A method for detecting radiation dose distribution and a radiation-resistant composition

Abstract

This invention provides a method for detecting actual radiation dose, comprising: A) mixing medical-grade polymer raw materials and dihydropyridine 3,5-dicarboxylic acid derivatives to prepare a standard plate; B) placing a dosing strip on the standard plate, irradiating it, and measuring the actual radiation dose received by the standard plate using the dosing strip; irradiating the standard plate under the same conditions, and measuring the fluorescence intensity using fluorescence spectroscopy; C) constructing a standard curve with the actual radiation dose as the abscissa and the fluorescence intensity as the ordinate; D) measuring the fluorescence intensity of the plate to be tested using fluorescence spectroscopy, and calculating the actual radiation dose using the standard curve. The method provided by this invention involves adding a radiation-resistant additive with fluorescence response to the medical polymer raw material, and calculating the actual radiation dose using a standard curve. This invention provides a method for monitoring radiation dose distribution, which has the advantages of high biosafety and accurate detection.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a method for detecting radiation dose distribution and a radiation-resistant composition. Background Technology

[0002] Statistics show that over 90% of medical devices in China currently use ethylene oxide sterilization. Ethylene oxide is highly chemically reactive; its sterilization principle stems from its ability to rapidly alkylate free carboxyl, amino, thio, and hydroxyl groups on proteins, RNA, and DNA, rendering them physiologically inactive in basic metabolism and leading to microbial death. The advantages of ethylene oxide sterilization include low temperature and low humidity, strong penetrating power, low cost, and minimal impact on the physicochemical properties of medical materials. It is particularly suitable for the final centralized sterilization of products from disposable sterile medical device manufacturers, hence its widespread use in China. However, this high biotoxicity also means that ethylene oxide has high human toxicity. Excessive inhalation of ethylene oxide can cause neurotoxicity, and long-term exposure may cause somatic cell mutations and genetic damage in germ cells, including chromosomal aberrations and gene mutations, leading to genotoxicity and carcinogenesis. Furthermore, 2-chloroethanol may be generated during the ethylene oxide sterilization process. Currently, in the domestic medical device product registration and testing process, although 2-chloroethanol is not a mandatory testing item except for some products with explicit industry standards, there is increasing evidence that its toxicity is no less than that of ethylene oxide. Today, countries worldwide have established regulations to strictly control the residual amount of ethylene oxide in medical devices. A particularly challenging problem is that many medical device materials exhibit strong adsorption and permeability to ethylene oxide. After sterilization, ethylene oxide can easily remain on the surface and inside of polymer materials and packaging for extended periods, especially in relatively sealed medical devices where the ethylene oxide desorption cycle is long and difficult. Residual ethylene oxide is gradually released during storage and use, endangering the health of medical personnel and patients.

[0003] Under current conditions, relatively mature sterilization methods include irradiation sterilization and high-temperature steam sterilization. Among them, irradiation sterilization has advantages such as high efficiency, thorough sterilization, no residue, and immediate use after sterilization, and has quickly become the preferred method for sterilizing medical devices. In response to the recent COVID-19 pandemic, the state urgently issued the "Emergency Specification for Irradiation Sterilization of Medical Disposable Protective Clothing (Temporary)" to ensure the supply of emergency medical disposable protective clothing during the epidemic prevention and control period. In developed countries in Europe and America, irradiation sterilization has become the mainstream sterilization method, with approximately 50% of disposable medical devices using irradiation sterilization, and this proportion is still on the rise. Commonly used irradiation sterilization methods include hemodialysis machines, disposable infusion sets, and syringes (medical devices related to human blood), implanted medical products such as cardiac stents and bone stents, as well as sutures, surgical packs, disposable medical dressings, and polymer dressings. In addition, irradiation modification has also been applied to the preparation of high-performance medical polymer materials, such as irradiated cross-linked ultra-high molecular weight polyethylene artificial joint materials, which have a wear rate reduced by more than 90% compared with uncross-linked ultra-high molecular weight polyethylene.

[0004] However, irradiation sterilization or irradiation modification places high demands on the manufacturing technology of medical polymer materials. This is because when the polymer materials used to make medical devices are bombarded by high-energy rays during irradiation, a large number of active free radicals are generated on their molecular chains. These active free radicals undergo complex free radical chemical reactions, and they also undergo slow and persistent chain-like oxidative degradation reactions with oxygen (i.e., rapid aging). This leads to a decline in the physical and mechanical properties of the polymer materials, changes in their chemical and biological properties, and is accompanied by a yellowing or even reddening of the appearance, which seriously affects the appearance and performance of the product.

[0005] In view of this, improving the radiation resistance of medical polymer raw materials has significant application value. Numerous solutions have been disclosed in this field. For example, US Patent Publication No. US7053139 indicates that phthalide and its derivatives can reduce the yellowness index of polyvinyl chloride (PVC) after irradiation. Chinese Patent Application Publication No. CN102827437A proposes using a blend of hindered phenols and phosphites to increase the radiation resistance of PVC. World Patent Publication No. WO 08238, 1997 mentions that a blend containing 99-50 wt% homopolymer or copolymer PP and 1-50 wt% single-point catalyzed polyethylene can improve the radiation aging resistance of PP; this material can be used in medical materials. Antioxidants such as vitamin E and hindered amines have been used to increase the aging resistance of radiation-crosslinked ultra-high molecular weight polyethylene (UHMWPE) artificial joint materials.

[0006] Besides improving the radiation resistance of medical polymer materials, the industry urgently needs a convenient method for monitoring radiation dose distribution. This is because uneven dose distribution occurs in certain areas during the sterilization process of actual medical devices. Practice has shown that the degree of dose unevenness is closely related to factors such as the placement of medical devices, their stacking density, and the density of raw materials. Typically, the dose distribution unevenness is between 1.2 and 2.0 times. Currently, it is known that dose indicator sheets are pasted at different locations to monitor dose unevenness, but this method is cumbersome. Furthermore, the dose indicator sheets themselves are packaged in aluminum-plastic film, which has a high density. When a large number of dose indicator sheets are pasted, it inevitably hinders the penetration of high-energy rays, leading to a deviation between the measured dose value and the actual dose value. When a small number of dose indicator sheets are pasted, it is difficult to obtain sufficient data to assess the dose distribution.

[0007] In summary, existing technologies cannot simultaneously solve the problems of radiation resistance and dose distribution monitoring in medical polymer materials. Summary of the Invention

[0008] In view of this, the technical problem to be solved by the present invention is to provide a method for detecting irradiation dose distribution. The method provided by the present invention can detect reagent irradiation dose and dose distribution. It has high biosafety and accurate detection.

[0009] This invention provides a method for detecting actual radiation dose, comprising:

[0010] A) Medical-grade polymer raw materials and 3,5-dicarboxylic acid dihydropyridine derivatives are mixed to form standard sheets; the medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride or medical-grade polypropylene and medical-grade styrene thermoplastics;

[0011] B) Place a dosing plate on the standard plate and irradiate it. The actual irradiation dose received by the standard plate is obtained by measuring the dosing plate.

[0012] Standard plates were irradiated under the same conditions, and the fluorescence intensity was obtained by fluorescence spectroscopy.

[0013] C) A standard curve was constructed with the actual received radiation dose as the x-axis and the fluorescence intensity as the y-axis;

[0014] D) The fluorescence intensity of the test plate is measured by fluorescence spectroscopy, and the actual irradiation dose is calculated by standard curve.

[0015] Preferably, the 3,5-dicarboxylic acid dihydropyridine derivative includes 3,5-dicarboxylic acid dihydropyridine dialkyl ester and 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid dialkyl ester.

[0016] Preferably, the 3,5-dicarboxylic acid dihydropyridine dialkyl ester has 6 to 22 carbon atoms.

[0017] Preferably, the irradiation dose is 10~80 kGy.

[0018] Preferably, the mass ratio of the medical-grade polymer raw material to the 3,5-dicarboxylic acid dihydropyridine derivative is 100:0.01~0.5.

[0019] Preferably, the standard plate raw material further includes 0.02 to 0.50 parts by weight of antioxidant; the antioxidant includes one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C;

[0020] The raw material of the test plate also includes 0.02 to 0.50 parts by weight of antioxidants; the antioxidants include one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C.

[0021] Preferably, the fluorescence spectral excitation wavelength is 350 nm to 450 nm.

[0022] This invention provides a radiation-resistant composition comprising:

[0023] 100 parts by weight of medical-grade polymer raw materials;

[0024] 0.01~0.5 parts by weight of 3,5-dicarboxylic acid dihydropyridine derivative;

[0025] The medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride or medical-grade polypropylene and medical-grade styrene thermoplastics.

[0026] Preferably, it further includes 0.02 to 0.50 parts by weight of an antioxidant; the antioxidant includes one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, or vitamin C.

[0027] Preferably, the 3,5-dicarboxylic acid dihydropyridine derivative includes 3,5-dicarboxylic acid dihydropyridine dialkyl ester and 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid dialkyl ester; the 3,5-dicarboxylic acid dihydropyridine dialkyl ester has 6 to 22 carbon atoms.

[0028] Compared with existing technologies, this invention provides a method for detecting actual irradiation dose, comprising: A) mixing medical-grade polymer raw materials and 3,5-dihydropyridine dicarboxylate derivatives to prepare a standard plate; the medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride, or medical-grade polypropylene and medical-grade styrene thermoplastics; B) placing a dosing plate on the standard plate, irradiating it, and measuring the actual irradiation dose received by the standard plate using the dosing plate; irradiating the standard plate under the same conditions, and measuring the fluorescence intensity using fluorescence spectroscopy; C) constructing a standard curve with the actual irradiation dose as the abscissa and the fluorescence intensity as the ordinate; D) measuring the fluorescence intensity of the plate to be tested using fluorescence spectroscopy, and calculating the actual irradiation dose using the standard curve. The method provided by this invention involves adding a radiation-resistant additive with fluorescence response to the medical polymer raw materials. During high-energy irradiation such as electron beam irradiation, the radiation-resistant additive itself is oxidized and loses its fluorescence response, and the actual irradiation dose is calculated using the standard curve. This invention provides a method that simultaneously increases the radiation resistance of medical polymer materials and enables the monitoring of radiation dose distribution, offering advantages such as high biosafety, accurate detection, and ease of use. Attached Figure Description

[0029] Figure 1 This is a graph showing the linear relationship between fluorescence intensity and the actual received dose. Detailed Implementation

[0030] This invention provides a method for detecting radiation dose distribution and a radiation-resistant composition. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and fall within the scope of this invention. The method and application of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the method and application described herein without departing from the content, spirit, and scope of this invention to implement and apply the technology of this invention.

[0031] This invention provides a method for detecting actual radiation dose, comprising:

[0032] A) Medical-grade polymer raw materials and 3,5-dicarboxylic acid dihydropyridine derivatives are mixed to form standard sheets; the medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride or medical-grade polypropylene and medical-grade styrene thermoplastics;

[0033] B) Place a dosing plate on the standard plate and irradiate it. The actual irradiation dose received by the standard plate is obtained by measuring the dosing plate.

[0034] Standard plates were irradiated under the same conditions, and the fluorescence intensity was obtained by fluorescence spectroscopy.

[0035] C) A standard curve was constructed with the actual received radiation dose as the x-axis and the fluorescence intensity as the y-axis;

[0036] D) The fluorescence intensity of the test plate is measured by fluorescence spectroscopy, and the actual irradiation dose is calculated by standard curve.

[0037] This invention provides a method for detecting actual radiation dose. First, medical-grade polymer raw materials and 3,5-dihydropyridine dicarboxylate derivatives are mixed to form a standard plate.

[0038] The medical polymer materials mentioned include, but are not limited to, medical ultra-high molecular weight polyethylene, medical polyvinyl chloride, medical polypropylene, and medical styrene thermoplastics, as well as other polymer materials used in the medical device industry.

[0039] The 3,5-dicarboxylic acid dihydropyridine diester comprises 3,5-dicarboxylic acid dihydropyridine dialkyl ester and 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid dialkyl ester. It is known that the 3,5-dicarboxylic acid dihydropyridine derivatives possess antioxidant activity and are used in biological antioxidants, thus helping to reduce the degree of oxidation induced by electron beam or gamma ray irradiation. Furthermore, although it is known that the reduced state of the 3,5-dicarboxylic acid dihydropyridine derivatives exhibits strong absorption and strong fluorescence in the 365-400 nm ultraviolet light spectrum, while its oxidized state loses these spectral characteristics, no reports have revealed or disclosed that the 3,5-dicarboxylic acid dihydropyridine derivatives can lose their fluorescence responsiveness when irradiated within the general dose range (10-100 kGy) for irradiation sterilization or irradiation crosslinking. This invention discovers that 3,5-dicarboxylic acid dihydropyridine derivatives mixed into polymer materials lose part of their fluorescence spectral response after sterilization by electron beam or gamma ray irradiation or after cross-linking by irradiation, and the degree of loss is closely related to the irradiation dose. Therefore, the 3,5-dicarboxylic acid dihydropyridine derivatives described in this invention can not only be used as radiation-resistant antioxidants, but also serve as indicators for monitoring the received dose of electron beams or gamma rays.

[0040] The 3,5-dicarboxylic acid dihydropyridine diester is further characterized in that the alkyl group contains 6 to 22 carbon atoms, preferably 10 to 14 carbon atoms. When the number of carbon atoms is low, the water leaching resistance is poor, making it difficult to meet the raw material regulations for medical polymer materials. When the number of carbon atoms is high, the compatibility with some polar polymer materials (such as polyvinyl chloride) decreases, and blooming is prone to occur on the material surface.

[0041] The preferred mass ratio of the medical-grade polymer raw material and the 3,5-dicarboxylic acid dihydropyridine derivative of the present invention is 100:0.01~0.5; more preferably 100:0.05~0.4; and most preferably 100:0.1~0.2.

[0042] The standard plate raw material of the present invention also includes 0.02 to 0.50 parts by weight of antioxidants; the antioxidants include one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C.

[0043] The raw materials may also contain antioxidants. This invention has found that antioxidants help reduce the sensitivity of the 3,5-dicarboxylic acid dihydropyridine derivative to electron beams or gamma rays; that is, in the presence of antioxidants, the 3,5-dicarboxylic acid dihydropyridine derivative can withstand higher radiation doses. This results in a wider detection range.

[0044] The antioxidants include phenolic, hydroxylamine, benzofuranone antioxidants, phosphites, thioethers, vitamin C, and mixtures thereof, with an addition amount between 0.02% and 0.50%. It is important to note that antioxidants are typically easily soluble small molecule compounds, and their addition amount in medical polymer materials must ensure that the physical, chemical, and biological properties of the medical polymer material meet regulatory requirements. For example, medical polyvinyl chloride conforms to GB / T 15593-Soft Polyvinyl Chloride Plastics for Blood Transfusion (Infusion) Devices, and medical polypropylene conforms to the pharmaceutical industry standard YY / T 0242 Special Polypropylene Material for Medical Infusion, Transfusion, and Injection Devices, etc. Therefore, preferably, the total amount of antioxidants added does not exceed 0.20%.

[0045] When monitoring irradiation dose distribution using the method described in this invention, the medical polymer material is further characterized by being a non-polyvinyl chloride (PVC) material. This invention has found that when a 3,5-dicarboxylic acid dihydropyridine derivative is applied to a polyvinyl chloride material, a significant loss in fluorescence response occurs even when the irradiation sterilization dose is only the minimum required dose of commonly used irradiation sterilization, 25 kGy, making it difficult to indicate the amount of dose received by means of fluorescence intensity. The mechanism involved in this process is unknown to the inventors and has not been clearly demonstrated.

[0046] More preferably, the medical polymer material is further characterized in that it does not contain fluorescent additives that respond to ultraviolet light or ultraviolet absorbers that absorb ultraviolet light, as these two additives interfere with the fluorescence response sensitivity of the 3,5-dicarboxylic acid dihydropyridine derivative to ultraviolet light.

[0047] More preferably, the medical polymer material is characterized by not containing organic acid additives, which interact with dihydropyridine 3,5-dicarboxylate in an acid-base manner, making it easier for dihydropyridine 3,5-dicarboxylate to precipitate on the surface of the medical polymer material.

[0048] A further feature of this invention is that the 3,5-dicarboxylic acid dihydropyridine diester is weakly basic, which helps maintain the pH value of the aqueous extract. Domestic medical device registration regulations typically require that the pH value of the aqueous extract of medical devices change within 1.0. After irradiation sterilization and during subsequent storage, medical devices inevitably undergo oxidative degradation. This oxidative degradation usually increases the pH value change of the aqueous extract, thereby shortening the shelf life of the medical devices. The 3,5-dicarboxylic acid dihydropyridine diester of this invention has an acid-neutralizing effect, thus helping to maintain the pH value of the aqueous extract of medical devices.

[0049] Dosage sheets are placed on a standard plate and irradiated. The actual irradiation dose received by the standard plate is obtained by measuring the dosage sheets.

[0050] This invention does not limit the specific dosage tablets used; any method known to those skilled in the art is acceptable. Preferably, the dose received on the upper and lower surfaces of the dosage tablet test plate is measured, and the average dose received on the upper and lower surfaces represents the actual received dose.

[0051] The irradiation dose described in this invention is 10-80 kGy. In some embodiments of this invention, the irradiation dose can be 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy.

[0052] Standard plates were irradiated under the same conditions, and the fluorescence intensity was obtained by fluorescence spectroscopy.

[0053] The irradiation dose is 10-80 kGy. In some embodiments of the present invention, the irradiation dose can be 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy. The above irradiation is the same as the irradiation of the above dose sheet, showing a corresponding relationship.

[0054] The preferred excitation wavelength for fluorescence spectroscopy in this invention is 350 nm to 450 nm.

[0055] A preferred method is to use a slicer to remove a 0.1 mm thick film from the center of the plate after irradiation, and then measure the fluorescence intensity of the plate at each dose using fluorescence spectroscopy at the excitation wavelength.

[0056] A standard curve was constructed with the actual received radiation dose as the x-axis and the fluorescence intensity as the y-axis.

[0057] The fluorescence intensity of the test plate was measured by fluorescence spectroscopy, and the actual irradiation dose was calculated using a standard curve.

[0058] The process and steps for obtaining fluorescence intensity by fluorescence spectroscopy of the test plate described in this invention are consistent with the standard plate measurement steps and methods, except that the dosing tablets are not required.

[0059] The raw material of the test plate of the present invention further includes 0.02 to 0.50 parts by weight of antioxidant; the antioxidant includes one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C.

[0060] The present invention can also measure the irradiation dose at different locations of the plate using the above method, thereby obtaining the irradiation dose distribution. The results are accurate and highly safe.

[0061] This invention provides a radiation-resistant composition comprising:

[0062] 100 parts by weight of medical-grade polymer raw materials;

[0063] 0.01~0.5 parts by weight of 3,5-dicarboxylic acid dihydropyridine derivative;

[0064] The medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride or medical-grade polypropylene and medical-grade styrene thermoplastics.

[0065] The radiation-resistant composition provided by the present invention comprises 100 parts by weight of medical-grade polymer raw materials.

[0066] The radiation-resistant composition provided by the present invention comprises 0.01 to 0.5 parts by weight of a dihydropyridine 3,5-dicarboxylic acid derivative; preferably 0.05 to 0.45 parts by weight; more preferably 0.1 to 0.2 parts by weight.

[0067] The radiation-resistant composition provided by the present invention preferably further includes 0.02 to 0.50 parts by weight of an antioxidant; more preferably, it includes 0.05 to 0.20 parts by weight of an antioxidant.

[0068] The antioxidants include one or more of the following: phenols, hydroxylamines, benzofuranones, phosphites, thioethers, or vitamin C.

[0069] The 3,5-dicarboxylic acid dihydropyridine derivatives of the present invention include dialkyl 3,5-dicarboxylic acid dihydropyridine and dialkyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid; the dialkyl 3,5-dicarboxylic acid dihydropyridine has 6 to 22 carbon atoms.

[0070] The specific components and proportions of the above-mentioned polymer raw materials, 3,5-dicarboxylic acid dihydropyridine derivatives and antioxidants have been clearly described above and will not be repeated here.

[0071] This invention provides a method for detecting actual radiation dose, comprising: A) mixing medical-grade polymer raw materials and dihydropyridine 3,5-dicarboxylic acid derivatives to prepare a standard plate; the medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene, medical-grade polyvinyl chloride, or medical-grade polypropylene and medical-grade styrene thermoplastics; B) placing a dosing plate on the standard plate, irradiating it, and measuring the actual radiation dose received by the standard plate using the dosing plate; irradiating the standard plate under the same conditions, and measuring the fluorescence intensity using fluorescence spectroscopy; C) constructing a standard curve with the actual radiation dose as the abscissa and the fluorescence intensity as the ordinate; D) measuring the fluorescence intensity of the plate to be tested using fluorescence spectroscopy, and calculating the actual radiation dose using the standard curve. The method provided by this invention involves adding a radiation-resistant additive with a fluorescence response to the medical polymer raw materials. During high-energy ray irradiation such as an electron beam, the radiation-resistant additive itself is oxidized and loses its fluorescence response, and the actual radiation dose is calculated using a standard curve. This invention provides a method that simultaneously increases the radiation resistance of medical polymer materials and enables the monitoring of radiation dose distribution, offering advantages such as high biosafety, accurate detection, and ease of use.

[0072] To further illustrate the present invention, the following describes in detail, with reference to embodiments, a method for detecting radiation dose distribution and a radiation-resistant composition provided by the present invention.

[0073] Example 1

[0074] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP) was mixed evenly with 850 g of ultra-high molecular weight polyethylene powder (UHMWPE) and pressed into sheets with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. The sheets were then crosslinked by electron beam irradiation at doses of 0 kGy, 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy. The received dose on the upper and lower surfaces of the sheets was measured using dosimeters. The average received dose on the upper and lower surfaces represents the actual received dose. The results are listed in Table 1.

[0075] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP) was mixed evenly with 850 g of ultra-high molecular weight polyethylene powder (UHMWPE), and pressed into sheets with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. The sheets were then crosslinked by electron beam irradiation at doses of 0 kGy, 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy. After irradiation, a 0.1 mm thick film was removed from the center of the sheet using a slicer. The fluorescence intensity of the sheet at each dose was measured by fluorescence spectroscopy at an excitation wavelength of 370 nm and compared with the 0 kGy sample. The results are listed in Appendix Table 1. A standard curve was constructed with the actual received irradiation dose as the x-axis and fluorescence intensity as the y-axis. Figure 1 As shown.

[0076] Example 2

[0077] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP), 1.0 g of vitamin E, and 850 g of ultra-high molecular weight polyethylene powder (UHMWPE) were mixed evenly and pressed into sheets with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. The sheets were then crosslinked by electron beam irradiation with doses set at 0 kGy, 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy. The received dose on the upper and lower surfaces of the sheets was measured using dosimeters, and the average received dose on the upper and lower surfaces represents the actual received dose.

[0078] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP), 1.0 g of vitamin E, and 850 g of ultra-high molecular weight polyethylene powder (UHMWPE) were mixed evenly and pressed into plates with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. The plates were then crosslinked by electron beam irradiation at doses of 0 kGy, 15 kGy, 30 kGy, 45 kGy, 60 kGy, and 75 kGy. After irradiation, a 0.1 mm thick film was removed from the center of the plate using a slicer. The fluorescence intensity of the plate at each dose was measured by fluorescence spectroscopy at an excitation wavelength of 370 nm and compared with the 0 kGy sample. The results are listed in Table 2. A standard curve was constructed with the actual received irradiation dose as the x-axis and the fluorescence intensity as the y-axis. Figure 1 As shown, Figure 1 This is a graph showing the linear relationship between fluorescence intensity and the actual received dose.

[0079] Table 1. Fluorescence intensity changes and actual received dose values ​​of the plate under different irradiation doses.

[0080]

[0081] The results in Appendix Table 1 show that: (1) the residual fluorescence intensity of the 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid derivatives varied under different irradiation doses, and there was a corresponding relationship between the irradiation dose and the fluorescence intensity. Figure 1 It can be seen that the standard curve of Example 1 is: fluorescence intensity (%) = 100 - 1.7 * received dose, the upper limit of detectable dose is 45 kGy, and when the irradiation dose exceeds 45 kGy, the linear relationship between fluorescence intensity and actual received dose deviates.

[0082] Table 2. Fluorescence intensity changes and actual received dose values ​​of the plate under different irradiation doses.

[0083]

[0084] While the presence of the antioxidant vitamin E reduces the sensitivity of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid derivatives to radiation dose, this principle can be used to monitor higher radiation doses.

[0085] Depend on Figure 1 As can be seen, the standard curve of Example 2 is: fluorescence intensity (%) = 100 - 1.08 * accepted dose, and the upper limit of the detectable dose is 75 kGy.

[0086] Example 3

[0087] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP), 1.0 g of vitamin E, and 850 g of ultra-high molecular weight polyethylene powder (UHMWPE) were mixed evenly and pressed into plates with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. Five plates were then stacked together, and dosing strips were attached to the center of the upper and lower surfaces of each layer. To prevent the dosing strips from overlapping and affecting the electron beam penetration depth, the positions of the dosing strips on each layer were staggered. The plates were then cross-linked by electron beam irradiation, with the irradiation dose set to 40 kGy. After irradiation, the actual received dose values ​​of each layer were measured, and the ratio of the actual received dose to the set dose is listed in Appendix Table 2.

[0088] 2.0 g of 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acid dodecyl ester (DHP), 1.0 g of vitamin E, and 850 g of ultra-high molecular weight polyethylene powder (UHMWPE) were mixed evenly and pressed into plates with dimensions of 300 mm * 300 mm * 10 mm at 200 °C. Five plates were then stacked together and crosslinked by electron beam irradiation at a dose of 40 kGy. After irradiation, a 0.1 mm thick film was removed from the center of the plate using a slicer. The fluorescence intensity of the plate at each dose was measured by fluorescence spectroscopy at an excitation wavelength of 370 nm and compared with the 0 kGy sample. The results are listed in Table 3.

[0089] Table 3. Irradiation dose uniformity obtained from Example 3

[0090]

[0091] As can be seen from the data in Appendix 3, the dose distribution results obtained by the method of the present invention are close to the results of dose tablet detection.

[0092] Example 4

[0093] Prepare the following UHMWPE sheets respectively

[0094] (1) Pure UHMWPE sheet with a thickness of 10 mm;

[0095] (2) 10 mm thick DHP sheet with 0.2% UHMWPE by mass added;

[0096] (3) 10 mm thick UHMWPE sheets with DHP added at a mass percentage of 0.2% and vitamin E added at a mass percentage of 0.1%.

[0097] The above-mentioned sheet was irradiated with an electron beam of 75 kGy and then vacuum annealed at 130°C for 12 h to obtain irradiated crosslinked UHMWPE sheet.

[0098] The obtained cross-linked UHWMPE boards were placed in an oxygen bomb aging apparatus at a set temperature of 70℃ and an oxygen pressure of 5 atm for accelerated aging for 14 days. The oxidation index at the center of the corresponding board was tested by infrared spectroscopy according to the Chinese pharmaceutical industry standard YY / T 0772.4.

[0099] Appendix Table 4, Oxidation Index of the Samples Prepared in Example 4

[0100]

[0101] As can be seen from the results in Appendix 4, the method of the present invention can increase the aging resistance and stability of medical polymer materials while monitoring dose distribution.

[0102] Example 5

[0103] 100 kg of suspended polyvinyl chloride powder (US-70, Liancheng Chemical Co., Ltd., Taiwan), 60 kg of diisooctyl phthalate, 4 kg of epoxidized soybean oil (Guangzhou Haierma Co., Ltd.), 0.2 kg of calcium stearate, 0.20 kg of zinc stearate, and 0.20 kg of docosyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (DHP) were added to a high-speed mixer. Mixing was stopped when the temperature reached 130°C, and the mixture was discharged into a cooler and cooled to below 60°C to obtain dry powder. The dry powder was then granulated using a conical twin-screw extruder with an extrusion temperature set at 160-175°C and a die temperature of 155°C. After melt extrusion, PVC granules were obtained.

[0104] The above PVC granules were pressed into a 0.1 mm thick transparent film, sterilized by irradiation for 25 kGy and 50 kGy, and its fluorescence intensity was tested. The results are listed in Appendix Table 5.

[0105] The above-mentioned PVC granules were processed into connecting hoses with an outer diameter of 2.05 ± 0.05 mm and an inner diameter of 1.00 ± 0.05 mm using a pipe drawing machine. The hoses were sterilized by irradiation at 25 kGy and 50 kGy, cut into 10 mm long segments, and extracted at 37°C for 3 days at a specific surface area / water volume ratio of 6 cm²: 1 mL. The pH values ​​of the water-soluble extracts are listed in Appendix Table 5.

[0106] Comparative Example 1

[0107] 100 kg of suspended polyvinyl chloride powder (US-70, Liancheng Chemical Co., Ltd., Taiwan), 60 kg of diisooctyl phthalate, 4 kg of epoxidized soybean oil (Guangzhou Haierma Co., Ltd.), 0.2 kg of calcium stearate, and 0.20 kg of zinc stearate were added to a high-speed mixer. Mixing was stopped when the temperature reached 130°C, and the mixture was discharged into a cooler to be cooled to below 60°C to obtain dry powder. The dry powder was then granulated using a conical twin-screw extruder, with the extrusion temperature set at 160-175°C and the die temperature at 155°C. After melt extrusion, PVC granules were obtained.

[0108] The above-mentioned PVC granules were processed into connecting hoses with an outer diameter of 2.05 ± 0.05 mm and an inner diameter of 1.00 ± 0.05 mm using a pipe drawing machine. The hoses were sterilized by irradiation at 25 kGy and 50 kGy, cut into 10 mm long segments, and extracted at 37°C for 3 days at a specific surface area / water volume ratio of 6 cm²: 1 mL. The pH values ​​of the water-soluble extracts are listed in Appendix Table 5.

[0109] Appendix 5: Fluorescence intensity and pH value of water-soluble substances after PVC irradiation sterilization.

[0110]

[0111] As can be seen from the results in Appendix 5, although the method of the present invention is not applicable to monitoring the irradiation dose distribution of medical devices made of PVC material, it can still indicate whether the PVC material has undergone irradiation treatment. During irradiation sterilization, PVC material releases a large amount of hydrogen chloride. This hydrogen chloride remains inside the PVC material and is slowly released, causing a decrease in the pH value of the water-soluble residues of the PVC material. National regulations generally require that the pH value of the water-soluble residues of PVC material decrease within 1.0. The results in Table 5 also show that the method of the present invention can solve the problem of a significant decrease in the pH value of the water-soluble residues of PVC material caused by irradiation sterilization.

[0112] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for detecting actual radiation dose, characterized in that, include: A) A standard plate is prepared by mixing medical-grade polymer raw materials and 3,5-dicarboxylic acid dihydropyridine derivatives; the plate to be tested includes a mixture of medical-grade polymer raw materials and 3,5-dicarboxylic acid dihydropyridine derivatives; the medical-grade polymer raw materials include medical-grade ultra-high molecular weight polyethylene; B) Place a dosing plate on the standard plate and irradiate it. The actual irradiation dose received by the standard plate is obtained by measuring the dosing plate. Standard plates were irradiated under the same conditions, and the fluorescence intensity was obtained by fluorescence spectroscopy. C) A standard curve was constructed with the actual received radiation dose as the x-axis and the fluorescence intensity as the y-axis; D) The fluorescence intensity of the test plate is measured by fluorescence spectroscopy, and the actual irradiation dose is calculated by standard curve.

2. The method according to claim 1, characterized in that, The 3,5-dicarboxylic acid dihydropyridine derivatives include 3,5-dicarboxylic acid dihydropyridine dialkyl ester and 2,6-dimethyl-1,4-dihydro-3,5-pyridine dicarboxylic acid dialkyl ester.

3. The method according to claim 2, characterized in that, The alkyl group in the 3,5-dicarboxylic acid dihydropyridine dialkyl ester has 6 to 22 carbon atoms.

4. The method according to claim 1, characterized in that, The irradiation dose is 10~80 kGy.

5. The method according to claim 1, characterized in that, The mass ratio of the medical-grade polymer raw material to the dihydropyridine 3,5-dicarboxylic acid derivative is 100:0.01~0.

5.

6. The method according to claim 1, characterized in that, The standard board material also includes 0.02 to 0.50 parts by weight of antioxidants; the antioxidants include one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C. The raw material of the test board also includes 0.02 to 0.50 parts by weight of antioxidants; the antioxidants include one or more of phenols, hydroxylamines, benzofuranones, phosphites, thioethers, and vitamin C.

7. The method according to claim 1, characterized in that, The excitation wavelength of the fluorescence spectrum is 350 nm to 450 nm.

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