DD203685A1 - ACTIVE COMPOUND FOR DISINFECTION - Google Patents

Abstract

The invention relates to active ingredient combinations for the field of skin and skin disinfection in human and veterinary medicine and in the food industry. It is intended to obtain disinfectants with significantly improved action properties and increased safety of action as well as long-lasting disinfecting action. The object has been achieved according to the invention by the fact that active compound combinations characterized by a content of ethanol and / or propan-2-ol and / or propan-1-ol between 40 and 80 wt.%, 0.5 to 10 wt. Hydrogen peroxide, 0.5 to 5 wt .-% surfactant, 0.5 to 2 wt .-% gesaettigte aliphatic alcohols in the C-number range of C & ind10! to C & ind30 !, water supplemented to 100 wt .-%, based on the total active ingredient combination and calculated as anhydrous substances are compiled.

Description

VEB Leuna-Werke Leuna, the

"Walter Ulbricht"

LP 81

Title of the invention

Active ingredient combination for disinfection

Field of application of the invention

The invention relates to combinations of active ingredients for safe and fast-acting disinfection in human medicine, which have an increased antimicrobial efficacy, a broad spectrum of action, low toxicity, skin-friendly properties and sufficient durability. Use is made of lower alcohols, their mixtures having the invention Hydrogen peroxide, surface-active compounds and higher saturated aliphatic alcohols for hand and skin disinfection are used * In addition to this application, the range of use for disinfecting sensitive instruments or «medical equipment and for slime skin antisepsics can be extended *

, r- ..m in η η ^ α fJi Ω C Π

238 130 1

Characteristic of the known technical solutions

The use of lower alcohols such as ethanol, propane-1-ol and propane-2 oil for hand and skin disinfection has long been known (Ullmanns Enzyklopadie der technischen Chemie, Vol. 5, Si 751 (1997))

For a successful disinfection of the hands or skin, a number of conditions have to be respected, which is not sufficiently guaranteed with the existing disinfectants. These include:

- use of the lowest possible toxic active ingredients while at the same time having sufficient effectiveness,

- Use of active ingredients that have no increased sensitization potential for the prevention of allergic diseases j

- the preservation of skin physiology for the prevention of the settlement of pathogens (approach flora); a damaged skin, z «B« damaged by disinfectants, is no longer disinfectable,

- as far as possible elimination of the approach flora while largely protecting the locus flora, because the latter in turn is the prerequisite for an intact skin physiological situation,

- with sufficient protection of the locus flora, a sufficient depth effect of the hand or skin disinfectant must nevertheless be ensured, since germs of inception (pathogens) also temporarily penetrate into deeper parts of the skin (eg crypts),

238130 1

- virucide and sporocide efficacy for proven indications of hand disinfection and skin disinfectionj In disinfection practice, this subdivision has either used insufficiently effective preparations or highly aggressive preparations (eg * B * spiritus iodi dilutus, peracetic acid containing preparations) *

Lower alcohols and hydrogen peroxide do not meet these requirements in any way, neither with respect to microbicidal effectiveness, nor with regard to skin compatibility and other application properties. The use of alcoholic disinfectants always results in a more or less pronounced degreasing and exfoliation of the skin. drying, which in turn equates to a disturbance of the physiology of the skin, as stated above. "Furthermore, the depth effect of the active ingredients is insufficient, so that the microflora is not reliably reached in deeper skin aorta (pores, crypts).

By adding small amounts of hydrogen peroxide, the germicidal effect of the alcohols on spores of Bacillus and Clostridienarten be extended (DE-OS 2 9Qk 217). However, with the exception of improving the effect, this combination has the same disadvantages as preparations based on only components «

Object of the invention

With the present invention, the above-mentioned multi-layered requirements to be met and provided for the health care hand and skin disinfectants are available that can be used with safe effect continuously, without causing adverse changes in skin physiology and without the risk of niikrotoxischen long-term damage

238130 1

Explanation of the essence of the invention

The present invention was based on the object of finding a hand and skin disinfectant that a safe, lasting, even in the deeper parts of the Eaut killing effect on bacteria, bacterial spores, fungi and viruses while preserving and maintaining the physiology of the skin and has a diminished toxic effect? »

This object is achieved by a drug combination for disinfection according to the invention in that a combination of active ingredients of ethanol and / or propane-1 oil and / or propane oil 2- with hydrogen peroxide, a surface-active compound and higher saturated aliphatic alcohols a safe disinfecting effect against the various pathogens (bacteria, bacterial spores, fungi, viruses) with a lasting effect: achieved with preserved skin physiology *

The concentration of the lower alcohols in the active substance combinations is at least kO $ & «These and all following percentages are by weight and refer to the total active ingredient combination and are calculated as anhydrous substances. The surfactant content is between 0.5 and 5 $ · The higher aliphatic alcohols are contained in a proportion of 0.5 to 2 % in the active ingredient combination * The residual content of the active ingredient combination to 100 i> is water »

The surfactants used are anionic or cationic and / or nonionic surfactants, in particular the sodium salts of long-chain alkane sulphonates, alkylbenzenesulphomatane, monoalkylsulphanate and ether sulphates. The use of alkyldimethylsilylammonium chloride as surface-active substance is particularly advantageous. The active substance combinations containing this substance show a particular advantage sustainable® germicidal effect and

238130 1

They are very well suited for surgical hand disinfection before putting on surgical gloves · They reliably prevent the proliferation of residual germs under the conditions of working with surgical gloves «As higher aliphatic alcohols, cL can be pure alcohols of the C-number range C. _Q to C_ _Q or alcohol mixtures of this C Number range can be used ·

EXAMPLES

There are combinations of active substances following composition:

Example 1

70 % ethanol

3 i> hydrogen peroxide

1 yi alkyldimethylbenzylammonium chloride

0.5 i »alcohol mixture C ₁ Q ^-0 ^ O 25» 5% water

_r Example 2

70 56 ethanol

3 % hydrogen peroxide

1 i> Sodium alkanesulfonate E 30 (VES Leuna-Werke "Walter

Ulbricht ») 0.5 % alcohol mixture C ₁ O ^-0 O ₀

25.5 % water

Example 3 (to dilute with water before use 1 s 1)

80 % propane «2-oi

4 % hydrogen peroxide

238 130 1

1 # Sodium alkanesulfonate E 1 # Alcohol mixture ^e ₁₀ ~ ^C 30 14 # Water

Example 4

60 % propan-1-ol

3 % hydrogen peroxide

1 % sodium alkanesulfonate E

1 $ Alkoholgemisoh C ₁₀ -C ₃₀

35 % water

The formulations of Examples 1-4 were tested for antimicrobial efficacy, co-fermentation, toxicity, soluteurase compatibility and shelf life and compared with the individual components or the respective binary mixture of lower alcohol / hydrogen peroxide

Bacteriostatic effectiveness

Methodikt

The bacteriostasis test was carried out according to the method of W. Weuffem, D Martin and m Schade (Pharmacy, J. (1963) 420-426)

In Examples 1 to 4, the tendency of an increase in bacteriostatic effectiveness is discernible in comparison with the individual components. "The test results of the 2- and 3-substance mixtures make it clear that a mutual influence of the components does not occur in the sense of a reduction in effectiveness (Table 1). * "

238130 1

Table 1

Growth inhibiting concentrations of Examples 1 to 4 compared to the individual components and their mixtures

Tested mixture

Example 1 Example 2 Example 3 Example 4

1)

Minimal inhibitory concentration II

Ii 2000 ti 500 15 500 1; 1000

H2000 1ί 500 Ii 500 1: 2000

1: 500 1 j 250 Ii 250 1: 500

Ii 500 1: 250 1: 250 1 j 500

Ethanol 70 % propane-1 oil 60 propan-2-ol 40

3% _N 2)

^H 2 ° 2

B 30

1 % 1 %

3)

1: 1i U

1: 250 Ii 500 128 1i 128

It 16

1:32

II 8

1i 500

1i 500

1i 128

1 year

U II

8 4

1i 250 128 <i1i 128 <1i 128

u 16

1! 16

1t 8

ti 250

i 128

Hi 128

i 128

Ethanol 70 po 3 % Ti 500 Propane 1 oil 60 % / B. 0 3 $ Ii 500 propan-2-ol 40 # / H _o 0 _o 2 % 1i 500 1i 500 1i1000 Ii 500

1i 500

1t 250 ii 250

1i 500 ti 500 Ii 250

Example 2 without Rf Example 2 without Rf Example 2 without E 30 Example 3 without Rf ¹ 'Example 3 without £ 30 Example 4 without Rf Example 4 without E 30

ti 1000 112000 ti 500 1i 500

1i 250 1i 500 1i 250 ti 500

ti 250 ti 250 1t 250 1i 250

1i 250 1i 500 1t 250 1i 250

U 128 Ii 500 1i 128 1i 250

IiIOOO ti 1000 1J1000 1i1000

IiIOOO U1000 Ii 500 1i1000

Legend t I II

a ss

h D

Staph. aureus SG

E. coli SG 770

absolute growth inhibition

it would be ahs t «sa

1 i 1 diluted

238130 1

2) ' =: Alkyl dime t hylb enzylammoni umcfalo chloride

* '= Sodium alkanesulfonate E ' as Alcohol mixture C ₁₀ -C ₃₀ ("Refatting agent ¹ ")

Fungistatic efficacy

Methodology: The fungistatic activity was tested according to the method given by W. Weuffern and B Herrmann (Z. med. Labortechnik 8 (196), 301, 31 * 0)

The results are summarized in Table Z ·

Table 2

Growth-inhibiting concentrations of Examples 1 bis against pathogenic fungi

tested Misunderstanding 1 I a 1 minimal b 1 a II inhibitory concentration 1 a III b 1 : 16 1 j64 1 : 16 1 i8 i32 1 : 16 1 i64 1 : 32 1 b 1 i8 1 64 example 1 1 J16 1 64 1 : 32 1 j 64 1 :8th 1 i32 example 2 "32 $ 128 t6k 1 i64 *8th 1 : 32 example 3 ¹⁾ 1 64 1 example 4 128

Legend} I s Trichophyton mentagrophytes

II s Microsporon canis III s Candida albleans

absolute growth inhibition diluted growth ¹ ^ = 1 ί 1 diluted

238130 1

Microbioidectivity

Methodikϊ

The tests were carried out in accordance with the Guideline for Testing and Evaluation of the Effectiveness of Chemical Disinfection Methods (ZBl, Bakt. Hyg. 1 * AbP * Orig. B 165 (1977), 335-380).

In Examples 1 to 3, the tendency of an increase in bactericidal effectiveness is discernible compared with the comparison mixtures (Table 3); "An increase in sporocidal effectiveness can be recognized by the shortening of the required exposure time (Table k) y

238 130 1

Table 3

From totungszeiten and concentrations of Examples 1 to 4 and the corresponding Vergleiehssaungen against bacteria in the suspension test

Tested Komzentra test germ

Mixing in % kill time in min.

StaphiauriSG 51i / £ Ucoli 3 / Pseud 2 5 10 15 2 5 10 15 2 5 10

VM 1 1 3 4 25 + ₊ 0 0 + + 0 0 + ₊ 0 0 (β VM 2) IM thinned 50 0 0 0 0 0 0 0 0 0 0 0 example 2 VH 4 25 0 0 0 0 0 0 0 0 * + 0 0 Diluted VM 3 IM 50 * 0 0 0 0 0 0 0 ₊ 0 0 0 example example example 25 ₊ 0 0 0 ₊ 0 0 0 0 ₊ 0 25 50 + ₊ 0 + ₊ 0 0 0 ₊ 0 0 25 0 + 0 0 0 0 0 0 0 0 0 0 50 0 0 0 0 0 0 0 0 0 0 0 0 25 0 0 0 0 0 0 0 0 + 0 0 0 50 0 0 0 0 0 0 0 ⁺ 0 0 0 25 * 0 0 0 0 0 0 0 0 0 0 50 0 0 0  0 0 0 0 0

Legend: TM 1 s comparison comparison 1 (70% ethanol, 3 %

^H 2 ° 2 ^ VM 3 ^s Comparison mixture 3 (80 % propan-2-ol,

VM 4 a comparison mixture 4 (% by weight of propane 1 oil,

+ s growth

0 ss no growth

238130

Table k

Defrosting times of Examples 1 to k and of the egg-soluble equalizer mixtures with respect to spores of Clostridium pex-fringeias in the suspension test

tested Misunderstanding 5 2 + + a Abtötongszeit in a min a b 10 15 30 Example 1 + + k + + 0 b a b 0 b Example VM 3, 1 * 1 + 0: * 0 0 Example VM k ⁺ ♦ 0 +. 0 example ♦ J * ♦ + 00

Legend i

VM 1 s Verglaichssischung 1 (70 % ethanol, .3 % H «0)

VM 3 = comparison mixture 3 (80 % propan-2-ol, 4 ^ ^H ₂ ⁰ 2

VM ^ f = Comparative mixture 4 (60 % propane-1-ol, 3 % H ₀ O ₀ )

CC Ä Ä

a = initial concentration 1 * ³

b = initial concentration 3> 8 + ss growth 0 ss no growth

Propane-1-ol, 3

" ³ spores / ml 10 spores / ml

238130 1

Bloekierurags-Aktivieruxigs tes t

Methodology:

2) he blocking song activation test was carried out according to the method © of Wi Weuffen and Mentel (Pharmacie 2 £ (1968), 579 - 582) «

From the individual results of the Biookierangs activation tests, the following statements are summarized:

Between the individual components of the combinations

Ethanol-HgO / E 30

- Propan-2-ol / H ₂ 0 ₂

- Propan-1-ol / HO ₀

there is an increase in the antimicrobial effect; "In the other combinations, there is no mutual impairment of the bacteriostatic effectiveness of the individual complex proteins with one another.

Determination of toxicity

Methodikί

¥ Mice, strain ICR Berlin, body mass 18 - 25 g, the test substances are subcutaneously injected »After application, food and Triiakwasser be discontinued * per dose 10 Maus® (sex ratio 1 i 1) are used ^ The -kÖ (- _ö becomes graphically according to Litchfield and Wilcoxoaa (J% Pharmacolr, Expj * Therapeut. 96 (194 <?), 99) »

In the acute systemic toxicity test (subcutaneous LD " _Q ), the most important finding was that all 2 and 3-material mixtures and Examples 2-4 are less toxic than the hydrogen peroxide dilution underlying the mixtures (Table 5) ) *

238130

"* I" J -

Efcenso, the mixtures of alcohols with hydrogen peroxide are no more toxic than the alcohols alone. "These results are surprising for several reasons;

- Combinations of different active substances often show an increase in toxicity compared to the individual components.

- The alcohol / H 2 mixtures do not even behave additively with respect to their toxicity; rather, the toxicity is significantly lower in comparison with the individual components.

Although toxicity is increased by the addition of the surfactants or greasing agents, the postulancy is still less toxic than H0 alone. Only Example 1 is toxic even less toxic than the analogs. 2- and 3-substance mixtures as well as propan-2-ol or HO alone ·

238130

Table 5

Acute süboutana L & erv of Examples 1 to 4 compared to the individual components and their mixtures

Tested mixture

trust

in g / kg body mass

example 1 2 % 3.8 3, Ow4,8 Example 2 8.8 7.6. ^. 10.2 Example 3 ¹ ' 12.1 10.5 ^ .14,1 Example 4 7.2 6,4 8,1 ··· Ethanol $ 70 6 15.6 12.3. ". 19.8 Propane-1-ol 60 $ 10.7 9,1i .. .12,6 Propane-2-ol 40 $ 9.0 7,6.j * .10,2 Propane-2-ol 60 $ ^ 3 5,6; · · 7,0 H ₂ O ₂ 3i 6.0 4.7. X 7.7 ^H 2 ° 2 ² * ^ 10.8 . 7.8. # 15.0 C 4 1 £ ' 5.5 4, % * · 7.3 E 30 1 % ^J ' Rf 0.5 $ ' > 50 Ethanol 70 # ^H 2 ° 2 ^ ^ 15.4 13.8, 17.2 .. Ethanol 70 % / C 4 1 Jt 13.6 12,2., .. 15,1 Propane 1 oil 60% H.Oa 14.9 12.7. ^. 17.2 Propan-2-ol 40 ^ / H_0_ 11.0 9,0? R ·! · 13,6 Example 1 without Rf 9.5 8.1 ... 11.2 Example 2 without Rf 10.4 8.1 ... 13.3 Example 3 without Rf ¹ ' 10.3 8,6 ^ _{ .12,2 Example 4 without Rf 9.8 8.2 ... 11.8

238130

¹ 'as diluted 1: 1

¹ = alkyldimethylammonium chloride

^ ss Natriuraalkansulfonat E 30

'- Alkoholgemisoh C. _o - C ₃₀ (' Refatting agent ⁿ )

Acute irritant effect of the ictic acid combinations

Methodology!

The heating effect was tested on the guinea pig saeye by the method of Kramer and co-workers (Z. Ges. Hygiene 2 (1978) 863-866).

The results from the tests for acute irritation in the ophthalmic test on guinea pig eye allow the following statements:

3 / 6ige aqueous hydrogen peroxide solution is clinically unimpressive tolerated guinea pig eye surprising that the irritant effect of the 2-substance mixture ethanol 70 $ / c h 1 $ is higher than that of the 3-substance mixture

Ethanol 70 % / C k I ^ / ^H 2 ° 2 ^^ ^b2w · ^{eS Beis} P ^{iels 1} · Apparently addition of HO causes a reduction of the acute irritation on guinea pig ^eye ·

Haltbarkaitsprüfung

Methodology:

Samples of drug combinations according to Examples 1 to k were stored for 12 months in polyethylene bottles at room temperature. The content of hydrogen peroxide was determined iodometrically according to DAB7-DDR.

238130

Results of the Haltbarksits investigations

Combination of the Η _Λ Ο content decreases

Months based on initial salary

do example 1 8.8 %

according to Example 2 7.8 %

according to Example 3 1.8 %

fiacfa Example 4 10 %

Claims (4)

Invention claim 1 · Active ingredient combinations for disinfection, characterized by a content of ethanol and / or propan-2-ol and / or propane-1-ol, hydrogen peroxide, surface-active substance and higher saturated aliphatic alcohols 2 · Active ingredient combinations according to item 1, characterized by a content of ethanol and / or propan-2-ol and / or propan-1-ol between kO and 80 Gew. ~ $, 0.5 to 10 GewJ & hydrogen peroxide, 0 5 to 5 weight "-% surfactant, 0.5 to 2 wt .- $ saturated aliphatic alcohol in the carbon number range of C _Q to C ^ and supplemented with water to 100 wt .- ^, based on the total active ingredient combination and calculated as anhydrous substances · 3 · Active substance combinations according to points 1 and 2, characterized in that alkyldimethylbenzylammonium chloride is used as the surfactant. 4 · active substance combinations according to the points 1 and Z ₉ characterized in that as surfactant Alkaneulfonate _t Alkylarylsulfcnate, alkyl sulfates or Etheraulfate used ·