DD299416A5 - DISINFECTANT SUBSTANCE FOR INACTIVATING GERMIN - Google Patents

Abstract

The invention relates to a disinfectant solution for disinfecting and disinfecting cleaning. The polyfunctional amidomethyl-sulfone-pyrrolidinium-sulfomethyl-betaine of the formula (I) is used, which is significantly synergistically enhanced by alcohol in its disinfecting action. 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; Melamine}

Description

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 for a multivalent mitigation, cleaning or disinfection are necessary.

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 respective 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 processes 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 the

In chemical germ killing the following means have been used so far (HORN, PRiVORA, WEUFFEN, "Handbook of Disinfection and Sterilization" Volumes 1 to 5, Verlag Volk und Gesundheit 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, e.g. Peracetic acid and aldehydes a very wide range of action. These However, substances are usually toxic, unstable in storage and / or have high corrosivity. Add to that a quick Inaktiviei tion of peracetic acid by blood, resulting in a significant effect restriction. Formaldehyde leads due

its sensitizing effect on occupational diseases. Spore killing preparations such as performic acid and ethylene oxide are considered to be particularly toxic, e.g. classified as carcinogenic. 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 hepadnaviruses can not be proven with certainty, therefore they are used in other risk areas. Also exist in the previously used cationic surfactants and the Carbobetainen

Activity gaps. 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 for germ killing viruses and Becteriensporen represent a major criterion. As test viruses have been used very often: Influenza viruses, vaccinia viruses, poliomyelitis viruses;

then follow:

Coxsackoviruses, ECHO viruses, adenoviruses, herpesviruses. Influenza and vaccinia viruses are about equal in their behavior towards disinfectants. B.

different ether resistance.

Particularly resistant are hepadnaviruses. Object of the invention

The aim of the invention are those disinfectant solutions that allow multivalento germ killing by chemical or physicochemical means in compliance with application criteria, at the same time directed against bacteria, fungi and viruses as well as 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 properties (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 in that the germ reduction / disinfection by a polyfunctional amidomethyl-sulfon-pyrrolidinium-sulfomethyl-betaine of the formula (I),

CH ₂ -SO ₂

SO ₂ -CH ₂ -HN

H-CH ₉ -SO ₉

'3

which are prepared by heating 1,1-dimethyl-3-sul (insäuremethyl-4-sulfomethyl-pyrrolidinium betaine (prepared according to DD-PS 225128), formaldehyde and melamine in a molar ratio of 3: 3: 1 in water to 10O ⁰ C very easily can, in aqueous solutions in total concentrations between 0.01 to 2 wt .-%, which may contain ethanol or a propanol for the synergistic increase in activity, is made.

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 cause strong inactivation of various germs, while highly resistant germs (e.g., hepatitis B viruses) are inactivated by the combination of the polyfunctional sulfobetaines with alcohols (ethanol, propanols); Such a synergistic effect-increasing effect occurs according to the invention in solutions containing 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 propanol 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 corrode, does not show an unpleasant odor, is non-toxic and can be stored indefinitely as a substance as well as in solution. If necessary, it can be combined with other aqueous or aqueous-alcoholic agents. By the aforementioned property image, it is superior to conventional disinfectant solutions in effect and use value and can be produced inexpensively.

embodiments example 1

To a microorganism mixture with 10 ⁹ germs / ml in stork viscous nutrient medium from Bacillus substilis, Endomycopsis bispora including their spores, the polyfunctional amidomethyl-sulfone-pyrrolidinium-sulfomethyl-betain of the 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, to such a volume of 10% solution of amidomethyl-sulfonpyrrolidinium-sulfomethyl-betaine of formula (I) in 10% ethanol, that the final concentration of active ingredient 0.25Gew .-% is. After renewed mixing and an exposure time of 10 minutes, the addition of at least 100 times

Volume of a buffered! NaCl solution deactivated. Thus, pre-incubated chicken eggs are inoculated according to the usual methods for the propagation of influenza viruses. Of these Eggs are sterile removed after an incubation period of at least 48 hours allantoic fluid and the Virus multiplication compared to control inoculated with NaCl solution and to the hatching eggs without active ingredient by means of the Haemagglutininationstestes assessed comparatively. Results:

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

- without active substance: full virus replication

Inactivation testing was performed according to WHO requirements for Influenza Vaccine (Inactivated).

-4- 299

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 amldomethyl-sulfone-pyrrolidinium-sulfomethyl-betains of

Formula (I) in sterile tap water, that the final concentration of active ingredient is 0.4%. After mixing and a contact time of 30 minutes, add at least 10 times the volume

deactivates a lactalbumin-containing phosphate buffer solution.

Thus, a permanent cell line suitable for the propagation of these alenoviruses is inoculated by the usual methods. From

Each subculture is subsected with several subcultures and viral replication compared to the unvaccinated control and the cell cultures with adenovirus without active substance using the cytopathic effect (CPE) and immunofluorescence

assessed comparatively.

Results:

with active substance of the formula (I): no CPE

- without active substance: CPE

Example 4 Inactivation of hepatitis B surface antigen (HBsAg) In the 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:

10mm 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. To disinfect the tail pieces are individually in 50 ml measuring cup, the bottom of which is covered with glass beads, inserted, 1 ml of disinfectant solution [0.1% solution of

Amidomethyl-sulfon-pyrrolidinium-sulfomethyl-betains of the formula (I) in 50% n-propanol] and 2 or

Shaken for 30 minutes. Thereafter, the sample is diluted 1:50 and the residual activity of HBsAg with a

Radioimmunoassay determined. The tail pieces are doused with 3 ml of physiological saline and again

Shaken for 5 minutes. The residual activity in the rinsing liquid is again determined by a radioimmunoassay.

Results: Residual activity of HBsAg; (Control = 100%)

Exposure time 2min Rinsing solution Exposure time 30min Rinsing solution Disinfectant solution 2.5% Disinfectant solution 1% 9% 6%

Example 6 Guinea pig skin test Fur pieces that have been removed from shaved dorsal skin of guinea pigs become buttons with a flat surface

Placed (diameter 2.5 cm), sewn on the back with surgical suture and fixed by inserted into the buttonholes wooden sticks. For each test, 2 germ carriers prepared in this way are required.

A germ carrier is charged with 0.05 ml HBsAg-containing serum and dried for 30 minutes at room temperature. After that

0.5 ml of the disinfecting solution to be tested is added and washed with the aid of the second germ carrier

Movements performed. After a contact time of 2 or 30 minutes, the disinfectant solution is washed off and

then rinse the germ carriers for 5 minutes with 3 ml 0.9% saline. The residual activity of HBsAg is with a

Radioimmunoassay determined. Results:

0.1% solution of amidomethyl-sulfon-pyrrolidinium-sulfomethyl-betaine of the formula (I) in 90% n-propanol; residual activity

of HBsAg.

Control substance = 100% Exposure time 2 min exposure time 30min

6% 2%

Example 7 Preparation of the polyfunctional amidomethylsulfone-pyrrolidinium-sulfomethyl-betaine of the formula (I): It melamine with!, I-dimethyl-S-sulfinic acid methyl ^ -sulfornethyl-pyrrolidinium betaine (prepared according to OD PS 225128)

and formaldehyde in water in the molar ratio 1: 3: 3 reacted.

102,3g (0.3mol) of 80% Sulfinsäurekomponente are stirred in 361 ml of water with 33 mL (0.3 mol) of 30% Formaiinlösung 1 hour at 6O ⁰ C; The solution is then mixed with 12.619 (0.1 mol) of melamine and heated to 80 to 100 ⁰ C for 30 min. To

Dissolution is filtered for clarification and concentrated in vacuo. This gives 95.2 g of colorless glassy solid product, which »at

270 to 28O ⁰ C melts with decomposition. It is very slightly soluble in water.

C ₃₀ H _n N ₈ Ot ₅ Sa (MW 952.4)

Claims (4)

1. disinfectant solution for inactivating germs, characterized in that the germ reduction, germ-reducing cleaning and / or disinfection by the polyfunctional amidomethyl-sulfon-pyrrolidinium-sulfomethyl-betain of the formula (I) CHRI-SO ₀ -ν> - ^S0 3 ° SO ₅ -CH ₅ -HN '^ W " ^N NH-CHjrrSO takes place, which can be used in water in concentrations of 0.01 to 2 wt .-% or for the synergistic increase in activity in the same concentration in water / alcohol mixtures with a share of 20 to 99 vol .-% water and 1 to 80 vol. % Alcohol is 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 disinfectant with specific activity against hepatitis B virus, the active ingredient of the formula (I) in water / alcohol mixtures having an alcohol content of 30 to 80 vol .-% is dissolved , 4. disinfectant solution according to claim 1, characterized in that for the complete dissolution of blood contaminants of the active ingredient of formula (I) in the concentration range of 0.1 to 2 wt .-% is used.