A composite oxide barrier layer reinforced pharmaceutical glass and its preparation method

Abstract

This invention discloses a composite oxide barrier layer reinforced pharmaceutical glass and its preparation method. The glass comprises a base glass with a designed composition and a dense composite oxide barrier layer. The composition of the base glass, by mass percentage, is: [SiO4] 60%~75%; [AlO4] 4%~8%; [BO3] 2%~4%; [BO4] 3%~6%; [PO4] 0.2%~1%; [SnO] x ] (4≤x≤6) 0.1%~0.3%; [ZrO x (4≤x≤6) 0.05%~0.15%. The barrier layer is composed of SiO2, Al2O3, and ZrO2, with a thickness of 30~80 nm. The preparation method includes melting the base glass, surface etching and pre-activation treatment, and forming the barrier layer on the glass surface through a sol-gel process. This glass has excellent water resistance and hydrolysis resistance, with water resistance reaching HGB1 level, making it suitable for pharmaceutical packaging with stringent water resistance requirements, such as for injectables and high-end pharmaceuticals.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical glass materials, specifically relating to a pharmaceutical glass reinforced with a composite oxide barrier layer and its preparation method, which is particularly suitable for Class I pharmaceutical glass containers with strict requirements for water resistance and ion dissolution performance. Background Technology

[0002] As the inner packaging material that comes into direct contact with pharmaceuticals, the chemical stability and safety of pharmaceutical glass containers are core elements in ensuring drug quality and patient safety. Especially for injectables, biological agents, blood products, vaccines, and high-value-added chemical drugs, glass containers must remain stable under long-term storage, transportation, and various sterilization conditions (such as high-temperature steam sterilization and radiation sterilization), without interacting with their contents, releasing harmful substances, or adsorbing active ingredients. Therefore, the performance standards for pharmaceutical glass are extremely stringent, and relevant regulations and pharmacopoeias have clear and detailed classifications and limitations regarding its physicochemical properties, particularly its water resistance and resistance to the leaching of alkali metals and heavy metal ions.

[0003] According to international and domestic standards (such as the Chinese Pharmacopoeia, USP, and EP), pharmaceutical glass is generally classified into Class I (borosilicate glass, including neutral glass), Class II (surface-treated soda-lime glass), and Class III (untreated soda-lime glass). Class I glass, due to its excellent chemical inertness, is mandated for packaging all injectable preparations, blood products, and vaccines—high-risk pharmaceutical products. However, while traditional borosilicate glass (such as the SiO2-B2O3-Al2O3-Na2O system) boasts superior performance, its melting temperature is generally above 1650 ℃, resulting in enormous energy consumption, extremely high requirements for kiln and mold materials, complex forming processes, and relatively low yields, leading to persistently high production costs. This has, to some extent, limited its widespread application in certain cost-sensitive generic drug packaging sectors. To balance performance and cost, industry and academia have conducted extensive research, mainly focusing on two directions: first, developing new base glass components with performance close to that of Class I glass but with lower melting temperatures; and second, modifying the surface of lower-cost soda-lime glass or low-borosilicate glass by applying functional barrier layers to improve their surface stability.

[0004] In the design of basic glass compositions, researchers have attempted to improve the network structure and enhance chemical durability by introducing components such as alumina (Al2O3), zinc oxide (ZnO), tin oxide (SnO2), and zirconium oxide (ZrO2). For example, Al2O3 can enter the silicon-oxygen network in the form of [AlO4] tetrahedra, replacing part of [SiO4] and enhancing network connectivity; small amounts of SnO2 and ZrO2, due to their high field strength, can effectively suppress the migration of alkali metal ions and improve hydrolysis resistance. However, the increased complexity of the composition often brings new challenges in terms of melting uniformity, phase separation tendency, and optical properties (clarity), requiring a fine balance in formulation design.

[0005] In terms of surface modification technology, there are currently many methods. For example, sulfur frosting treatment forms a hydrophobic sulfide layer on the glass surface. However, this layer is relatively thin, has poor wear resistance, and may oxidize or peel off during long-term storage or in humid and hot environments. Etching the surface with reagents such as ammonium bifluoride removes some alkali metal ions, forming a silicon-rich layer. However, this process generates fluoride-containing wastewater, posing a significant environmental burden, and the resulting porous silicon layer has low mechanical strength. Vapor deposition coating produces uniform and dense coatings, but the equipment investment is expensive, the process is complex, and it is difficult to use for containers with complex shapes. Furthermore, the mismatch between the thermal expansion coefficients of the coating and the glass substrate can lead to thermal stress cracking. The sol-gel method uses metal alkoxides as precursors, forming a gel film on the glass surface through impregnation, lifting, or spraying, followed by heat treatment to convert it into an oxide coating. This method has simple equipment, low cost, is suitable for complex shapes, and allows for flexible design of the coating composition. However, traditional single-component SiO2 sol-gel coatings have two major bottlenecks: first, the gel is prone to shrinkage and cracking during drying and sintering, forming microcrack channels; second, there is a difference in the coefficient of thermal expansion between the pure SiO2 coating and the soda-lime glass substrate (SiO2 approximately 0.5 × 10⁻⁶). -6 / ℃, soda-lime glass approximately 8×10 -6 / ℃), during thermal cycling, interfacial stress can easily lead to coating peeling or failure.

[0006] In recent years, with the introduction of nanotechnology and composite material concepts, research and development has shifted towards developing multi-component composite sol systems. For example, the introduction of components such as Al2O3, TiO2, and ZrO2 into SiO2 sol aims to utilize their different structural properties: Al2O3 can improve the thermal stability and hardness of the coating; TiO2 can provide additional functions such as photocatalytic self-cleaning; and ZrO2 has attracted particular attention due to its high chemical inertness, high hardness, and ability to mitigate microcrack propagation through phase transformation toughening. However, simple physical mixing of multi-component sols often faces problems such as mismatched precursor hydrolysis-condensation rates, uneven coating component distribution, and easy crystallization. Achieving uniform composite and amorphous densification of multi-component oxides such as SiO2-Al2O3-ZrO2 at the nanoscale remains a technical challenge. Therefore, developing effective glass surface pre-activation processes to clean the surface, increase surface energy, and even form chemically bonded transition layers is an indispensable part of improving overall performance. Summary of the Invention

[0007] The purpose of this invention is to overcome the problems of insufficient chemical stability and weak interfacial adhesion of ordinary pharmaceutical glass in the prior art, and to provide a novel pharmaceutical glass and its preparation method that are synergistically enhanced by bulk composition optimization and chemical bonding of a surface composite oxide barrier layer. This glass exhibits excellent water resistance, extremely low ion dissolution rate, and outstanding long-term reliability.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] In a first aspect, the present invention provides a pharmaceutical glass reinforced with a composite oxide barrier layer. This glass comprises a base glass matrix with a specially designed composition and a dense composite oxide barrier layer on its surface.

[0010] The composition of the basic glass matrix, by mass percentage, is as follows:

[0011] [SiO4] 60% ~ 75%: As the framework of the glass network, it provides basic structural strength and chemical stability.

[0012] [AlO4] 4% ~ 8%: As a network intermediate, it enhances network connectivity and significantly improves the glass's resistance to hydrolysis.

[0013] The total amount of [BO3] and [BO4] is 5% to 10%, of which [BO3] accounts for 2% to 4% and [BO4] accounts for 3% to 6%. The borooxy group can adjust the thermal expansion coefficient and melting performance of the glass and form a stable composite structure with the silicon-aluminum network.

[0014] [PO4] 0.2% ~ 1%: can improve the homogenization of glass melt and serve as a potential bonding site in surface treatment.

[0015] [ZrO y (4≤y≤6) 0.05% ~ 0.15%: using Zr 4+ The high field strength further enhances the local stability of the network and plays a strong bridging role at the interface.

[0016] Na⁺ (12% ~ 14%), Li⁺ (1.5% ~ 2.5%), Ca²⁺ (7% ~ 10%): Network exosome ions provide the necessary melting and forming properties, and their content is precisely controlled to balance processability and chemical stability.

[0017] [SnO x (4≤x≤6) 0.1% ~ 0.3%: Partial Sn during glass melting process 4+ They tend to agglomerate on the surface, providing an active interface for the chemical anchoring of subsequent barrier layers.

[0018] The composition of the composite oxide barrier layer, by mass percentage, is as follows:

[0019] SiO2: 84.0% ~ 87.0%, constitutes the main body of the barrier layer, providing excellent chemical inertness and barrier properties.

[0020] Al2O3: 11.5% ~ 13.0%, significantly improves the thermal stability, mechanical hardness and adhesion to the substrate of the barrier layer.

[0021] ZrO2: 2.0% ~ 3.0%, dispersed at the nanoscale in the SiO2-Al2O3 matrix, effectively inhibits the initiation and propagation of microcracks in the barrier layer under thermal or mechanical stress by utilizing its high chemical inertness and "phase transformation toughening" effect.

[0022] The SiO2-Al2O3-ZrO2 composite oxide layer has an amorphous structure with a thickness controlled between 30 and 80 nm. It forms a gradient transition interface with the glass substrate through chemical bonds, rather than a simple physical adhesion.

[0023] Secondly, this invention provides a method for preparing the aforementioned pharmaceutical glass. The key to this method lies in achieving high-quality melting of the base glass and strong atomic-scale bonding between the barrier layer and the substrate, specifically including the following steps:

[0024] (1) Weigh each oxide or corresponding precursor raw material (such as SiO2, CaO, Na2CO3, Al2O3, H3BO3, NH4H2PO4, SnO2, ZrO2, etc.) precisely according to the design ratio, mix thoroughly, place in a corrosion-resistant crucible, and melt in an air atmosphere at 1500~1650 ℃ for 1~3 hours to ensure complete homogenization. Pour or draw the glass melt, and then perform precision annealing at 480~550 ℃ to eliminate internal stress and obtain a smooth, macro-defect-free basic glass product. Immerse the annealed glass in a treatment solution with a specific composition. This treatment solution contains 0.5~2.0 mol / L HNO3 (to provide an acidic environment), 0.1~0.5 mol / L NH4HF2 (to gently etch the glass surface, forming micro-roughness and exposing active silanol groups), and 0.05~0.2 mol / L SnCl4 (to promote Sn 4 ⁺ Sn-OH active sites are enriched and formed on the surface. Treatment is carried out at 40–60 °C for 5–15 minutes. This step not only cleans the surface but, more importantly, constructs an activated interface rich in Sn active sites with suitable roughness.

[0025] (2) Using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (Al(O-iPr)3), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, the molar ratio n(TEOS):n(Al(O-iPr)3):n(ZrOCl2·8H2O) = 1 : (0.18~0.22) : (0.035~0.045) was controlled according to the composition ratio of the final barrier layer. The mixture underwent catalytic hydrolysis and condensation in an alcohol-water solution to form a uniform and stable composite sol. A pre-activated glass substrate, preheated to approximately 100 °C, was immersed in the sol, and a uniform wet gel film was formed using a dip-coating method. The coated sample was first slowly dried at 80~100 °C for 30~60 minutes to allow the solvent to fully evaporate and the gel network to initially solidify. Subsequently, it was further heat-treated at 150~200 °C for 1~2 hours to completely remove organic residues. Finally, the gel is subjected to high-temperature heat treatment at 550-600 °C in air or an inert atmosphere for 1-2 hours. This process completely transforms the gel into a dense amorphous SiO2-Al2O3-ZrO2 composite oxide layer. Simultaneously, the heat treatment energy drives the formation of strong covalent bonds such as Sn-O-Si, Sn-O-Al, and Zr-O-Si at the interface, thereby achieving chemical bonding between the barrier layer and the glass substrate.

[0026] Thirdly, this invention elucidates the multi-level protection mechanism and excellent performance of the reinforced glass.

[0027] Matrix strengthening: By introducing Al2O3 and B2O3 and controlling the alkali metal content, a base matrix with inherent water resistance superior to ordinary soda-lime glass was obtained, laying a solid foundation for overall performance.

[0028] Interfacial chemical bonding: A unique surface pre-activation process enables Sn 4 ⁺ At the interface enrichment, in subsequent heat treatment, these Sn 4 ⁺ Reacts with the sol network and the silanol groups on the glass surface to form strong Sn-O bonds. Simultaneously, Zr in the sol... 4 ⁺ also acts as a strong cross-linking point, further "anchoring" the interface. This chemical bonding method fundamentally solves the problem of easy peeling of coatings.

[0029] Intrinsic properties of the barrier layer: The SiO2-Al2O3-ZrO2 composite oxide barrier layer combines the inertness of SiO2, the strengthening effect of Al2O3, and the crack resistance of ZrO2. Its dense structure can effectively block the penetration of water molecules and various ions.

[0030] Overall performance: The pharmaceutical glass prepared in this way achieves HGB1 level water resistance according to GB / T6582—2021 standard "Test method and classification of water resistance of glass particles at 98 ℃". Attached Figure Description

[0031] Figure 1 XRD curve of the glass of this invention.

[0032] Figure 2 Infrared spectrum of the glass of this invention.

[0033] Figure 3 : The transmittance curve of the glass of this invention. Detailed Implementation

[0034] The present invention will now be described in detail with reference to the accompanying drawings. Unless otherwise specified, the features of the following embodiments and implementations can be combined with each other.

[0035] This invention proposes a composite oxide barrier layer reinforced pharmaceutical glass, wherein the composition of the base glass, by mass percentage, is as follows:

[0036] [SiO4] 60%~75%

[0037] [AlO4] 4%~8%

[0038] [BO3] 2%~4%

[0039] [BO4] 3%~6%

[0040] [PO4] 0.2%~1%

[0041] [SnO x (4≤x≤6) 0.1%~0.3%

[0042] [ZrO x (4≤x≤6) 0.05%~0.15%

[0043] Na + 12%~14%

[0044] Li + 1.5%~2.5%

[0045] Ca 2+ 7%~10%

[0046] The composition of the composite oxide barrier layer, by mass percentage, is as follows:

[0047] SiO2 84.0%~87.0%

[0048] Al2O3 11.5%~13.0%

[0049] ZrO2 2.0%~3.0%

[0050] Wherein, [SiO4] represents silicon-oxygen tetrahedron; [AlO4] represents aluminum-oxygen tetrahedron; [BO3] [BO4] represents boron-oxygen trigonal and boron-oxygen tetrahedron; [PO4] represents phosphorus-oxygen tetrahedron; Na + Li + Ca 2+ Indicates network exosome cations; [SnO x ]、[ZrO y [] represents the oxygen coordination unit of tin and zirconium.

[0051] The composite oxide barrier layer reinforced pharmaceutical glass proposed in this invention is prepared according to the following steps:

[0052] (1) Weigh the required mass of SiO2, CaO, Na2O, Al2O3, B2O3, Li2O, P2O5, SnO2, and ZrO2 powder raw materials according to the mass percentage ratio. After mixing the powder raw materials evenly, place them in a corundum crucible, and then place them in a box furnace at 1300~1580 ℃ for 0.5~2 hours for holding and melting. Pour the mixture into a mold to form a glass block, and then place it in a box furnace at 200~400 ℃ for 2~6 hours for annealing to remove internal stress. Subsequently, perform surface etching and pre-activation treatment. The treatment solution used is a mixed aqueous solution of 0.5~2.0 mol / L HNO3, 0.1~0.5 mol / L NH4HF2 and 0.05~0.2 mol / L SnCl4. The treatment temperature is 40~60 ℃ and the treatment time is 5~15 min.

[0053] (2) Prepare a composite sol with a precursor molar ratio of n(TEOS):n(AIP):n(ZrOCl2·8H2O)=1:0.20:0.04. Immerse a preheated (~100 ℃) glass block into the sol to form a uniform wet gel film on the surface. First, dry at 80 ℃ for 30 minutes, then dry at 150 ℃ for 1 hour (to remove the solvent). Finally, heat-treat in a muffle furnace at 550~600 ℃ for 1~2 hours to completely decompose the organic components and transform the gel into a dense SiO2-Al2O3-ZrO2 amorphous composite oxide layer with a thickness of about 30~80 nm.

[0054] Example 1:

[0055] To form the aforementioned pharmaceutical glass reinforced with composite oxides, the required masses of SiO2, CaO, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 68%, Al2O3 6%, B2O3 8% (introduced by boric acid), P2O5 0.5%, SnO2 0.2%, ZrO2 0.1%, Na2O 13.5% (introduced by sodium carbonate), and CaO 8.7%. The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1550 ℃ for 1 hour. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 300 ℃ for 4 hours to remove internal stress. Subsequently, the prepared and polished base glass sheet (20mm × 20mm × 2mm) underwent surface treatment. First, the sample was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 °C for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, and in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, the mixture was stirred and hydrolyzed for 4 hours at 60 °C to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. The gel was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer.

[0056] like Figures 1-3 As shown, after measurement, the XRD pattern of the glass exhibits diffuse peaks indicating an amorphous state, with no characteristic diffraction peaks, confirming its amorphous nature. In the infrared spectrum, at 450 cm⁻¹... −1 600 cm −1 740 cm −1 1000 cm −1 1120cm −1 1400 cm −1 and 1630 cm −1 Vibrations corresponding to XO (X = Na / K / Ca) bonds, symmetric stretching vibrations of Zr-O bonds, bending vibrations of Al-O bonds, stretching vibrations of Si-O-Si bonds, stretching vibrations of Si-O-Si bonds, stretching vibrations of BO bonds, and stretching vibrations of -OH groups were observed at various locations. In the transmittance test, the transmittance in the visible light region was consistently above 80%. Finally, the water resistance of the glass was measured. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", its water resistance reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0057] Example 2:

[0058] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 60%, Al2O3 4%, B2O3 5% (introduced by boric acid), P2O5 0.2%, SnO2 0.1%, ZrO2 0.05%, Na2O 12% (introduced by sodium carbonate), Li2O 1.5% (introduced by lithium carbonate), and CaO 7% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1480 ℃ for 2.0 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 480 ℃ for 4 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip-coating speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0059] Example 3:

[0060] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 62%, Al2O3 8%, B2O3 9% (introduced by boric acid), P2O5 0.4%, SnO2 0.25%, ZrO2 0.1%, Na2O 13.5% (introduced by sodium carbonate), Li2O 2.0% (introduced by lithium carbonate), and CaO 8.75% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1500 ℃ for 2.0 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 500 ℃ for 5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0061] Example 4:

[0062] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 65%, Al2O3 6%, B2O3 8% (introduced by boric acid), P2O5 0.3%, SnO2 0.2%, ZrO2 0.1%, Na2O 13.8% (introduced by sodium carbonate), Li2O 2.0% (introduced by lithium carbonate), and CaO 7.6% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1520 ℃ for 1.8 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 490 ℃ for 4.5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0063] Example 5:

[0064] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 66%, Al2O3 6%, B2O3 7.5% (introduced by boric acid), P2O5 0.6%, SnO2 0.2%, ZrO2 0.12%, Na2O 13.8% (introduced by sodium carbonate), Li2O 1.8% (introduced by lithium carbonate), and CaO 8.98% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1550 ℃ for 2.0 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 500 ℃ for 5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0065] Example 6:

[0066] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 68%, Al2O3 5%, B2O3 7% (introduced by boric acid), P2O5 0.5%, SnO2 0.15%, ZrO2 0.08%, Na2O 13% (introduced by sodium carbonate), Li2O 1.8% (introduced by lithium carbonate), and CaO 8.5% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1550 ℃ for 2.0 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 500 ℃ for 5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0067] Example 7:

[0068] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 70%, Al2O3 5%, B2O3 6% (introduced by boric acid), P2O5 0.8%, SnO2 0.15%, ZrO2 0.08%, Na2O 13.2% (introduced by sodium carbonate), Li2O 2.2% (introduced by lithium carbonate), and CaO 9.57% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1600 ℃ for 2.0 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 500 ℃ for 5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, under nitrogen protection, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0069] Example 8:

[0070] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 72%, Al2O3 7%, B2O3 6% (introduced by boric acid), P2O5 0.8%, SnO2 0.25%, ZrO2 0.12%, Na2O 12.5% ​​(introduced by sodium carbonate), Li2O 2.2% (introduced by lithium carbonate), and CaO 9% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1600 ℃ for 2.2 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 510 ℃ for 5.5 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50 ℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60 ℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100°C and coated with the above-mentioned sol using a dip-coating method (dip-coating speed 2 mm / s) to form a wet film. It was then dried in an oven at 80°C for 30 minutes, followed by heat treatment at 180°C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580°C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98°C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0071] Example 9:

[0072] To form the aforementioned pharmaceutical glass reinforced with a composite oxide barrier layer, the required masses of SiO2, CaCO3, Na2CO3, Al(OH)3, H3BO3, NH4H2PO4, SnO2, and ZrO2 powder raw materials were weighed. The mass percentages of each raw material are as follows: SiO2 75%, Al2O3 8%, B2O3 10% (introduced by boric acid), P2O5 1%, SnO2 0.3%, ZrO2 0.15%, Na2O 14% (introduced by sodium carbonate), Li2O 2.5% (introduced by lithium carbonate), and CaO 10% (introduced by calcium carbonate). The uniformly mixed batch was placed in a corundum crucible and then heated in a box furnace at 1650 ℃ for 2.5 hours. The mixture was then poured into a mold to form a glass block. The glass block was then placed at 520 ℃ for 6 hours to remove internal stress. The prepared and polished base glass sheet (20mm × 20mm × 2mm) was then surface-treated. First, it was immersed in a mixed aqueous solution consisting of 1.0 mol / L HNO3, 0.3 mol / L NH4HF2, and 0.1 mol / L SnCl4, and treated in a constant temperature water bath at 50℃ for 10 minutes. After treatment, it was thoroughly rinsed with deionized water and dried, resulting in a uniformly rough surface morphology. Subsequently, using tetraethyl orthosilicate (TEOS), aluminum isopropoxide (AIP), and zirconium oxychloride octahydrate (ZrOCl2·8H2O) as precursors, in a molar ratio of n(TEOS): n(AIP): n(ZrOCl2·8H2O) = 1: 0.20: 0.04, in an ethanol / water mixed solvent with hydrochloric acid as a catalyst, it underwent hydrolysis and condensation at 60℃ for 4 hours to prepare a uniform and transparent composite sol. The surface-activated glass substrate was preheated to 100 °C and coated with the above-mentioned sol using a dip-coating method (dip speed 2 mm / s) to form a wet film. It was then dried in an oven at 80 °C for 30 minutes, followed by heat treatment at 180 °C for 1 hour. Finally, it was heat-treated in a muffle furnace at 580 °C for 1.5 hours to densify the gel layer into an amorphous composite oxide barrier layer. The pharmaceutical glass produced by this formulation exhibits amorphous properties and high transparency. According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", the water resistance of this glass reaches HGB1 level, making it suitable for packaging of injectable drugs, high-end pharmaceuticals, and other applications requiring stringent water resistance.

[0073] The above embodiments are only used to illustrate the design concept and features of the present invention, and their purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. The protection scope of the present invention is not limited to the above embodiments. Therefore, all equivalent changes or modifications made based on the principles and design ideas disclosed in the present invention are within the protection scope of the present invention.

Claims

1. A composite oxide barrier layer reinforced pharmaceutical glass, characterized in that, The composition of the base glass, by mass percentage, is as follows: [SiO4] 60%~75% [AlO4] 4%~8% [BO3] 2%~4% [BO4] 3%~6% [PO4] 0.2%~1% [SnO x ] (4≤x≤6) 0.1%~0.3% [ZrO x ] (4≤x≤6) 0.05%~0.15% That + 12%~14% That + 1.5%~2.5% That 2+ 7%~10% The composition of the composite oxide barrier layer, by mass percentage, is as follows: SiO2 84.0%~87.0% Al2O3 11.5%~13.0% ZrO2 2.0%~3.0% Wherein, [SiO4] represents silicon-oxygen tetrahedron; [AlO4] represents aluminum-oxygen tetrahedron; [BO3] [BO4] represents boron-oxygen trigonal and boron-oxygen tetrahedron; [PO4] represents phosphorus-oxygen tetrahedron; Na + Li + Ca 2+ Indicates network exosome cations; [SnO x ]、[ZrO y [] represents the oxygen coordination unit of tin and zirconium.

2. The composite oxide barrier layer for reinforcing pharmaceutical glass according to claim 1, characterized in that, The thickness of the dense SiO2-Al2O3-ZrO2 composite oxide barrier layer is 30~80 nm.

3. The preparation of the base glass in the pharmaceutical glass according to claim 1, characterized in that, Weigh the required amounts of SiO2, CaO, Na2O, Al2O3, B2O3, Li2O, P2O5, SnO2, and ZrO2 powders according to the specified mass percentages. After uniform mixing, place the powders into a corundum crucible and then heat-melt it in a box furnace at 1300–1580 °C for 0.5–2 hours. Pour the melt into a mold to form a glass block, then anneal it in a box furnace at 200–400 °C for 2–6 hours to remove internal stress. Subsequently, perform surface etching and pre-activation treatment using a mixed aqueous solution of 0.5–2.0 mol / L HNO3, 0.1–0.5 mol / L NH4HF2, and 0.05–0.2 mol / L SnCl4. The treatment temperature is 40–60 °C, and the treatment time is 5–15 minutes.

4. The preparation of the composite oxide barrier layer in pharmaceutical glass according to claims 1 and 2, characterized in that, A composite sol with a precursor molar ratio of n(TEOS):n(AIP):n(ZrOCl2·8H2O) = 1:0.20:0.04 was prepared according to the mass percentage ratio. A preheated (~100 °C) glass block was immersed in the sol, forming a uniform wet gel film on the surface. The film was first dried at 80 °C for 30 minutes, then at 150 °C for 1 hour (to remove the solvent). Finally, it was heat-treated in a muffle furnace at 550~600 °C for 1~2 hours to completely decompose the organic components, transforming the gel into a dense SiO2-Al2O3-ZrO2 amorphous composite oxide layer with a thickness of approximately 30~80 nm.

5. The composite oxide barrier layer enhancing the water resistance of pharmaceutical glass according to claim 1, characterized in that, According to GB / T6582—2021 "Test Method and Classification of Water Resistance of Glass Particles at 98 °C", its water resistance reaches HGB1 level.

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