DE29924225U1 - disinfectant - Google Patents

Description

Disinfectants

This invention relates to disinfectants containing a mixture of primary amines having a molecular weight of 130 to 270 Daltons.

Medical equipment and surfaces in hospitals, doctor's offices, outpatient clinics and ambulances must be hygienically perfect to protect patients and staff.

Given the large number of diseases whose pathogens can adhere to surfaces, safety for the user cannot be achieved by simply cleaning, but only by disinfecting the surfaces and equipment. To date, aldehydes or phenols have been used for this purpose.

However, since phenols have been recognized as poorly biodegradable and aldehydes pose a health risk to the personnel handling them due to their volatility, invert soaps are increasingly used to disinfect equipment and surfaces. In contrast to aldehydes, invert soaps are practically non-volatile, so that contamination of the air we breathe is essentially non-existent.

However, invert soaps have the disadvantage that their Lewis acid structure can stabilize the cell membrane of microorganisms adapted to them. Disinfectants based on invert soaps are often ineffective, particularly against water germs. Mycobacteria cannot be effectively combatted with invert soaps either. Due to the stabilization of the cell wall, the effectiveness of other active ingredients, possibly used in combination, is reduced.

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From DE 27 11 577, amines in combination with ammonium compounds are known which, when mixed with invert soaps, are intended to improve the effectiveness of the disinfectant against pathogens.

EP 0 333 143 A2 further discloses that oligomeric amines with an alcohol content of approximately 50% are effective against non-enveloped viruses. However, the products described foam and are highly alkaline. Another problem with their use is their lack of effectiveness when diluted.

What all the products described in the patents listed above have in common is that the amine compounds used do not have a carbon chain with a defined number of atoms. The starting materials for their production are palm oil, mineral oil or other oils that are common in nature and contain a wide range of different compounds that differ, among other things, in terms of the number of carbon atoms in the chain. If the number of carbon atoms in the chain is therefore plotted against the concentration in the oil, a Boltzmann or Gaussian distribution with different shapes is obtained depending on the source of the oil.

The raw materials contain both short-chain and long-chain compounds.

After the primary amines have been produced from these raw materials, the short-chain compounds are known to produce highly effective short-chain amines. However, these short-chain primary amines are highly volatile and are the cause of the strong odor and the associated disadvantages.

The proportion of long-chain molecules present in the oils used is also a disadvantage for use in the amines produced from them. The long-chain impurities are only slightly soluble in water, so that the use

Dilutions of disinfectants made with such amines tend to become cloudy.

Due to the ambiphilic nature of the amines, there is a strong tendency to foam, whereby an enrichment takes place on the surface of the solution or in the foam. If they accumulate in the foam, they stabilize it and, once the foam has collapsed, they can no longer be dissolved in the water of the working dilution.

The various difficulties with amines are the reason why amines are rarely used in disinfectants and sometimes even gaps in the effectiveness of the product are accepted so that the poor performance properties of the amines do not spoil the performance properties of a disinfectant according to the state of the art.

During disinfection, viruses must be combated in addition to bacteria or bacteria-like microorganisms. Apart from enveloped viruses, whose lipid envelope is formed from parts of the host organism's cell membrane, there are also a large number of so-called non-enveloped viruses that do not have an envelope made of parts of the host's cell membrane.

While enveloped viruses such as hepatitis B or hepatitis C viruses can be essentially inactivated by invert soaps, non-enveloped viruses such as polio, hepatitis A or echoviruses or even Papova SV 40 viruses are resistant to invert soaps.

One object of the present invention is therefore to provide disinfectants which are toxicologically safe for users, non-corrosive for medical devices and effective against mycobacteria and non-enveloped viruses. A further object is to impart these properties to various types of disinfectants without changing the properties of these disinfectants which have been customary up to now.

This task was solved by a disinfectant containing a mixture of primary amines with a molecular weight of 130 to 270 Dalton.

According to a preferred embodiment, the amine mixture used contains branched carbon chains, the preferred molecular weight range of the amines being from 160 to 200 Dalton, more preferably around 178 Dalton.

During the lengthy investigations leading to the present invention, it was found that there are certain amine compounds that are highly effective against both mycobacteria and non-enveloped viruses and that also have such a low vapor pressure that there is no danger to staff and patients when disinfecting large areas in enclosed spaces. This also applies if the people remain in the room during the drying phase.

The low toxicity of the amines according to the invention is all the more surprising since their effectiveness against mycobacteria or non-enveloped viruses is greater than that of all substances known to date. The previously valid rule that mycobicidal substances are more effective the more toxic they are to mammals and humans, surprisingly does not apply to the mixtures of primary amines according to the invention.

The amines/amine mixtures according to the invention have not previously been used as disinfectants because they do not have sufficient bactericidal or fungicidal activity themselves and have therefore not previously been recognized and used as active ingredients in disinfectants.

The amines/amine mixtures according to the invention are now used to combine known disinfectant active ingredients, such as invert soaps, guanidines or phenols, with a sufficient

To confer efficacy against mycobacteria and/or viruses, particularly non-enveloped viruses such as picornaviruses.

It was found that the spectrum of activity of combinations of disinfectant active ingredients that are actually ineffective against mycobacteria or non-enveloped viruses with the amine mixtures according to the invention is even better than that of combinations of invert soaps with, for example, aldehydes, or that of aldehydes alone.

For example, a working dilution of 0.3 percent didecyclmethyloxethylammonium propionate with the addition of 0.22% formaldehyde and 0.15% glutardialdehyde is inactive against picornaviruses for three hours. In contrast, it was surprisingly found that the quaternary ammonium compound became polio-effective after the addition of an amine mixture according to the invention.

It was also found that the amines/amine mixtures according to the invention do not have a corrosive effect, in contrast to the short-chain amines used to date as disinfectants. Corrosion of plastics and rubber is also no longer detectable, so that their use in the processing of medical devices is possible without any problems.

The agents according to the invention are so effective that they greatly increase the effectiveness of disinfectant active ingredients against viruses, even picornaviruses, such as polio viruses.

The aminic mixtures according to the invention are amines, preferably primary amines, which can be prepared from synthetically produced chloroalkanes. In principle, however, other synthesis routes are also possible. The raw materials for the production of the amines can be produced, for example, by linking pentenes, pentadienes, butadienes, ethylene and propylene, with the substances mentioned being used individually or

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can be used in changing mixtures. Both the type of starting materials and the mixing ratios of the raw materials can be varied. Depending on the type and mixture of the various gaseous and volatile starting components, mixtures of different raw materials for the amines are created, which generally do not have a defined structure but do have a defined molecular weight. Mixtures of different primary amines can then be produced from these materials, which also do not have a defined structure but do have a defined molecular weight.

The aminic mixtures according to the invention are characterized by a low melting point, which is preferably below 0 ^° C, and a high boiling point of over 200 ^° C (both at atmospheric pressure).

Preference is given to mixtures of substances which have a narrow boiling range of 10 ^° C or less. Very particular preference is given to mixtures of substances in which the boiling range at normal pressure begins above ^240° C and whose melting point is below ^-50° C. The mixtures are characterized in that the alkyl chain is branched at least once in the vast majority of molecules and the length of the longest alkyl chain in the molecules of the mixture varies. Secondly, the mixtures of amines according to the invention are characterized in that the amino group is primary, the position of which in the molecule is not defined, so that in the amine mixture according to the invention the position of the primary amino groups is randomly distributed.

The molecular weights of the amine mixtures can vary between 130 and 270 Dalton depending on the starting material. Amine mixtures with a molecular weight of 160 - 200 Dalton are preferred, and amine mixtures with a molecular weight of 178 Dalton are particularly preferred. Such a product is available on the market under the trade name Isotridecylamine (available from Lonza, DE).

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The effectiveness of the amine mixtures according to the invention against mycobacteria is maintained during neutralization up to pH values of approximately 7 to 8, with the optimum in terms of effectiveness and application properties being in the range of pH values around 9.

The mixtures according to the invention can be combined not only with cationic surface-active compounds, but also with anionic ones. For example, combinations with phenols are possible. Combinations of lauryldipropylenetriamine with the mixtures according to the invention of anionic surfactants that are in acid form are advantageous. For example, combinations of laurylpropylenediamine with ethercarboxylic acids and the amine mixtures according to the invention are possible. The amine mixtures according to the invention retain their full effectiveness against M.terrae even when the pH of the solutions is buffered, with the proviso that the pH of the solution or the working dilution remains above about 7.

The amines/amine mixtures are contained in the disinfectant formulations in an amount of 0.1% to 5%, preferably 0.1% to 3%. Concentrates naturally contain higher concentrations, and the expert will adjust this accordingly, taking into account his general specialist knowledge.

Commercially available products can also be used, such as suspending agents, corrosion inhibitors, solubilizers, perfume oils or paint. Solvents that can be used include alcohols such as ethanol, isopropanol, n-propanol, or ethers such as butyl diglycol or polypropylene glycol, or short-chain surfactants such as hexyl diglycol.

Due to the low toxicity and volatility of the agents according to the invention, the agents according to the invention can also be incorporated into spray disinfectants, which are sprayed onto the surface to be disinfected as a dilution and then dried. In addition, the use in alkaline alcoholic solutions

for cleaning and disinfecting the drill heads of dentist drills. The disinfectant solution can then contain not only the mixture according to the invention, the alcohol, preferably ethanol, isopropanol or n-propanol, and a second active ingredient, but also a complexing agent whose complex formation constant with calcium is so high that it can dissolve calcium phosphate salts even at pH values of around 9. Of course, such complexing agents, or others with a lower complex formation constant, can also be incorporated into all other products containing the mixtures according to the invention.

At pH values of about 9 and less in the working solution, disinfectants containing the agents according to the invention are not more corrosive than the comparison samples without the mixtures according to the invention and are significantly less corrosive than agents containing amines according to the prior art and therefore require a higher pH value to be effective.

The performance of the amine mixtures according to the invention will be described in more detail using the following examples.

example 1

To evaluate the performance of the amines according to the invention, the disinfectant formulations listed in Table 1 were prepared.

Table 1

Example No.: Oil 02 03 04 05 06 07 Benzalkonium chloride 20,00 10.00 20,00 20,00 20,00 10.00 20,00 Polyhexamethylene biguanide 5.00 5.00 Isotridecylamine 2.00 1.50 Isoundecylamine 1.50 1.50 Isopentadecacylamine 2.50 Octylamine 3.00 Lauryldipropylenetriamine 10.00 Isotridecyl ethoxylate 7 EO 10.00 10.00 10.00 10.00 12,50 10.00 2.50 Isundecyl ethoxylate 3 EO 5.00 5.00 5.00 2.50 5.00 12,50 citric acid to pH 9 to pH 9 to pH 9 to pH 9 to pH 9 to pH 9 to pH 9 Water to 100 to 100 to 100 to 100 to 100 to 100 to 100

While the inventive formulations of examples one to five were effective against Mycobacterium terrae at a concentration of 2% after an exposure time of fifteen minutes in the suspension test according to DGHM, the agent from example 6 was only effective at a concentration of 3% in the same time. The agent from example 7 was also not effective at a concentration of 1 % , although the vapor pressure of the octylamine and the technical lauryldipropylenetriamine was so high that an amine smell was noticeable in the room when used as an instrument disinfectant and employees who carried out the tests complained of headaches after a short time.

The amine mixtures according to the invention are therefore already effective at concentrations of approx. 400 ppm, as demonstrated for example by tridecyclamine, whereas known amines are only effective against mycobacteria at approx. 900 ppm, as the example of octylamine suggests.

Since the boiling point of the amine mixtures according to the invention at normal pressure is approximately 70 ^° C higher than the boiling point of, for example, octylamine, the exposure of employees who handle products containing the amine mixtures according to the invention is much lower than when handling known products.

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Example 2

The virucidal activity of Examples 2 and 6 and of variants of Example 1 without the amines according to the invention, in which the pH was adjusted with sodium hydroxide solution to the same value as in the examples according to the invention, is summarized in Table 2:

Table 2

Conc. polio Adeno Papova SV 40 Hepatitis B Example 2 with amine 1.00 60 min 2.00 30 min 15 minutes 3.00 4.00 15 minutes 6.00 30 min Example 2 without amine 1.00 30 min 2.00 60 min 60 min 3.00 4.00 30 min 30 min 6.00 n.w. in 120' Example 6 with amine 1.00 60 min • 2.00 30 min 15 minutes 3.00 120 min 4.00 15 minutes 6.00 60 min Example 6 without amine 1.00 30 min 2.00 60 min 60 min 3.00 4.00 30 min 30 min 6.00 n.w.in 120'

n.w.: not effective Rf < 4.0

Examples 2 and 6 demonstrate a significant improvement in the performance of disinfectants containing amines according to the invention.

Mixtures of 20 percent benzalkonium chloride with 5 percent biguanide according to Example 2 showed even after addition of 11 % glutaraldehyde at a concentration of

concentration of 6% for 2 hours was not effective against poliovirus strain Mahoney.

Table 2 also shows that the mixtures of branched primary amines according to the invention with a known and defined molecular weight are more effective than short-chain amines with a straight alkyl chain and a defined molecular weight distribution. This is of great importance for a low exposure of personnel to evaporating amines, as this further increases the advantage of the mixtures according to the invention.

Example 3

The following formulations according to Table 3 were prepared.

Table 3

Example No. 8th 9 10 11 12 13 14 &eegr; - Octylamine 3.00 sec. Tridecylamine 1.50 3.00 sec. hexylamine 1.50 Dioctylamine 3.00 Laurylpropylenediamine 2.00 Lonzabac-12 20,00 Lauryl biguanide 10.00 10.00 10.00 10.00 10.00 10.00 C 11 Fatty alcohol 8EO 5.00
10.00 5.00
10.00 5.00
10.00 5.00
10.00 10.00
15,00 5.00
10.00 10.00
15,00 2-Propanol 20,00 -
30.00 20,00 -
30.00 20,00 -
30.00 20,00 -
30.00 20,00 -
30.00 20,00 -
30.00 20,00 -
30.00 Alkyl ether acetic acid 0.50-
1.00 Perfume / Color what is this what is this what is this what is this what is this what is this what is this Water to 100 to 100 to 100 to 100 to 100 to 100 to 100 pH value, approx. 9.5 8.5 9.0 8.5 9.5 12.0 8.5

The formulations were tested on different materials. The results are summarized in Table 4.

8th 9 Table 4 11 12 13 Φ Φ
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&bull; φ φ 10 &phgr;&phgr;&phgr;&phgr;&phgr; φφφ φ
&bull; φφφ φφφ φ φφφφ. φ φ &bull; Φ φ t
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Φ Φ 4
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Red rubber swells swells
few swells swells
few swells swells
strong swells Silicone rubber something
harder if. something
harder if. something
harder harder something
harder aluminum IF. if. if. if. if. Corr. if. copper dark bright dark dark dark schw. dark Endoscope parts IF. IF. if. if. IF. destroyed if.

Legend: n.b.: without noticeable change

The results were obtained after 3 weeks of storage at 40 ^° C in solutions containing 5% product. The formulations according to the invention also showed no corrosive properties.

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Claims (8)

1. Disinfectant, characterized in that it contains a mixture of primary amines having a molecular weight of 130 to 270 daltons, comprising tridecylamine. 2. Disinfectant according to claim 1, characterized in that the chain of the amine compounds is branched. 3. Disinfectant according to one of claims 1 and 2, characterized in that the compounds of the amine mixture have molecular weights of 160 to 200 Dalton, preferably 178 Dalton. 4. Disinfectant according to one of the preceding claims, characterized in that it contains anionic surfactants. 5. Disinfectant according to one of the preceding claims, characterized in that invert soaps are included. 6. Disinfectant according to one of the preceding claims, characterized in that non-ionic surfactants are included. 7. Disinfectant according to one of the preceding claims, wherein the amine mixture is contained in an amount of 0.1% to 5%. 8. Disinfectant concentrate, characterized in that it contains a disinfectant according to one of the preceding claims.