CN114200499A

CN114200499A - Method for detecting irradiation dose distribution and irradiation-resistant composition

Info

Publication number: CN114200499A
Application number: CN202111519097.3A
Authority: CN
Inventors: 杨华伟; 殷敬华; 李春明; 沈杰; 栾世方; 刘文涛
Original assignee: Shanghai Perli Medical Materials Co ltd
Current assignee: Shanghai Perli Medical Materials Co ltd
Priority date: 2021-12-13
Filing date: 2021-12-13
Publication date: 2022-03-18

Abstract

The invention provides a method for detecting actual irradiation dose, which comprises the following steps: A) mixing medical grade high molecular raw materials and 3, 5-dihydropyridine diformate derivative to prepare a standard plate; B) setting a dose sheet on the standard plate, irradiating, and measuring by the dose sheet to obtain the irradiation dose actually received by the standard plate; irradiating the standard plate under the same condition, and measuring by fluorescence spectrum to obtain fluorescence intensity; C) taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve; D) and measuring the plate to be measured by adopting a fluorescence spectrum to obtain fluorescence intensity, and calculating by using a standard curve to obtain the actual irradiation dose. The method provided by the invention is to add an irradiation-resistant additive with fluorescent response into a medical polymer raw material, and calculate the actual irradiation dose through a standard curve. The invention provides a method for monitoring radiation dose distribution capability, which has the advantages of high biological safety and accurate detection.

Description

Method for detecting irradiation dose distribution and irradiation-resistant composition

Technical Field

The invention relates to the technical field of biomedicine, in particular to a method for detecting irradiation dose distribution and an irradiation-resistant composition.

Background

According to statistics, more than 90 percent of the medical instruments in China currently adopt an ethylene oxide sterilization method. Ethylene oxide is highly chemically active, and its sterilization principle results from its ability to rapidly alkylate with free carboxyl, amino, thio and hydroxyl groups on proteins, RNA and DNA, rendering them biologically inactive in essential metabolism, resulting in microbial death. The ethylene oxide sterilization method has the advantages of low temperature and low humidity, strong penetrating power, low cost, small influence on the physical and chemical properties of medical materials and the like, is particularly suitable for the final concentrated sterilization of products of disposable sterile medical equipment production enterprises, and is widely applied in China. However, this high degree of biotoxicity also means that ethylene oxide has high human toxicity, excessive inhalation of ethylene oxide can cause neurotoxic reactions, human exposure to ethylene oxide for prolonged periods or can cause somatic mutations, and genetic damage in germ cells, including chromosomal aberrations and genetic mutations, can cause genotoxicity and canceration. In addition, 2-chloroethanol may be derived during ethylene oxide sterilization. At present, in the registration and inspection process of domestic medical equipment products, although 2-chloroethanol is a non-mandatory detection item except for a part of products with clear industrial standard requirements, more and more data show that the toxicity of 2-chloroethanol is not inferior to that of ethylene oxide. Today, legislation has been set by countries around the world to strictly control the residual amount of ethylene oxide in medical devices. The difficult problem is that many medical appliance materials have strong adsorbability and permeability to ethylene oxide, the ethylene oxide is easy to exist on the surfaces and the interiors of high polymer materials and packaging boxes for a long time after the medical appliances are sterilized, particularly some relatively closed medical appliances, the ethylene oxide analysis period is long and difficult, and residual ethylene oxide is gradually released in the storage and use processes and is harmful to the health of medical staff and patients.

Under the existing conditions, the mature sterilization modes comprise irradiation sterilization and high-temperature steam sterilization, wherein the irradiation sterilization has the advantages of high efficiency, thorough sterilization, no residue, immediate use after sterilization and the like, and the method quickly becomes the first choice of the sterilization method of the medical instruments. Recent novel coronavirus epidemic situation, national emergency release of irradiation sterilization emergency regulations (temporary) for medical disposable protective clothing, so as to ensure the supply of emergency medical disposable protective clothing during epidemic situation prevention and control. In developed countries in europe and the united states, radiation sterilization has become the mainstream sterilization method, and about 50% of disposable medical appliances are sterilized by radiation, and the proportion thereof is still on the rise, wherein the commonly used radiation sterilization methods are medical appliances related to human blood, such as hemodialyzer, disposable infusion set and syringe, medical products implanted into human body, such as cardiac stent and bone stent, and also suture, operation bag, disposable medical dressing and polymer dressing, and the like. In addition, the irradiation modification is also applied to the preparation of high-performance medical high polymer materials, such as irradiation cross-linked ultrahigh molecular weight polyethylene artificial joint materials, and compared with uncrosslinked ultrahigh molecular weight polyethylene, the wear rate of the materials is reduced by more than 90%.

However, the requirements of radiation sterilization or radiation modification on the manufacturing technology of medical polymer materials are high because the polymer materials for manufacturing medical devices are bombarded by high-energy rays during radiation, a large amount of active free radicals are generated on the molecular chains of the polymer materials, the active free radicals can generate complex free radical chemical reactions, and the active free radicals also generate slow and durable chain-locking type oxidative degradation reactions (namely, rapid aging phenomenon) with oxygen, so that the physical and mechanical properties of the polymer materials are reduced, the chemical and biological properties are changed, and the appearance color turns yellow or even turns red, which seriously affects the appearance and the service performance of the products.

In view of this, it has important application value to improve the radiation resistance of medical polymer raw materials. In this field, a number of solutions have been disclosed. For example, U.S. Pat. No. 7053139 discloses that the yellowness index of polyvinyl chloride after irradiation can be reduced by using phthalide and its derivatives, and Chinese patent application with publication No. CN102827437A proposes to increase the irradiation resistance of polyvinyl chloride by using a combination of hindered phenol and phosphite. WO 08238,1997 mentions that blending of 99-50 wt% of homo-or co-PP with 1-50 wt% of single-site catalyzed polyethylene improves the radiation aging resistance of PP, which is useful as a medical material. Antioxidants such as vitamin E and hindered amine are used to increase the aging resistance of the irradiation crosslinked ultra-high molecular weight polyethylene artificial joint material.

In addition to improving the radiation resistance of medical polymer materials, there is an urgent need in the industry for a method for monitoring the radiation dose distribution more conveniently, because the local dosage of medical equipment is not uniform during the sterilization process. Practice proves that the received dose unevenness degree is closely related to factors such as the product arrangement mode of the medical instrument, the stacking density of the medical instrument, the density of raw materials and the like, and the dose distribution unevenness is 1.2-2.0 times under the common condition. It is known to those skilled in the art to monitor dose non-uniformity by applying dose indicators at different locations, but this is cumbersome. In addition, the dosage sheet is packaged by an aluminum plastic film, the density is high, and when the dosage sheet is pasted in a large quantity, the penetrating capacity of high-energy rays is inevitably hindered, so that the measured dosage value and the actual dosage value are deviated; when the number of patch sticks is small, it is difficult to obtain sufficient data to evaluate the dose distribution.

In summary, none of the prior art methods can simultaneously solve the problems of radiation resistance and dose distribution monitoring of medical polymer materials.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a method for detecting an irradiation dose distribution, which can detect an irradiation dose and a dose distribution of a reagent. The biological safety is high, and the detection is accurate.

The invention provides a method for detecting actual irradiation dose, which comprises the following steps:

A) mixing medical grade high molecular raw materials and 3, 5-dihydropyridine diformate derivative to prepare a standard plate; the medical grade high molecular raw material comprises medical ultra-high molecular weight polyethylene, medical polyvinyl chloride or medical polypropylene and medical styrene thermoplastic;

B) setting a dose sheet on the standard plate, irradiating, and measuring by the dose sheet to obtain the irradiation dose actually received by the standard plate;

irradiating the standard plate under the same condition, and measuring by fluorescence spectrum to obtain fluorescence intensity;

C) taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve;

D) and measuring the plate to be measured by adopting a fluorescence spectrum to obtain fluorescence intensity, and calculating by using a standard curve to obtain the actual irradiation dose.

Preferably, the 3, 5-dicarboxylic acid dihydropyridine derivatives include 3, 5-dicarboxylic acid dihydropyridine dialkyl ester and 2, 6-dimethyl-1, 4-dihydro-3, 5-dicarboxylic acid dialkyl ester.

Preferably, the number of carbon atoms in the dihydropyridine 3, 5-dicarboxylate dialkyl ester is 6-22.

Preferably, the irradiation dose is 10-80 kGy.

Preferably, the mass ratio of the medical grade high molecular raw material to the 3, 5-dicarboxylic acid dihydropyridine derivative is 100: 0.01 to 0.5.

Preferably, the standard board raw material further comprises 0.02-0.50 parts by weight of an antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers and vitamin C;

the board to be detected also comprises 0.02-0.50 parts by weight of antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers and vitamin C.

Preferably, the fluorescence spectrum excitation wavelength is 350nm to 450 nm.

The invention provides an irradiation-resistant composition, which comprises:

100 parts of medical grade high molecular raw material;

0.01-0.5 part by weight of 3, 5-dicarboxylic acid dihydropyridine derivative;

the medical grade high molecular raw material comprises medical ultra-high molecular weight polyethylene, medical polyvinyl chloride or medical polypropylene and medical styrene thermoplastic.

Preferably, the composition also comprises 0.02-0.50 weight part of antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers or vitamin C.

Preferably, the 3, 5-dicarboxylic acid dihydropyridine derivatives include 3, 5-dicarboxylic acid dihydropyridine dialkyl ester and 2, 6-dimethyl-1, 4-dihydro-3, 5-dicarboxylic acid dialkyl ester; the number of carbon atoms in the 3, 5-dihydropyridine dialkyl ester is 6-22.

Compared with the prior art, the invention provides a method for detecting actual irradiation dose, which comprises the following steps: A) mixing medical grade high molecular raw materials and 3, 5-dihydropyridine diformate derivative to prepare a standard plate; the medical grade high molecular raw material comprises medical ultra-high molecular weight polyethylene, medical polyvinyl chloride or medical polypropylene and medical styrene thermoplastic; B) setting a dose sheet on the standard plate, irradiating, and measuring by the dose sheet to obtain the irradiation dose actually received by the standard plate; irradiating the standard plate under the same condition, and measuring by fluorescence spectrum to obtain fluorescence intensity; C) taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve; D) and measuring the plate to be measured by adopting a fluorescence spectrum to obtain fluorescence intensity, and calculating by using a standard curve to obtain the actual irradiation dose. The invention provides a method for adding an irradiation-resistant additive with fluorescent response into a medical polymer raw material, wherein the irradiation-resistant additive is oxidized to lose the fluorescent response in the irradiation process of high-energy rays such as electron beams, and the actual irradiation dose is calculated through a standard curve. The invention provides a method for simultaneously improving the radiation resistance of a medical high polymer material and monitoring the radiation dose distribution capacity, and the method has the advantages of high biological safety, accurate detection and convenience in use.

Drawings

FIG. 1 is a plot of a linear fit between fluorescence intensity and actual received dose.

Detailed Description

The invention provides a method for detecting radiation dose distribution and a radiation-resistant composition, and a person skilled in the art can appropriately improve process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope of the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The invention provides a method for detecting actual irradiation dose, which comprises the steps of mixing medical grade high molecular raw materials and 3, 5-dihydropyridine diformate derivatives to prepare a standard plate.

The medical polymer material includes but is not limited to medical ultra-high molecular weight polyethylene, medical polyvinyl chloride, medical polypropylene, medical styrene thermoplastic and other polymer materials used in the medical appliance industry.

The 3, 5-dicarboxylic acid dihydropyridine diester comprises 3, 5-dicarboxylic acid dihydropyridine dialkyl ester and 2, 6-dimethyl-1, 4-dihydro-3, 5-dicarboxylic acid dialkyl ester. The 3, 5-dicarboxylic acid dihydropyridine derivative is known to have antioxidant activity and is applied to biological antioxidants, so that it is advantageous to reduce the degree of oxidation induced by electron beam or gamma ray irradiation. In addition, although the 3, 5-dicarboxylic acid dihydropyridine derivative is known to have strong absorption of 365-400 nm ultraviolet rays in a reduced state and emit strong fluorescence, and the oxidized state of the derivative loses the spectral characteristics, no relevant report discloses or discloses that the 3, 5-dicarboxylic acid dihydropyridine derivative can lose the fluorescence responsiveness when irradiated within a general dose range (10-100 kGy) of radiation sterilization or radiation crosslinking. The invention finds that the 3, 5-dicarboxylic acid dihydropyridine derivative mixed in the high molecular material loses partial fluorescence spectrum response after electron beam or gamma ray irradiation sterilization or irradiation crosslinking, and the loss degree is closely related to the irradiation dose, so the 3, 5-dicarboxylic acid dihydropyridine derivative not only can be used as an anti-oxidant with radiation resistance, but also has an indicator for monitoring the electron beam or gamma ray receiving dose.

The 3, 5-dihydropyridine diester is characterized in that the alkyl group contains 6-22 carbon atoms, preferably 10-14 carbon atoms. When the number of carbon atoms is relatively low, the water leaching resistance is poor, and raw material regulations of medical polymer materials are difficult to meet, and when the number of carbon atoms is relatively high, the compatibility in some polar polymer materials (such as polyvinyl chloride) is low, and the surface of the material is easy to generate a blooming phenomenon.

The mass ratio of the medical grade high molecular raw material and the 3, 5-dicarboxylic acid dihydropyridine derivative is preferably 100: 0.01 to 0.5; more preferably 100: 0.05 to 0.4; most preferably 100: 0.1 to 0.2.

The standard plate raw material also comprises 0.02-0.50 part by weight of antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers and vitamin C.

Namely, the raw material may further comprise an antioxidant, and the present invention has found that the antioxidant contributes to the reduction of the sensitivity of the dihydropyridine 3, 5-dicarboxylate derivative to electron beams or gamma rays, that is, the dihydropyridine 3, 5-dicarboxylate derivative can withstand a higher irradiation dose in the presence of the antioxidant. The detection range is wider.

The antioxidant comprises phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers, vitamin C and a mixture thereof, and the addition amount of the antioxidant is 0.02-0.50%. It should be noted that the antioxidant is usually a small molecule compound easy to dissolve out, and the addition amount thereof in the medical polymer material must ensure that the physical, chemical and biological properties of the medical polymer material meet the requirements of the regulations, such as medical polyvinyl chloride meeting the requirements of GB/T15593-soft polyvinyl chloride plastic for blood (liquid) transfusion instruments, medical polypropylene meeting the medical industry standard of YY/T0242 polypropylene special material for medical transfusion, blood transfusion and injection instruments, etc., so the total amount of the antioxidant added preferably does not exceed 0.20%.

When the method of the present invention is used for monitoring the irradiation dose distribution, the medical polymer material is also characterized by being a non-polyvinyl chloride material. The invention finds that when the 3, 5-dicarboxylic acid dihydropyridine derivative is applied to the polyvinyl chloride material, when the irradiation sterilization dose is only 25kGy which is the minimum required dose of common irradiation sterilization, the fluorescence response is remarkably lost, so that the received dose is difficult to indicate through the size of fluorescence intensity. The mechanism involved in this process is unknown to the inventors and has not been clearly demonstrated.

More preferably, the medical polymer material is further characterized by not containing a fluorescent additive having a fluorescent response to ultraviolet rays and an ultraviolet absorber having an absorption function to ultraviolet rays, which interfere with the sensitivity of the 3, 5-dihydropyridine dicarboxylate derivative to the fluorescent response to ultraviolet rays.

More preferably, the medical polymer material is further characterized by not containing an organic acid additive, and the additive and the 3, 5-dihydropyridine diformate have acid-base interaction, so that the 3, 5-dihydropyridine diformate is more easily precipitated on the surface of the medical polymer material.

The invention is also characterized in that the 3, 5-dicarboxylic acid dihydropyridine diester has weak alkalinity and is helpful for maintaining the pH value of water leachate. The registration regulation of domestic medical instruments generally requires that the pH value of the water leachate of the medical instruments changes within 1.0, the medical instruments inevitably undergo oxidative degradation after irradiation sterilization and in the subsequent storage process, and the oxidative degradation generally increases the pH value change of the water leachate of the medical instruments, so that the quality guarantee period of the medical instruments is shortened. The dihydropyridine 3, 5-dicarboxylate diesters of the present invention have an acid neutralizing effect and thus help maintain the pH of the aqueous medical device extract.

And arranging a dose sheet on the standard plate, irradiating, and measuring by the dose sheet to obtain the irradiation dose actually received by the standard plate.

The dosage tablets of the present invention are not limited and are well known to those skilled in the art. The received doses on the upper and lower surfaces of the sheet are preferably tested by dose tablets, the average of the received doses on the upper and lower surfaces representing the actual received dose,

the irradiation dose is 10-80 kGy. In some embodiments of the invention, the irradiation dose may be 15kGy, 30kGy, 45kGy, 60kGy, and 75 kGy.

And irradiating the standard plate under the same condition, and measuring by a fluorescence spectrum to obtain the fluorescence intensity.

The irradiation dose is 10-80 kGy. In some embodiments of the invention, the irradiation dose may be 15kGy, 30kGy, 45kGy, 60kGy, and 75 kGy. The irradiation is the same as the irradiation of the dose plate, and a corresponding relationship is presented.

The excitation wavelength of the fluorescence spectrum is preferably 350nm to 450 nm.

Preferably, the following may be used: after irradiation, a 0.1mm thick film was removed from the center of the plate using a microtome, and the fluorescence intensity of the plate at each dose was measured by fluorescence spectroscopy at the excitation wavelength.

And (3) taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve.

And measuring the plate to be measured by adopting a fluorescence spectrum to obtain fluorescence intensity, and calculating by using a standard curve to obtain the actual irradiation dose.

The process and steps of obtaining the fluorescence intensity of the plate to be detected by adopting fluorescence spectrum measurement are consistent with the method of measuring the standard plate, and only dose tablets are not needed.

The raw material of the board to be detected also comprises 0.02-0.50 weight part of antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers and vitamin C.

The invention can also determine the irradiation dose of different positions of the plate by the method, thereby obtaining the irradiation dose distribution with accurate result and high safety.

The invention provides an irradiation-resistant composition, which comprises:

100 parts of medical grade high molecular raw material;

0.01-0.5 part by weight of 3, 5-dicarboxylic acid dihydropyridine derivative;

The radiation-resistant composition provided by the invention comprises 100 parts by weight of medical-grade high-molecular raw materials.

The radiation-resistant composition provided by the invention comprises 0.01-0.5 part by weight of 3, 5-dihydropyridine diformate; preferably 0.05 to 0.45 parts by weight; more preferably 0.1 to 0.2 parts by weight.

The radiation-resistant composition provided by the invention preferably further comprises 0.02-0.50 weight part of antioxidant; more preferably, the antioxidant is included in an amount of 0.05 to 0.20 parts by weight.

The antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers or vitamin C.

The 3, 5-dihydropyridine diformate derivative comprises 3, 5-dihydropyridine dialkyl ester and 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid dialkyl ester; the number of carbon atoms in the 3, 5-dihydropyridine dialkyl ester is 6-22.

The specific components and proportions of the polymer raw material, the 3, 5-dihydropyridine diformate and the antioxidant are clearly described in the invention, and are not repeated herein.

The invention provides a method for detecting actual irradiation dose, which comprises the following steps: A) mixing medical grade high molecular raw materials and 3, 5-dihydropyridine diformate derivative to prepare a standard plate; the medical grade high molecular raw material comprises medical ultra-high molecular weight polyethylene, medical polyvinyl chloride or medical polypropylene and medical styrene thermoplastic; B) setting a dose sheet on the standard plate, irradiating, and measuring by the dose sheet to obtain the irradiation dose actually received by the standard plate; irradiating the standard plate under the same condition, and measuring by fluorescence spectrum to obtain fluorescence intensity; C) taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve; D) and measuring the plate to be measured by adopting a fluorescence spectrum to obtain fluorescence intensity, and calculating by using a standard curve to obtain the actual irradiation dose. The invention provides a method for adding an irradiation-resistant additive with fluorescent response into a medical polymer raw material, wherein the irradiation-resistant additive is oxidized to lose the fluorescent response in the irradiation process of high-energy rays such as electron beams, and the actual irradiation dose is calculated through a standard curve. The invention provides a method for simultaneously improving the radiation resistance of a medical high polymer material and monitoring the radiation dose distribution capacity, and the method has the advantages of high biological safety, accurate detection and convenience in use.

In order to further illustrate the present invention, a method for detecting radiation dose distribution and a radiation-resistant composition provided by the present invention are described in detail below with reference to the following examples.

Example 1

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP) and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. The sheet was radiation-crosslinked using electron beams at irradiation doses set to 0kGy, 15kGy, 30kGy, 45kGy, 60kGy and 75kGy, respectively, and the received doses of the upper and lower surfaces of the sheet were tested by dose tablet, and the average of the received doses of the upper and lower surfaces represents the actual received dose, and the corresponding results are shown in table 1.

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP) and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. The sheet was radiation-crosslinked using electron beams at irradiation doses set to 0kGy, 15kGy, 30kGy, 45kGy, 60kGy, and 75kGy, respectively. After irradiation, a film with the thickness of 0.1mm is taken down from the center of the plate by using a slicer, the fluorescence intensity of the plate under each dosage is measured under the excitation wavelength of 370nm through fluorescence spectrum, and is compared with a 0kGy sample, and corresponding results are listed in an attached table 1; taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve; as shown in fig. 1.

Example 2

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP), 1.0g of vitamin E and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. Carrying out irradiation crosslinking on the plate by adopting an electron beam, setting irradiation doses to be 0kGy, 15kGy, 30kGy, 45kGy, 60kGy and 75kGy respectively, testing the receiving doses of the upper surface and the lower surface of the plate by using a dose sheet, wherein the average value of the receiving doses of the upper surface and the lower surface represents the actual receiving dose,

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP), 1.0g of vitamin E and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. The sheet was radiation-crosslinked using electron beams at irradiation doses set to 0kGy, 15kGy, 30kGy, 45kGy, 60kGy, and 75kGy, respectively. After irradiation, a 0.1mm thick film was removed from the center of the plate using a microtome, and the fluorescence intensity of the plate at each dose was measured by fluorescence spectroscopy at an excitation wavelength of 370nm and compared with a 0kGy sample, and the corresponding results are shown in Table 2. Taking the actual received irradiation dose as an abscissa and the fluorescence intensity as an ordinate to prepare a standard curve; as shown in fig. 1, fig. 1 is a plot fitted with a linear relationship between fluorescence intensity and actual received dose.

TABLE 1 fluorescence intensity variation and actual received dose values of panels under different irradiation doses

The results of the attached Table 1 show: (1) the residual fluorescence intensity of the 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid derivative is different when the derivative is subjected to different irradiation doses, and the irradiation dose and the fluorescence intensity have corresponding relation. As can be seen from fig. 1, the standard curve of example 1 is: the fluorescence intensity (%) was 100 to 1.7 × received dose, the upper detectable dose limit was 45kGy, and when the irradiation dose exceeded 45kGy, the linear relationship between the fluorescence intensity and the actual received dose deviated.

TABLE 2 fluorescence intensity variation and actual received dose values of panels under different irradiation doses

The presence of the antioxidant vitamin E, while reducing the sensitivity of the 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid derivative to the radiation dose, allows monitoring of higher radiation doses using this principle.

As can be seen from fig. 1, the standard curve of example 2 is: fluorescence intensity (%). 100-1.08 @ received dose, with a detectable upper limit of 75 kGy.

Example 3

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP), 1.0g of vitamin E and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. Then 5 sheets are overlapped together, dosage pieces are adhered to the center positions of the upper surface and the lower surface of each layer of sheet, meanwhile, in order to prevent the dosage pieces from being overlapped up and down to influence the penetration depth of electron beams, the positions of the dosage pieces on each layer of sheet are staggered, the sheet is irradiated and crosslinked by the electron beams, and the irradiation dose is respectively set to be 40 kGy. After irradiation, the actual received dose values of the layers are detected, and the ratio result of the actual received dose to the set dose is listed in the attached table 2.

2.0g of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid docosanyl ester (DHP), 1.0g of vitamin E and 850g of ultra-high molecular weight polyethylene powder (UHMWPE) are mixed uniformly and pressed into a plate with the size of 300mm 10mm at 200 ℃. Then, 5 sheets were stacked together, and the sheets were subjected to irradiation crosslinking with electron beams at irradiation doses set to 40kGy, respectively. After irradiation, a 0.1mm thick film was removed from the center of the plate using a microtome, and the fluorescence intensity of the plate at each dose was measured by fluorescence spectroscopy at an excitation wavelength of 370nm and compared with a 0kGy sample, and the corresponding results are shown in Table 3.

Table 3, example 3 test the uniformity of the dose

As can be seen from the data in the attached Table 3, the dose distribution results obtained by the method of the present invention are close to the dose patch test results.

Example 4

The following UHMWPE sheets were prepared separately

(1) Pure UHMWPE sheets of 10mm thickness;

(2) adding 0.2 mass percent of 10 mm-thick DHP into an UHMWPE plate;

(3) the 10 mm-thick UHMWPE plate is formed by adding 0.2 mass percent of DHP and 0.1 mass percent of vitamin E.

And irradiating the plate with electron beams to 75kGy, and carrying out vacuum annealing at 130 ℃ for 12h to obtain the irradiation crosslinking UHMWPE plate.

The obtained cross-linked UHWMPE sheet material is put in an oxygen bomb aging instrument, the temperature is set to be 70 ℃, the oxygen pressure is set to be 5atm, and the aging is accelerated for 14 days. And testing the oxidation index of the center position of the corresponding plate by infrared spectroscopy according to the Chinese medicine industry standard YY/T0772.4.

TABLE 4 accompanying, example 4 oxidation index of the prepared samples

Sample numbering	Oxidation index
		1	0.13
2	0.05
		3	-0.03

As can be seen from the results shown in the attached Table 4, the method of the present invention can increase the aging resistance stability of the medical polymer material while monitoring the dose distribution.

Example 5

100kg of suspended polyvinyl chloride powder (Taiwan co-chemical company US-70), 60kg of diisooctyl phthalate, 4 kg of epoxidized soybean oil (Guangzhou Haima company), 0.2 kg of calcium stearate, 0.20 kg of zinc stearate and 0.20 kg of 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid Docosanol (DHP) are put into a high-speed mixer, the mixing is stopped when the temperature rises to 130 ℃, and the dried powder is obtained after the materials are discharged to a cooling machine and cooled to below 60 ℃. And (3) granulating the dry powder by a conical double-screw extruder, setting the extrusion temperature to be 160-175 ℃, setting the temperature of a neck ring mold to be 155 ℃, and carrying out melt extrusion to obtain the PVC granules.

Pressing the PVC granules into a transparent film with the thickness of 0.1mm, and testing the fluorescence intensity after irradiating and sterilizing 25kGy and 50kGy, wherein the results are shown in an attached table 5;

and (3) preparing the PVC granules into a connecting hose with the outer diameter of 2.05 +/-0.05 mm and the inner diameter of 1.00 +/-0.05 mm by using a tube drawing machine. The pipeline is irradiated and sterilized by 25kGy and 50kGy, cut into small sections with the length of 10mm, and treated according to the specific surface area/water volume ratio of 6cm 2: 1mL of the extract was extracted at 37 ℃ for 3 days, and the pH of the aqueous extract is shown in the attached Table 5.

Comparative example 1

100kg of suspended polyvinyl chloride powder (Taiwan co-chemical company US-70), 60kg of diisooctyl phthalate, 4 kg of epoxidized soybean oil (Guangzhou Haima company), 0.2 kg of calcium stearate and 0.20 kg of zinc stearate are put into a high-speed mixer, the mixing is stopped when the temperature is raised to 130 ℃, and the dry powder is obtained after the materials are discharged into a cooling machine and cooled to below 60 ℃. And (3) granulating the dry powder by a conical double-screw extruder, setting the extrusion temperature to be 160-175 ℃, setting the temperature of a neck ring mold to be 155 ℃, and carrying out melt extrusion to obtain the PVC granules.

Table 5 attached, fluorescence intensity after PVC irradiation sterilization and pH of the aqueous extract.

Dose of radiation	Intensity of fluorescence	pH value-example 5	pH value-comparative example
				0	100	6.08	6.05
25kGy	10.4	6.02	5.12
				50kGy	6.7	5.96	4.56

From the results of the attached table 5, it can be seen that the method of the present invention, although not suitable for monitoring the irradiation dose distribution of medical devices made of PVC material, can still indicate whether the PVC material has been subjected to irradiation treatment. When the polyvinyl chloride material is subjected to radiation sterilization, a large amount of hydrogen chloride is released, and the hydrogen chloride remains in the polyvinyl chloride material and is slowly released, so that the pH value of a water-soluble storage substance of the polyvinyl chloride material is reduced, and the national regulation generally requires that the pH value of a water-soluble substance of the polyvinyl chloride material is reduced within 1.0. It can also be seen from the results in Table 5 that the method of the present invention can solve the problem of the much decreased pH of the aqueous PVC material extract caused by the radiation sterilization.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. A method of detecting an actual radiation dose, comprising:

2. The method of claim 1, wherein the dihydropyridine 3, 5-dicarboxylate derivatives comprise a dialkyl dihydropyridine 3, 5-dicarboxylate and a dialkyl 2, 6-dimethyl-1, 4-dihydro-3, 5-dicarboxylate.

3. The method of claim 2, wherein the number of carbon atoms in the dialkyl 3, 5-dicarboxylate is from 6 to 22.

4. The method according to claim 1, wherein the irradiation dose is 10-80 kGy.

5. The method according to claim 1, wherein the mass ratio of the medical grade high molecular weight raw material to the 3, 5-dicarboxylic acid dihydropyridine derivative is 100: 0.01 to 0.5.

6. The method of claim 1, wherein the standard board stock further comprises 0.02 to 0.50 parts by weight of an antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers and vitamin C;

7. The method of claim 1, wherein the fluorescence spectrum excitation wavelength is 350nm to 450 nm.

8. An irradiation resistant composition comprising:

100 parts of medical grade high molecular raw material;

0.01-0.5 part by weight of 3, 5-dicarboxylic acid dihydropyridine derivative;

9. The composition of claim 7, further comprising 0.02 to 0.50 parts by weight of an antioxidant; the antioxidant comprises one or more of phenols, hydroxylamines, benzofuranones antioxidant, phosphites, thioethers or vitamin C.

10. The composition of claim 7, wherein the dihydropyridine 3, 5-dicarboxylate derivatives comprise a dialkyl dihydropyridine 3, 5-dicarboxylate and a dialkyl 2, 6-dimethyl-1, 4-dihydro-3, 5-dicarboxylate; the number of carbon atoms in the 3, 5-dihydropyridine dialkyl ester is 6-22.