DD292136A5 - NEW DISINFECTANTS WITH PARTICULAR HIGH USER FRIENDLINESS - Google Patents

Abstract

The invention relates to new disinfectants, which are characterized by a particularly high level of user-friendliness. As active ingredients they contain aldehyde-free, water-soluble and storage-stable acetal-type compounds which are prepared by reaction of * or equimolar amounts of formaldehyde and ethanolamine with aliphatic or aromatic mono- or dialdehydes. Further advantages of the disinfectants according to the invention are the good skin compatibility, the low corrosiveness towards materials and the low odor concentration. aldehyde-free, acetal-type compounds; * Formaldehyde; Ethanolamine; aliphatic or aromatic mono- or dialdehydes; hautvertraeglich}

Description

Field of application of the invention

The invention relates to new Dosinfektionsmittel, especially for the health care and the Tiorhygione, with a particularly high level of user-friendliness.

Characteristic of the known state of the art

Disinfectants are indispensable aids in many areas, especially in health care and animal hygiene, which are used to prevent infections and to break chains of infection.

(Lists of in the GDR state approved disinfectants for health care and animal hygiene).

Here are faster, comprehensive onset with high ease of use in terms of toxic effect, especially skin friendliness, environmental side effects, corrosion and odor nuisance not nearly reached demands. Particularly effective remedies are made up of active substances from the classes of aldehydes, substituted phenols and the strong oxidizing agents (peracids, chlorine-releasing agents) and synergistic active substance mixtures, including other classes of substances.

(Horn, H., Privora, M. and W. Weuffen, Handbook of Disinfection and Sterilization, K. H. Wallhüußer, Practice of Sterilization, Disinfection, Conservation, 3rd Edition Thieme-Verlag Stuttgart, New Yoi k, 1984). Trot »good effect, these disinfectants each have significant negative properties for the Pioduzenteii and users.

For example, aldehydes, especially formaldehyde, are toxic, allergenic, highly noxious in terms of odor, and also chemically unstable.

Oxidizing agents such as peracids, especially peracetic acid, are highly corrosive, less resistant, toxic and highly odoriferous. Also Chlorabspalter have similar properties. Highly effective phenol derivatives are limited in their use by high toxicity, odor nuisance and ecological Γ, -ubleme. If the ease of use is increased by chemical modification, the efficacy decreases, e.g. some peroxides, more stable chlorine cleavage and many aldehyde derivatives.

At present, predominantly disinfectants based on phenol are used in patient-occupied rooms. For the Ticrhygieno phenolic disinfectants are only applicable in special cases because of the danger of the transition to the food kotte. In both areas, user-friendly agents based on alcohols, quaternary ammonium compounds, peroxides and ampholytes are frequently used, although they are not effectively effective on the surface, in the wash or in excrements. Usually only a germ reduction, but no disinfection is achieved. These deficiencies are addressed by applying special antimicrobial regimes adapted to the particular problem, which are based on a labor-intensive concept of cleaning and disinfection measures.

Another way out is to use effective agents in patient-free rooms or animal hygiene in empty stables, which also entails increased expenses.

Formaldehyde-reduced or dialdehyde-based compounds, often in combination with quaternary ammonium salts, alcohols or else with phenols, also permit only gradual improvements (eg DDPS 233941).

In recent years, O- and N-aldehyde derivatives, especially formaldehyde, have been found to be good in that they reduce some of the adverse effects of use.

This concerned acetals with alcohols such as ethanol and benzyl alcohol, N-methylols, e.g. From ChIo. acetamide, or amine adducts, e.g. N, N ', N "-tris- (2-hydroxyethyl) -1,3,5-hexahydrotriazine (HHT).

However, all of these products show a partial significant loss of effect and guarantee no real formaldehyde, so that allergenic effect remains.

Although 1,3,5-hexahydrotriazines are described as active ingredients for disinfectants (DE-AS 1160985, DE-OS 2023760, DE-OS 903864, DE-AS 2004647), but are inadequate effect so far only as a preservative (DE-OS 1148708 , DE-OS 1133632) has been prewired. They were also claimed for the protection of seed and seedlings in combination preparations (DD-PS 248500)

 Reactions of the HHT with other aldehydes in non-stoichiometric reactions have not been previously known.

Aim of the egg

The aim der.Erfindung is the development of new Dosinfektionsmittel, which are characterized in addition to rapid onset of particularly high Anwonderfreundlichkeit with regard to odor, toxicology, skin compatibility and corrosivity over materials.

Explanation of the essence of the invention

The object of the invention is the discovery of new disinfectants with a particularly high level of user-friendliness, which can be effectively produced and contain no free Aldohydantoile.

The object was achieved according to the invention in which in the new disinfectants in addition to known mlkrobiziden quaternary ammonium compounds and N, N ', N "-Trls (2-hydroxyethyl) -1,3,5-hexahydrotriazine (hereinafter referred to as HHT) and conventional galenic excipients as active ingredients aldohydgruppenfreien acetal-like compounds (ethanolamine acetals, hereinafter referred to as EA acetals) are used by reaction of HHT or equimolar amounts of formaldehyde and ethanolamine with aliphatic or aromatic mono- or dialdehydes in equivalence ratios dor OH groups in the HHT the aldehyde groups in the aliphatic or aromatic mono- or dialdehydes of 10: 1-9 are prepared and which can be adjusted to pH values of preferably 7 to 10 by addition of acids. Suitable aldehydes are butyraldohyde, isobutyralclohydric acid, trichloroacetaldehyde, glyoxal, 2-ethylhexanol, glutardialdehyde, etc.

Glutardialclehyd is particularly recommended, The EA acetals according to the invention are neutralized and alkaline stable, water-soluble, low-toxic, good skin-friendly, low-corrosive compounds that have only low odor. They have good bactericidal, fungicidal and viricidal properties. For neutralization are organic acids such. As formic acid and acetic acid, but also inorganic such. For example, hydrochloric or sulfuric acid. Aldehyde groups are not detectable analytically. In the new disinfectants are the EA acetals with microbicidal quaternary ammonium compounds such. B. DimethylbenzylalkyKCn-C ^ lammoniumchlorid (benzalkonium chloride, CJ or Dimethylbenzylacetamidododezylammoniumchlorid (methalconium chloride, quartolane) and HHT combined in weight ratios of 0.5-20: 0.1-10-1.

In addition, conventional galenic adjuvants such as perfume oils, surfactants u.a.m. be included.

The new disinfectants contain mainly 10-60% active ingredients and show already from 0.1% significant biological effectiveness. For practical use in disinfection 1-5% solutions are recommended depending on the application. It is also possible to use the new disinfectants in combination with other known active ingredients or disinfectants.

embodiments

example 1

Comparison sample and composition of the disinfectants according to the invention

Table 1 Comparison sample

Disinfectants from the following active ingredients or mixtures of active ingredients and conventional galenic excipients

Sample drugs or drug combinations

V1 formaldehyde (known)

V 2 glutaric dialdehyde (known)

V3 Methalconium Chloride (Quartolan) (known)

V4 HHT (known)

V 5 mixture of formaldehyde, glutardialdehyde and methalconium chloride in the weight ratio 5: 1: 1 (known) V6 mixture of formaldehyde, tributyltin benzoate and methalconium chloride in a weight ratio 4: 1: 1 (known) V7 xylenol / cresol mixture in a weight ratio of 1: 1 (known)

In the following tables the following abbreviations were used for components of the disinfectants according to the invention:

aldehydes

Glutaraldehyde AG

Butyraldehyde AB

Isobutyraldehyde Al

Trichloroacetaldehyde AT

Glyoxal AGL

2-ethylhexen-2-al AH

acids SA relationship additional agents otherwise. Active ingredients weight ratio EA acetals: Quat: HHT formic acid SE OH to Alde Effective% based on - kind acetic acid SO hydgruppen the sum of all _ of 1: 0.8: 1 sulfuric acid SH 10: 3 _ quat 0.5: 0.5: 1 hydrochloric acid 10: 3 - - QM 20: 5: 1 QM 10: 5 - 10 QM 5: 4: 1 QB 10: 9 _ 20 QM 2: 0.5: 1 QD 10: 1 - 10 QB 1.5: 1: 1 10: 4 PR 20 QB 0.9: 1: 1 PR 10: 3 PB 10 QB 1,2: 4: 1 PB 10: 5 P - QD 3: 0.8: 1 PX 10: 2 e 20 QD 5: 1: 1 10: 3 TB - QD 0,5: 4: 1 P 10: 9 - 20 QM 10: 0.8: 1 e 10: 1 P - QM 1: 3: 1 Quaternary ammonium compounds TB 10: 5 - 10 QM 3: 10: 1 Methalkoniumchlorid Tobelle 2 Disinfectants of the invention (E 1-E 21) 10: 4 e - QB 20: 8: 1 benzalkonium chloride Ser. components 10: 8 - 10 QB 0.9: 5: 1 No. EA acetals 10: 1 TB - QB 0.5: 0.5: 11 Alde 10: 9 - 10 QD 1.5: 1: 1 Dimethldidodecylammoniumchlorid hyd 10: 4 PR - QD 1.0: 1: 1 phenols E1 AG 10: 3 - 10 QM 0.8: 0: 1 p-chloro-m-cresol E 2 AG 10: 3 PX QM 0.9: 0: 1 E3 AG 10: 3 - - E4 AG e - o-benzyl-p-chlorophenol E 5 AG Xylenol / cresol mixture 1: 1 E 6 AG alcohols E7 AG n-propanol E8 AG ethanol E9 AG E10 AB E11 AB E12 Al Tributylzlnnbenzoat E13 Al E14 AT E15 AT E16 AGL E17 AGL E18 AH E19 AG E 20 AG E 21 AG

Neutralization PH value acid 13 - 8.5 SE 8.0 SO 8.5 SA 8.5 SH 12.5 - 8.5 SE 8.0 SA 8.5 SH 12.5 - 7.5 SE 13.5 - 8.0 SA 75 SE 8.0 SA 7.5 SE 7.0 SE 9.0 SE 7.5 SE 7.5 SE 7.5 SE

Example 2:

Test of bactericidal and fungicidal activity The following test microbes were used:

Bacteria: ν

Staphylococcus aureus (1)

Escherichia coli (2)

Pseudomonas aeruginosa (3)

mushrooms:

Candida albicans (4)

Trichophyton geophytes (5)

Penicilliumspec. (6)

Aspergillus Niger (7)

The effectiveness is rated as follows:

0 no effect (in each case against the test germ concerned)

1 weak effect

2 medium effect

3 good effect

4 very good effect

2, test methods

1st Suspenal test *

To 10mL test solution of different concentrations of active ingredient is given to 0.1 ml of a standardized bouillon culture of the test germs and the whole well mixed. After exposure times of 2 to 120 minutes, a platinum-soluble mixture is removed in each case and transferred into 10 ml of suitable nutrient medium. The NShrmedien are zugosotzt for inactivating the drugs specific acting inhibitors. Then incubate for testbaktorion 5 days at 37 ⁰ C, for test fungi 3 weeks at 22 ° C.

2. Surface Dose Feeding (praxisanalorjerTestj

2.1. For bacteria

On sterilized germ carriers made of lacquered wood and PVC in the size of 2cm x 5cm, 0.1 ml each of a standardized test microbial suspension is applied and evenly distributed with a glass spatula. After drying for 30 minutes at 20 ° C., 0.1 ml of the test solution is applied and likewise distributed uniformly. After exposure times of 1, 2, 3 and 4 h, the test surfaces are placed on suitable solid nutrient media and left there for 2 h. The nutrient media, to which inhibitors specific for the inactivation of the active ingredients were added, were incubated for 3 days at 37.degree.

2.2. For mushrooms

Sterilized wooden sticks of 2 cm length, 2 mm width and 2 mm thickness are contaminated by lOminütiges insertion in standardized test fungus suspension, dried for 1 h at 37 ⁰ C and then placed for 5min in 10ml of the test solution. Thereafter, the wooden sticks are placed obliquely in sterile glass jars and remain there for exposure times of 1,2,3 and 4 h. Then 50% of the wood immediately, 50% after an intermediate rinse with sterile water obliquely placed on Sabouraud glucose agar, so that the lower edge of the wood is just above the condensed water level. Specific inhibitors are added to the agar to inactivate the active ingredients. The nutrient media are incubated at 22 ° C for up to 4 weeks.

3. Instrument disinfection (practice-oriented test)

Sterilized germ carriers are placed in a standardized test microbial suspension τ · contamination 10min.

As a germ carrier serve Glasplättcnen (2.5 χ 1 cm), plastic platelets (2.5cm x 1 cm), rubber hose (halved, 2cm) and metal screws (2cm). The contaminated germ carriers are dried for 15 min at 2O ⁰ C, then placed in each 10ml test solution. After exposure times of 15,30,45,60 and 120 min, they are removed, rinsed with sterile water and transferred in 10 ml of suitable liquid nutrient medium. Rinsing fluid and nutrient media contain specific inhibitors to inactivate the drugs. It is incubated for 7 days at 37 ° C.

The comparative tests were carried out at the same total active substance concentrations. The results of the tests are shown in tabular form:

The comparative tests were carried out at equal total active substance concentrations. The results of the tests are shown in tabular form:

Table 3: Suspension test (0.1% total active substance)

Bonitur Scoring against test germs (2) (3) (4) (5) (6) (7) (D 2 4 2 2 2 2 V1 1 4 4 1 2 1 1 V2 4 4 4 1 1 1 1 V3 4 1 1 1 2 0 0 V4 1 4 4 4 4 4 4 V5 4 4 4 4 3 4 3 V6 4 2 1 2 2 2 2 V7 1 4 4 4 4 4 3 E1 4 4 4 4 4 4 4 E2 4 4 4 4 4 3 4 E3 4 4 4 4 4 3 4 E4 4 4 4 4 4 4 4 E5 4 4 4 4 4 4 4 E6 4 4 4 4 4 4 4 E7 4 4 4 4 4 4 4 E8 4 4 4 4 · < 4 4 E9 4 4 4 4 4 3 3 E10 4 4 4 4 4 4 4 E11 4 4 4 4 3 3 3 E12 4 4 4 4 4 4 4 E 13 4 4 4 4 3 3 3 E14 4 4 4 4 4 4 4 E15 4 4 4 4 4 4 4 E16 4 4 4 4 4 4 4 E17 4 4 4 4 4 4 4 E18 4 4 4 4 4 4 4 E19 4 4 4 4 4 3 4 E 20 4 4 3 4 4 4 3 E 21 4

Table 4 Surface Disinfection (1.0% Gosam Active)

medium Scoring against test germs (2) (3) (4) , (5) (1) 3 3 3 3 V1 3 3 3 3 3 V2 3 2 2 2 2 V3 3 0 1 0 0 V4 1 3 3 2 2 V7 2 3 4 3 3 E1 4 3 4 3 3 E2 4 3 4 3 3 E3 3 4 4 4 3 E6 4 4 3 4 4 E9 3 3 4 4 4 E 10 3 3 4 3 4 E14 4 4 4 4 4 E17 q 3 4 4 4 E18 3 4 4 4 4 E19 4 4 4 4 4 E 20 4 4 4 4 4 E21 4

Table 5 Instrument disinfection (0.5% total active substance)

Medium rating against test germs (1) (2) (3)

V1 2 2 2

V2 3 2 3

V3 0 0 0

V4 0 0 0

V6 3 2 3

E1 3 44

E2 444

E4 4 3 4

E5 4 3 3

E7 3 3 3

E8 3 4 3

E11 4 3 4

E14 4 3 3

E17 4 3 3

E18 4 3 3

E19 3 3 4

E20 3 3 4

E21 4 3 4

Example 3

Virucidal activity

methodology

The test was carried out against enveloped Aujetzky viruses (1) and unencumbered Talfan / Teschen viruses (2) according to a standardized log carrier model at 20 ° C. The initial titer was determined after drying and the residual titer determined after certain Einwkzeiten.

The results were rated: 0 no effectiveness

1 weak effectiveness

2 good effectiveness

3 very good effectiveness

The results are presented in a table at 0.3% total active ingredient:

Table 6 (2) Bonitur • 0 not or extremely low toxic (B) skin treaty Geruchsbe (B) Materialver (B) 3 1 low toxicity 2 friendliness nuisance 3 compatibility 1 0 2 mediocre toxic 2 (a) (b) (A) 3 (A) 1 0 3 very toxic 2 3 3 3 0 2 0 Medium scoring against test organism 2 0 no skin damage 1 2 2 3 1 2 0 (1) 1 1 slight skin irritation 2 2 0 1 2 1 1 V1 3 1 2 moderate skin irritation 2 2 1 1 2 1 1 V3 0 1 3 severe skin damage 2 2 2 3 1 2 1 V4 0 1 0 not o. Hardly annoying 0 2 2 3 0 2 0 V5 3 1 1 easily annoying 0 2 2 3 0 1 0 E1 '2 1 2 mediocre harassing 0 1 0 1 0 1 0 E4 2 3 harassing 0 1 0 1 0 1 0 E10 2 0 1 0 1 0 1 0 E16 2 1 1 0 1 1 1 0 E 20 2 0 1 0 1 0 1 0 E 21 2 0 1 1 2 0 1 0 Example 4 1 0 1 1 1 0 1 1 0 not o. Or hardly damaging Ease-AW (1) toxicity (a) preparation (b) 2% solution (2) Skin compatibility (a) preparation (b) 2% solution (3) odor nuisance (a) preparation (b) 2% solution 1 damaging to individual materials 2 moderately damaging (4) Material compatibility 3 badly damaged (a) preparation The assessment is presented in tabular form: (b) 2% solution Table 7 Medium rating of the toxicity (A) V1 3 V2 3 V3 3 V4 2 V5 3 V6 3 V7 3 E1 0 E2 0 E7 0 E8 0 E14 0 E17 1 E18 0 E 20 0

Claims (4)

1. disinfectant with particularly high user-friendliness with the addition of galenic excipients, known microbicidally active compounds and 1,3,5-tris (2-hydroxyethyl) hexahydrotriazine, characterized in that they contain as active ingredients aldehydegruppenfreie, water-soluble and storage-stable acetal-like compounds, which are prepared by reacting 1,3,5-tris- (2-hydroxyethyl) -hexahydrotriazine or equimolar amounts of formaldehyde and ethanolamine with aliphatic or aromatic mono- or dialdehydes having an equivalence ratio of the OH groups of 10: 1 to 9. 2. disinfectant with a particularly high level of user-friendliness according to claim 1, characterized in that is preferably used for the reaction as aliphatic or aromatic mono- or dialdehydes glutaraldehyde. 3. disinfectant with a particularly high level of user-friendliness according to claim 1, characterized in that the water-soluble active ingredients have a pH word of 7 to 13, preferably 7 to 10, have. 4. disinfectant with particularly high ease of use according to claim 1, characterized in that the components in weight ratio acetal-like compounds to known microbicidally active compounds to 1,3,5-tris (2-hydroxyethyl) hexahydrotriazine = 0.5 to 20: 0 , 1 to 10: 1 are included.