Radiation sterilization of cellulose dressing materials

The results of investigations in the field of application of 60 Co gamma-irradiation for sterilization of cellulose dressing materials have been presented on the ground of our own experiments. The investigations were carried out for the model objects which are contents of all dressing materials, nowadays used in medical practice: cotton gauze, viscose-cotton gauze, cotton wool and cotton-viscose wool. In the present report there have been discussed the results of the test estimation of sterilized materials immediately after irradiation and during long storage as well (3-5 years after irradiation). The estimation was carried out according to the requirements of Pharmacopoeia. Moreover, the choice of parameters of sterilization process from the view-point of microbiological experiments and estimation of initial contamination degree of irradiated materials have been discussed.     

Resistance of polysterenes and styrene-acrylonitrile copolymer to sterilizing doses of accelerated electron radiation]

The results of the study on the resistance of certain home-made polystyrenes to sterilizing doses of accelerated electron radiation are shown. The properties of studied materials were found to undergo no changes after sterilization and one-year's storage which, in a majority of cases, qualifies them suitable for manufacture of medical and bacteriological equipment to be sterilized in electron accelerators. One of the materials under study - type KM polystyrene with increased impact resistance - was found to be relatively unstable in its commercial form before irradiation. The styrene-acrylonitrile copolymer, although completely radiation resistant within the examined dosage range, requires special caution because of free actylonitrile found in extracts.     

Effects of gamma-irradiation on trehalose-hydroxyethylcellulose microspheres loaded with vancomycin.

Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, the drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on hydroxyethylcellulose/trehalose spherical micromatrices, containing the antibiotic vancomycin. Our experimental results showed that gamma-rays did not alter the chromophore groups of vancomycin (UV measurements), and did not modify the kinetic behavior of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. The electron spin resonance (ESR) spectroscopy was proven to be a valid identification method of the executed radiation treatment, even after 5 years. The experimental results showed that the therapeutic application of the pharmacological system investigated was not compromised by irradiation, and that ESR spectroscopy can be used to distinguish irradiated from non-irradiated products.     

Effects of gamma-irradiation on PLGA microspheres loaded with thienorphine

Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, its drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on PLGA microspheres, containing thienorphine. Thienorphine PLGA microspheres were prepared by the O/W solvent evaporation method and characterized by HPLC, SEM and laser particle size analysis. Our experimental results showed that gamma-rays did not alter the drug content, and did not modify the kinetics of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. In conclusion, the sterilization method is adequate because microspheres not underwent any change after exposition to gamma-irradiation.     

Polymer materials for biomedical purposes obtained by radiological methods. I. Review of research trends

The authors present a review of publications connected with the production of the materials for biomedical purposes using of radiation technology. The general characteristic of the radiation methods and examples of applications of the results of investigations are given.     

60Co-γ射线对盐酸四环素原料灭菌的研究

采用不同剂量的60Co-γ射线对盐酸四环素原料进行辐射灭菌,结合稳定性考察数据,最终确定盐酸四环素原料的60Co-γ射线的辐射剂量为9 kGy时,其理化检测指标符合USP的要求,且无菌检查符合要求。     

钴-60照射活血通脉胶囊的灭菌效果及对其抗凝活性的影响

目的通过^60Co γ-射线辐照灭菌使活血通脉胶囊的微生物限度达到药典标准。方法用5个剂量的^60Co γ-射线对活血通脉胶囊进行辐照灭菌试验，并以抗凝活性为指标，采用凝血酶滴定法进行含量测定，比较辐照前后药物抗凝活性的变化。结果 ^60Co γ-射线辐照活血通脉胶囊进行灭菌，微生物限度可达到药典标准，剂量达到10kGy时可完全灭活，且抗凝活性成分水蛭素含量在辐照前后无差畀。结论^60Co γ-射线辐照活血通脉胶囊灭菌效果显著，且对药物的抗凝活性无影响，是一种有效可行的灭菌方法。     

Influence of radiation sterilization on the stability of trifluorothymidine.

The influence of radiation sterilization on the stability of trifluorothymidine (TFT) was investigated. TFT was irradiated under ambient atmosphere with a 60Co-source and with an electron accelerator at 25, 50, and 100 kGy, respectively. The radiation-induced effects were determined by chromatographic and spectroscopic methods as well as potentiometrically with a fluoride selective electrode. TFT was moderately stable to ionizing radiation. The degradation induced by electron-beam irradiation was significantly (P=95%) smaller than by gamma-irradiation. The radiolysis products amounted to about 0.25% after electron-beam irradiation at 25 kGy, and to about 0.50% after gamma-irradiation, respectively. The main irradiation product was 5-trifluoromethyluracil (TFMU). In addition five further impurities were detected with HPLC. Identification of degradation products was performed using HPLC-ESI-MS. A degradation path of TFT after radiation sterilization was shown.     

Comparison of residues of glutaraldehyde and formaldehyde in urologic instruments after sterilization in aseptic conditions or in a formaldehyde gas sterilizer

The aldehyde residues of thermolabile urological instruments, after the formaldehyde sterilization or sterilization in aseptic preparation from a 2% glutaraldehyde solution will be examined and compared. The results are discussed together with experimental toxicologic work from the literature. It is concluded that after sterilization in the 2% glutaraldehyde solution, the glutaraldehyde residues on the experimental materials are safe.     

Evaluation of the effects of fragmented steam exposure cycles on the survival of bacterial spores.

The purpose of this study was to examine the population and resistance characteristics of bacterial spores which have been exposed to an abbreviated steam sterilization cycle. The philosophy of many pharmaceutical manufacturers is to require a second complete terminal sterilization cycle in the event of an unplanned interruption during the terminal sterilization of a production batch. The impact of abbreviated steam sterilization cycles was examined for their effect on the survivability and resistance of bacterial spores following an inadequate sterilization cycle. Steam sterilization cycles of two minutes and four minutes were performed on separate groups of Biological Indicator spore strips. These groups were then held at room temperature and re-exposed to a range of sterilization conditions after 24, 48, and 72 hours, i.e., start cycle, abort, hold, start cycle, abort. Spore survivor curves were calculated and resistance estimations were determined. The results of the study indicated that the log level of the surviving spores remained fairly constant, but variability within groups increased as sterilization time increased. The resistance of these surviving spores, as measured by D value, also remained relatively constant throughout the holding period. Abbreviated cycles were similarly conducted on ampules containing a spore suspension, and the spore populations and moist heat resistances were determined over time. Contrary to the spore strip, the population of the subject ampules was less stable showing a gradual decline over the same observation period. The study also included a comparison of the surviving population of short and long fragmented cycles. The results of this study demonstrate that a second complete sterilization cycle is unnecessary to assure the absence of living matter in the sterilized units.     

Anti-epidermal growth factor receptor strategies to enhance radiation action

The epidermal growth factor receptor (EGFR) has emerged as a central molecular target for modulation in cancer therapeutics, since EGFR signaling affects many factors that in turn promote tumor growth, progression and metastasis. In addition, radiobiological investigations have also defined a critical role for EGFR in mediating cytoprotective and pro-proliferative responses in human cancer cells after ionizing radiation, that contribute at least in part to accelerated tumor cell repopulation. This led to the additional development of EGFR as a target to enhance radiation efficacy. Several anti-EGFR strategies have been put forth demonstrating a favorable biological interaction between EGFR blockade and radiation. However, further preclinical investigations are necessary to better explore mechanisms of action and efficacy of combined treatment modalities. Although some of the anti-EGFR approaches have already reached clinical testing in combination with radiation, it is still too early to establish a clinical proof for the ultimate role of EGFR inhibition in combination with radiation. This article focuses primarily on anti-EGFR approaches to modulate radiation response.     

60Co-γ辐照对红花药材及醇提取物羟基红花黄色素A的影响

目的 考察60Co-γ射线辐照灭菌效果及对中药红花和红花25％乙醇提取物中有效成分羟基红花黄色素A的影响.方法 选择5、10kGy 2种辐照剂量对红花和红花25％乙醇提取物进行辐照.比较辐照前后杂菌和霉菌总数及其有效成分羟基红花黄色素A的含量.结果 红花药材及红花25％乙醇提取液在经过5kGy的辐照后,都能达到卫生学标准要求.红花药材经过5kGy辐照后,红花所含有效成分羟基红花黄色素A不发生明显的变化,10kGy辐照后,红花所含有效成分羟基红花黄色素A降低34％;而红花25％乙醇提取液经5、10kGy辐照后,羟基红花黄色素A分别降低44％、71％.结论 60Coγ射线辐照灭菌的效果理想,但不是任何药材和制剂都能采用这种灭菌方法.     

灭菌方法对牡丹皮粉体主要成分含量的影响

目的探讨不同灭菌方法对牡丹皮粉体主要成分含量的影响。方法采用高效液相色谱法测定牡丹皮超微粉与细粉中丹皮酚、芍药苷含量,比较流通蒸汽灭菌法、微波灭菌法及60Co辐射灭菌法对其含量及微生物限度的影响。结果 3种方法在选择的条件参数下,牡丹皮超微粉与细粉均可达到灭菌效果,芍药苷含量基本无变化;流通蒸汽灭菌法使细粉、超微粉中丹皮酚含量分别下降18.54%、21.94%;微波灭菌法分别使丹皮酚的含量下降约5%,60Co辐射灭菌前后丹皮酚含量基本无变化。结论流通蒸汽灭菌法不适合牡丹皮粉体的灭菌,宜采用60Co辐射灭菌的方法处理。     

The effect of ionizing radiation on some derivatives of 1,4-dihydropyridine in the solid state

The effect of gamma and beta radiation in doses between 10 and 100 kGy on physico-chemical properties of four derivatives of 1,4-dihydropyridine (nifedipine, nitrendipine, felodipine and nimodipine) in the solid state was analysed. A number of qualitative and quantitative methods such as UV, IR, TLC, GLC, DSC, EPR as well as organoleptic and gravimetric analysis were used to determine and analyse any changes resulting from irradiation. In order to determine the effectiveness of sterilization with ionizing radiation of doses from 10 to 25 kGy, various microbiological tests were used. It was established that only doses 10-20 kGy of both kinds of radiation ensure total sterilization without any degradation of physico-chemical properties of the compounds studied. For the doses 50-100 kGy a decrease in the content of the compounds, appearance of the products of their decomposition and changes in the melting point and IR spectra appeared. Felodipine (with chlorophenyl substituent) was found to be much more sensitive to ionising radiation than nifedipine, nitrendipine and nimodipine (all with nitrophenyl substituent).     

影响聚酯微球中药物释放的因素

聚酯材料因其原料易得、容易加工、生物相容性好、具有可生物降解性等优点,已经成为当今药物载体材料中的一大研究热点。现综合国内外的有关报道对可生物降解聚酯材料作为药物载体制备微球制剂的研究进展进行了综述。针对目前限制聚酯材料微球制剂临床应用存在的问题,从聚合物、药物、制备工艺、附加剂、辐射灭菌5个方面对影响聚乳酸(PLA)和聚乳酸乙醇酸共聚物(PLGA)缓释微球中药物释放的因素进行了重点介绍,为研究聚酯微球中药物的释放提供思路。     

γ-Irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine

Gamma-irradiation is currently the method of choice for terminal sterilization of drug delivery systems made from biodegradable polymers. However, the consequences of gamma-sterilization on the immune response induced by microencapsulated antigens have not yet been reported in the literature. The aim of the present work was to evaluate the effect of gamma-irradiation on the biopharmaceutical properties of PLGA microspheres containing SPf66 malarial antigen. Microspheres were prepared by a (w/o/w) double emulsion/solvent extraction method. Once prepared, part of the formulation was irradiated at a dose of 25 kGy using 60Co gamma as radiation source. The in vitro results obtained showed that the gamma-irradiation exposure had no apparent effect on SPf66 integrity and formulation properties such us morphology, size and peptide loading. Only the release rate of SPf66 was slightly faster after gamma-irradiation. Subcutaneous administration of irradiated and non-irradiated microspheres into mice induced a similar immune response (IgG, IgG1, IgG2a levels) and was comparable to that obtained with SPf66 emulsified with Freund's complete adjuvant. These observations illustrate the applicability of gamma-irradiation as a method of terminal sterilization of microparticulate delivery systems based on chemically synthesized antigens encapsulated into biodegradable PLGA microspheres.     

Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro

Radiotherapy may be effectively combined with plant derived radiosensitizers. Ferulic acid, a naturally occurring phenolic acid, has been reported to have free radical producing properties. In the present study, the radiosensitisation potential of ferulic acid has been tested in two cervical cancer cell lines (HeLa and ME-180) in vitro. Percentage of growth inhibition (MTT assay), colony survival, levels of lipid peroxidation (TBARS, CD and LHP), antioxidant status (SOD, CAT, GPx and GSH), oxidative DNA damage (% tail DNA, tail length, tail moment and Olive tail moment), apoptotic morphological changes (AO/EtBr staining) and intracellular ROS levels (DCFH-DA) were estimated. The present results show that ferulic acid (FA) enhances radiation effects by increasing lipid peroxidative markers in HeLa and ME-180 cells. We observed significant enhancement of ROS levels during ferulic acid plus radiation treatment. FA treatment alone increased intracellular ROS levels indicate its prooxidant nature. Similarly, we observed enhanced oxidative DNA damage and apoptotic morphological changes in FA plus radiation treated cells. The present data suggest radiation sensitizing property of FA in cervical cancer cells. Further investigations warrants to substantiate the present findings.     

Study of polyolefine plastics for the manufacture of medical and bacteriological equipment to be sterilized in electron accelerators]

The resistance of several kinds of polyethylenes and polyproylenes to sterilizing doses of accelerated electron radiation was studied. Polypropylene Polypro J-600 articles were shown to be unfit for sterilization using isotope sources with low-power dosages, and the use of electron accelerator was found to enable their radiation sterilization.     

A new approach to sterilization conditions. The IMO concept

The sterilization requirements for medical/pharmaceutical applications are traditionally based on an extensive overkill. In the past few years, however, an evolution towards bioburden related sterilization processes has been started (F₀ theory). Especially manufacturers of large volume parenterals have — forced by the thermolability of the product — contributed to this development. In this paper both philosophies are combined, resulting in a concept in which the bacteriological and physical bases of the sterilization process are mathematically related by using the F₀ theory and by introducing an Imaginary Micro-Organism (imo). Theimo concept provides the opportunity for anyone in the field of sterilization to raise the quality control level, which can be achieved by:

selecting optimum sterilization conditions without performing pre-sterilization counts;

step by step introducing the pre-sterilization count which results in even more favourable sterilization conditions.

     

Evaluation of the Effects of Gamma Radiation Sterilization on Rhein-Loaded Biodegradable Microparticles for the Treatment of Osteoarthritis

In previous work, we reported on the design of biodegradable rhein-loaded PLGA microparticles for the treatment of osteoarthritis. Considering that a formulation designed for intra-articular administration must meet sterility requirements to guarantee its safety, in this study the effect of gamma radiation sterilization on these microparticles was evaluated. The size, morphology, and surface characteristics of the microparticles and the encapsulation efficiency of rhein were not affected by the sterilization process. Although DSC and PXRD analyses suggested otherwise, rhein release profiles were not altered by gamma radiation. The release of rhein from the microparticles was fitted to a Gompertz model. In conclusion, the results of this study suggest that gamma radiation is a suitable method for the sterilization of rhein-loaded PLGA microparticles to enable their intra-articular administration in order to provide a therapeutic solution to patients suffering from chronic joint diseases.