A method for irradiation sterilization treatment of silicone rubber breathing tubes

Abstract

The application provides a kind of irradiation sterilization processing method for silicon rubber breathing tube, comprising the following steps: S1: treatment agent is sprayed on the surface of breathing tube, after 10-30min, the breathing tube is dried, then is loaded into sterile packaging bag;S2: the sterile packaged breathing tube obtained in step S1 is irradiated, and the sterilization is obtained.The sterilization processing method of the application adopts the method of cobalt source irradiation, has high sterilization efficiency, can effectively kill bacteria and viruses.And it has a certain protective effect on materials, can effectively avoid the problems of mechanical property change, yellowing, material decomposition and other problems of material performance change after high molecular material is subjected to irradiation sterilization, and is suitable for medical devices of high molecular material, especially the irradiation sterilization processing of silicon rubber breathing tube.

Description

Technical Field

[0001] This invention relates to the field of medical device irradiation sterilization technology, specifically to an irradiation sterilization method for silicone rubber breathing tubes. Background Technology

[0002] Medical devices need to be sterilized before use. Common sterilization techniques include dry heat sterilization, moist heat sterilization, ethylene oxide sterilization, irradiation sterilization, plasma sterilization, and filtration sterilization.

[0003] Radiation sterilization is an effective method that uses ionizing radiation to kill microorganisms on most materials. Electromagnetic waves used for sterilization include microwaves, ultraviolet (UV), X-rays, and gamma rays. These can all control microbial growth or kill microorganisms in specific ways. Compared to traditional autoclaving and ethylene oxide sterilization, irradiation sterilization has the following advantages: ① Strong physical penetration, resulting in uniform and thorough sterilization; ② No sterilizing agent residue; ③ Can be used to sterilize heat-sensitive materials at room temperature; ④ No water vapor during sterilization, suitable for sterilizing moisture-sensitive medical devices; ⑤ High sterilization efficiency and simple operation; ⑥ Stable process and low energy consumption. Irradiation sterilization has become one of the commonly used sterilization methods for terminal sterilization-type sterile medical devices.

[0004] However, medical devices containing polymeric materials undergo changes in their polymers after sterilization by cobalt irradiation. Polymethyl methacrylate (PMMA), ultra-high molecular weight polyethylene (UHMWPE), polyvinyl chloride (PVC), and silicone rubber are radiation-sensitive polymers. Standard-measured gamma radiation (25 kGy) sterilization will induce irreversible structural changes in these materials. For example, gamma radiation induces α-methyl or methylene dehydrogenation in PMMA and generates free radicals in UHMWPE, leading to irreversible structural changes in devices containing PMMA and UHMWPE. Chinese patent CN109069697B discloses a method for irradiating and sterilizing corneas, and the sterilized corneas thereof. After gamma irradiation sterilization, the corneas show almost no change in transparency, toughness, and hydrophilicity, which is beneficial for extending the preservation time of the corneas. However, this irradiation sterilization method has narrow applicability and the processing technology is relatively complex.

[0005] Therefore, developing an irradiation sterilization method that is suitable for medical devices containing polymer materials, can effectively kill bacteria and viruses, and is simple and efficient remains an urgent problem to be solved. Summary of the Invention

[0006] To address the above problems, this invention provides an irradiation sterilization method for silicone rubber breathing tubes, which uses cobalt source irradiation, resulting in high sterilization efficiency and effective killing of bacteria and viruses.

[0007] This invention provides a method for irradiation sterilization of silicone rubber breathing tubes, specifically including the following steps:

[0008] S1: Spray the treatment agent onto the surface of the breathing tube, leave it for 10-30 minutes, dry the breathing tube, and then put it into a sterile packaging bag;

[0009] S2: Sterilize the aseptically packaged breathing tubes obtained in step S1 by irradiation.

[0010] Preferably, the irradiation sterilization in step S2 is performed using... 60 Sterilization by Co-γ ray irradiation.

[0011] Preferably, the temperature for irradiation sterilization is 5-50°C.

[0012] More preferably, the irradiation sterilization temperature is 20-30℃.

[0013] Preferably, the irradiation sterilization dose is 15-40 KGy.

[0014] More preferably, the irradiation sterilization dose is 20-30 KGy.

[0015] Preferably, the humidity of the irradiation sterilization is 10-100%.

[0016] More preferably, the humidity of the irradiation sterilization is 20-50%.

[0017] Preferably, the irradiation sterilization time is 15-45 minutes.

[0018] Preferably, the thickness of the treatment agent spray is 1-100 μm.

[0019] Preferably, the treatment agent comprises, by weight, 3-8 parts of free radical scavenger, 1-4 parts of persulfate, 5-10 parts of chitosan, 1-8 parts of alcohol, and 70-100 parts of water.

[0020] Preferably, the free radical scavenger is one or more of vitamin E, tea polyphenols, vitamin C, β-carotene, and the trace element selenium.

[0021] More preferably, the free radical scavenger is vitamin C and tea polyphenols.

[0022] More preferably, the mass ratio of vitamin C to tea polyphenols is 1:1-2.5.

[0023] When materials are sterilized by irradiation with gamma rays, the rays can oxidize other substances or generate free radicals that then act on biomolecules, or act directly on biomolecules, breaking hydrogen bonds, oxidizing double bonds, destroying ring structures, or causing certain molecules to polymerize, thereby disrupting and altering the structure of biomolecules and inhibiting or killing microorganisms. However, after medical devices made of polymer materials are sterilized by irradiation, on the one hand, their polymer structure may be altered; on the other hand, the large number of free radicals generated by irradiation have strong oxidizing properties, especially for materials containing silicone rubber. 60 Co irradiation sterilization resulted in reduced elasticity and deteriorated mechanical properties.

[0024] The inventors discovered that when vitamin C and tea polyphenols are used as free radical scavengers, especially when the mass ratio of vitamin C to tea polyphenols is 1:1-2.5, they exhibit excellent free radical scavenging effects, effectively preventing the oxidation of silicone rubber materials. The inventors analyzed that this may be because the simultaneous action of vitamin C and tea polyphenols helps promote their reaction with free radicals. Through a coupling oxidation reaction based on the redox potential difference, tea polyphenols and vitamin C reduce the potential difference between the two substances, facilitating the reaction. Furthermore, the oil-water distribution coefficients of the two antioxidants complement each other, resulting in a rational distribution within the system and maximizing the effect of each antioxidant. Moreover, the inventors analyzed that when vitamin C and tea polyphenols form an antioxidant system, the tocopherol-based antioxidant can donate hydrogen atoms to become tocopherol free radicals, which have lost their antioxidant properties. Simultaneously, vitamin C can donate hydrogen atoms to tocopherol, allowing it to regain its antioxidant capacity, effectively maintaining and enhancing the free radical scavenging effect. However, excessive use of vitamin C can actually reduce its free radical scavenging effect. It is possible that excessive vitamins can disrupt the balance of the antioxidant system, thereby reducing its antioxidant effect.

[0025] More preferably, the free radical scavenger further includes peroxidase.

[0026] More preferably, the peroxidase shown is 10-20% of a free radical scavenger.

[0027] More preferably, the peroxidase is one or a mixture of superoxide dismutase, catalase, and glutathione peroxidase.

[0028] Preferably, the peroxidase is superoxide dismutase.

[0029] Preferably, the persulfate is one or a mixture of ammonium persulfate, potassium persulfate, and sodium persulfate.

[0030] More preferably, the persulfate is potassium persulfate.

[0031] To better reduce the oxidation and changes in the molecular structure of silicone rubber materials and avoid affecting their elasticity and other properties, the chitosan is preferably phenolic acid modified chitosan.

[0032] More preferably, the mass ratio of phenolic acid to chitosan is 0.1-0.3:1.

[0033] Preferably, the phenolic acid is one or a mixture of gentian acid, protocatechuic acid, caffeic acid, and gallic acid.

[0034] Preferably, the phenolic acid is gallic acid.

[0035] More preferably, the average molecular weight of the chitosan is 2000-3000 Da.

[0036] Chitosan is a natural amino polysaccharide with certain antioxidant and antibacterial activities, but its antioxidant activity is relatively low. However, the inventors discovered that when chitosan is used, the material properties after sterilization treatment show minimal changes, effectively maintaining its elasticity and exhibiting excellent aging resistance. The inventors analyzed that this may be because chitosan can form a protective film on the material surface, effectively preventing moisture transfer between the material and the environment, avoiding the generation of free radicals by water molecules on the material surface under irradiation conditions that could affect the material's properties, and reducing the contact reaction between free radicals and polymers, thus preventing oxidation and loss of elasticity in silicone rubber materials.

[0037] In particular, the effect is further enhanced when using phenolic acid-modified chitosan. The inventors analyzed that this may be because the hydrogen bonds between the functional groups (-OH / -NH2) of the modified chitosan material and water molecules are disrupted by phenolic acid, further reducing the water molecule content on the surface of the silicone rubber material and lowering the content of surface free radicals. Simultaneously, the inventors unexpectedly discovered that using modified chitosan can further enhance its long-lasting antioxidant properties, exhibiting a sustained free radical scavenging effect. This may be because the treatment agent system also contains vitamin C. The phenolic esters used undergo a redox reaction with reactive oxygen molecules, producing phenoxy free radicals. Vitamin C can reduce phenoxy free radicals, promoting the regeneration of phenolic esters. Working together with other components in the system, a reaction equilibrium is reached, thus maintaining a long-term free radical scavenging effect and preventing problems such as oxidative yellowing of silicone rubber materials, decreased elasticity, and reduced aging resistance. However, if the free radical scavenging effect of the treatment agent is too strong, it may negatively affect the sterilization effect of irradiation.

[0038] A further preferred embodiment is the preparation method of the phenolic acid modified chitosan as follows:

[0039] Step 1: Add dried chitosan to the acetic acid solution and stir until homogeneous to obtain mixed solution A;

[0040] Step 2: Dissolve phenolic acid and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in ethanol, then add N-hydroxysuccinimide, stir in an ice bath for 1 hour to obtain mixed solution B;

[0041] Step 3: Add solution B dropwise to solution A and stir in an ice bath for 40 minutes;

[0042] Step 4: After the mixture has been left to stand for 24 hours, centrifuge it, take the supernatant, dialyze it, and dry it to obtain the phenolic acid modified chitosan.

[0043] Preferably, the alcohol is one or a mixture of isopropanol, ethanol, n-butanol, n-octanol, n-pentanol, and polyethylene glycol.

[0044] Preferably, the alcohol is polyethylene glycol.

[0045] More preferably, the average molecular weight of the polyethylene glycol is 2500-5000 Da.

[0046] Compared with the prior art, the present invention has the following beneficial effects:

[0047] The sterilization method of this invention employs cobalt source irradiation, which boasts high sterilization efficiency and effectively kills bacteria and viruses. Furthermore, it provides a certain degree of protection to the materials, effectively preventing problems such as deterioration of mechanical properties, yellowing, and material decomposition that can occur after irradiation sterilization of polymer materials. It is particularly suitable for the irradiation sterilization of silicone rubber breathing tubes. Detailed Implementation

[0048] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be noted that the following embodiments are further illustrative of the invention, and not intended to limit it.

[0049] Example

[0050] Example 1

[0051] This embodiment provides a method for irradiation sterilization of silicone rubber breathing tubes, specifically including the following steps:

[0052] S1: Spray the treatment agent onto the surface of the breathing tube, leave it for 15 minutes, dry the breathing tube, and then put it into a sterile packaging bag.

[0053] S2: Sterilize the aseptically packaged breathing tubes obtained in step S1 by irradiation.

[0054] The irradiation sterilization in step S2 is performed using 60Co-γ ray irradiation sterilization.

[0055] The irradiation sterilization temperature was 25℃; the irradiation sterilization dose was 25KGy; the irradiation sterilization humidity was 30%; the irradiation sterilization time was 30min; and the coating thickness of the treatment agent was approximately 30μm.

[0056] The treatment agent, by weight, comprises 3 parts free radical scavenger, 1 part persulfate, 5 parts chitosan, 1 part alcohol, and 70 parts water.

[0057] The free radical scavenger is vitamin C and tea polyphenols in a mass ratio of 1:2 (total mass of vitamin C and tea polyphenols is 3 parts), and 0.45 parts of superoxide dismutase; the persulfate is potassium persulfate; the chitosan is gallic acid modified chitosan; and the alcohol is polyethylene glycol.

[0058] The preparation method of gallic acid modified chitosan is as follows:

[0059] Step 1: Add 2g of dried chitosan to 100ml of acetic acid solution and stir well to obtain mixed solution A;

[0060] Step 2: Dissolve 0.4g gallic acid and 0.3g 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in 10ml ethanol, then add 0.25g N-hydroxysuccinimide, stir in an ice bath for 1h to obtain mixed solution B;

[0061] Step 3: Add solution B dropwise to solution A and stir in an ice bath for 40 minutes;

[0062] Step 4: After the mixture has been left to stand for 24 hours, it is centrifuged at 1000 r / min for 30 min. The supernatant is collected and dialyzed with deionized water for 3 days. The sample is then freeze-dried to obtain the phenolic acid modified chitosan.

[0063] Vitamin C was purchased from Shanghai Maclean Biotechnology Co., Ltd.; tea polyphenols were purchased from Shanghai Maclean Biotechnology Co., Ltd.; superoxide dismutase was purchased from Shanghai Maclean Biotechnology Co., Ltd.; chitosan was purchased from Shanghai Maclean Biotechnology Co., Ltd.; gallic acid was purchased from Shanghai Maclean Biotechnology Co., Ltd.; and polyethylene glycol was purchased from Shandong Kunbo Biotechnology Co., Ltd.

[0064] The CAS number for 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride is 25952-53-8; the CAS number for N-hydroxysuccinimide is 6066-82-6.

[0065] Example 2

[0066] This embodiment provides a method for irradiation sterilization of silicone rubber breathing tubes, specifically including the following steps:

[0067] S1: Spray the treatment agent onto the surface of the breathing tube, leave it for 15 minutes, dry the breathing tube, and then put it into a sterile packaging bag.

[0068] S2: Sterilize the aseptically packaged breathing tubes obtained in step S1 by irradiation.

[0069] The irradiation sterilization in step S2 is performed using 60Co-γ ray irradiation sterilization.

[0070] The irradiation sterilization temperature was 25℃; the irradiation sterilization dose was 25KGy; the irradiation sterilization humidity was 30%; the irradiation sterilization time was 30min; and the coating thickness of the treatment agent was approximately 30μm.

[0071] The treatment agent, by weight, comprises 8 parts free radical scavenger, 4 parts persulfate, 10 parts chitosan, 8 parts alcohol, and 100 parts water.

[0072] The free radical scavenger is vitamin C and tea polyphenols in a mass ratio of 1:2 (total mass of vitamin C and tea polyphenols is 8 parts), and 1.2 parts of superoxide dismutase; the persulfate is potassium persulfate; the chitosan is gallic acid modified chitosan; and the alcohol is polyethylene glycol.

[0073] The preparation method of gallic acid modified chitosan is the same as in Example 1.

[0074] The specific source of raw materials in this embodiment is the same as in Embodiment 1.

[0075] Example 3

[0076] This embodiment provides a method for irradiation sterilization of silicone rubber breathing tubes, specifically including the following steps:

[0077] S1: Spray the treatment agent onto the surface of the breathing tube, leave it for 15 minutes, dry the breathing tube, and then put it into a sterile packaging bag.

[0078] S2: Sterilize the aseptically packaged breathing tubes obtained in step S1 by irradiation.

[0079] The irradiation sterilization in step S2 is performed using 60Co-γ ray irradiation sterilization.

[0080] The irradiation sterilization temperature was 25℃; the irradiation sterilization dose was 25KGy; the irradiation sterilization humidity was 30%; the irradiation sterilization time was 30min; and the coating thickness of the treatment agent was approximately 30μm.

[0081] The treatment agent, by weight, comprises 5 parts free radical scavenger, 2.5 parts persulfate, 8 parts chitosan, 4 parts alcohol, and 85 parts water.

[0082] The free radical scavenger is vitamin C and tea polyphenols in a mass ratio of 1:2 (total mass of vitamin C and tea polyphenols is 5 parts), and superoxide dismutase is 0.75 parts; the persulfate is potassium persulfate; the chitosan is gallic acid modified chitosan; and the alcohol is polyethylene glycol.

[0083] The preparation method of gallic acid modified chitosan is the same as in Example 1.

[0084] The specific source of raw materials in this embodiment is the same as in Embodiment 1.

[0085] Example 4

[0086] This embodiment provides an irradiation sterilization method for silicone rubber breathing tubes. The specific implementation steps are the same as in Embodiment 3, except that the mass ratio of vitamin C and tea polyphenols is 1:1.

[0087] Example 5

[0088] This embodiment provides a method for irradiation sterilization of silicone rubber breathing tubes. The specific implementation steps are the same as in Embodiment 3, except that the mass ratio of gallic acid to chitosan in the modified chitosan is 0.1:1.

[0089] Comparative Example 1

[0090] This embodiment provides an irradiation sterilization method for silicone rubber breathing tubes. The specific implementation steps are the same as in Embodiment 3, except that the free radical scavengers are tea polyphenols and superoxide dismutase.

[0091] Comparative Example 2

[0092] This embodiment provides an irradiation sterilization method for silicone rubber breathing tubes. The specific implementation steps are the same as in Embodiment 3, except that the chitosan used is unmodified chitosan.

[0093] Comparative Example 3

[0094] This embodiment provides an irradiation sterilization method for silicone rubber breathing tubes. The specific implementation steps are the same as in Embodiment 3, except that the mass ratio of vitamin C to tea polyphenols is 1:0.5.

[0095] Performance testing

[0096] 1. Colony count detection

[0097] Initial contamination bacteria were tested according to the testing methods in GB16383-2014 Quality Control of Radiation Sterilization and Disinfection of Medical and Health Products. The sterilized materials were then subjected to sterility testing according to the sterility testing methods in the Pharmacopoeia of the People's Republic of China (Part II) (2020 Edition).

[0098] 2. Yellowing resistance test

[0099] The yellowing resistance level was tested using a lamp-type yellowing resistance tester. Ultraviolet lamps were installed in the test chamber and the temperature inside the test chamber was controlled at 50℃. Ultraviolet lamps with specifications of 15W and wavelengths of 280 to 400 mm were selected to irradiate the samples for 12 hours. The irradiated samples were then compared with the colorimetric card for standard determination.

[0100] The sterilization effect of the silicone rubber breathing tubes of Examples 1-5 and Comparative Examples 1-3 was tested, and the test results are shown in Table 1 below.

[0101]

Claims

1. A method for irradiation sterilization of silicone rubber breathing tubes, characterized in that, Specifically, the steps include the following: S1: Spray the treatment agent onto the surface of the breathing tube, leave it for 10-30 minutes, dry the breathing tube, and then put it into a sterile packaging bag; S2: Sterilize the aseptically packaged breathing tubes obtained in step S1 by irradiation; The treatment agent in step S1, by weight, includes 1-8 parts of free radical scavenger, 1-4 parts of persulfate, 5-10 parts of chitosan, 1-10 parts of alcohol, and 80-100 parts of water. The free radical scavenger is vitamin C and tea polyphenols, with a mass ratio of vitamin C to tea polyphenols of 1:1-2; the chitosan is phenolic acid modified chitosan, with a mass ratio of phenolic acid to chitosan of 0.1-0.2:1, and the phenolic acid is gallic acid; The irradiation sterilization in step S2 is performed using... 60 Co-γ ray irradiation sterilization, wherein the irradiation sterilization temperature is 5-50℃, the irradiation sterilization dose is 15-40 KGy, and the irradiation sterilization time is 15-45 min.

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