Sterile bottle for radiopharmaceuticals

Abstract

The invention discloses a sterile bottle for radiopharmaceuticals, and relates to the field of medical instruments, the sterile bottle comprises a bottle body, the bottle body is made of high density polyethylene and nano yttrium oxide composite modified materials; the bottle opening gasket is of a sandwich layered structure and comprises a puncture contact layer made of a medical-grade polytetrafluoroethylene film and with the thickness of 1-2.5 mm; the elastic sealing layer is made of brominated butyl rubber, and the thickness of the elastic sealing layer is 3-5 mm; and the adhesive interface layer is positioned between the puncture contact layer and the elastic sealing layer and is used for realizing the compounding of the layered structure. According to the present invention, the modified bottle body is formed by compounding the HDPE and the Y2O3 material, such that the gamma ray energy can be effectively captured and can be converted into the heat energy for diffusion, the breakage of the HDPE molecular chain due to the high energy ray impact can be reduced, the radiation aging resistance can be significantly enhanced, and the service life of the sterile bottle in the radioactive environment can be prolonged so as to meet the long-term safe storage requirement of the radioactive drug.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a sterile vial for radiopharmaceuticals. Background Technology

[0002] Radiopharmaceuticals (such as 18F-FDG and 68Ga-PSMA containing gamma rays) play an irreplaceable role in medical diagnosis (e.g., positron emission tomography) and treatment (e.g., radionuclide therapy). Their storage and transportation require the use of specialized sterile containers to ensure the biosafety of the drugs and the airtightness of the radioactive materials. This is especially true in the transportation and storage of medical radioisotopes in nuclear power plants, where containers are exposed to gamma-ray radiation for extended periods (the irradiation dose often needs to withstand 10...). 4 The radiation resistance of the bottle material is extremely high (above Gy), which places extremely high demands on its resistance to radiation aging.

[0003] Currently, commonly used sterile vials for radiopharmaceuticals are mainly made of traditional glass or ordinary plastic. While glass has good chemical stability, it is brittle and has poor impact resistance, making it prone to breakage and radioactive leakage during transportation or handling. Ordinary plastic, although more flexible, is susceptible to molecular chain breakage under gamma-ray irradiation, leading to gradual embrittlement and cracks or decreased sealing of the vials. Therefore, sterile vials made of traditional materials have a short service life in radioactive environments (typically only one year), failing to meet the requirements for long-term safe storage of radiopharmaceuticals.

[0004] Therefore, it is necessary to improve upon the shortcomings of existing technologies in order to solve the above problems. Summary of the Invention

[0005] This invention overcomes the shortcomings of the prior art and provides a sterile bottle for radiopharmaceuticals.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is: a sterile vial for radiopharmaceuticals, comprising:

[0007] The bottle body is made of a composite modified material of high-density polyethylene and nano-yttrium oxide;

[0008] A bottle neck gasket, wherein the bottle neck gasket has a sandwich layered structure, comprising:

[0009] The puncture contact layer is made of medical-grade polytetrafluoroethylene film with a thickness of 1-2.5mm;

[0010] The elastic sealing layer is made of brominated butyl rubber and has a thickness of 3-5mm.

[0011] An adhesive interface layer, using fluorosilicone adhesive, is located between the puncture contact layer and the elastic sealing layer to achieve a composite layered structure.

[0012] In a preferred embodiment of the present invention, the high-density polyethylene accounts for 92-95 wt% and the nano-yttrium oxide accounts for 5-8 wt% in the composite modified material; the melt flow rate of the high-density polyethylene is 0.3-0.5 g / 10 min, and the density is 0.955-0.965 g / cm³. 3 The particle size of the nano-yttrium oxide is 50-100 nm.

[0013] In a preferred embodiment of the present invention, the preparation of the bottle body includes the following steps:

[0014] S1. High-density polyethylene is dried at 70-90℃ for 3-5 hours under a vacuum environment of ≤-0.08MPa to obtain pretreated high-density polyethylene.

[0015] S2. Modify nano-yttrium oxide with a silane coupling agent to obtain modified nano-yttrium oxide;

[0016] S3. Pretreated high-density polyethylene and modified nano-yttrium oxide are melt-extruded through a twin-screw extruder, granulated through an underwater pelletizer, and dried to obtain composite granules;

[0017] S4. The composite granules are injection molded using an injection molding machine to obtain the bottle body.

[0018] In a preferred embodiment of the present invention, the modification treatment in step S2 specifically includes the following steps:

[0019] S21. Add nano-yttrium oxide to anhydrous ethanol and disperse it by ultrasonication to obtain a suspension with a concentration of 10-15 wt%. Dissolve the silane coupling agent in anhydrous ethanol to prepare a solution with a concentration of 5-10 wt%. Adjust the pH to 4-5 with acetic acid and hydrolyze to obtain a modified solution.

[0020] S22. Mix the modified solution and suspension at a mass ratio of 1:1-3, stir in a water bath at 60-80℃ at a speed of 400-600 rpm for 2-3 hours, filter to separate the modified nano-yttrium oxide particles, wash three times with anhydrous ethanol, and dry to obtain modified nano-yttrium oxide.

[0021] In a preferred embodiment of the present invention, in step S3, the process parameters for melt extrusion are:

[0022] The temperatures from the feed inlet to the die head are as follows: feeding section 180-190℃, compression section 190-200℃, melting section 200-210℃, mixing section 210-220℃, homogenization section 205-210℃, and die head 200-210℃.

[0023] The screw speed is 200-220 rpm.

[0024] In a preferred embodiment of the present invention, in step S3, the pelletizer rotates at a speed of 300-350 rpm, and the pellet size is a cylindrical shape of 2-3 mm × 2-3 mm.

[0025] In a preferred embodiment of the present invention, in step S4, the injection molding process parameters are as follows:

[0026] Barrel temperature: rear section 190-200℃, middle section 200-210℃, front section 210-220℃, nozzle 205-210℃;

[0027] Mold temperature: 60-70℃;

[0028] Injection pressure: 80-100MPa, holding pressure: 60-70MPa, holding time: 5-8s;

[0029] Cooling time: 15-20s, cooling method is water cooling circulation, water temperature 25-30℃.

[0030] In a preferred embodiment of the present invention, the puncture contact layer is provided with a target thin area, specifically the thickness of the puncture contact layer within a center diameter of 8 mm is reduced to 0.7-2 mm.

[0031] In a preferred embodiment of the present invention, the side of the elastic sealing layer is provided with a double-ring concentric sealing rib, the height of the sealing rib being 0.5-1mm and the width being 0.4-0.7mm;

[0032] The elastic sealing layer comprises, by mass parts: 100 parts of brominated butyl rubber, 1-3 parts of magnesium oxide, and 0.5-1 parts of stearic acid; its preparation process is as follows: the raw materials are mixed in an internal mixer at 70-80℃ for 8-10 minutes, and then molded and vulcanized at 160-170℃ and 15-18MPa for 300-350 seconds.

[0033] In a preferred embodiment of the present invention, the fluorosilicone adhesive comprises, by weight percentage: 60% fluorosilicone resin, 0.5% platinum catalyst, and 39.5% xylene solvent;

[0034] The composite step includes: applying fluorosilicone adhesive at a concentration of 3-5 g / cm³. 2 The coating is sprayed onto the surfaces of the puncture contact layer and the elastic sealing layer, and after lamination, it is hot-pressed at 140-150℃ and 3-5MPa for 180-210s to form chemical cross-linking.

[0035] This invention addresses the shortcomings of the prior art and has the following beneficial effects:

[0036] (1) This invention provides a sterile bottle for radiopharmaceuticals. The modified bottle body is constructed by combining HDPE and Y2O3 materials. Y2O3 is uniformly dispersed in the HDPE matrix after being modified by a surface silane coupling agent. Nano-Y2O3 acts as a γ-ray absorber, which can effectively capture γ-ray energy and convert it into thermal energy diffusion, reducing the breakage of HDPE molecular chains caused by high-energy ray impact. At the same time, the two enhance compatibility through interfacial chemical bonding, forming a stable composite structure, so that the bottle body can still maintain high mechanical properties after γ-ray irradiation. Compared with the problem of traditional glass being brittle and easy to crack, and ordinary plastics being embrittled due to molecular chain breakage, the sterile bottle of this invention has significantly enhanced anti-radiation aging ability, thereby extending the service life of the sterile bottle in the radioactive environment, thus meeting the needs of long-term safe storage of radiopharmaceuticals.

[0037] (2) In this invention, the surface of Y2O3 is modified by using a silane coupling agent. The silanol groups generated by its hydrolysis condense with the hydroxyl groups on the surface of Y2O3 to form YO-Si covalent bonds. At the same time, the methacryloyloxy group at the end of the coupling agent physically entangles with the HDPE molecular chain, which can build a stress transmission bridge at the nanoparticle-polymer interface, thereby eliminating inorganic / organic phase interface defects and strengthening the deformation coordination ability of the composite material under irradiation-thermal cycling, thus comprehensively improving the impact toughness of the bottle body.

[0038] (3) The bottle mouth gasket of the present invention adopts a sandwich layered structure of puncture contact layer, adhesive interface layer and elastic sealing layer, and utilizes the target thin area and double ring sealing ribs. The low surface energy molecular structure of PTFE in the puncture contact layer can reduce needle friction. The molecular chain slip mechanism can disperse puncture stress and avoid rubber breakage. The high resilience molecular structure of BIIR in the elastic sealing layer can compensate for the deformation of the puncture hole. The double ring sealing ribs enhance the sealing redundancy through physical structure. As a result, the rubber particles generated during the puncture process can be significantly reduced, and good sealing performance can still be maintained after multiple punctures. For the traditional butyl rubber gasket, the problem of repeated puncture shedding and resilience decay caused by the fragile molecular chain is greatly improved by the puncture contamination resistance and sealing durability of the bottle mouth gasket of the present invention, thereby reducing the risk of radioactive drug liquid being contaminated by particles, and reducing the possibility of microorganisms entering through the puncture hole, ensuring the quality of the drug and the safety of clinical use. Attached Figure Description

[0039] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0040] Figure 1 This is a half-sectional view of the aseptic bottle according to a preferred embodiment of the present invention;

[0041] Figure 2 This is a half-sectional view of the bottle mouth gasket structure according to a preferred embodiment of the present invention;

[0042] In the diagram: 1. Bottle body; 2. Bottle neck gasket; 21. Puncture contact layer; 211. Target thin area; 22. Elastic sealing layer; 221. Sealing rib; 23. Adhesive interface layer. Detailed Implementation

[0043] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0044] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein. Therefore, the scope of protection of the invention is not limited to the specific embodiments disclosed below.

[0045] like Figure 1 and Figure 2 As shown, a sterile vial for radiopharmaceuticals includes:

[0046] The bottle body is made of a composite modified material of high-density polyethylene (HDPE) and nano-yttrium oxide (Y2O3);

[0047] Bottle neck gasket, the bottle neck gasket has a sandwich layered structure, including:

[0048] The puncture contact layer is made of medical-grade polytetrafluoroethylene (PTFE) membrane with a thickness of 1-2.5mm;

[0049] The elastic sealing layer is made of brominated butyl rubber (BIIR) and has a thickness of 3-5mm.

[0050] An adhesive interface layer, made of fluorosilicone adhesive, is located between the puncture contact layer and the elastic sealing layer to achieve a composite layered structure.

[0051] In some specific embodiments, the composite modified material contains 92-95 wt% high-density polyethylene and 5-8 wt% nano-yttrium oxide; the high-density polyethylene has a melt flow rate of 0.3-0.5 g / 10 min and a density of 0.955-0.965 g / cm³. 3 The particle size of nano-yttrium oxide is 50-100 nm.

[0052] In some specific embodiments, the preparation of the bottle body includes the following steps:

[0053] S1. High-density polyethylene is dried at 70-90℃ for 3-5 hours under a vacuum environment of ≤-0.08MPa to obtain pretreated high-density polyethylene.

[0054] S2. Modify nano-yttrium oxide with a silane coupling agent to obtain modified nano-yttrium oxide;

[0055] S3. Pretreated high-density polyethylene and modified nano-yttrium oxide are melt-extruded through a twin-screw extruder, granulated through an underwater pelletizer, and dried to obtain composite granules;

[0056] S4. The composite granules are injection molded using an injection molding machine to obtain the bottle body.

[0057] In some specific implementations, the modification process in step S2 specifically includes the following steps:

[0058] S21. Add nano-yttrium oxide to anhydrous ethanol and disperse it by ultrasonication to obtain a suspension with a concentration of 10-15 wt%. Dissolve the silane coupling agent in anhydrous ethanol to prepare a solution with a concentration of 5-10 wt%. Adjust the pH to 4-5 with acetic acid and hydrolyze to obtain a modified solution.

[0059] S22. Mix the modified solution and suspension at a mass ratio of 1:1-3, stir in a water bath at 60-80℃ at a speed of 400-600 rpm for 2-3 hours, filter to separate the modified nano-yttrium oxide particles, wash three times with anhydrous ethanol, and dry to obtain modified nano-yttrium oxide.

[0060] In some specific implementations, the process parameters for melt extrusion in step S3 are as follows:

[0061] The temperatures from the feed inlet to the die head are as follows: feeding section 180-190℃, compression section 190-200℃, melting section 200-210℃, mixing section 210-220℃, homogenization section 205-210℃, and die head 200-210℃.

[0062] The screw speed is 200-220 rpm.

[0063] In some specific embodiments, in step S3, the pelletizer speed is 300-350 rpm, and the pellet size is 2-3 mm × 2-3 mm cylindrical.

[0064] In some specific implementations, the injection molding process parameters in step S4 are as follows:

[0065] Barrel temperature: rear section 190-200℃, middle section 200-210℃, front section 210-220℃, nozzle 205-210℃;

[0066] Mold temperature: 60-70℃;

[0067] Injection pressure: 80-100MPa, holding pressure: 60-70MPa, holding time: 5-8s;

[0068] Cooling time: 15-20s, cooling method is water cooling circulation, water temperature 25-30℃.

[0069] In some specific implementations, the puncture contact layer has a target thin area, which specifically refers to the thickness of the puncture contact layer within a center diameter of 8 mm being reduced to 0.7-2 mm.

[0070] In some specific embodiments, the side of the elastic sealing layer is provided with double-ring concentric sealing ribs, the height of which is 0.5-1mm and the width is 0.4-0.7mm.

[0071] The components of the elastic sealing layer, measured by mass parts, include: 100 parts of brominated butyl rubber, 1-3 parts of magnesium oxide, and 0.5-1 parts of stearic acid; its preparation process is as follows: the raw materials are mixed in an internal mixer at 70-80℃ for 8-10 minutes, and then molded and vulcanized at 160-170℃ and 15-18MPa for 300-350 seconds.

[0072] In some specific embodiments, the fluorosilicone adhesive comprises, by weight percentage: 60% fluorosilicone resin, 0.5% platinum catalyst, and 39.5% xylene solvent;

[0073] The lamination process includes: applying fluorosilicone adhesive at a concentration of 3-5 g / cm³. 2 The coating is sprayed onto the surfaces of the puncture contact layer and the elastic sealing layer, and after lamination, it is hot-pressed at 140-150℃ and 3-5MPa for 180-210s to form chemical cross-linking.

[0074] To further simplify and make the present invention achieve its objectives and effects, the present invention will be further illustrated in conjunction with the following specific embodiments and comparative examples, but the present invention is not limited to the scope of the embodiments described herein.

[0075] It should be noted that the raw materials, equipment, and reagents used in this invention can all be purchased from the market or obtained through existing preparation methods; wherein, the melt flow rate of HDPE is 0.4 g / 10 min, and the density is 0.960 g / cm³. 3The particle size of Y2O3 is 80nm; the thickness of the puncture contact layer is 2mm; the thickness of the elastic sealing layer is 4mm; the thickness of the target thin area is reduced to 1.3mm within a diameter of 8mm in the center of the puncture contact layer; the height of the sealing rib is 0.8mm and the width is 0.5mm.

[0076] Example 1

[0077] A sterile vial for radiopharmaceuticals, comprising:

[0078] Firstly, the preparation of the bottle body includes the following steps:

[0079] S1. HDPE is dried at 80°C for 4 hours in a vacuum environment of -0.08MPa to remove moisture and avoid material degradation or bubbles caused by moisture during processing, thus obtaining pretreated HDPE.

[0080] S2. Add Y2O3 to anhydrous ethanol and ultrasonically disperse it for 20 minutes at 400W to obtain a suspension with a concentration of 12wt%. Dissolve KH-570 in anhydrous ethanol to prepare a solution with a concentration of 8wt%. Adjust the pH to 5 with acetic acid and hydrolyze to obtain a modified solution.

[0081] S3. Mix the modified solution and suspension at a mass ratio of 1:2, stir at 500 rpm for 2 hours in a water bath at 70°C, filter to separate the modified Y2O3 particles, wash three times with anhydrous ethanol, and vacuum dry at 60°C for 4 hours to obtain modified Y2O3.

[0082] S4. A co-rotating twin-screw extruder is selected, and preheating is set according to the following segment temperature settings: feeding section 180℃, compression section 190℃, melting section 200℃, mixing section 210℃, homogenization section 205℃, and die head 200℃. Pretreated HDPE and modified Y2O3 are mixed at a ratio of 93.5wt%:6.5wt% and fed into the main feed port and side feed port respectively. The screw speed is 210rpm to form a composite melt, which is extruded into a continuous strip through the die head. The extruded composite melt strip directly enters the underwater pelletizer. The pelletizer speed is controlled at 320rpm to cut the melt strip into 2mm×2mm cylindrical particles, which are then dried to obtain composite granules.

[0083] S5. Select a medical-grade injection molding machine and set the barrel temperature as follows: rear section 190℃, middle section 200℃, front section 210℃, nozzle temperature 205℃. Add the composite melt obtained by adding composite granules and inject the composite melt into the mold cavity at 70℃ with an injection pressure of 90MPa to ensure that the melt quickly fills the cavity. Apply a holding pressure of 65MPa for 7s. After the holding pressure is completed, cool it with circulating water at 25℃ for 20s, open the mold and eject to obtain the bottle body.

[0084] Secondly, the preparation of the bottle neck gasket includes the following steps:

[0085] A1. By mass, 100 parts BIIR, 1 part magnesium oxide and 0.7 parts stearic acid are mixed in an internal mixer at 80°C for 9 minutes, and then molded and vulcanized at 165°C and 15MPa for 300 seconds to obtain an elastic sealing layer.

[0086] A2. By mass percentage, 60% fluorosilicone resin, 0.5% platinum catalyst and 39.5% xylene solvent are stirred at room temperature for 30 minutes to obtain fluorosilicone adhesive;

[0087] A3. PTFE membrane is used as the puncture contact layer, with fluorosilicone adhesive applied at 3 g / cm³. 2 The coating is sprayed onto the surfaces of the puncture contact layer and the elastic sealing layer, and after being laminated, it is hot-pressed at 140℃ and 4MPa for 180s to obtain a sandwich-structured bottle mouth gasket.

[0088] Example 2

[0089] This embodiment is basically the same as Embodiment 1, except that the concentrations of pretreated HDPE and modified Y2O3 are different. In step S4, pretreated HDPE and modified Y2O3 are melt-extruded in a ratio of 95wt%:5wt%.

[0090] Example 3

[0091] This embodiment is basically the same as Embodiment 1, except that the concentrations of pretreated HDPE and modified Y2O3 are different. In step S4, pretreated HDPE and modified Y2O3 are melt-extruded in a ratio of 92wt%:8wt%.

[0092] Comparative Example 1

[0093] The performance description of the aseptic bottle body in this comparative example is basically the same as that in Example 1, except that the polyethylene in the bottle body is PE granules purchased from Binzhou Huayuan Plastics, with a density of 0.46 g / cm³. 3 , particle size 169 mesh.

[0094] Comparative Example 2

[0095] The performance description of the bottle body in this comparative example for aseptic bottles is basically the same as that in Example 1, except that no modified Y2O3 was added to the bottle body, and HDPE was used alone for melt extrusion, granulation and injection molding.

[0096] Comparative Example 3

[0097] The comparative example describes the bottle body performance of sterile bottles in a manner that is basically the same as in Example 1, except that the Y2O3 in the bottle body is not modified and steps S2 and S3 are not performed.

[0098] Comparative Example 4

[0099] The comparative example describes the bottle body performance of sterile bottles in a manner that is basically the same as in Example 1. The difference is that the concentrations of pretreated HDPE and modified Y2O3 in the bottle body are different. In step S4, the pretreated HDPE and modified Y2O3 are melt-extruded in a ratio of 96wt%:4wt%.

[0100] Comparative Example 5

[0101] The comparative example describes the bottle body performance of sterile bottles in a manner that is basically the same as in Example 1. The difference is that the concentrations of pretreated HDPE and modified Y2O3 in the bottle body are different. In step S4, the pretreated HDPE and modified Y2O3 are melt-extruded in a ratio of 90wt%:10wt%.

[0102] Comparative Example 6

[0103] The performance description of the bottle neck gasket used in this comparative example for sterile bottles is basically the same as that in Example 1, except that the bottle neck gasket uses only a traditional butyl rubber gasket, which was purchased from Hebei Jiateng Technology.

[0104] Performance testing: The bottle bodies obtained in Examples 1-3 and Comparative Examples 1-5 were irradiated and then subjected to mechanical property tests. The bottle mouth gaskets obtained in Example 1 and Comparative Example 6 were subjected to puncture simulation and particle detection. The test structures are shown in Table 1.

[0105] Irradiation treatment: Place the bottle sample in a Co-60 γ-ray irradiation device, set the total irradiation dose to 50 kGy (simulating the long-term storage environment of radiopharmaceuticals), and control the irradiation rate to 2 kGy / h to ensure that the sample is irradiated uniformly (the temperature inside the irradiation chamber is ≤30℃ to avoid thermal aging interference).

[0106] Mechanical properties: Using an electronic universal testing machine, the bottle body was tested at a tensile rate of 50 mm / min for both unirradiated and irradiated surfaces. The tensile strength (σ0 and σ1) and elongation at break (ε0 and ε1) were recorded for both unirradiated and irradiated surfaces. The performance retention rate was calculated as follows: tensile strength retention rate = σ1 / σ0 × 100%, elongation at break retention rate = ε1 / ε0 × 100%. The anti-radiation aging effect was evaluated.

[0107] Puncture simulation and particle detection: A universal testing machine was used to simulate clinical puncture procedures, equipped with a 16G medical stainless steel needle with an outer diameter of 1.65 mm. The puncture rate was 10 mm / min, the puncture depth was 4.7 mm (penetrating 90% of the pad thickness), and a single sample was punctured 5 times (with an interval of ≥2 mm between each puncture site to avoid overlap). After each puncture, the pad surface and needle body were wiped with a sterile cotton swab soaked in 0.9% physiological saline. The eluent was transferred to a laser particle size analyzer (detection range 0.5-1000 μm) to count the number of particles ≥10 μm.

[0108] Table 1: Performance test results of bottle bodies of Examples 1-3 and Comparative Examples 1-5, and bottle neck gaskets of Example 1 and Comparative Example 6

[0109]

[0110] As shown in Table 1:

[0111] A comparison between Example 1 and Comparative Example 1 reveals that: Comparative Example 1, which replaces HDPE with ordinary PE, has a looser molecular chain structure. Under gamma-ray irradiation, high-energy particles can more easily penetrate the intermolecular gaps and directly bombard the C-C bonds, resulting in a significantly faster molecular chain breakage rate. At the same time, the melt flow rate of ordinary PE is often higher than that of HDPE, indicating that its molecular weight is lower and the entanglement density between molecular chains is smaller. After breakage, it is difficult to maintain the material strength through physical entanglement. Therefore, the tensile strength retention rate of Comparative Example 1 is only 65.8%, and the elongation at break retention rate is 60.2%, which is far lower than the 93.4% and 89.6% of Example 1, respectively.

[0112] A comparison of Example 1 and Comparative Examples 2-3 reveals that: Comparative Example 2, without the addition of nano-Y2O3, exposes the HDPE molecular chains directly to γ-rays. The tertiary carbon atoms in the HDPE molecular chains are the main sites of γ-ray attack, generating alkyl free radicals and initiating β-fracture after irradiation. This significantly shortens the average length of the molecular chains, leading to severe material embrittlement. Consequently, its tensile strength retention rate is only 50.1%, and its elongation at break retention rate is only 47.5%. In Comparative Example 3, the unmodified Y2O3 nanoparticles do not form YO-Si covalent bonds on their surface and are only bonded to the HDPE matrix through van der Waals forces. This results in interfacial incompatibility between the unmodified Y2O3 and the nonpolar alkane chains of HDPE. During γ-ray irradiation, the unmodified Y2O3 is prone to debonding from the matrix due to differences in thermal expansion coefficients, forming stress concentration points. This easily leads to microcracks during irradiation thermal cycling. Therefore, its tensile strength retention rate is only 75.3%, and its elongation at break retention rate is only 69.8%, significantly lower than that of Example 1.

[0113] A comparison of Examples 1-3 and Comparative Examples 4-5 shows that: the appropriate Y2O3 concentration in Examples 1-3 allows Y2O3 nanoparticles to be uniformly dispersed in the HDPE matrix, forming a percolation network in the HDPE. γ photons are absorbed by the shell electrons of Y atoms through the photoelectric effect, and the energy is converted into lattice vibration energy for diffusion. This not only enhances stress transfer through interfacial chemical bonding but also fully absorbs γ-ray energy through the specific surface area advantage of nanoscale particles, inhibiting molecular chain breakage.

[0114] In Comparative Example 4, due to the low concentration, the interparticle spacing of Y2O3 increased, failing to completely cover the HDPE molecular chains. Some areas of the HDPE molecular chains remained directly exposed to γ-rays, resulting in a decrease in tensile strength retention to 80.2% and elongation at break retention to 74.9%. In Comparative Example 5, due to the high concentration, the interparticle spacing of Y2O3 was too small. Due to van der Waals forces, the particles agglomerated into micron-sized aggregates, increasing interface defects. During γ-ray irradiation, the interface between the aggregates and the matrix became a stress concentration point, triggering local fractures. This resulted in a decrease in tensile strength retention to 82.4% and elongation at break retention to 77.8%.

[0115] A comparison between Example 1 and Comparative Example 6 reveals that: Comparative Example 6 uses a traditional butyl rubber gasket, whose molecular chains exist as a single rubber phase. During puncture, the friction between the needle and the rubber surface is high (the surface energy is higher than that of the PTFE film), and the molecular chains are prone to breakage due to shear stress, forming microparticles. At the same time, the traditional gasket lacks a target thin area design, and the stress is concentrated in a fixed area during puncture, leading to aggravated local molecular chain breakage. In addition, the lack of a double-ring sealing rib structure results in insufficient sealing redundancy, and the elasticity decays faster after multiple punctures (BIIR molecular chains break due to repeated deformation, resulting in a decrease in elastic modulus). Therefore, the microparticle contamination number of Comparative Example 6 is as high as 877 particles / mL, which is much higher than the 289 particles / mL of Example 1, and the resistance to puncture contamination is significantly reduced.

[0116] The above description is based on the preferred embodiments of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects. The scope of the invention is defined by the appended claims rather than the foregoing description, and all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0117] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A sterile vial for radiopharmaceuticals, characterized in that, include: The bottle body is made of a composite modified material of high-density polyethylene and nano-yttrium oxide; A bottle neck gasket, wherein the bottle neck gasket has a sandwich layered structure, comprising: The puncture contact layer is made of medical-grade polytetrafluoroethylene film with a thickness of 1-2.5mm; The elastic sealing layer is made of brominated butyl rubber and has a thickness of 3-5mm. An adhesive interface layer, using fluorosilicone adhesive, is located between the puncture contact layer and the elastic sealing layer to achieve a composite layered structure.

2. The sterile vial for radiopharmaceuticals according to claim 1, characterized in that: In the composite modified material, the high-density polyethylene accounts for 92-95 wt%, and the nano-yttrium oxide accounts for 5-8 wt%; the melt flow rate of the high-density polyethylene is 0.3-0.5 g / 10 min, and the density is 0.955-0.965 g / cm³. 3 The particle size of the nano-yttrium oxide is 50-100 nm.

3. The sterile vial for radiopharmaceuticals according to claim 1, characterized in that: The preparation of the bottle body includes the following steps: S1. High-density polyethylene is dried at 70-90℃ for 3-5 hours under a vacuum environment of ≤-0.08MPa to obtain pretreated high-density polyethylene. S2. Modify nano-yttrium oxide with a silane coupling agent to obtain modified nano-yttrium oxide; S3. Pretreated high-density polyethylene and modified nano-yttrium oxide are melt-extruded through a twin-screw extruder, granulated through an underwater pelletizer, and dried to obtain composite granules; S4. The composite granules are injection molded using an injection molding machine to obtain the bottle body.

4. A sterile vial for radiopharmaceuticals according to claim 3, characterized in that: In step S2, the modification process specifically includes the following steps: S21. Add nano-yttrium oxide to anhydrous ethanol and disperse it by ultrasonication to obtain a suspension with a concentration of 10-15 wt%. Dissolve the silane coupling agent in anhydrous ethanol to prepare a solution with a concentration of 5-10 wt%. Adjust the pH to 4-5 with acetic acid and hydrolyze to obtain a modified solution. S22. Mix the modified solution and suspension at a mass ratio of 1:1-3, stir in a water bath at 60-80℃ at a speed of 400-600 rpm for 2-3 hours, filter to separate the modified nano-yttrium oxide particles, wash three times with anhydrous ethanol, and dry to obtain modified nano-yttrium oxide.

5. A sterile vial for radiopharmaceuticals according to claim 3, characterized in that: In step S3, the process parameters for melt extrusion are: The temperatures from the feed inlet to the die head are as follows: feeding section 180-190℃, compression section 190-200℃, melting section 200-210℃, mixing section 210-220℃, homogenization section 205-210℃, and die head 200-210℃. The screw speed is 200-220 rpm.

6. A sterile vial for radiopharmaceuticals according to claim 3, characterized in that: In step S3, the pelletizer rotates at 300-350 rpm, and the pellet size is a cylindrical shape of 2-3 mm × 2-3 mm.

7. A sterile vial for radiopharmaceuticals according to claim 3, characterized in that: In step S4, the injection molding process parameters are as follows: Barrel temperature: rear section 190-200℃, middle section 200-210℃, front section 210-220℃, nozzle 205-210℃; Mold temperature: 60-70℃; Injection pressure: 80-100MPa, holding pressure: 60-70MPa, holding time: 5-8s; Cooling time: 15-20s, cooling method is water cooling circulation, water temperature 25-30℃.

8. A sterile vial for radiopharmaceuticals according to claim 1, characterized in that: The puncture contact layer has a target thin area, which specifically refers to the area within an 8mm diameter center of the puncture contact layer where the thickness is reduced to 0.7-2mm.

9. A sterile vial for radiopharmaceuticals according to claim 1, characterized in that: The side of the elastic sealing layer is provided with double-ring concentric sealing ribs, the height of which is 0.5-1mm and the width is 0.4-0.7mm. The components of the elastic sealing layer, measured by mass parts, include: 100 parts of brominated butyl rubber, 1-3 parts of magnesium oxide, and 0.5-1 parts of stearic acid; Its preparation process is as follows: the raw materials are mixed in an internal mixer at 70-80℃ for 8-10 minutes, and then molded and vulcanized at 160-170℃ and 15-18MPa for 300-350 seconds.

10. A sterile vial for radiopharmaceuticals according to claim 1, characterized in that: The fluorosilicone adhesive comprises, by weight percentage: 60% fluorosilicone resin, 0.5% platinum catalyst, and 39.5% xylene solvent; The composite step includes: applying fluorosilicone adhesive at a concentration of 3-5 g / cm³. 2 The coating is sprayed onto the surfaces of the puncture contact layer and the elastic sealing layer, and after lamination, it is hot-pressed at 140-150℃ and 3-5MPa for 180-210s to form chemical cross-linking.

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