DE102019109210A1 - Device and method for the sterilization of medical products using X-rays - Google Patents

Abstract

The device has a radiation source and preferably a detector, between which a medical product is inserted, the radiation source being controllable by means of a control and / or regulating device and feedback from the detector or being controllable by means of a result of dose mapping or a simulation. The method for sterilizing medical products comprises the steps: introducing a medical product into a sterilization device; Irradiating the medical product with a radiation source, preferably an X-ray source, of the sterilization device; Determination of the radiation intensity at each position of the medical device, control and / or readjustment of the radiation source according to the relationship between the radiation intensity at the detector and the minimum dose in the medical device at the corresponding point, so that the medical device is homogeneous is irradiated and sterilized.

Description

The invention relates to a device and a method for sterilizing 3-dimensional medical products with low-energy X-rays.

Background of the invention

Sterility is a key requirement for many medical devices. A medical device is referred to as sterile if the probability that a viable microorganism is on or in the product is less than or equal to 10-6 (EN 556-1: 2001).

A medical product refers to an object or a substance that is used for medical therapeutic or diagnostic purposes for people., In contrast to medicinal products, the main intended effect of medical products is primarily not pharmacological, metabolic or immunological, but physical or physicochemical. Medical devices are therefore all instruments, apparatus, devices, software, materials or other objects used individually or in combination, which are intended by the manufacturer for people for the following purposes: detection, prevention, monitoring, treatment or alleviation of diseases; Detecting, monitoring, treating, alleviating or compensating for an injury or disability; Investigation, replacement or modification of the anatomical structure or a physiological process; Conception regulation and its intended main effect. Likewise, "products that are specifically designed for cleaning, disinfection or sterilization" of medical devices are considered medical devices.

Radiation sterilization

One way to sterilize medical products is to use ionizing radiation (radiation sterilization). The methods used on a large scale for irradiating medical products are sterilization with gamma radiation (gamma sterilization), sterilization with accelerated electrons (e-beam sterilization, electron beam sterilization, beta sterilization) and sterilization with high-energy X-rays (X-ray sterilization, X-ray sterilization).

Gamma sterilization

Gamma radiation is a particularly penetrating electromagnetic radiation that is created during the spontaneous transformations (“decay”) of the atomic nuclei of many naturally occurring or artificially produced radioactive nuclides. Gamma radiation is the term used to describe short-wave photons that are generated by nuclear reactions, while X-rays result from the change in the speed of charged particles. Gamma radiation is often used to sterilize single-use medical devices such as syringes, needles, cannulas and IV sets as well as food, as its penetration depth is usually more than 50 cm. It is emitted by a radioisotope, usually cobalt-60 (60Co) or cesium-137 (137Cs), with photon energies of up to 1.3 or 0.66 MeV.

Gamma rays are electromagnetic waves (as well as light, infrared, X-ray or UV rays). However, gamma rays have a shorter wavelength and therefore have more energy. During irradiation, this energy is transferred to the electrons in the molecules of the products, generating highly reactive radicals. This is why one speaks of ionizing radiation. These free radicals now break the DNA of the existing microorganisms so that they can no longer multiply and die. The irradiated product is therefore sterile. Since the gamma radiation only affects the electron shell of the molecules, it is physically impossible for the irradiated product itself to become radioactive.

The irradiation process takes place in a special facility. The gamma rays required for this result from the decay of the radioactive isotope cobalt-60. This is stored in stainless steel cylinders within the system and represents the radiation source. During the irradiation operation, the radiation source is surrounded by the products to be irradiated on a conveyor system. In order to be able to enter the facility safely, the radiation source can be lowered into a water basin, the water column of which shields the rays. A great advantage is the good penetration ability of the gamma radiation, which makes it possible to sterilize the products in the final packaging. This simplifies the production process and ensures that the products are not re-contaminated by subsequent packaging work.

The energy absorbed during irradiation is measured in kilogray (kGy). This absorbed energy depends on various factors (including exposure time, dosage of radiation, density of the material, package size) and is checked using a dosimeter. This ensures that each product receives the specified radiation dose.

Electron beam sterilization

Electrons emitted by an electron source are accelerated in an electric field, either on curved paths ( Rhodotron) or linear with the help of alternating electric fields (linear accelerator). The accelerated electrons are then deflected (scanned) by a magnetic field and guided onto the product through an exit window. The actual process takes place under normal conditions. Electron beam sterilization takes place at an electron energy of up to 10 MeV.

In the e-beam irradiation process, the beam generation begins with electrons generated in a hot cathode, which are introduced into the acceleration unit, the so-called cavity. With the rhodotron principle, they pass through the cavity several times with the help of magnetic deflection systems until they have reached the intended energy. In the electron beam treatment of medical products, the electrons are channeled out of the cavity with a maximum energy of 10 MeV. The generated electrons are set in a horizontally oscillating movement by a scanning magnet, whereby the electrons or the X-ray photons sweep over the entire product to be sterilized.

X-ray sterilization

The spectrum of X-rays begins below extreme UV radiation at a wavelength of around 10 nm (super-soft X-rays) and extends down to less than 1 pm (super-hard or high-energy X-rays). The energy ranges of gamma and X-rays overlap in a wide range. Both types of radiation are electromagnetic radiation and therefore have the same effects with the same energy. The differentiating criterion is the origin: in contrast to gamma radiation, X-rays are not produced by processes in the atomic nucleus, but by high-energy electron processes. The radiation spectrum generated in X-ray tubes is a superposition of a continuous and a discrete spectrum. Photons from X-ray tubes have an energy of around 1 keV to 250 keV

In the case of electron beam sterilization and X-ray sterilization, high-energy electrons are generated with an electron accelerator. In electron beam sterilization, the electrons are used directly for sterilization. In product treatment with X-Ray technology (X-ray technology), the electrons leave the cavity of the electron accelerator at an earlier point in time with a slightly lower energy and, after being sluiced out of the cavity, are shot onto a metal plate, the so-called target. When immersed in this plate, they lose part of their energy in the form of X-rays, which are used for product sterilization.

X-rays, like gamma radiation, represent a very penetrating radiation source that allows larger volumes and higher densities to be sterilized than with e-beam technology. Gamma and X-ray sterilization are suitable for the sterilization of palletized goods due to the high penetration depth of the photons.

Disadvantages of radiation sterilization

The 3 The sterilization processes explained have specific disadvantages. Systems for gamma sterilization are dependent on a radioactive isotope. Both the production of Co-60 by neutron activation of Co-59 in nuclear reactors and the transport and disposal of the decay products are associated with safety risks and high costs. In addition, long-term availability cannot be guaranteed.

Electron beam sterilization is only suitable for medical products of small dimensions and densities due to its low penetration capacity compared to gamma or x-ray radiation of the same energy.

With X-ray sterilization, there is the problem that a large part of the electrical energy used is not converted into X-rays due to the principle involved, but instead drops off as heat at the X-ray target, which results in a low degree of efficiency. An expensive high-energy electron accelerator is also necessary for electron beam and X-ray sterilization systems.

Elaborate shielding measures are necessary for all 3 processes in order to ensure adequate radiation protection. Gamma, electron beam and X-ray sterilization systems are therefore operated in a radiation protection bunker. The construction of compact sterilization units that can be integrated directly into the manufacturing process of medical products is difficult and very time-consuming with the conventional sterilization processes described.

Low-energy X-rays

One possibility for realizing a sterilization process that is based on the sterilizing effect of ionizing radiation and that can be integrated into the continuous production process of many medical products is to use ionizing radiation of low energy from the corresponding particles. This has two main advantages. On the one hand, the measures for shielding the radiation are reduced, since the penetration depth of the particles decreases as the particle energy decreases. On the other hand are used to generate low-energy Electron radiation does not require high-energy electron accelerators, but compact electron guns or X-ray tubes can be used. With these devices electron or X-ray energies of up to about 600 keV can be generated. In the following, the term “low-energy” or “soft” X-ray radiation denotes the energy range up to this limit.

Low-energy X-rays can be generated without the use of a high-energy electron accelerator and require less effort for radiation shielding, which allows the implementation of a sterilization process that can be integrated into the continuous production process of many medical products.

Penetration depth

In order to sterilize a medical device with ionizing radiation, the radiation must be able to penetrate sufficiently deep. Accelerated electrons (in electron beam sterilization) have a high probability of interaction with matter due to their mass and charge. Their depth of penetration is therefore low. For example, electrons with an energy of 600 keV have a penetration depth of approx. 2 mm in polyethylene and are therefore only suitable for the sterilization of 2-dimensional, i.e. H. very thin medical devices or the sterilization of surfaces. For the sterilization of 3-dimensional medical products, i. H. Medical products whose height / thickness is in the same order of magnitude as their length and width and in the range of centimeters or greater are therefore not suitable for low-energy electrons.

In contrast to electrons, photons (gamma / X-rays) have neither a charge nor a mass. The interaction probability of photons when penetrating matter is therefore much lower than with electrons. Gamma or X-rays can therefore penetrate much deeper into matter than electron beams of the same energy. For penetration of many 3-dimensional medical products such as Dialyzers with photon radiation, photon energies in the low double-digit keV range are sufficient. An increase in the energy of the photon radiation leads to an increase in the dose homogeneity. If the absorbed dose entered is too homogeneous, doses that are so high that the material is damaged can occur at points at which dose maxima develop. These can affect the usage properties of the medical device such as B. reduce the biocompatibility.

State of the art

The WO 2014/132049 A2 (Apparatus for the generation of low-energy X-rays) discloses a device which is used to generate X-rays with low energy, as well as a method for sterilizing products with this device. Medical products and pharmaceutical products are named as areas of application for sterilization with this device. The device differs in some points from a classic X-ray tube (for example the X-ray radiation generated at the anode (X-ray target) is scattered back to the cathode and penetrates it, whereas in an X-ray tube the anode has a defined angle and the X-ray radiation is emitted at an angle).

The GB 2 440 310 A (Surface Sterilization) discloses a device that generates X-rays with an energy of less than 50 keV. The device can be used to sterilize surfaces and thin materials.

The EP 2 668 963 A1 (Device for sterilizing containers with sterilization check) discloses a device for sterilizing containers which are guided past a sterilization device with a transport device, where they are sterilized with radiation. The containers are then moved past another facility that checks the success of the sterilization. Electron radiation is mentioned as the preferred type of radiation for sterilization and explains that X-rays or UV radiation can also be used to sterilize the containers. In addition to containers, no further application examples are given. The purpose of the procedure is exclusively to sterilize surfaces.

The WO 2008/129397 A2 (Sterilization system for PET containers and bottles) discloses a system for the sterilization of containers made of PET. Electron beams are used for sterilization. The sterilization effect of the electron beams is supported by the fact that X-ray targets are arranged within the system, which convert the incident electron beams into X-rays.

The WO 93/17446 A1 (A microwave X-ray source and methods of sterilization) discloses a device that generates X-rays by means of a cyclotron resonance plasma. One of the applications disclosed is the sterilization of medical equipment and instruments.

Disadvantages in the prior art

X-ray sources in the low-energy range are mainly used for analytical purposes. They are therefore designed to achieve the highest possible image quality. Sterilization, on the other hand, requires the generation of high radiation power in order to achieve the required level of sterility security (SAL) in the shortest possible time. The use of commercial X-ray tubes for the sterilization of medical products is therefore not expedient.

Conventional sterilization processes for medical products that are based on the sterilizing effect of ionizing radiation (gamma, electron beam and high-energy X-ray sterilization) can only be integrated into the production process of medical products with great effort. The main reason for this is the high radiation energy that occurs, which requires complex radiation protection measures. In the case of electron beam and high-energy X-ray sterilization, the use of a high-energy electron accelerator with high radiation energy and power is also required, which takes up a lot of space and is cost-intensive.

Object of the invention

The present invention is therefore based on the object of providing a device and a method for sterilizing medical products that are compact, have high sterilization efficiency, enable a high penetration depth or achieve a homogeneous dose in the product to be sterilized.

As explained above, low X-ray energies lead to a reduced homogeneity of the dose entered into the medical product, which can lead to material damage in these areas if a local overdose is then necessary. Furthermore, many medical products are inhomogeneous in terms of their geometric shape and material composition. H. There are areas in which the medical product has a greater thickness and / or density than in other areas, which can also cause high local overdoses and thus material damage.

Thus, it is preferably also an object of the invention to irradiate an inhomogeneous medical product / 3-dimensional medical product as homogeneously as possible even with low x-ray energies or to reduce the maximum energy doses that occur.

Brief description of the invention

The object or objects of the invention is / are achieved by a method for sterilizing medical products according to claim 1 and a device for sterilizing medical products according to claim 9.

The device for sterilizing at least one medical product has at least one radiation source, preferably at least one detector for detecting a radiation intensity, at least one holder for holding a medical product in front of the radiation source, preferably between the radiation source and the detector and at least one control unit for controlling or regulating the radiation source and preferably the holder. The intensity of the radiation from the radiation source can be regulated by the control unit, preferably continuously or clocked, by means of feedback and / or by means of a feedforward control so that the radiation intensity at every position of the medical product assumes a predetermined or predeterminable value that is minimally necessary for the sterilization . In other words, the intensity of the radiation of the radiation source can be regulated by the control unit, preferably continuously or clocked, by means of a feedback and / or by means of a feedforward control so that a predetermined optimal intensity distribution of the X-ray radiation is achieved that is necessary to achieve the required Sterilization dose at every point of the medical device, a more homogeneous dose distribution in the medical device and a reduced irradiation time (= time to achieve the required sterilization dose). A predetermined optimal intensity distribution of the X-ray radiation is preferably determined experimentally by means of dose mapping or with a simulation. Every position of the medical device means at every position in / on the 3-dimensional body of the medical device.

The device for sterilizing at least one medical product can also be referred to as a sterilization device or sterilization unit or as a sterilization device or sterilization unit, provided and adapted for the sterilization of medical products.

The radiation source is preferably a directed radiation source, preferably an electromagnetic radiation source, preferably an X-ray source and particularly preferably a low-energy X-ray source, which is provided and adapted to provide / generate photon energies of 100 to 800 keV. The radiation source is also provided and adapted to the radiation intensity / the absorbed dose of the radiation locally / spatially resolved / locally determined / individually, i.e. clocked or continuously along a medical device, individually set. The absorbed dose entered in the medical product can thus be controlled or regulated locally, which generally results in an inhomogeneous / controllable radiation intensity along the medical product.

The detector is preferably provided and adapted to detect the radiation from the radiation source. The detector is also preferably an area detector (detector with a large area sensor), preferably an X-ray detector or an area X-ray detector. The detector is further preferably a digital detector which generates data signals and forwards them to a control device. The radiation source emits radiation and sends the radiation out in a directed manner, the detector is preferably placed in the directed radiation / in the beam path. This means that the detector is irradiated by the radiation source. The detector preferably has at least the required size to detect the entire area shaded by the medical product in order to be able to draw conclusions about the absorbed dose in the entire medical product.

A medical device is generally known and defined in the introduction. The method and the device are provided and adapted to sterilize at least one medical product at a time.

The device has a holder / clamping device / holding device / medical product holder, which is preferably provided and adapted to hold at least one medical product, particularly preferably between the radiation source and the detector. The holder further preferably has a transport device by means of which the medical product can be transported between the radiation source and the detector. In other words, the transport device moves the medical product into the beam path for a certain period and then out again. Furthermore, the holder preferably has a rotation device / rotating device which rotates or rotates the medical product about at least one axis. In other words, the at least one medical product can be fixed / stabilized / held in the holder and, preferably, rotatable about the longitudinal axis. The holder is placed in the directed radiation / the beam path of the radiation source, preferably an X-ray beam path. The holder and thus the medical product are arranged between the radiation source and the detector. In one variant, the holder can also bring only part of the medical product into the beam path if it exceeds a certain size, but it can also insert a single or multiple medical products into the beam path at the same time and thus sterilize it.

In a further aspect of the invention, the holder has a transport device with which the at least one medical product can be transported through a beam path between the X-ray source and the X-ray detector. In other words, the at least one medical product can be transported mechanically / electromechanically through the beam path, preferably by means of a conveyor belt or the like.

The device can thus consist of a radiation source and a detector between which the medical product is introduced, but also of several radiation source-detector pairs, the medical product being arranged between these. The device preferably has at least two, preferably three, x-ray sources and x-ray detectors.

1. a. Einbringen eines Medizinproduktes in eine Sterilisationsvorrichtung;
2. b. Örtliches Bestrahlen des Medizinproduktes mit einer Strahlungsquelle der Sterilisationsvorrichtung;
3. c. Örtliches Ermitteln der Strahlungsintensität mittels (Dose Mapping) oder mit Simulationen,
4. d. Steuern oder Regeln der Strahlungsquelle durch eine Steuereinheit, so dass an jeder Position des Medizinproduktes zumindest eine für die Sterilisation minimal nötige Strahlungsintensität erreicht wird. In anderen Worten ausgedrückt wird eine vorbestimmte optimale Intensitätsverteilung der Röntgenstrahlung erzielt, die zu einem Erreichen der geforderten Sterilisationsdosis in jedem Punkt des Medizinprodukts, einer homogeneren Dosisverteilung im Medizinprodukt und einer verringerten Bestrahlungszeit führt.

The procedure for sterilizing medical devices has the following steps:

1. a. Introducing a medical product into a sterilization device;
2. b. Local irradiation of the medical product with a radiation source of the sterilization device;
3. c. Local determination of the radiation intensity by means of (dose mapping) or with simulations,
4. d. Controlling or regulating the radiation source by a control unit so that at least one radiation intensity that is minimally necessary for sterilization is achieved at every position of the medical product. In other words, a predetermined optimal intensity distribution of the x-ray radiation is achieved, which leads to the required sterilization dose being reached at every point of the medical product, a more homogeneous dose distribution in the medical product and a reduced irradiation time.

The introduction of the medical product into the sterilization device / irradiation device / device for sterilizing medical products can take place manually and / or mechanically, preferably between the radiation source and the detector or the sensor of a detector. Furthermore, the introduction and / or a subsequent change of the medical product takes place automatically, preferably computer-controlled. In addition, the medical product is further preferably held / fixed / stored by a holder / clamping device between the radiation source and the detector. The holder has a rotation device and / or a transport device. The The rotation device of the holder rotates the medical product around at least one axis and the transport device changes or transports the medical product.

The local / individual irradiation, preferably step by step and / or continuously / continuously, of the medical product (along / along the medical product) with a radiation source of the sterilization device is preferably carried out by means of a directed radiation source or electromagnetic radiation source or X-ray source or low-energy X-ray source or low-energy X-ray source which is intended and adapted to emit a photon energy of 100 to 800 keV. Local irradiation is to be understood as irradiation with spatial resolution that can irradiate different areas / locations / locations / positions of an object or medical product with radiation / radiation intensity / radiation dose / dose / energy dose / photon energy that are different relative to one another. This means that the medical device can be irradiated with a different intensity at each point / individual points / other points.

The determination of the radiation intensity at each position of the medical product shows how much of the radiation emitted by the radiation source is absorbed by the medical product.

The radiation source is controlled or regulated in such a way that at each position of the medical device a radiation intensity that is minimally necessary for sterilization is achieved in the medical device Medical device, a more homogeneous dose distribution in the medical device and a reduced irradiation time. In yet other words, an (intensity) model for irradiation for the medical product can be set up in advance and loaded onto a storage unit of the control unit / CPU so that the control unit controls the spatial resolution of the radiation source. The (intensity) model can be determined by a simulation / calculation or reference measurement.

In a further aspect of the invention, the medical product is irradiated from several sides and / or rotates around at least one axis, preferably in / on / with the holder. This means that the medical product is introduced into a sterilization device with several radiation sources and / or rotates on / in / with the holder, preferably around its own axis. In addition to the multiple radiation sources, the device can also have multiple detectors.

In the variant with several radiation sources, the medical device is irradiated from 2, 3 or more sides at the same time. The device for generating the low-energy X-ray radiation is accordingly designed several times and arranged uniformly offset around the medical product. Multi-sided irradiation has the advantage that the use of multiple X-ray sources with the same power as with one-sided irradiation shortens the sterilization time. Alternatively, by reducing the power of the individual X-ray sources, the thermal load on the targets can be reduced and their service life increased. Since the medical device does not have to be rotated, the holder can be constructed in a simpler way. The dose homogeneity increases with an increasing number of X-ray sources that are arranged around the medical device. The rotation of the medical device during the irradiation is comparable to the arrangement of an infinite number of X-ray sources around the medical device and therefore provides the best dose homogeneity.

In a further alternative embodiment variant, the structure of two-sided or multiple-sided irradiation is selected and arranged two or more times one behind the other. This results in a sterilization tunnel through which several medical products can be transported by means of a transport device and thereby irradiated and thus sterilized. With a given target dose, the transport speed and thus the achievable throughput are dependent on the intensity of the radiation sources and on the number of radiation sources arranged one behind the other in the transport direction.

Further design variants can be obtained by combining the design variants explained above. For example, the rotating irradiation can also take place from two or more sides in order to achieve a high dose homogeneity with a reduced irradiation time or reduced thermal load on the target.

In a further aspect of the invention, the medical product is irradiated in such a way that the radiation intensity of the X-ray radiation varies locally and is set so that the dose is distributed as homogeneously as possible in the medical product. This means that at least the minimum dose occurs at every point / every position of the medical device. In this case, a specific intensity distribution of the transmitted X-ray radiation is preferably established, which can be measured by a detector located behind it in order to readjust the radiation source accordingly if necessary. This distribution of the Radiation intensity is called the optimal intensity distribution.

As already explained above, the radiation source can be controlled or regulated by the control unit, so that the optimal intensity distribution is achieved at every position of the medical product. The control takes place in that the position and the shape of the medical product is stored in the device for sterilization on the control device and the medical product is irradiated with a previously determined intensity by the radiation source in a spatially resolved manner. An (intensity) model (a model for spatially resolved irradiation with a predetermined intensity) is thus set up for the respective medical product in advance. The (intensity) model is determined by a reference measurement or by means of a simulation. The reference measurement includes, among other things, a dose mapping.

With dose mapping, a test sample is equipped with dosimeters (e.g. alanine dosimeters). The dosimeters are placed wherever minimums and maximums of the dose are expected. The medical device is then irradiated and the dosimeter is evaluated.

To determine the optimal intensity distribution, the medical product is divided over its length into several areas, which differ significantly in their geometry and / or material composition. For each area i, a factor k_i is determined with which the intensity of the X-ray radiation is multiplied in the corresponding area in order to achieve the optimal intensity for this area. k_i is chosen so that the minimum dose in the area under consideration corresponds to the required sterilization dose. To determine the factor k_i, the occurring minimum dose D_min, i must be determined for each area, either by means of a dose mapping or by means of simulations. The harmonic mean D_min, HM is calculated from the dose minima D_min, i of each range: $${\mathrm{D.}}_{min,H\mathrm{M.}}=\frac{n}{{\displaystyle {\sum }_{i=1}^{\mathrm{<figure-callout\; id="1"\; label="n"\; filenames="DE102019109210A1\_0003.png"\; state="\{\{state\}\}">n</figure-callout>}}\frac{1}{{\mathrm{D.}}_{min,i}}}}\left({\mathrm{D.}}_{min,i}>0\right)$$

The factor k_i for each range results from the harmonic mean of the minimum doses divided by the dose minimum of the respective range: $$k_i={\mathrm{D.}}_{min,H\mathrm{M.}}{\text{/ D}}_{min,i}$$

The data obtained in this way for the intensity distribution are valid for all medical devices of this type and can be used as long as the geometry and materials of the medical device as well as the parameters of the sterilization apparatus (radiation energy, distance between target and medical device, etc.) remain unchanged.

The simulation can be a Monte Carlo simulation or a simulation based on the law of attenuation or the like.

The detector can be used to check the dose introduced into the medical device in order to release the medical device directly after the irradiation. For this purpose, the determined intensity distribution is set in a pre-test and a medical device equipped with dosimeters is irradiated. Because the medical product is located in the beam path, a “shadowing” occurs on a detection surface of the detector. The doses measured at the detector during the irradiation are recorded. The dosimeters in the medical device are then evaluated and checked to determine whether the required sterilization dose has been achieved at each point. If this is the case, then the data recorded by the detector can be used for all subsequent irradiations of medical devices of the same type or size. During each sterilization process, the doses determined on the detector are compared with the doses recorded. If the deviations do not exceed a specified limit, the irradiated medical devices can be designated as sterile and approved.

The variation of the intensity of the radiation source or of an electron beam impinging on an X-ray target over the surface of the target allows a spatially resolved adaptation of an X-ray radiation field to the medical product. The holder allows for at least one medical product to move the medical product in space, preferably an axial rotation along an axis. The detector enables the measurement of the X-rays absorbed by the medical device. Shielding the device for sterilization protects the operator. The method for using this sterilization unit for the sterilization of medical products is carried out using the above device. The X-ray field is, so to speak, adapted to the medical product to be sterilized, also continuously over time, if the medical product rotates in order to adjust the energy dose. The intensity distribution is preferably determined prior to the serial irradiation on test samples of the medical product to be irradiated. For this purpose, either a can mapping or computer simulations (e.g. Monte Carlo simulation) are carried out.

The shielding of the sterilization unit is designed in such a way that the production staff and the environment are protected from the effects of radiation and the applicable laws, regulations and standards are complied with.

The holder is designed in such a way that it can hold at least one or more medical products at the same time and does not hinder the desired radiation exposure to the product. In one embodiment variant, the holder makes it possible to move the medical product during the irradiation, to rotate it in the preferred embodiment for the example product. With this system, the dose inhomogeneity due to the depth dose distribution that occurs at low energies because of the limited penetration depth of the X-ray radiation can be improved. The dose homogeneity can be increased by increasing the number of X-ray sources that are arranged around the medical device. The rotation of the medical product corresponds to an infinite number of X-ray sources and thus represents the best possible case in terms of achieving high dose homogeneity. The holder is preferably designed so that fully automatic loading and unloading of the medical product (s) is made possible.

The invention makes it possible to achieve a high dose homogeneity despite the low energy of the X-ray radiation. Furthermore, due to the low radiant energy and the associated fewer shielding measures required, e.g. Compared to Co-60 gamma radiation systems or 10 MeV e-beam radiation systems, the integration into the continuous production process of medical products. There is no longer any dependency on service providers who carry out the sterilization with gamma radiation, high-energy electron beams or high-energy X-rays. The system is easily scalable: depending on the throughput of the production system, the necessary number of sterilization units is purchased. A high level of production reliability can be achieved through the redundant operation of several sterilization units. The sterilization with low-energy X-ray radiation also has the known advantages of methods that are based on the sterilizing effect of ionizing radiation. This includes avoiding the use of toxic substances such as B. ethylene oxide, the possibility of sterilization in the final packaging and parametric product release based on the applied absorbed dose.

Process monitoring is preferably provided for monitoring the sterilization process. This consists of at least one X-ray detector which is arranged in such a way that it is possible to draw conclusions about the absorbed dose absorbed in the medical product. For this purpose, electronically readable detector plates are preferably arranged in such a way that the medical product to be sterilized is located between the X-ray source and the detector plates. The size of the detector plate is chosen so that it fully detects the X-ray radiation shadowed by the medical device and also covers an area in which the X-ray radiation was not attenuated by the medical device. From the difference in the intensity of the X-ray radiation attenuated by the medical device and the non-weakened X-ray radiation, conclusions can be drawn about the energy absorbed by the medical device. A method for the sterilization of 3-dimensional medical products with low-energy X-rays can be carried out in the following steps.

• • Bereitstellung und Einbringung des Medizinprodukts in ein strahlenbeständiges, für die Sterilisation mit ionisierender Strahlung geeignetes Sterilbarrieresystem/ Verpackung (optional: Entfernung des Sauerstoffs aus der Verpackung bei Medizinprodukten, bei denen die Bestrahlung in Anwesenheit von Sauerstoff Materialschädigungen hervorrufen kann);
• • Bestückung der Sterilisationseinheit mit dem verpackten Medizinprodukt, bevorzugt mit einem automatischen Handlingsystem
• • Einleiten aller notwendigen Maßnahmen zur Gewährleistung der Strahlensicherheit der Anordnung;
• • Bestrahlung des Medizinprodukts mit örtlich voneinander abweichender Strahlungsintensität gemäß vorstehender Beschreibung über eine definierte Bestrahlungszeit, um die erforderliche Bestrahlungsdosis zu erreichen, die z.B. gemäß nationaler Normen gefordert wird Entnahme des sterilen Medizinprodukts, bevorzugt mit einem automatischen Handlingsystem;
• • Auswertung der Daten der Röntgendetektoren und dosimetrische Freigabe des Medizinprodukts.

For the sake of simplicity, the specific sequence of the procedure is only explained for a single medical device:

• • Provision and placement of the medical device in a radiation-resistant sterile barrier system / packaging suitable for sterilization with ionizing radiation (optional: removal of oxygen from the packaging for medical devices where radiation in the presence of oxygen can cause material damage);
• • Equipping the sterilization unit with the packaged medical product, preferably with an automatic handling system
• • Initiation of all necessary measures to ensure the radiation safety of the arrangement;
• • Irradiation of the medical device with locally differing radiation intensities according to the above description over a defined irradiation time in order to achieve the required irradiation dose, which is required, for example, according to national standards Removal of the sterile medical device, preferably with an automatic handling system;
• • Evaluation of the data from the X-ray detectors and dosimetric approval of the medical device.

The device thus preferably has a radiation source and preferably a detector, between which a medical product is inserted, the radiation source being controllable by means of a control and / or regulating device and a feedback of the detector or controllable by means of a result of dose mapping or a simulation is. The method for sterilizing medical products comprises the steps: introducing a medical product into a sterilization device; Irradiate the medical device with a radiation source, preferably an X-ray source, the sterilization device; Determination of the radiation intensity at each position of the medical device, control and / or readjustment of the radiation source according to the relationship between the radiation intensity at the detector and the minimum dose in the medical device at the corresponding point [determined in a reference measurement or simulation and stored] in the control device, so that the medical device is homogeneous is irradiated and sterilized.

Figure list

• 1 shows abstractly the structure of the device.
• 2 shows an X-ray source with a solid target in a vacuum (classic X-ray tube).
• 3 shows a through-target x-ray source.
• 4th shows a simplified model for the effect of an adapted intensity distribution
• 5 shows the targeted change in the intensity distribution of the X-ray radiation field depending on the geometry and material composition of a medical product (here an example of a dialyzer).
• 6th shows the increase in dose homogeneity by increasing the number of X-ray sources.
• 7th shows a second embodiment of the invention, a three-sided irradiation (holder and shield not shown).
• 8th shows a third embodiment of the invention, a two-sided arrangement of several X-ray modules to form a sterilization tunnel (X-ray detector, holder and shield not shown)

1 shows abstractly the structure of the device for the sterilization of medical products according to a preferred embodiment of the invention. In a device for sterilization 1 is an X-ray source 2 (Radiation source) introduced. The x-ray source is controlled by a CPU / control unit 3 controlled. The radiation source 2 emits directional radiation 4th with a locally determined absorbed dose or intensity. In the direction of the directed radiation 4th there is a detector 6th . In front of the detector 6th is in the directional radiation 4th , i.e. between the radiation source 2 and the detector 6th , a medical device 8th introduced, for example a dialyzer. The medical device 8th is held by a holder 10 held and can also be rotated by this.

2 shows an X-ray source 2 with a solid target in a vacuum (classic X-ray tube). The radiation source 2 consists of an electron source 12 the one electron beam 14th directionally emitted. The electron radiation 14th meets an X-ray target 16 and there generates directed X-rays 4th . The X-ray radiation passes through the exit window 18th out of the vacuum.

3 shows an X-ray source 2 with through target. The structure of the X-ray source in 3 is analogous to the in 2 , with the exception that the electron target does not hit a fixed X-ray target and the X-ray radiation is generated there, but that the electron radiation 14th onto an exit window with an integrated X-ray target 22nd where the directed X-ray radiation hits 4th is produced.

In other words, the arrangement of the X-ray target 16 and 22nd be possible in 2 variants: The X-ray target can be designed as a massive target (thick target) 16, which is located within the vacuum vessel of the electron accelerator (this structure corresponds to the classic X-ray tube). The X-ray target can, however, also be designed as a thin target (transmission-type target) 22.

The electron source 12 has subsequently, i.e. between the electron source 12 and target 16 , 22nd a system for the spatially resolved increase or decrease of the intensity of the X-ray target 16 , 22nd impinging electron stream in defined areas (along the medical device). The X-ray target then converts the kinetic energy of the accelerated electrons into X-rays with a spatially resolved increase or decrease in intensity.

The X-ray target 16 , 22nd preferably consists of a metal with a high atomic number. One example is tungsten because of its high X-ray yield and very good heat resistance. Another embodiment is silver, since its emission lines of the characteristic X-ray radiation are in a lower energy range than with tungsten. In this lower energy range, the mass energy absorption coefficient µen / ρ of the materials of the medical product is greater than with higher energies, which means that the energy dose entered into the medical product is greater, which can lead to increased efficiency of the irradiation process. The X-ray target 16 , 22nd preferably has a device for its cooling.

4th shows the energy doses that occur, greatly simplified, using two single, 1-dimensional, parallel, monoenergetic X-rays 24 and 26th . Both X-rays penetrate a medical device 8th consisting of a homogeneous material, being the thickness of the material by beam 24 is penetrated is only half the thickness of the material that is penetrated by the beam 26th is penetrated. In the direction of the beam behind the medical device 8th is a detector 6th shown. In the high density area, a longer irradiation time is required to achieve the sterilization dose than in the low density area. As the medical device 8th however, when irradiated as a whole, each area experiences the same irradiation time. The area of low density is thus irradiated for longer than would be necessary to achieve the sterilization dose.

5 shows the targeted change in the intensity distribution of the X-ray field depending on the geometry and material composition of the medical product 8th , here as an example for a dialyzer (top picture: schematic representation of the medical product, bottom picture: location-dependent radiation intensity) In the area of the PUR potting ( 9 ) a dialyzer has a higher density at both ends of the dialyzer than in the middle area. In order to achieve a more homogeneous dose input, the intensity of the radiation field is increased in the high density area and reduced in the low density area (total intensity or power remains constant). This results in a more homogeneous dose distribution overall. The irradiation time over the entire medical device is reduced. This reduced exposure time in combination with the reduced radiation intensity in the low density range leads to a lower maximum dose in the low density range, which reduces potentially harmful radiation-induced material changes. In the high density range, however, the maximum dose remains unchanged, since the reduced irradiation time and the increased radiation intensity are balanced out. The reduced exposure time results in an increased efficiency of the process.

6th shows the increase in dose homogeneity by increasing the number of X-ray sources, with a rotation of the medical device in front of an X-ray source being the best case (here simulated with 16 sources). Simulation parameters: solid tungsten target, target angle: 45 °, electron energy: 400 keV, 1 mm Al filter, distance from the X-ray source (s) to the center of the dialyzer: 12 cm, the dose absorbed in water is shown. A shows one source on the left, B shows two sources, left and right, and C shows 16 sources evenly distributed around the medical device.

7th shows a second embodiment of the invention, more precisely a three-sided irradiation of the medical product 8th (Holder and shield not shown). This is where the medical device 8th of three radiation sources evenly angularly spaced on a plane 2 (in a circular angle of approx. 120 °) with a directed X-ray radiation 4th irradiated. In the direction of the X-ray radiation is behind the medical device 8th one detector each.

8th shows a third embodiment of the invention, more precisely an embodiment in which a two-sided arrangement of several X-ray modules to form a sterilization tunnel is shown (X-ray detector, holder and shield not shown). The medical devices 8th are from two opposite sides of radiation sources 2 irradiated and in a transport direction shown schematically 28 transported by means of a transport device (not shown). The medical devices 8th are thus funded through a "radiation tunnel". Here, too, there would be a different arrangement of the radiation sources 2 , for example as in 7th shown possible.

List of reference symbols

1

Device for sterilization

2

Radiation source

3

CPU

4th

directional X-rays

6th

detector

8th

Medical device

9

PUR potting

10

holder

12

Electron source

14th

Electron beam

16

X-ray target

18th

Exit window

20th

vacuum

22nd

Exit window with integrated X-ray target

24

Low intensity x-ray

26th

High intensity x-ray

28

Transport direction

QUOTES INCLUDED IN THE DESCRIPTION

This list of the documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent literature cited

• WO 2014/132049 A2 [0022]
• GB 2440310 A [0023]
• EP 2668963 A1 [0024]
• WO 2008/129397 A2 [0025]
• WO 9317446 A1 [0026]

Claims (13)

Method for sterilizing medical devices (8), comprising the steps: a. Introducing a medical product (8) into a sterilization device (1); b. Step-wise or continuous local irradiation of the medical product (8) with a radiation source (2) of the sterilization device (1); c. Local determination of the radiation intensity in the medical device (8), using dose mapping and / or a simulation, d. Controlling or regulating the radiation source (2) by a control device (3) so that a radiation intensity that is minimally necessary for sterilization is achieved everywhere at every position of the medical product (8). Procedure according to Claim 1 characterized in that the medical product (8) is irradiated simultaneously from several sides and / or rotates around an axis. Procedure according to Claim 1 or 2 , characterized in that the radiation intensity is variable with spatial resolution. Procedure according to Claim 1 characterized in that the medical product (8) is introduced between the radiation source (2) and a detector (6). Method according to one of the Claims 1 to 4th characterized in that the radiation source (2) is regulated by means of feedback from the detector (6). Method according to one of the Claims 1 to 5 characterized in that the detector (6) has an area which is larger than the medical product (8) and determines the radiation intensity. Method according to one of the Claims 1 to 5 , characterized in that the radiation source (2) is controlled by means of the simulation or by means of the can mapping. Device (1) for sterilizing at least one medical product (8), comprising - at least one radiation source (2), - preferably at least one detector (6) for detecting a radiation intensity, - at least one holder (10) for holding a medical product (8) ) in front of the radiation source (2), preferably between the radiation source (2) and the detector (6) and - at least one control unit (3) for controlling or regulating the radiation source (2) and preferably the holder (10), characterized in that the intensity of the radiation from the radiation source (2) by the control unit (3) can be continuously or cyclically regulated by means of feedback and / or by means of a feedforward control so that at each position of the medical product (8) at least one radiation intensity that is minimally necessary for sterilization is achieved .. Device (1) according to Claim 8 , characterized in that the radiation source (2) is provided and adapted to provide photon energy of 100 to 800 keV. Device (1) according to one of the Claims 8 or 9 characterized in that the holder (10) has a transport device by means of which the medical product (8) can be transported between the radiation source (2) and the detector (6). Device (1) according to one of the Claims 8 to 10 , characterized in that the holder (10) is rotatable, preferably about at least one axis. Device (1) according to one of the Claims 8 to 10 , characterized in that the device (1) each has at least two, preferably three radiation sources (2) and detectors (6). Device (1) according to one of the Claims 8 to 12 , characterized in that the control unit (3) has a storage medium on which the method steps after Claim 1 are stored.

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