DE2922347A1 - Antimicrobial surface treatment of materials - by covalent coupling with antimicrobial agent - Google Patents

Abstract

Prodn. of prods. with antimicrobial properties is carried out by treating with a cpd. (I) which has an antimicrobial fragment and >=1 reactive gp. capable of reacting with surface gps. on the material being treated to form covalent bonds. Process can be used to impart antimicrobial properties to fibres, fabrics, air filters, membranes, containers, packaging materials for use in the foodstuffs and pharmaceutical industries, etc., and for protecting textiles, wooden structures, electronic and engineering components, etc., from microbial attack.

Description

Process for the production of materials with anti-

microbial properties and those produced by this process Materials or objects.

The invention relates to a method for producing materials with antimicrobial properties.

The application also relates to those produced by this process Materials or objects.

It is known that objects of various types, construction elements and complete constructions due to the action of microorganisms such as putrefactive bacteria or molds can be damaged and destroyed to the point of uselessness. The damage caused by this microbial corrosion is almost immeasurable Heights. An example is the infestation of wooden structures with fungi in the form of the Dry rot, the destruction of textiles by mold and putrefactive bacteria, the infestation of electronic components by microorganisms etc. mentioned.

It is also known that microorganisms affect food and cosmetics cause extraordinary losses and also damage to health can be evoked. The warranty also prepares in the clinical area an extensive asepsis, the greatest difficulties. That this problem of asepsis has not been drawn to this day despite the latest technology, information shows what the average hospital stay of patients as a result of wound infections should be extended by about 50%. In many cases, wound infection is the cause lethal outcome. These Facts underline that modern technology such as germ filter systems for room ventilation, sterilization and all precautionary measures are unable to counter the latent danger posed by germs.

In practice, the control of microorganisms is mostly physical and chemical methods combined, such as ilite treatment and antimicrobial application effective means. Sterilization is not possible everywhere; then you have to try to fight pathogenic germs with purely chemical means. These as disinfectants known substances are only suitable for external use. Disinfectants are therefore of the chemotherapeutic and antibiotic substances to combat to distinguish from pathogenic germs. Compatibility is required of the latter with the host system.

The protection of materials from microbial attack is currently taking place by impregnating the object to be protected with highly active, antimicrobial acting substances.

On the one hand, however, these can be detached and removed on the other hand, they exert a highly toxic effect on higher organisms such as humans and animals Effect.

Especially in closed rooms and in contact with higher organisms objects treated according to this process represent a latent danger.

As already mentioned, the requirements for sterility are particularly high in the ventilation of cosmetic, food and clinical spaces Area. To ventilate these rooms, the air supplied is used in germ filter systems cleaned. HEPA filters are of particular importance here, next to mechanical impurities also include microorganisms such as bacteria, fungi and viruses have to hold back. The retained micro-organisms are currently so harmless made that the filters are irradiated with UV radiation.

Disadvantages of this procedure are the regulatory effort that Constant monitoring and replacement of the filters. Structurally essential more attractive area filters cannot be used with this method.

It has been found that antimicrobial substances act on the Surfaces of materials are grafted on to form a real chemical bond and above all that the grafted and chemically fixed antimicrobial active substances retain their antimicrobial activity.

This means that those fixed by covalent chemical bonds are antimicrobial active substances not only secured against detachment, but also able to killing microorganisms or inhibiting their growth this way to keep their surroundings aseptic; they are also able to use the Protect substrate materials from microbial corrosion.

It has been found that for making materials with antimicrobial Properties, i.e. for fixing antimicrobial substances on solids or solid surfaces different methods are possible.

1. Treatment of the solids to generate reactive surface groups, as long as they do not have them by nature, e.g.

Cellulose in the form of hydroxyl groups, fixation of a coupling component such as BrCN or cyanuric chloride Init at least two reactive functional Groups. Coupling of an antimicrobial substance that, in addition to its (il) antimicrobial group (s) have at least one reactive group must, to the unreacted functional group (s) of the coupling component. as reactive group of an antimicrobial compound is, for example Amino group suitable.

2. Based on an antimicrobial substance that is next to her or her antimicrobial group (s) a further functional group must have, is by reaction with a bi- or multifunctional coupling component a reactive microbicide is generated. This reactive microbicide is then applied to the solid surface grafted in such a way that the free functional group (s) of the coupling component with reactive surface groups of the solid with the formation of a chemical Bond react. The reactive microbicide used is a 'coupling-capable' antimicrobial Understood substance that both kill microorganisms and their reproduction can inhibit 3. If suitable reactive groups are present, both on the solid as well as the antimimicrobial substance may also be a chemical one The antimicrobial substance can be fixed without a coupling component.

As an example of a suitable solid, cellulose may be mentioned which very reactive aldehyde surface groups due to a special oxidation treatment owns. In this case, the antimicrobial substance with an additional amino group is sufficient, to achieve chemical fixation.

4. Another elegant variant of the method is that one due to the special chemical treatment of solids, it has a direct antimicrobial effect Surface groups generated. An example of this variant is the conversion the vicinal hydroxyl groups of collulose in aldehyde groups by periodate oxidation the.

Aldehydes are known to be among the most effective disinfectants.

The individual process variants are illustrated below using examples explained. In these examples it is demonstrated above all that the chemically fixed, antimicrobial substances and the antimicrobial surface groups actually have antimicrobial effects, i.e. that they occur Kill microorganisms or prevent them from multiplying and thus also the substrate material protect against microbial destruction. This results in a wide range of applications the process and the objects produced by the process. As characteristic Examples are the protection of materials, fine mechanical, optical and electronic Devices of various types against microbial infestation and microbial corrosion are mentioned. Further application examples are given in the hygienic area, for example the treatment of surgical cladding, drapes in the operating theater, pre-band materials and last but not least in the treatment of filter materials in germ filter systems.

Example 1: On cellulose in the form of cotton fabric was made without any further pretreatment of BrCN as a coupling component by reacting with two in each case Hydroxyl groups of cellulose with the formation of superficial imidocarbonate groups rnnnetted. This conversion took place with elimination of HBr. The superficial Imidocarbonate groups were then with 4-aminobutyraldehyde diothylacetal as Starting molecule of an antimicrobial substance implemented. The scored Bonding can be in the form of an isourea derivative, an N-imidocarbonate derivative and as an N-carbamate derivative. 4-aminobutyraldehyde diethyl acetal was made by acid hydrolysis into the aldehyde as a matter of fact effective antimicrobial Substance transferred. The use of the acetal was necessary as the aldeliyd group knew to protect during the grafting reaction.

Untreated cellulose and treated as above Celluloses have been used comparatively for their antimicrobial effectiveness of Escherichia coli (E. coli) as test organism on standard I nutrient agar and Endo C agar as nutrient medium and of Micrococcus luteus (M. luteus) as test organism on standard I nutrient agar examined as a breeding ground. After inoculating the samples with the microorganisms was the exposure time 3-12 days. The samples were then put on the indicated nutrient agars given and incubated at 30 OC for up to three days. It turned out that the organism E. coli had died on the untreated and treated sample.

In the case of the much more resistant M. luteus, it was untreated Sample completely monitored after incubation.

On the other hand, no M. luteus could be detected on the treated sample will.

Example 2: Cellulose in the form of cotton fabric was produced with the aid of Sodium periodate treated in an oxidizing manner. This succeeded in overflowing the vicinal Cellulose hydroxyl groups in much more reactive aldehyde groups. These aldehyde groups could be reacted directly with aminophonylacetic acid, with the amino group reacts with the aldehyde groups to form an unstable garbinolamine. The unstable carbinolamine could be converted into a stable alkylamine by reduction with NaBJJ4 be transferred. Thus, the chemical fixation of the aminophenylacetic acid succeeded as an antimicrobial substance.

The investigation of the antimicrobial effect of the fixed aminophenylacetic acid was carried out according to example 1.

It has been found that the E. coli organism is also based on both Specimen has died. The Waciistum of M. luteus was just on the treated sample corresponds to it, while there is no inhibition of growth on the untreated sample was observed. A killing of M. luteus could not be determined with certainty will.

Example 3: Cellulose in the form of Ualllllwolle was again with Na-l '(rjodat treated, whereby the vicinal hydroxyl groups were converted into aldehyde groups. Because of the known antimicrobial effect of the aldehyde groups, those treated in this way were treated Samples examined for their antimicrobial effect without further treatment. the Investigation was carried out again in analogy to Example 1. It was found that the E. coli germs have died on untreated and treated samples. In contrast the treated sample behaves with its aldehyde surface groups the M. luteus clearly microbistatic.

With the help of these examples it is shown that not only one chemical Fixation of antimicrobial substances on solids is possible, rather also that these substances or groups are also microbistatic or

have a microbicidal effect.

Claims (1)

P a t e n t a n s p r ü c h e: (1) Procedure for the creation of Materials with antimicrobial properties, characterized in that they are antimicrobial active substances which, in addition to the antimicrobial properties Molecular groups have at least one reactive group on the molecule, by implementing this reactive group or groups with those responsible for the implementation given and suitable, or generated by chemical treatment, reactive surface groups of the materials to be covalently bound. (2) Method of making materials with antimicrobial Properties according to claim (1), characterized in that the reactive Surface groups of the materials hydroxyl and / or carbonyl and / or aldehyde and / or carboxyl and / or amino and / or amido and / or thiol and / or diazo and / or sulfato groups and / or halogens. (3) Method of making materials with antimicrobial Properties according to claim (i) and (2), characterized in that the reactive (s) Group or groups of the antimicrobial substance hydroxyl and / or carbonyl and / or aldehyde and / or carboxyl and / or amino and / or diazo and / or Thiol and / or vinyl and / or epoxy and / or tosyl and / or sulfato groups and / or halogens. (1i) Process for making materials with antimicrobial Properties according to claim (1) to (3), characterized in that the covalent Binding of the antimicrobial substance to the surface groups of the materials a bi- or multifunctional coupling component with the surface groups of the Materials with the formation of a covalent bond to reaction is brought, and then the antimicrobial substance with the or the remaining reactive groups of the coupling component reacted and is thereby covalently bonded, or that the bi- or multifunctional coupling component with the reactive group (s) of the antimicrobial substance, which do not have the antimicrobial properties of the antimicrobial ones Substance-causing groups may be, is implemented, with at least one functional group of the coupling component must be retained, which with the Surface groups of the materials used to react and bonded covalently will. (5) Method of making materials with antimicrobial Properties according to Claims (1) to (4), characterized in that as a coupling component Cyanuric chloride or tetrachloropyrimidine or 2,3-flichloroquinoxaline-6-carboxylic acid chloride or -chloropropionylamine or M-halogenocarbonylamine or methyl-β-hydroxyethyl-γ-aminopropylamine or γ-chlorobutyrilamine or -chlorosulfonylamine or t-aminopropyltriithoxysilane or di-t-aminopropyldietlloxysilane or γ-aminopropylmethyldichlorosilane or dialdehydes or divinyl sulfones or diisocyanates or epichlorohydrin or cyanogen bromide or chloroacetic acid or a haloacetyl halide or carbodiimide is used will. (6) Process for making materials with antimicrobial Properties according to claim (1) to (5), characterized in that the antimicrobial Functional group acting to reduce its reactivity in the grafting reaction is protected by reversible reaction with suitable compounds and after The grafting reaction is released or is reactivated. (7) Method of making materials with antimicrobial Properties according to claim (1), characterized in that antimicrobially effective functional groups through targeted chemical treatment on the solid surface be generated. (8) Antimicrobial materials or objects such as Fibers, fabrics, felts, filters, membranes and articles of clothing, as well as articles such as containers, pipes, food and pharmaceutical packaging materials Industry, cooling according to the method according to claim (1) to (7}. (9 | Materials or objects protected against microbial corrosion, such as textiles, wooden structures, electronic and precision mechanical components, produced according to the method according to claims (1) to (7).