 2, where the peaks in the infrared spectrum of the glass are greatly broadened, indicating that the molecules within the phenylalanine glass are disordered. Further measurements showed that the manufactured glass has a glass transition temperature Tg=400K, a melting point Tm=556K, and a Tg / Tm ratio of 0.72, indicating that it has relatively good glass-forming ability. Example 3

[0034] A method for producing bioglass based on histidine includes the following steps: 250 ml of 0.1 M hydrochloric acid aqueous solution was prepared and ready for use. 1 g of L-histidine powder was weighed and placed in a mortar and pestle, and then uniformly ground. The histidine powder from step (2) was placed in a 500 ml round-bottom flask, and 20 ml of ultrapure water and 1 ml of ethanol were added to completely dissolve the histidine powder and obtain a histidine solution. Add 20 ml of the hydrochloric acid solution from step (1) to the histidine solution from step (3) to adjust the pH of the histidine solution to 5.0. The histidine solution from step (4) is heated at a constant temperature for 50 K min. -1 The round-bottom flask was heated to 383K at the following heating rate and maintained at 383K for 1.5 hours. Afterward, the apparatus was cooled to 50K min. -1 The temperature was lowered to 293K at the specified rate, and then maintained for 30 minutes to obtain histidine (His) solid glass. Figure 7 shows the DSC and TGA spectra of the histidine solid glass produced in Example 3, which have a glass transition temperature Tg=375K, a melting point Tm=559K, and a Tg / Tm ratio of 0.67, indicating that the solid histidine glass has relatively good glass-forming ability. Example 4

[0035] A method for producing biological glass based on tyrosine includes the following steps: 100 ml of 0.5 M acetic acid aqueous solution was prepared and ready for use. Two grams of L-tyrosine powder were weighed and placed in a mortar, then uniformly ground. The tyrosine powder from step (2) was placed in a 500 ml round-bottom flask, 30 ml of ultrapure water was added, and the tyrosine powder was completely dissolved to obtain a tyrosine solution. 20 ml of the acetic acid solution from step (1) was added to the tyrosine solution from step (3) to adjust the pH of the tyrosine solution to 5.5. The tyrosine solution from step (4) is heated at a constant temperature for 50 K min. -1 The round-bottom flask was heated to 383K at the following heating rate and maintained at 383K for 10 minutes. The apparatus in step (5) is subjected to a cooling treatment for 50K min. -1 The temperature was reduced to 293K at this rate of cooling. The solvent was evaporated from the tyrosine solution in step (6) at room temperature and allowed to stand for 20 days to obtain tyrosine biological glass. Figure 8 shows the XRD patterns of tyrosine crystal powder and glass in Example 4, demonstrating that the tyrosine glass is amorphous. Further measurements showed that the fabricated glass had a glass transition temperature Tg=344K, a melting point Tm=617K, and a Tg / Tm ratio of 0.67, indicating that this glass has relatively good glass-forming ability. Example 5

[0036] A method for producing biological glass based on aspartic acid includes the following steps: 500 ml of 0.3 M citric acid aqueous solution was prepared and ready for use. Weighed 500 mg of L-aspartic acid powder, put it into a mortar, and pulverized it uniformly. Put the aspartic acid powder in step (2) into a 500 ml round-bottom flask, added 30 ml of ultrapure water, and completely dissolved the aspartic acid powder to obtain an aspartic acid solution. Added 20 ml of the citric acid aqueous solution in step (1) to the aspartic acid solution in step (3) to adjust the pH of the aspartic acid solution to 5.0. The aspartic acid solution in step (4) was heat-treated at a constant temperature, and the round-bottom flask was heated to a temperature of 383 K at a heating rate of 30 K min -1 , and the temperature of 383 K was maintained for 3 h. Then, it was cooled to a temperature of 293 K at a cooling rate of 50 K min -1 , and kept warm for 30 min to obtain aspartic acid (Asp) bioglass. Figure 9 shows the transmittance of the aspartic acid solid glass in Example 5, and its transmittance is about 99%. Further measurement results show that the produced glass has a glass transition temperature Tg = 377 K, a melting point Tm = 503 K, and a Tg / Tm ratio of 0.75, indicating that this glass has relatively good glass-forming ability. Example 6

[0037] The method for producing bioglass based on valine includes the following steps. Prepared 500 ml of 0.01 M malic acid aqueous solution for use. Weighed 500 mg of N-tert-butyloxycarbonyl-L-valine (Boc-Val) powder, put it into a mortar, and pulverized it uniformly. Put the Boc-Val powder in step (2) into a 500 ml round-bottom flask, added 30 ml of ultrapure water and 3 ml of glycerol respectively, and completely dissolved the Boc-Val powder to obtain a Boc-Val solution. Added 20 ml of the malic acid aqueous solution in step (1) to the Boc-Val solution in step (3) to adjust the pH of the Boc-Val solution to 5.5. The Boc-Val solution in step (4) was heat-treated at a constant temperature, and heated to a temperature of 323 K at a heating rate of 10 K min -1 , and the temperature of 323K was maintained for 5h. When the solution in the round-bottom flask in step (5) became a viscous fluid, a glass based on N-tert-butyloxycarbonyl-L-valine (Boc-Val) was obtained. Figure 10 shows the XRD patterns of the Boc-Val glass and crystalline powder in Example 6, demonstrating that the Boc-Val glass is amorphous. Further measurements showed that the fabricated glass had a glass transition temperature Tg=406K, a melting point Tm=588K, and a Tg / Tm ratio of 0.69, indicating that this glass has relatively good glass-forming ability. Example 7

[0038] A method for producing glass based on a composition of threonine and arginine includes the following steps: A 50 ml solution of 0.01 M citric acid was prepared and ready for use. 1 g of N-acetyl-L-threonine powder and 1 g of L-arginine powder were weighed out, placed in a mortar, and ground until uniformly mixed. The mixed powder of N-acetyl-L-threonine and arginine from step (2) was placed in a 500 ml round-bottom flask, and then 40 ml of ultrapure water was added to completely dissolve the amino acid mixture powder and obtain an amino acid solution. Add 40 ml of the citric acid solution from step (1) to the amino acid solution from step (3) to adjust the pH of the amino acid solution to 5.0. The amino acid solution from step (4) is heated at a constant temperature for 50K min. -1 The round-bottom flask was heated to 383K at the following heating rate and maintained at 383K for 1.5 hours. After the solution in the round-bottom flask in step (5) becomes a viscous fluid, maintain a constant temperature for 20 minutes, then cool the apparatus for 50K min. -1 The mixture was cooled to 293K at a low cooling rate and then kept warm for 30 minutes to obtain a solid glass composition of N-acetyl-L-threonine and L-arginine. Figure 11 shows polarized light microscope images of the solid glass of the N-acetyl-L-threonine and L-arginine composition in Example 7 (bright-field on the left, polarized-field on the right), demonstrating that the mixed solid glass is amorphous. Example 8

[0039] A method for producing solid glass based on thymopentin includes the following steps: A 50 ml solution of 0.01 M citric acid was prepared and ready for use. 10 mg of thymopentin powder was weighed, placed in a mortar, and ground until uniformly mixed. The thymopentin powder from step (2) was placed in a 250 ml round-bottom flask, and then 10 ml of ultrapure water was added to completely dissolve the thymopentin powder and obtain a thymopentin solution. To the amino acid solution from step (3), 10 ml of the citric acid aqueous solution from step (1) was added to adjust the pH of the thymopentin solution to 6.0. The amino acid solution from step (4) is heated at a constant temperature for 50K min. -1 The round-bottom flask was heated to 383K at the following heating rate and maintained at 383K for 1.5 hours. After the solution in the round-bottom flask in step (5) became a viscous fluid, the constant temperature was maintained for 20 minutes, and then the apparatus was cooled for 50K minutes. -1 The temperature was lowered to 293K at the specified cooling rate, and then maintained for 30 minutes to obtain a solid glass based on thymopentine. Figure 12 shows an actual image of the thymopentine glass in Example 8, which is transparent. Example 9

[0040] The method for manufacturing glass based on tuftosine includes the following steps: A 50 ml solution of 0.01 M malic acid was prepared and ready for use. 10 mg of tuftosin powder was weighed, placed in a mortar, and ground until uniformly mixed. The tuftosin powder from step (2) was placed in a 250 ml round-bottom flask, and then 10 ml of ultrapure water was added to completely dissolve the tuftosin powder and obtain a tuftosin solution. To the amino acid solution from step (3), 10 ml of the malic acid solution from step (1) was added to adjust the pH of the tuftosin solution to 6.0. The amino acid solution from step (4) is heated at a constant temperature for 10K min. -1The round-bottom flask was heated to 363K at the following heating rate and maintained at 363K for 2 hours. After the solution in the round-bottom flask in step (5) became a viscous fluid, the constant temperature was maintained for 30 minutes, and then the apparatus was cooled down for 40K minutes. -1 The temperature was lowered to 293K at the specified cooling rate, and then maintained for 30 minutes to obtain a solid glass based on tuftosine. Figure 13 shows glass formed using a mold with thymopentine glass in Example 9, demonstrating the processability of peptide glass. Example 10

[0041] A method for manufacturing glass based on exenatide includes the following steps: A 50 ml solution of 0.01 M malic acid was prepared and ready for use. 10 mg of exenatide powder was weighed, placed in a mortar, and ground until uniformly mixed. The exenatide powder from step (2) was placed in a 250 ml round-bottom flask, and then 10 ml of ultrapure water was added to completely dissolve the exenatide powder and obtain an exenatide solution. To the amino acid solution from step (3), 10 ml of the malic acid aqueous solution from step (1) was added to adjust the pH of the exenatide solution to 6.0. The amino acid solution from step (4) is heated at a constant temperature for 10K min. -1 The round-bottom flask was heated to 363K at the following heating rate and maintained at 363K for 2 hours. After the solution in the round-bottom flask in step (5) became a viscous fluid, the constant temperature was maintained for 30 minutes, and then the apparatus was cooled down for 40K minutes. -1 The temperature was lowered to 293K at the specified cooling rate, and then maintained for 30 minutes to obtain a solid glass based on exenatide. Figure 14 shows an actual image of the exenatide glass in Example 10, which is transparent. Examples 11-20

[0042] The exenatide in Example 10 was replaced with equal masses of Arg-Arg, Arg-Gly-Asp, Thr-Lys-Pro-Arg, glutathione, vancomycin hydrochloride, Ac-Ala, Ac-Ala-Gln, Cbz-Phe-Phe, Cbz-Phe-Phe-Gly, and Tyr-Ser-Pro-Thr-Ser-Pro-Ser to obtain the corresponding biomolecular glasses, and the transmittance and hardness of the manufactured glasses were measured. Method for measuring transmittance: The glass produced in each example was processed into a glass disc with a diameter of 1 cm and a thickness of 1 mm, and the transmittance at 500 nm was measured using an ultraviolet spectrophotometer (model: Shimadzu UV-1900i).

[0043] Hardness Measurement Method: The hardness of biomolecular glass was measured using a G200 nanoindenter (manufactured by Agilent). Measurement Method: A triangular pyramidal diamond indenter was used to measure the hardness at a constant strain rate (0.05 s). -1 An indentation was made in the glass material using a pressure test. Hardness data for each biomolecular glass was obtained by plotting the load and displacement. The results are shown in the table below. [Table 1] Example 21: Lightstability Test of Glass

[0044] Specifically, the glass produced in each example was processed into a glass disc with a diameter of 1 cm and a thickness of 1 mm, and placed in a light environment with a xenon lamp (Philips) and an illuminance of 6000 lux. The appearance of the glass discs was observed on the 7th, 15th, and 30th days, and the transmittance at 500 nm was measured. The results are shown in Table 2. [Table 2] The results above demonstrate that the manufactured glass possesses excellent photostability. Example 22: High-temperature stability test of glass

[0045] Specifically, the glass produced in each example was processed into a glass disc with a diameter of 1 cm and a thickness of 1 mm, placed in a high-temperature, high-humidity environment (ambient temperature 50°C, relative humidity 96%), and observed on day 0, day 15, and day 30. The results are shown in Table 3. [Table 3] The results above demonstrate that the manufactured glass possesses excellent high-temperature stability. Example 23: Slow-release curve of manufactured exenatide glass

[0046] Specifically, the initial mass of the exenatide glass was 30±1 mg for all samples, the sustained-release solvent was 10 mL of phosphate buffer (0.01 M, pH=6.8), and the stirring speed was 100 rpm. -1 The upper layer of the solution was collected at different time points, and the eluted exenatide was detected by high-performance liquid chromatography (HPLC). High-performance liquid chromatography (HPLC) conditions: Liquid phase elution conditions: Mobile phase A - water (0.1% TFA), Mobile phase B - acetonitrile (0.1% TFA), Elution gradient: Mobile phase B 20%~60%, 0~16 min, Flow rate: 1 mL min -1 Detection wavelength: 214 nm. The sustained-release curve of exenatide was plotted, and the results are shown in Figure 15. These results demonstrate that exenatide glass can achieve sustained drug release. Example 24 Comparison of release rates between aspartate glass and crystals

[0047] Specifically, the initial mass of the aspartate glass was 15 ± 1 mg, the sustained-release solvent was PBS (0.01 M, pH=6.8) 10 mL, and the stirring speed was 100 rpm. -1 The eluted aspartic acid was detected by high-performance liquid chromatography (HPLC). High-performance liquid chromatography (HPLC) conditions: Liquid phase elution conditions: Mobile phase: methanol and sodium acetate solution (volume ratio 43:57), flow rate: 0.5 mL min -1Column temperature: 40°C, detection wavelength: 267 nm. The sustained-release curve of glassy aspartic acid was plotted. As a control, an equal mass of amino acid crystalline formulations was weighed and added to the above sustained-release solution, incubated with stirring, and the concentration of aspartic acid in the sustained-release solution was detected. Figure 16 shows the release curves of the aspartic acid glass and crystals produced in Example 5, demonstrating that the glassy drug can accelerate the elution rate of amino acids. Example 25: Evaluation of the in vivo efficacy of aspartate glass.

[0048] Specifically, six spontaneously developing type II diabetes model mice (male, 8 weeks old) were purchased and divided into three groups. The mice in the experimental group were given 4 mg of glassy aspartate daily. -1 The drug was administered intragastricly at the specified dose, while the control group of mice received an equal mass of physiological saline intragastricly. The test cycle was 30 days. Blood was collected daily from the tails of the mice, and fasting blood glucose levels were measured using a blood glucose meter. A curve was plotted with time on the x-axis and the fasting blood glucose level of the experimental mice on the y-axis. Figure 17 shows the blood glucose control curve for spontaneously diabetic type II mice using aspartate glass produced in Example 5, demonstrating that aspartate glass can effectively control the blood glucose levels of mice. Example 26: Detection of exenatide glass stability by high-performance liquid chromatography (HPLC)

[0049] High-performance liquid chromatography (HPLC) conditions: Liquid phase elution conditions: Mobile phase A - Water (0.1% TFA), Mobile phase B - Acetonitrile (0.1% TFA), Elution gradient: Mobile phase B 20%~60%, 0~16 min, Flow rate: 1 mL min -1 Detection wavelength: 214 nm. The exenatide glass prepared in Example 10 was placed in a storage chamber maintained at 40°C and 96% relative humidity (RH) with an equivalent volume of exenatide solution. After storage in the chamber for 1, 3, 7, and 14 days, the exenatide content was measured. At the specified time points, the array was removed from the chamber and 0.1 mol L of the exenatide glass was added. -1The exenatide solution was obtained by dissolving it in acetic acid (1 mL). The exenatide content in the obtained washing solution was analyzed by high-performance liquid chromatography (HPLC). The stability of the exenatide in the manufactured glass was compared with that of the exenatide solution measured under the same storage conditions, using the measured exenatide solution as a baseline. The percentage of undegraded exenatide remaining in the glass or solution at each time point was determined by measuring the peak area of ​​exenatide in the selected sample and dividing it by the peak area of ​​exenatide measured initially. The results are shown in Table 2. [Table 4] The results above demonstrate that the stability of exenatide glass is significantly superior to that of the solution group in a 14-day accelerated stability experiment, indicating that the manufactured exenatide glass effectively protects the activity of bioactive molecules and is advantageous for long-term storage. Example 27: In vivo pharmacodynamic evaluation of thymopentin glass in rats

[0050] Experimental Method: Twenty-eight SPF-grade male SD rats weighing 180-220g were used. No other drugs were administered before the experiment. A thymopentin solution was prepared by dissolving thymopentin powder in physiological saline, and this was used as the control formulation. The test formulation was the thymopentin glass dosage form drug prepared in Example 8. The 28 SD rats were randomly divided into four groups (Groups 1-4) of seven rats each, and in vivo pharmacodynamic studies were conducted. An immunosuppressive model was constructed before the start of the experiment. Cyclophosphamide powder, an immunosuppressant, was purchased from Jiangsu Hengrui Pharmaceutical Co., Ltd., and 1 mg L was added to physiological saline. -1 The cyclophosphamide solution was prepared. Rats in the three groups excluding group 1 were given 35 mg / kg to suppress their immune function. -1 d -1 Immunosuppressants were administered intraperitoneally by injection at the specified dose for three consecutive days. Group 1 served as a blank control group, receiving 35 mL of physiological saline (kg). -1 It was administered by intraperitoneal injection. After establishing the model by administering injections for three consecutive days, pharmacodynamic evaluations were performed. Rats in Group 1 were used as the blank control group, and rats in Group 2 were used as the negative control group. Both groups of rats received 1 mL / kg of physiological saline. -1 The drug was administered by subcutaneous intravenous injection for seven consecutive days. The third group of rats served as the positive control group and received 100 μg / kg of thymopentin solution. -1 The drug was administered subcutaneously at the dose indicated. Rats in Group 4 received 100 μg / kg of the thymopentin glass drug prepared in Example 8. -1 The drug was implanted subcutaneously for seven consecutive days at the specified dose. Three groups of rats were sacrificed by cervical dislocation. The thymus and spleen were harvested from each rat, weighed, and the organ index was calculated. The formula for calculating the organ index is as follows:

number

[0051] Experimental Model and Methods: Autoimmune encephalomyelitis (EAE) mice were constructed for experimental purposes. Specifically, in the EAE group, 200 μg of MOG35-55 was dissolved in 200 μl of PBS buffer and thoroughly mixed with 200 μl of complete Freund's adjuvant (CFA) to form an emulsion (final concentration of inactivated tuberculin bacteria was 5 mg / ml). -1In the normal control group, 200 μl of PBS was thoroughly mixed with 200 μl of CFA directly. 200 μg of emulsion was subcutaneously injected into two locations on the back of the mice. 500 ng of pertussis toxin was intraperitoneally injected at 0 and 48 hours post-immunization. On day 1 after the establishment of the EAE model, 100 μg kg of glass tuftosin was administered. -1 The solid glass tuftosin intervention group was created by implanting it subcutaneously into the backs of mice at a specified dose and administering it continuously for 7 days. The neurological function scores of the experimental mice in each group were scored daily after immunization and observed continuously for 30 days. Neurological function was scored according to the following criteria: 0 points: no symptoms, 1 point: hypotonia of the tail (complete weakness, inability to bend the tip of the tail) or weakness of the hind limbs (unstable gait), 2 points: weakness of the tail and hind limbs, 3 points: hind limb paralysis (some movement of one or both hind limbs), 4 points: complete hind limb paralysis (complete immobility of the hind limbs, or forelimbs dragging the hind limbs), and 5 points: death. The results are shown in Figure 19, demonstrating that solid glass tuftosin intervention can effectively restore the nervous system of mice. Example 29: Processing of biomolecular glass into microneedle devices

[0052] Microneedle devices can be fabricated from biomolecular glass based on the casting method of PDMS molds. Fabrication method: After preheating the arginine glass produced in Example 1 to 80°C, it was injected into a PDMS microneedle female mold so that the tip and base material portions of the microneedle mold were filled. The mold was rapidly depressurized with a vacuum pump for 10 minutes to remove bubbles, and then cooled to room temperature. After the microneedle body hardened, the microneedle glass was released from the mold to obtain arginine-soluble glass microneedles. The obtained arginine-soluble glass microneedles are shown in Figure 20. The left photograph is a top view of the microneedle, and the right photograph is a side view of the microneedle. The fabricated microneedle bodies were found to be neat and complete. Example 30: Preparation of a rigid biodegradable coating on biomolecular glass.

[0053] In the manufacturing process of Example 14, a vancomycin viscous fluid was applied to the surface of a PEI flexible electrode, and it was continuously heated to obtain a flexible electrode coated with vancomycin glass. When the electrode is implanted in the body, rigidity can be given to the flexible electrode. After the electrode is implanted in a mouse, the vancomycin glass coating gradually decomposes upon contact with the physiological fluid environment, thereby returning the electrode to a flexible state and maintaining good conformal deformation. When the vancomycin glass coating is released as an anti-inflammatory agent, damage caused by electrode implantation can be reduced. Example 31: Processing of biomolecular glass into optical waveguide devices

[0054] The phenylalanine glass produced in Example 2 was melt-stretched to obtain the corresponding glass wire. Optical waveguide tests were performed using 532 nm and 616 nm lasers. The results are shown in Figure 21. The left side of Figure 21 shows the conduction image of the 532 nm laser, and the right side shows the conduction image of the 616 nm laser. It was found that the laser could conduct along the glass wire, indicating that biomolecular glass can be used in optical waveguide devices. Example 32 Processing of biomolecular glass into temporary electronic devices

[0055] The arginine glass produced in Example 1 was 3D printed to form a simulated circuit (Figure 22a). The machining accuracy of the simulated circuit was 0.2 mm. In an aqueous environment (trigger condition) (Figure 22b), the biomolecular glass rapidly dissolved, and the simulated circuit pattern rapidly broke down and disappeared (Figure 22c). This property indicates that the biomolecular glass can be used as an interconnecting wire material for fabricating temporary electronic devices. Example 33: Processing of biomolecular glass into temporary electronic devices

[0056] A transparent substrate film was obtained from the arginine glass produced in Example 1 by casting, and an interdigital electrode was formed by vacuum deposition using a stainless steel mask (Figure 23a). The processing accuracy of the interdigital electrode was 0.1 mm. In an aqueous environment (trigger condition), the biomolecular glass substrate film rapidly dissolved within 10 seconds (Figure 23b), the interdigital electrode disappeared instantaneously, and the biomolecular glass substrate film also dissolved completely (Figure 23c). This property indicates that the biomolecular glass can be used as a substrate material, encapsulating material, etc., for processing temporary electronic devices.

Claims

1. A biomolecular glass, characterized in that the biomolecular glass is obtained by volatilizing a solvent from a solution of biomolecular raw materials, the solution of biomolecular raw materials comprises biomolecular raw materials, a modifier, and a solvent, and the biomolecular raw materials comprise natural amino acids, peptides, amino acid derivatives, peptide derivatives, or a mixture of two or more of the above.

2. The aforementioned natural amino acids are glycine, alanine, valine, leucine, isoleucine, methionine, proline, tryptophan, serine, tyrosine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, histidine, selenocysteine, pyrrolicin, or one or more of these salts. The peptide is a molecule or salt thereof formed by condensing n of the above-mentioned natural amino acids via peptide bonds, where n ≥ 2, preferably 2 ≤ n ≤ 10. The amino acid derivative is an amino acid derivative having a protecting group over the above-mentioned natural amino acid, wherein the protecting group is one or more selected from Trt, Boc, Fmoc, Cbz / Z, Allyl, C2-C18 acyl, benzoyl, naphthoyl, OFm, Otbu, OBzl, OAll, OMe, and OEt. The biomolecular glass according to claim 1, wherein the peptide derivative refers to a peptide in which at least one natural amino acid is replaced with the amino acid derivative.

3. The modifier is selected from nucleotides, nucleotide polymers, RNA, DNA, and other modifiers, or a mixture of two or more of the above, wherein the nucleotide is selected from one or more of adenosine-5'-monophosphate (AMP), nicotinamide mononucleotide (NMN), guanosine-5'-monophosphate (GMP), uridine-5'-monophosphate (UMP), cytidine-5'-monophosphate (CMP), and adenosine-3'-monophosphate (3-AMP). The biomolecular glass according to claim 1, wherein the other adjusting agent is a combination of one or more selected from D / L-tartaric acid, hydrochloric acid, sulfuric acid, phosphoric acid, lactic acid, polylactic acid, hyaluronic acid, alginic acid, lactobionic acid, citric acid, tartaric acid, oxalic acid, D / L-malic acid, maleic acid, pseudo-phosphate, acamprosate, quinic acid, adipic acid, fumaric acid, hexanoic acid, heptanoic acid, caprylic acid, valeric acid, butyric acid, propionic acid, and glacial acetic acid.

4. The biomolecular glass according to claim 1, wherein the solvent is water or a salt solution thereof.

5. The biomolecular glass is a glassy amorphous body, and when its thickness is 1 mm, it has a light transmittance of 40 to 99% at a wavelength of 500 nm, preferably 80 to 99%, and a hardness greater than 10 MPa, preferably greater than 50 MPa, as described in any one of claims 1 to 4.

6. The biomolecular glass according to any one of claims 1 to 5, characterized in that the mass fraction of biomolecular raw materials in the glass is 50 to 100%, preferably 85 to 100%, and the mass fraction of adjusting agents in the glass is 0 to 50%, preferably 0 to 15%.

7. The aforementioned biomolecular glass is Step (1) involves weighing, mixing, and uniformly grinding the biomolecular raw materials, Step (2) involves dissolving the raw material powder from step (1) in a solvent to obtain a biomolecular solution, Step (3) involves adding a adjusting agent to the biomolecular solution in step (2) and controlling the amount of the adjusting agent to adjust the final pH of the solution. The biomolecular glass according to any one of claims 1 to 6, characterized in that it is produced by a manufacturing method comprising step (4), which involves placing the aqueous solution from step (3) into a container and evaporating the solvent by adjusting the temperature of the solution and / or pressurizing and / or vacuuming the solution to produce the biomolecular glass.

8. The biomolecular glass according to claim 7, wherein the final pH is 1 to 8, preferably 4 to 7.

9. An implantable or non-implantable medical material and / or device, filler and stent material, electronic sensing material and / or device, temporary electronic material and / or device, manufactured from a biomolecular glass as described in any one of claims 1 to 8.

10. Use of biomolecular glass according to any one of claims 1 to 9 in healthcare, health monitoring, security encryption, information transmission and storage.

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