Abstract:
Described is the use of microbicidal phenolic compounds in combination with glutaraldehyde for the preparation of disinfectants which are suitable for the disinfection of surfaces and instruments, but also of parts of the body (for example hands) in hospitals and doctors&#39; surgeries.

Description:
This is a continuation of application Ser. No. 08/553,483, filed on Nov. 21, 1995 now U.S. Pat. No. 5,696,170, which is a 371 of PCT/EP 94/01572 filed on May 16, 1994. 
    
    
     The invention relates to the use of microbicidal phenolic compounds in combination with glutaraldehyde for the preparation of disinfectants which are suitable for the disinfection of surfaces and instruments, but also of parts of the body (for example hands) in hospitals and doctors&#39; surgeries. 
     BACKGROUND OF THE INVENTION 
     It is known that there is a considerable risk of infection for patients and staff in hospitals and in doctors&#39; surgeries from microorganisms such as bacteria, yeasts and viruses which are pathogenic to humans. Taking into account this risk of infection for patients and staff, the disinfection of surfaces and instruments in hospitals and doctors&#39; surgeries is of particular importance. Apart from the known causative agents of hospitalism from amongst the bacteria and yeasts, viruses have gained increasing importance amongst disinfection procedures. 
     The requirements regarding the effectiveness of disinfectants are described, for example, in the regulations of the DGHM (Dt. Gesellschaft fur Hygiene und Mikrobiologie [German Society for Hygiene and Microbiology]) and the guideline of the Bundesgesundheitamt (BGA [Federal Health Office]) and the Dt. Vereinigung zur Bekampfung von Viruserkrankungen (DVV [German Association for Viral Disease Research]). Disinfectants which meet the DGHM requirements are listed in the VII list as per 1.1.92. Nothing is mentioned as yet in these lists on the virucidal properties of the disinfectants. 
     When used at concentrations, and over periods, which are relevant under realistic conditions, the combination according to the invention guarantees a greatly reduced number of pathogenic microorganisms amongst bacteria and yeasts and also inactivation of, for example, DVV-listed, naked and enveloped viruses while fully meeting current requirements. The invention is based on a combination of microbicidal phenolic compounds (ph) and glutaraldehyde (glu). 
     Phenolic active substances for the disinfection of surfaces and instruments are known (Ullmann-Enzyklopadie der tech. Chemie [Ullmann&#39;s Encyclopaedia of Chemical Engineering], 4th Edition, 1975, Volume 20, pp. 41-58). It is furthermore known that microbicidal phenolic compounds have an insufficient activity against naked viruses. It is also known that inactivation of naked viruses, such as polio, is made possible by concentrations from 1% of glutaraldehyde (10,000 ppm) in alkaline solution. 
     CA 2.015.079 describes a disinfectant composed of glu, o-phenylphenol, p-tert-amylphenol, sodium arylalkylsulphonate, citric acid and water. A combination of the abovementioned active substances allows stabilization and an activity specifically against bacteria which are pathogenic to humans, even in the acidic range. A virucidal activity is not described. Moreover, this formulation comprises an extremely large amount of glu, which results in odour and corrosion problems and might, under certain circumstances, cause allergic reactions. 
     SUMMARY OF THE INVENTION 
     The invention therefore relates to the use of a combination of glutaraldehyde and 2-phenyl-phenol and/or para-chloro-meta-cresol for the disinfection of surfaces, instruments and parts of the body. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The combinations according to the invention meet the following requirements as disinfectants: 
     broad activity against bacteria (yeasts) and viruses which are pathogenic to humans; 
     within a realistic timespan, the numbers of microorganisms or viruses which exist on the surfaces are reduced reliably to a level that meets requirements; 
     the active substance components employed were chosen in such a way that optimal effectiveness is achieved using the lowest possible use concentrations, both of phenolic microbicides and of glu; 
     very low concentrations of glu in the use solutions minimize the hazard potential of odour nuisance, of a potential sensitization and of discolouring (of the skin) while maintaining full virucidal effectiveness; 
     use of readily biodegradable surfactants which are kind to the skin; 
     the shelf life of the disinfectant concentrates is not less than a year. 
     The combinations according to the invention are generally in the form of liquid concentrated formulations which are generally used according to the invention after dilution with water. 
     In general, the concentrates according to the invention comprise 2-20% by weight, preferably 3-15% by weight, and especially 3-12% by weight, of the microbocidal phenolic compounds. If appropriate, the ratio between o-phenylphenol and para-chloro-meta-cresol is 100:0 to 0:100 parts by weight. 
     Moreover, the concentrates according to the invention comprise 2-50% by weight, preferably 2-10% by weight and especially 2-5% by weight, of glutaraldehyde. 
     Moreover, the concentrates according to the invention preferably comprise acidifiers, such as citric acid, lactic acid and malic acid to bring the pH of the preparations to 2 to 7, preferably 2.3 to 5, especially 2.5 to 4. 
     The concentrates according to the invention furthermore preferably comprise up to 50% by weight, in particular 10 to 40% by weight, of auxiliaries, such as surfactants, preferably anionic, optionally ethoxylated surfactants, such as, for example, secondary alkylsulphonates having 12 to 14 carbon atoms on average, alkylsulphosuccinates and/or alkyl ether sulphonates, diluents such as, for example, alcohols, preferably isopropanol, 1,2-propanediol, glycols and/or diluents which are miscible with water, and customary auxiliaries such as perfumes, corrosion inhibitors such as benzotriazole or tolyltriazole, colourants and/or complexing agents and, if appropriate, other substances which act as disinfectants. 
     The concentrates according to the invention furthermore comprise up to 75% by weight, in particular 10 to 50% by weight, of water. 
     A preferred concentrate comprises 
     
         ______________________________________ 5-15       % by weight of phenolic compounds  3-4   % by weight of glutaraledehyde  10-20  % by weight of organic diluents   5-25   % by weight of surfactants______________________________________ 
    
     and water up to 100% by weight. 
     The preparations according to the invention are commercially available as concentrates and are generally used in the form of aqueous dilutions. The aqueous dilutions preferably comprise 0.5 to 5% of the combinations according to the invention. 
     The preparations according to the invention are prepared in the customary manner by adding the individual components and mixing thoroughly until clear solutions are obtained. 
    
    
     EXAMPLES 
     To test the disinfectant combination according to the invention for its microbicidal and virucidal activity, a concentrate of the following composition is prepared by mixing the individual components. 
     
         __________________________________________________________________________Example l   Example 2                Example 3                         Example 4__________________________________________________________________________4.5% by weight of para-       --       11.5% by weight of                         4.8% by weight of  chlor-meta-cresol     PCMC           PCMC  7.0% by weight of       11.5% by weight of --        4.8% by weight of                          ortho-phenylphenol      OPP                                             pine oil  3.75% by weight of             11.5% by weight of --        4.8% by                         weight of  glutaraldehyde   OPP                                    pine oil                          2.0% by weight of lactic  11.5% by weight                         of --        4.8% by weight of  acid     OPP                                    pine oil  15.0% by weight of   11.5% by weight of --        4.8% by weight of                          isopropanol    OPP                                    pine oil  10.0% by weight of             11.5% by weight of --        4.8% by                         weight of  diisooctyl sulfosuccinate  OPP                                    pine                         oil  10.0% by weight of   11.5% by weight of --        4.8% by weight of                          sodium lauryl ether   OPP                                           pine oil  sulfate (2 EO)  made up to 100% with  demineralized water__________________________________________________________________________ 
    
     Testing for Bacteriological Activity 
     A. Qualitative Suspension Disinfection 
     In accordance with the Guidelines for Testing and Assessing Chemical Disinfectant Methods/DGHM (as per 01.01.81) (Deutsche Gesellschaft fur Hygiene und Mikrobiologie, Stuttgart-New York; Fischer Section 1 (J. Borneff; Special Edition 1.1.1981)). 
     100% of the microorganisms indicated in Table 1 are destroyed after a contact period of 5 minutes by the following dilutions of the concentrate of Example 1. 
     
                       TABLE 1______________________________________                Use concentration in %,  Test microorganisms     contact period of 5 minutes______________________________________Staphyococcus aureus        ATCC 6538   0.75  Escherichia coli          ATCC 11229           0.50  Proteus mirabilis         ATCC 14153           0.50  Pseudomonas aerugiosa     ATCC 15442           0.50  Candida albicans          ATCC 10231           0.25  Aspergillus flumigatus    DSM 819              1.00______________________________________ 
    
     B. Tuberculocidal Activity, Test with Carriers of Microorganisms 
     Modified in accordance with DGHM Guideline I/2.4.2 (Test report; L &amp; S GmbH Bad Bocklet, Leimbeck/Grotsch 8.1.1993) 
     
                       TABLE 2______________________________________After the exposure times indicated, a tuberculocidal activity was found with the following use concentrations in %:             Exposure time in minutesTest organism     15     30     60   120______________________________________Mycobakterium terrae ATCC 15755             3      2      2    2    %______________________________________ 
    
     Vinicidal Efficacy Data 
     C. Virucidal Effectiveness against Hepatitis B (HBV) and HIV 
     In accordance with &#34;DNS polymerase test&#34; and HIV after the &#34;Richtlinie des Bundesgesundheitsamt und der Deutschen Vereinigung zur Bekampfung der Viruskrankheiten zur Prufung von chemischen Desinfektionsmitteln auf Wirksamkeit gegen Viren&#34; [Guideline of the Federal Health Office and the German Association for Virus Disease Research for Testing chemical Disinfectants for antiviral activity]. (Test report; Steinmann 28.1.1993, Staatl. Hygieneinstitut Bremen) 
     The following use concentrations in % and the following exposure times are determined. 
     
         ______________________________________Virus         %     Exposure time in miutes______________________________________Hepatitis B   1.0   30      0.5                   60  HIV-1                 1.0                   30      0.5                   60______________________________________ 
    
     D. Virucidal Activity against Viruses as Stipulated by the DVV 
     In accordance with &#34;Richtlinie des Bundesgesundheitsamt (BGA) und der Deutschen Vereinigung zur Bekampfung der Viruskrankheiten (DVV) zur Bekampfung von chemischen Desinfektionsmitteln auf Wirksamkeit gegen Viren&#34; [Guideline of the Federal Health Office and the German Association for Viral Disease Research for the control of chemical Disinfectants for antiviral Activity]. (Test report; Steinmann 28.1.1993, Staatl. Hygieneinstitut Bremen) 
     The following use concentrations in % are required for inactivating the important viruses given below: 
     
         ______________________________________Virus           %     Exposure time in minutes______________________________________Papovavirus SV 40           3.0   60  Herpes simplex virus                0.5                5  (HSV) type 1  Polio virus type 1                  4.0                5  strain Malhony/Pette  Vacciniavirus strain  Elstree                             0.5                5  Adenovirus type 2                   1.0               30  strain adenoid______________________________________