Medical articles from synthetics materials containing sterilization indicators.

The invention relates to medical devices made of plastics, in particular single-use devices, which consist of polymers that contain indicators for sterilization treatments.

In the manufacture of medical and sanitary articles such as bandages, surgical instruments, disposable articles made of plastics for use in the medical field, it is necessary that these are delivered to the consumer in the sterilized, sterile state and that they are sterile without having to sterilize them again can take from their packaging and use. Various sterilization methods are known, but because of the different thermal load capacities of the individual materials, they cannot be applied indiscriminately to all objects. In a "classic" sterilization method, the objects are exposed to flowing steam in an autoclave at 120 ° C for 30-60 minutes. This steam sterilization is simple to carry out, but for obvious reasons it is only suitable for objects and materials which, under the sterilization conditions, retain their composition, their shape, generally speaking, their use value. Textiles or metallic devices are examples of this.

In cases where heat & sensitive products cannot be sterilized under these conditions, this applies e.g. B. for only one-time use devices made of plastics that would deform to uselessness in steam sterilization, other sterilization methods must be used.

Plastics, especially thermoplastics, are not exclusively, but for the most part no longer dimensionally stable at temperatures above 100 ° C, and it is precisely the inexpensive standard plastics such as polyethylene, polystyrene, polyvinyl chloride, polymethylacrylates and styrene copolymers that are used to manufacture disposable medical articles. used.

Alternative sterilization methods, which are also superior in the technical process of steam sterilization for economic reasons, are sterilization with ethylene oxide and sterilization with high-energy radiation.

With regard to quality control, product and consumer safety, it is essential that objects subjected to a sterilization process can be recognized as sterilized in one form or another in the further course up to the consumer. This can be done by providing a written note on the sterilization that has been carried out on individual or samnel packaging, which can be read by the interested and affected group of people.

When sterilizing with high-energy radiation, e.g. B. Co 60 radiation, it is common for e3 that the effect of this radiation on radiochromic dyes or pigments is used, with the dyes forming differently colored chemical compounds from radiolysis. To indicate that radiation has been sterilized, z. B. Adhesive labels in yellow color affixed to packaging that has turned red after the usual radiation dose of 2.5 Mrad. In this case, the visually easily identifiable red labels are proof of the scerilization.

Another common method is based on the observation that halogen-containing polymers such as vinyl chloride or vinylidene chloride polymers or low molecular weight, non-volatile halogen-containing substances such as chlorinated paraffins, under the influence of high-energy, ionizing radiation, form the corresponding halogen acid, for example hydrochloric acid (HCl) and thereby the color an acid-sensitive dye, e.g. of a titration indicator common in chemical analysis can be changed. Accordingly, for radiation-sensitive, color-changing indicators, halogen-containing and hydrogen halide compounds are combined with a dye which reacts to hydrohalic acid with a change in color.

A color change resulting under the sterilization conditions is also used in steam sterilization by means of irreversibly changing ternochromic dyes and also in the sterilization with ethylene oxide, chemically triggered color reactions are used as a sterilization indicator.

DE-OS 29 29 582 may be mentioned as an example of the prior art.

DE-OS 29 29 582 relates to a method for producing sterilizable packaging, in particular for articles for use in the medical field, in which a packaging part consisting of germ-proof, liquid-tight and gas-tight material with a part made of germ-proof, but gas and / or vapor permeable material connected packaging part, for example is welded, and the gas- and / or vapor-permeable packaging part before or after the connection to the impermeable packaging part is provided with an indicator color on at least one surface that is visible from the outside on the closed packaging, which is characterized in that such an indicator color is used , which changes permanently on contact with moisture.

In industrially carried out sterilization of disposable medical devices, which, as mentioned, are predominantly made of thermolabile plastics, these are mainly applied to self-adhesive indicators such. B. can be extracted as labels or tape sections on the individual or bulk packaging and brought into the organism. Examples of this include protective caps to be removed from single-use devices or flow regulators in infusion or transfusion devices before use.

There is therefore a need to label medical devices and in particular single-use medical devices and also individual medical devices from multipacks so that a sterilization treatment carried out on these devices is displayed correctly and permanently.

The object of the invention is therefore to create medical devices in which a sterilization treatment carried out by the action of heat, by the action of high-energy radiation or by the action of germicidal gaseous agents is indicated permanently and safely.

This object is achieved by the medical devices made available according to the invention.

The invention accordingly relates to medical devices made of plastics, in particular single-use devices made of plastics, which are characterized in that they consist of polymers which contain indicators for sterilization treatments. In principle, all indicators can be used that result in a clear, distinguishable color change. The thermochromic or radiochromic or chemically reacting color indicators are particularly suitable.

Indicators that appear colorless before sterilization and colored after sterilization are preferred.

Also preferred are indicator substances which, depending on the type of sterilization, result in a different shade of color and thus later allow an indication of the sterilization method used.

Examples of sterilization treatments are the usual methods of steam sterilization, radiation sterilization, for example with cobalt-60, or ethylene oxide sterilization.

According to the invention, indicators are added to the materials used for the manufacture of plastics, that is to say the polymeric masses, and these are incorporated into the materials as additives so that they change color during a sterilization process due to the action of the sterilizing agent, which kills the living and reproductive microorganisms suffer. The color of the structural parts equipped with it is thus permanently changed and, depending on the type and function of the structural part, is recognizable until or even after use that it was subjected to sterilization.

For toxicological reasons, toxicologically untested substances or their secondary products will only be considered permissible in those parts that do not come into contact with a patient's body or from which these reaction products cannot be extracted and brought into the organism. Examples of this include protective caps to be removed from disposable devices or flow regulators in infusion or transfusion devices before use.

Radioehrome or thermochromic or chemically reacting color indicators are generally known.

A large number of radiochromic dyes are known which, depending on the size of the radiation dose, are subject to color changes. The phenolic stabilizers (antioxidants) of the general formula that are usually recommended for the oxidative and chemical stabilization of polyolefins (polyethylene, polypropylene)<chemistry id="chem0001" num="0001"><img file="EP0069342A2_D0001.tif" /></chemistry>in the R₁, R₂and R₃ Substituents in the 2-, 4- and 6-position are subject to a reaction when exposed to high-energy radiation, in which chromophore aromatic dye molecules are formed which are formed by oxidation and absorb in the visible part of the spectrum. This color change can serve as an indication of radiation sterilization.

Indicators that can be used for the use of hydrogen halide are in principle all chemical compounds that have a clearly discernible color change when changing from the basic or neutral to the acidic pH range. According to GB-PS 920 689, such compounds are dimethyl yellow (p-dimethylamino-azo-benzene), phenyl-2-azo-1-naphthylamine, methyl red (p-dimethylamino-a-zo-benzenecarboxylic acid), Congorot (pp'-diphenylene- bis-2-azo-naphthylamine-4-sulfonic acid) and thymol blue (sulfonated triphenylmethane dye). Other useful indicator dyes are also given in the Reagent Diagnostica Chemicals catalog of E. Merck, Darmstadt, 1978, Part 3, p. 24.

Furthermore, indicators are known in the sense of the procedure for ethylene oxide, which change color under its action and reaction. U.S. Patent 3,852,034 describes the use of para-rosaniline hydrochloride in a buffer system. The color change when exposed to ethylene oxide changes from red to blue. In US Pat. No. 4,094,642 4- (4-nitrobenzyl) pyridine is given as an indicator in the basic medium. As an example of a chemical which responds to steam and ethylene oxide sterilization, reference is made to US Pat. No. 3,667,916, which changes from practically colorless to dark and consists of silver nitrate and a further preservative compound.

The invention is explained below using examples.

example 1

To 25 kg of a commercially available high density polyethylene (HDPE) 25 g of ß- (3,5-di-tert-butyl-4-hydroxiphenyl) propionic acid n-octadecyl ester are added as an indicator for the radiation sterilization and in a mixer of a suitable design onto the polyethylene granulate , possibly with the addition of small amounts of an adhesive. The granulate treated and prepared in this way, which contains the indicator distributed over the surface, is processed in the usual manner on an injection molding machine in an injection molding process to form a closure part for cone connections which is common in medicine. When the packaged item is sterilized with ionizing radiation from a cobalt 60 source at a dose of 2.5 Mrad, the color changes from colorless to light yellow.

Example 2

To 25 kg of a commercially available propylene homopolymer (PP) in granular form, 20 g of 2,4-dimethyl-6-tert-butylphenol are added as an indicator for the radiation sterilization and evenly in a mixing process, possibly with the addition of a small amount of an adhesion promoter such as butyl stearate distributed over the granulate surface. In the usual injection molding process, protective caps for infusion devices are produced from them on an injection molding machine, and after the protective caps have been installed, the complete devices are packaged and sterilized in a sterilization system with a Cobalt 60 source at a dose of 2.5 Mrad. The protective caps are colored yellow after sterilization has been completed and thus allow a distinction to be made between non-sterilized devices.

Example 3

To produce a tube made of hard PVC used in a urine collection device, 25 kg of ready-to-use PVC powder compound are mixed intensively with 12 g of thymol blue and a tube with an outer diameter of 5 mm is extruded from this mixture in a conventional manner in an extruder. Sections of the tube thus obtained are installed as an overflow tube in the collecting device and this device is subjected to radiation sterilization with a 2.5 Mrad dose after packaging. Due to the small amount of hydrochloric acid released from the PVC hard polymer during radiation sterilization, the indicator has changed from yellow to red. The reddish colored tube shows that the sterilization has taken place.

Example 4

25th kg of polystyrene in granular form are mixed well with 18.7 g m-cresol purple in a mixer until the indicator dye is evenly distributed on the granulate. From the granulate prepared in this way, connecting pieces with an outer cone, which are common in medical disposable devices for producing, for example, hose line connections, and the hose sections representing the line are combined in an injection molding process. After moisture conditioning, the packaged items are subjected to sterilization with an ethylene oxide / carbon dioxide gas mixture. The indicator changes its color from red to yellow, indicating that ethylene oxide treatment has taken place.

Example 5

To produce a one-piece hose clamp, which is used to interrupt the line routes for medicinally used infusion solutions, 25 kg of methyl methacrylate polymer (PMMA) are mixed with 13.4 g of bromocresol green and processed into the molded part in an injection molding process. The hose clamp enclosed with the medical device is subjected to an ethylene oxide sterilization together with it, the indicator changing from yellow to blue.