DD299417A5 - DISINFECTANT SOLUTION FOR MULTIVALENT RENEWAL REMOVAL - Google Patents

Abstract

The invention relates to a disinfectant solution for multivalent germ replacement and for disinfecting cleaning. There are hydroxyarylmethylsulfone-pyrrolidinium-sulfomethyl betaines of z. As the formulas (I) used, which are strengthened significantly synergistically by alcohol in its disinfecting effect. According to the invention, a comprehensive germ-reducing effect against viruses, bacteria, fungi, parasitic protozoa and helmints is achieved, which can be used both for skin disinfection and for disinfecting smooth and rough surfaces. In contrast to peracetic acid there is no weakening by blood. Conventional disinfectants with acidic, oxidative, irritating, sensitizing or corrosive properties can be replaced. Formula (I) {Degradation; Disinfection; disinfecting cleaning; synergistic effect; sulfobetaines; sulfone; viruses; bacteria; mushrooms; parasitic protozoa; Pyrrolidinium betaine; Phenol derivatives}

Description

)H

(V)

R = -CH

in which R is the methylene-sulfone-pyrrolidinium-sulfomethyl-betaine radical is carried out, which can be used in water in concentrations of 0.01 to 2 wt .-% or for synergistic increase in activity in the same concentration in water / alcohol mixtures with a Content of 20 to 99 vol .-% water and 1 to 80 vol .-% alcohol are dissolved.

2. disinfectant solution according to claim 1, characterized in that are used as the alcohol, ethanol or a propanol.

3. disinfectant solution according to claim 1 and 2, characterized in that the skin disinfection nit specific activity against hepatitis B viruses, the active compounds of the formulas (I) to (V) in water / alcohol mixtures with an alcohol content of 30 to 80 VoI. -% to be solved.

4. disinfectant solution according to claim 1, characterized in that for the complete dissolution of blood contaminants, the active compounds of the formulas (I) to (V) in the concentration range of 0.1 to 2 wt .-% are used.

Field of application of the invention

The application relates to germ killing / inactivation of germs with a broad effect in the human and veterinary field as well as in the food industry.

The application is possible for facilities in which measures are required for a mulituitive germ reduction, a germ-reducing cleaning or disinfection.

Characteristic of the known state of the art

Multivalent agents for killing germs, which are characterized by user-friendliness, high efficiency as well as by toxicological and ecological criteria, consider the capillary problem and which are not least economical to produce, do not yet exist. Due to the diversity of germs, the fields of application, products and processes or the compatibility and environmental impact of disinfectants, the area is very confusing and in need of improvement. A classification according to chemical substance classes with reference to the corresponding fields of application is also difficult. On the other hand, because of the diversity of the germs, the disinfectants used are also made variable, and the chemical agents are often used in combination or together with physical means (e.g., temperature elevation).

Because of the versatility of the application criteria, therefore, the individual disinfectants are adapted for the individual disinfection procedures and especially disinfection tasks (hand, skin, instrument disinfection, etc.). The demands for faster and safer disinfection are difficult to reconcile with the requirement for compatibility, the requirement not corrosive effect and other environmental and economic aspects such as durability, shelf life, odor, skin irritation and handling. According to the state of the art, high efficiency and safety are accompanied by disadvantages in handling. In the search for new, safe disinfectants antiviral agents have not been dealt with comprehensively enough, whereby the above-mentioned disadvantages for virus disinfection exist in a special way and the range of usable antiviral disinfectants is still small. Be! chemical germ killing the following means have been used (HORN, PRIVORA, WEUFFEN, "Handbook Disinfection and Sterilization" Volume 1 to 5, Publisher Volk and Health 1972 to 1984):

- / aldehydes or mixtures of aldehydes;

Alcohols, especially ethanol and the propanols;

- halogen compounds, especially iodine compounds and hypochlorites;

- lactones;

- metal compounds (mercuric chloride, copper sulfate);

- Oxydants (peracetic acid, ozone), epoxides;

Phenols, xylenols;

- Quaternary ammonium compounds;

- special surfactants, eg. Carbobetaines,

where new types of disinfectant have not yet prevailed.

Of the compounds mentioned z. As peracetic acid and aldehydes a very wide range of action. However, these substances are usually toxic, unstable in storage and / or have high corrosivity. In addition, there is a rapid inactivation of peracetic acid by blood, which leads to a significant effect restriction. Due to its sensitizing effect, formaldehyde leads to occupational diseases. Spore killing preparations such as performic acid and ethylene oxide are particularly toxic, e.g. T. as carcinogenic, to classify. Phenols have clear gaps in the spectrum of action and are usually unpleasant odor-intensive. Hypochlorites are used despite the considerable user-friendliness. The effect of alcohols against hepadnavlren is not reliably demonstrable, so they are used in other risk areas. There are also gaps in the effectiveness of the cationic surfactants and carbobetaines used hitherto.

Effect against selected viruses has been demonstrated for:

- aldehydes (formaldehyde, glutaraldehyde);

- alcohols (ethanol, propanol);

- halogen compounds (especially hypochlorites);

- peracetic acid;

- some zwitterionic detergents.

In the evaluation of disinfectants used to kill germs, viruses and bacterial spores are a major criterion. Test viruses have been used very frequently:

Influenza viruses, vaccinia viruses, poliomyelitis viruses;

then follow:

Coxsackieviruses, ECHO viruses, adenoviruses, herpesviruses.

Influenza and vaccinia viruses are considered to be about the same in their behavior towards disinfectants-despite e.g.

different ether resistance.

Hepadnaviruses are considered to be particularly resistant.

Object of the invention

The aim of the invention are those disinfectant solutions that allow a multivalent germ killing by chemical or physicochemical means in compliance with application criteria, at the same time directed against bacteria, fungi and viruses and against other germs, which achieved by adapting to different conditions of use safe germ killing and a toxic damage is counteracted by the user.

Explanation of the essence of the invention

The object, which is solved by the invention, is to find such disinfectant solutions by which a multivalent germ killing / inactivation of germs without reactivation of the germs is achieved. These disinfectant solutions are geared to

high activity against viruses, bacteria, spores and worm eggs;

- ease of use (little or no skin irritant, no corrosion effect, some cleaning effect, low odor, water solubility);

- favorable characteristics (toxicological, carcinogenic, mutagenic, teratogenic and ecological criteria);

- Consideration of the capillary problem or penetration into pores or rough surfaces;

- dirt dissolution; Dissolution of blood admixtures;

- economic and raw material-side producibility.

The object is achieved according to the invention in that the germ reduction / disinfection by hydroxyarylmethyl-sulfonpyrrolidinol-sulfomethyl-betalne of the formulas (I) to (V),

OH OH OH

-R

(ID

(V)

R =

in which R denotes a 1,1-dimethyl-4-sulfomethyl-3-methylene-sulfon-methylrecycle, by heating 1,1-dimethyl-3-sulfinic acid methyl 't-sulfomethyl-pyrrolidinium betaine (prepared according to DD PS 225128) , Formaldehyde and phenol, phloroglucinol or 8-hydroxyquinoline of the formulas (I) to (V) corresponding molar ratios of phenol component, formaldehyde and sulfinic acid component in water at 100 ° C can be easily prepared in aqueous solutions in total concentrations between 0.01 to 2% by weight, which may contain ethanol or a propanoi for the synergistic increase in activity. In the concentration range of 0.1 to 2Gew .-% active ingredient, a complete resolution of blood contamination is achieved.

Surprisingly, it has been found that even aqueous solutions in low concentrations bring about a strong inactivation of various germs, while highly resistant germs (eg hepatitis B viruses) are produced by the combination of the polyfunctional sulfobetaines of the formulas (I) to (V) with alcohols ( Ethanol, propanols) are inactivated; Such a synergistic effect-increasing effect occurs according to the invention in solutions which contain 20 to 99% by volume of water and 1 to 80% by volume of alcohol. Against hepatitis B viruses, 30 to 80% by volume of ethanol or propanoi are used in combination with the sulfobetaines according to the invention. This favorable combinability makes it possible to adapt the disinfectant solution for multivalent germ killing to a wide variety of application conditions. This also makes it possible to achieve specific effects against bacteria, spores, fungi, viruses, parasitic protozoa and worm eggs.

The disinfectant solution according to the invention is suitable for skin disinfection as well as for reducing the germ on hard or rough surfaces, for example devices, painted surfaces, metals, enamels and ceramics. It does not irritate the skin, does not corrosive and can be stored without problems as a disinfectant solution. If necessary, it can be combined with other aqueous or aqueous-alcoholic agents. By the aforementioned property image, it is superior to conventional desiofektionslösungen in effect and use value and can be produced inexpensively.

-4 299 417 EXAMPLES

example 1

To a microorganism mixture with 10 ⁸ germs / ml in strongly viscous nutrient medium from Bacillus subtilis, Endomycopsis bispora including their spores, the polyfunctional hydroxyarylmethyl-sulfon-pyrrolidinium-sulfomethyl-betain of formula (I) in a final concentration of 0.2 wt. % mixed and incubated for 30 minutes. After deactivation of the active ingredient by dilution with sterile tap water, the test for sterility with the nutrient media according to Pharmacopoeia-DDR, Volume I, X, 4.0.1.ff. and 7.0.1.ff.

Results:

- with the active substance of the formula (I): sterile

- Control without active ingredient: germination

Example 2 To chicken blood containing 10% by volume citrate buffer, influenza virus type A strain A / PR / 8/34 in allantoic fluid

given. After thorough mixing, such a volume of a 10% solution of the polyfunctional is added

Hydroxyarylmethylsulfon-pyrrolidinium-sulfomethyl-betalns of the formula (II) in 10% lges ethanol, that the Final concentration of active ingredient 0.26 wt .-% is. After renewed mixing and a contact time of 10 minutes

is deactivated by the addition of at least 10 times the volume of a buffered NaCl solution.

Thus, after the usual disinfectant solution for the proliferation of influenza viruses, pre-incubated chicken eggs

inoculated. From these eggs, after an incubation period of at least 48 hours, allantoic fluid is removed in a sterile state and the virus multiplication is compared to the control inoculated with NaCl solution and to the hatching eggs without active ingredient by means of the

Hemagglutination test comparatively assessed. Results:

- with active substance of formula (II): no virus replication

- without active substance: full virus replication

The test for inactivation was carried out according to the "WHO Requirements for Influenza Vaccine (Inactivated)". Example 3 To a buffered virus suspension containing at least 10 ⁴ infectious units per ml of adenovirus (human) type 2

such a volume of a 10% solution of the polyfunctional hydroxyarylmethylsulfone-pyrrolidinium-sulfomethyl-betaine of formula (IV) is added to sterile tap water so that the final active ingredient concentration is 0.4%.

After mixing and an exposure time of 30 minutes, the volume is increased by at least 100 times

deactivates a lactalbumin-containing phosphate buffer solution.

This is after the usual disinfectant solutions suitable for the propagation of these adenoviruses permanent Inoculated cell line. From each culture vessel several subcultures are created and the virus replication compared to

uninoculated control and compared to the cell cultures with adenovirus without active ingredient using the cytopathic effect (CPE) and the immunofluorescence:

Results:

with active substance of the formula (VI): no CPE without active ingredient: CPE

Example 4 Inactivation of hepatitis B surface antigen (HBsAg) in suspension test:, Equal parts of a HBsAg-containing serum pool in various dilutions and the disinfectant to be tested

be mixed. After a reaction time of 30 minutes, the samples are inactivated by a dilution of 1: 100.

The residual activity of HBsAg is determined by radioimmunoassay compared to a control batch. Results:

0.1% active ingredient of formula (I) in 70% ethanol (1:11 = 4: 1) 0.1% in water

rest control activity approach = 100% serum pool serum pool neat. 1:50 10% 8th% 90% 65%

Example 5 Mäuseschwänzchentest:

10 mm long tail pieces are inserted after thorough pre-cleaning for 5 minutes in a HBsAg-containing serum pool and dried for 30 minutes at room temperature. For the disinfection test, the tail pieces are placed individually in 50 ml measuring cups, the bottom of which is covered with glass arrays, 1 ml of disinfectant solution (0.1% solution of the mixture of hydroxyarylmethylsulphonopyrrolidinium-sulfomethylbetaine of the formulas (II) and (III) in 50% n-propanol), and

Shaken for 2 or 30 minutes. Thereafter, the sample is diluted 1: C0 and the residual activity of HBsAg determined by radioimmunoassay. The tail pieces are covered with 3 ml of physiological saline solution and shaken again for 6 minutes. The residual activity in the rinsing fluid is again determined with a radioimmunoassay.

Ergebnliie:

Residual activity of HBsAg (control = 100%)

Exposure time 2min. Injection voltage 30min

Disinfection, rinsing, disinfection, rinsing

Solution Solution Solution Solution

9% 2.5% 6% 1%

Examples

Guinea pig skin test

Furred pieces of skin from the shaved dorsal skin of guinea pigs are placed around buttons with a flat surface (diameter 2.5 cm), sutured with surgical suture material on the back and fixed with wooden sticks inserted into the buttonholes. For each test, 2 germ carriers prepared in this way are required.

A germ carrier is charged with 0.5 ml HBsAp-containing serum and dried for 30 minutes at room temperature. Thereafter, 0.5 ml of the disinfectant solution to be tested is added and washing movements are carried out with the aid of the second germ carrier. After a reaction time of 2 or 30 minutes, the disinfectant solution is washed off and then the germ carriers are rinsed for 5 minutes with 3 ml of 0.9% saline. The residual activity of HBsAg was determined by radioimmunoassay.

Results:

0.1% solution of hydroxyaryl-sulfone-pyrrolidinium-sulfomethylbetaine of the formula (IV) in 90% n-propanol; Residual activity of HBsAg.

Control substance -100%

Exposure time 2 min exposure time 30min

6% 2%

Example 7

To a virus suspension (virus-containing allantoic fluid) containing at least 10 ⁷ to 10 ⁹ ID _M / ml of influenza virus (type A, WHO reference strain A / PRS / 34 or type B, WHO reference strain A / Arbor 1/86) , such a volume of a 10% solution of hydroxyarylmethylsulfone-pyrrolidinium-sulfomethylbetaine of formula (III) in sterile tap water is added so that the final concentration of active ingredient is 0.1%. After mixing and an exposure time of 15 minutes, the addition of the 10 ofechen volume of HANKS medium is deactivated.

Thus, about 5 mm × 5 mm pieces of eggshell with chorioailantiosmembrane (CAM) of 13 to 14 days embryonated chicken eggs are inoculated in HANKS medium according to the method known as propagation system for influenza virus method Allantols-on shell. After an incubation period of 48 hours (type A) or 72 hours (type B), the eggshell pieces are removed with the CAM and the virus multiplication in the HANKS medium is compared with the virus control without disinfectant by means of the hemagglutination test.

The toxicity of the disinfectant solution is investigated by a known method directly on the DAM. Virus promotion after disinfectant exposure is checked with non-toxic doses.

Results: ι

with active ingredient of formol (III): reduction of the infection titer by> 4 titer levels (log 10) without active substance: virus titer unchanged

Baisplel 8

Manufacture g the Hydioxyarylmethyl-sulfon-pyrrolidin-sulfomethyl-betaines of the formulas (I) to (V) The phenol component is in the molar ratio corresponding to the formula with 1,1-Dim 3thyl-3-sulfinic acid-methyl-4-sulfomethylpyrrolidinium-betaine (prepared according to DD PS 225128) and formaldehyde in water to boiling.

Molar ratio for the preparation of the compound (II):

Phlorogucin: sulfinic acid component: formaldehyde = 1: 1: 1

Molar ratio for the preparation of the compound (IV):

Phenol: sulfinic acid component6: formaldehyde = 1: 2: 2

Preparation of compound (I)

10,46g (0.1 mol) are added to a Phencl heated to 7O ⁰ C solution of 102,3g (0.3 mol) of 80% Sulfinsäurekomponente and 33ml (0.3mol) of 30% formalin solution in 360 ml of water. The mixture is heated with stirring for 2 hours at 100 ° C, cooled, allowed to stand for a few days and separates the clear 20% solution of compound (I) from a small amount of oily, water-insoluble bottom body. The 20% product solution wi.d used directly as a disinfectant active ingredient in the prescribed further dilution.

For the preparation of the compounds (II) to (V), the procedure is accordingly using the respective Ausgengsphenols. The procedure is transferable to other phenolic compounds.

Claims (1)

claims: 1. disinfectant solution for multivalent germ killing, characterized in that the germ reduction, germ-reducing cleaning and / or disinfection by hydroxyarylmethylsulfone-pyrrolidinium-sulfomethyl-betaines of the formulas (I) to (V) OfI OH QH (H)