DE2110602A1 - Antimicrobial surfactants - Google Patents

Description

FARBWERKE HOECHST AG formerly Master Lucius Ss Brüning File number: HOE 71 / FO72

Date: Dr.Gr/dor

Antimicrobial surfactants

The present invention relates to antimicrobially active compounds with surface-active properties. These connections retain their antimicrobial effectiveness, d. H. their effectiveness against fungi, radiation fungi, bacteria and viruses even in the presence of detergent surfactants.

The well-known surface-active compounds that have good cleaning properties usually have no antimicrobial effect. On the other hand, have certain cation-active Means such as B. quaternary ammonium compounds, which are effective against certain types of bacteria, only moderate cleaning -. properties. Should cleaning be carried out at the same time

Fighting bacteria and fungi can be achieved so far generally two separate treatments are necessary, namely a normal wash and then a separate treatment the washed goods with an antimicrobial agent in a suitable physical form, e.g. B. as a solution or dispersion.

In many cases it would be more practical and effective if the detergent and the antimicrobial agent were used at the same time Could be used only, or both effects, as the case may be would be combined in a single preparation. Such attempts have already been made, but they did not lead to satisfactory results.

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One of the reasons for the previous failures is in to see a disturbing interaction between most of the antimicrobial agents on the one hand and the Soap or the synthetic detergent raw material on the other hand occurs. This incompatibility shows up in either one decreased detergency of the surfactant or the partial or total ineffectiveness of the antimicrobial By means of or in both aspects.

Striking examples of such mutual interference are preparations containing anionic detergent surfactants including soaps and non-soap compounds as well contain previously known antimicrobial agents. In these cases, the cleaning effect is usually the anionic Detergent is less good than using the same alone and also the effect of the antimicrobial agent is much less than when used on its own. A similar interaction also occurs with preparations that contain nonionic, cationic and amphoteric surfactants.

Recently, some are compatible with certain cleaning agents antimicrobial agents available such as B. bromosalicylanilide and carbanilide, the soaps and synthetic detergents an inhibiting or killing effect against gram-positive bacteria such as Staphylococcus aureus, Bact. Ammoniagenes, Lactobacillus casei, etc. On the other hand, there is still a lack of suitable agents that are compatible with soap and cleaning agents and they have a noteworthy effect against resistant gram-negative bacteria such as Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and against fungi such as Candida albicans etc. confer.

209840 / 11S9

To this day it is not possible to predict how a given antimicrobial agent in a detergent preparation will. Some of the numerous unknowns that can have an influence on the behavior of the agent include the complex nature of the detergent preparation itself, the existing one Dirt, the diversity of the tissues and the different ionogenicity of the compounds.

Suitable antimicrobial agents are particularly sought for use in detergent preparations which are to be used for washing laundry. It is desirable here that a certain residue of the disinfectant remains on the fabric after washing, so that a longer-lasting effect is achieved. It is thus desirable in laundry washing antibacterial agents that can be used in a washing solution that remain on the fabric and prevent the growth of bacteria and / or fungi and the development of body odor on the fabric. Such a washing treatment is particularly advantageous for underwear, especially when the adherent antimicrobial agent is also effective against gram-negative bacteria. Antibacterial agents compatible with soaps and synthetic detergents also find use in the field of deodorant and cosmetic soaps. Here, it is desired that the active compound ä adhesiveness has on human skin, so that a residue of the agent according to a washing treatment on the skin and can serve to inhibit the bacterial flora, which decomposes the welding with simultaneous formation of odor.

It has now been found that ampholytes of the general formula I

R ₁ -N- (CH ₉ ) ,, - NH I),

X ₁ <5 X,

^R 2 ^R 3

in which R- is an alkyl or alkenyl radical having 8 to 18 carbon atoms, one of the radicals R ₀ and R is the radical of the formula II

209840/1159

_ 4 - i

-CH-CO ₂ Y CH _n - CONH

and the other of the radicals R ₁ and R 3 also denote the radical of the formula II or hydrogen and Y denotes hydrogen or an alkali metal ion and χ denotes 2 or 3, excellent antimicrobially active surface-active substances which also demonstrate their antimicrobial effectiveness in the presence of others Keep surfactant detergents and cleaning agents.

As a lipophilic group IL. the new ampholytes come saturated or branched aliphatic hydrocarbon radicals which have 8 to 18, preferably 12 to 18, carbon atoms.

The ampholytes according to the invention can be prepared by reacting an N-alkyl-alkylenediamine of the formula

R ₁ - NH (CH ₂ ) _x NH ₂ ,

in which R- and χ have the abovementioned meaning, with maleic acid half-amide. The reaction is carried out in the aqueous or aqueous alcoholic phase; Temperature. The salts, especially the alkali or ammonium salts of maleic acid half-amide can be used. The reaction with the ammonium salt is preferably carried out of maleic acid half-amide, since this is more easily accessible and since ammonia is released when it is converted and. the ampholytic compound is obtained directly in the form of the inner salt. When using alkali salts, e.g. B. the sodium or The potassium salt of maleic acid half-amide results in the reaction with the diamine, the compounds of the formula I in the form of the corresponding ones Alkali salts which, if desired, can be added to the isoelectrolytic point by adding acid allow internal salts to transfer.

2098A0 / 1 1 59

A particular advantage of the ampholytes according to the present invention Invention is that they maintain their antimicrobial effectiveness even in the presence of anionic, cationic and nonionic surface-active substances and also in the presence of organic and inorganic builders are retained. The ampholytes of the invention. can sorait washing and Cleaning agents, as well as fabric softeners, can be added or used together with them.

Surface-active substances, as well as builders like them

for the manufacture of detergents and cleaning agents Use J

find and how they can be used together with the new ampholytes according to the invention are, for. B. listed in Schwarz, Perry, Berch, "Surface-aetiν agents and detergents", Volume II (1958), pages 25-138 and 288-317. The detergents and cleaning agents can also have optical brightening agents, Contain perborates and enzymes without impairing the antimicrobial effect of the ampholytes. Also through others Usual additives and diluents such as perfumes, dyes, fluorescent agents, foam promoting and foam inhibiting agents, as well as aids against settling, the advantageous effect of the ampholytes according to the invention is not reduced.

As a result of the high effectiveness of the ampholytes according to the invention the use of small amounts is sufficient to give the detergents and cleaning agents an antimicrobial effect. The amount of ampholytes to be added to the detergents or cleaning agents can vary within wide limits. The amount used is directed especially according to the desired antimicrobial effectiveness of the detergent or cleaning agent. The amounts used are generally 0.1-10%, based on weight detergent and cleaning agent or fabric softener. However, P is the preferred concentration range of the ampholytes zv / ischen 0.5 and 5 percent by weight, based on the detergent or cleaning agent. For the upper limit of the amount used

209840/1169

Ampholytes according to the invention are mainly economic considerations, as well as possibly also solubility properties authoritative. As expected, an increase in the application concentration increases the antimicrobial effectiveness of the detergent and Detergent,. '",

The ampholytes according to the invention can be incorporated into the soaps, washing or cleaning preparations by any desired method as long as an even distribution in the entire mass is ensured. This shows a good one Compatibility of the ampholytes according to the invention with the above specified soaps and non-soapy washing uride Detergents in the form of bars, liquids, flakes, granules and the like. The ampholyte is also under the influence of sunlight does not cause any discolouration of the soaps, detergents or cleaning agents. The invention Ampholytes are superior to the known antimicrobial additives based on bisphenolic compounds.

Another surprising advantage of using the ampholyte according to the invention is also that when washing or rinsing textiles from z. B. wool or cotton with ampholytes containing detergents or dishwashing detergents apply noun to the textiles. This gives the textiles a antimicrobial protection that lasts for a long time.

The fabric protection test is used to test the antimicrobial effectiveness on the textile goods. This essentially consists in that you wash samples first with a normal washing liquor and then in an aqueous solution with a fabric softener, that contains the antimicrobial agents, is treated, the samples are dried and placed on nutrient agar, the the bacteria used for the test are added. After a short time, the fabric samples are removed again and incubate the agar plates for 24 hours at 37 ° C. In the case of antibacterial effectiveness, the contact surfaces and in

whose surroundings no bacterial growth was found.

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The ampholytes according to the invention have such a broad spectrum of activity, that they z. B. can be used as a disinfectant, especially for medical and hygienic purposes can. Of particular interest is their use in soaps and detergents, such as. B. heavy duty detergents, mild detergents and fabric softeners, since their antibacterial effectiveness is retained in the presence of such agents. This favorable behavior of the ampholytes according to the invention thus enables the detergent, cleaning agent or detergent and to combine the antimicrobial agent in one preparation.

The following examples serve to explain the present invention without it being restricted to the examples. Unless expressly stated otherwise, the quantitative data are parts by weight and the percentages are percentages by weight .

example 1

A solution of 52.8 parts by weight of the ammonium salt of Maleic acid half-amide (made from maleic anhydride and gaseous ammonia in chloroform) in 200 parts by weight of water with 53 parts by weight of coconut oil propylene dxamine (with a " Basic nitrogen content of 10.6%) stirred at 92 ° C for 2 1/2 hours. Ammonia is evolved during the conversion. The liquid is under reduced pressure (rotary evaporator) concentrated by distilling off water. The pasty residue is stored in a vacuum cabinet at a temperature of approx. 50 ° C dried. You get the connection

R ₁ -N-CH ₂ -CH ₂ -CH ₂ -NH

CH-CO ₂ H CH-CO ₂ HA) CH ₂ -CONH ₂ CH ₂ -CONH ₂

R ₁ = Cg- ^ jg-alkyl radical corresponding to the chain distribution of the coconut fatty acid.

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as a yellowish solid substance that turns into a fine powder

lets marry.

The acid number is 230 (calc. 227) and the basic content

Nitrogen 6.1 % (calc. 5.66%).

The pH of the 1% pure solution in water is 5.5

(potentiometric).

Are in the implementation with otherwise the same procedure instead of 52.8 parts by weight of the ammonium salt of maleic acid half-amide 54.7 parts by weight of the sodium salt of maleic acid half-amide are used, the abovementioned compound A) is not obtained in Form of the inner salt but as the sodium salt.

A mixture of 132 parts by weight of the ammonium salt of maleic acid half-amide, 274 parts by weight of coconut fatty propylenediamine with a basic nitrogen content of 10.2% and 500 parts by weight of water is stirred at 83 ° C. for 3 hours. The blank water-dilutable solution is concentrated in vacuo and then in a vacuum oven at 50 - 60 ⁰ C dried. The yellowish solid substance (B), which consists of a mixture of the compounds of the formulas

^B l ^B 2

R ₁ -NHCH ₂ -CH ₂ -CH ₂ -NH-Ch-CO ₂ H and R 1 -N-CHg-CHg-CHg-NHg

CH ₂ CONH ₂ CH-CO ₂ H

CH ₂ -CONH ₂

(R ₁ - Cg-C ₁ g-AlkyIrest corresponding to the chain distribution of the coconut fatty acid)

exists, whereby the proportion of B predominates, is completely soluble in water.

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132 parts by weight of the ammonium salt of maleic acid half-amide in 100 parts by weight of water and 381 parts by weight of N-tallow fat propylenediamine with a basic nitrogen content of 7.3% are 3 1/2 hours at a temperature of 86 - 88 ° C touched. The alkaline reaction solution can be adjusted to a pH of 6.5 - 7.5 with acetic acid and is as these can be used, or they can be converted into powder form by drying. The light yellow product (C), which is a mixture of the Connections of the formulas

^C l ^C 2

R ₁ -NHCH ₀ -CH ₀ -Ch ₀ -NH-CH-CO ₀ H and R ₁ -N-CH ₀ -CH ₀ -CH ₀ -NH ₀

CH ₂ -CONH ₂ CH-CO ₂ H

CH ₂ -CONH ₂

(R ₁ = C ^ -Co hydrocarbon radical according to the chain distribution of the tallow fatty acid)

with a predominant proportion of C- represents, has a basic one Nitrogen of 5.7% (calc. 5.64%) and an acid number of 111/112 (calc. 113).

In the reaction, with otherwise the same procedure, 172 parts by weight of N-n-octyl-ethylenediamine can also be used instead of 381 parts by weight of tallow fat propylenediamine, a yellowish one Product (D) is obtained, which is a mixture of compounds of the formulas

D "D,

CH ₃ - (CH ₂ ) ₇ -NH-CH ₂ -CH ₂ -NH-CH-CO ₂ H and CH ₃ -

CH ₂ -CONH ₂ CH-CO ₂ H

CH ₂ -CONH ₂

with a predominant proportion of D ₁ represents.

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-ίο -

The good surface-active properties of ampholytes according to the present invention are shown by those made with the product A as an example of these compounds Investigations, the results of which are summarized in Table I.

The antimicrobial effectiveness of the ampholytes according to the invention is surprisingly diverse. The ampholytes are bacteriostatic and bactericidally effective against gram-positive and gram-negative organisms. However, they are beyond that also fungistatically effective. The good bacteriostatic and fungistatic effectiveness of the ampholytes according to the invention is demonstrated using the data summarized in Table II. The results of these investigations show that surprisingly broad antimicrobial spectrum of activity of the invention Ampholytes compared to typical, known surface-active ampholytes I and II (see Dr.K.H. Wallhäusser, "Sterilization, Disinfection, Conservation, Chemotherapy", Stuttgart (1967), pages 234-236).

Comparison I:

CH ₃

R-CONH-CH ₂ -CH ₂ -N-CH ₂ -Co ₂ H

R = C ₀ -C _1O alkyl radical corresponding to the chain

O J-O

distribution of coconut fatty acid

Comparison II:

RN-CH _o tC0 _o H

R = Cq-C _1Q alkyl radical corresponding to the chain

o JLo

distribution of coconut fatty acid

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- Il -

Table I.

Application properties of the product A

concentration

1 g / l in water of 0 ° dH

1 g / l in water of 0 ° dH

Temperature network values according to DIN 53901 / 3ek _# 7

50 ° C

7O ° C

85 38

Foam values according to DIN 53902 j | / cm foam7 (5 min. whipping)

1 g / l in water of 0 ° dH

40 ° C

240

Cotton laundry in the launderometer lightening £ 7

Test fabric with standard soiling (WFK)

1 g / l + 2 g / l sodium tripolyphosphate in water at 0 ° dH

80 ° C

63

Delicates for wool in the launderometer lightening £ 7

Test fabric with standard soiling (WFK)

1 g / l + 2 g / l sodium tripolyphosphate in water of 15 dH

20 ° C

79

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Table II

Minimal inhibitory concentration

- 12 -

Type of germ Staph. aureus Strept. faecium E. coli Proteus Pseudom. Cand. albicans SG 54 MD8b 055 mirabilis aeruginosa Product A. 32 jf / ml 40 tf / ml 80 tf / ml 5 mg / ml 80 tf / ml 60 vml Product B 10 χ / ml 63 ^ / ml 42 lbs / ml 5 mg / ml «32 jj / ml 63 xVml Product C 12.5 jr / ml 12.5 tf / ml 12.5 sVml > 10 mg / ml 62.5 / ml - Comparison I. 160 K / ml - ineffective ineffective ineffective 65 ^ / ml Comparison II
ro 80 y / ml 10 mg / ml 10 mg / ml ineffective 65 // ml

^ Table III

- Bactericidal concentration

_JKeimart Staph. aureus E. coli 055 Proteus mirab. Ps. Aerug inosa Cand. albicans cnProduct A ⁴⁰ 5 « 350 lbs / ml 350 X / ml > 10 mg / ml 1.25 mg / ml 1.25 mg / ml 15 ' 350 lbs / ml 160 lbs / ml 5 mg / ml 350 ^ / ml 625 tf / ml Comparison I. 5 ' ineffective ineffective ineffective ineffective ineffective 15 ' ineffective ineffective ineffective ineffective ineffective Comparison II 5 ' 156 tf / ml ineffective ineffective ineffective 1.25 mg / ml 15 ' 156 tf / ml ineffective ineffective 16 mg / ml 350 ^ / ml

The test results were obtained from a serial dilution test received, based on the "Guidelines for Testing of chemical disinfectants "(Gustav-Fischer-Verlag, Stuttgart (1969)), published by the German Society for hygiene and microbiology.

In these examinations, the minimum inhibitory concentration is used (MIC) determined. This is the one found in the dilution-only test Minimum concentration in weight unit per cubic centimeter of test solution of an antimicrobial substance for which no Growth of the organisms tested is more noticeable.

The bactericidal effect (bactericidal concentration) was tested in germ suspension experiments also checked according to the above guidelines. The results of these studies are shown in Table III contain.

Example 2

A synthetic coarse detergent with a granular builder substance be consists of the following components:

8.00 % secondary alkanesulfonate sodium (medium

Molecular weight 328), produced by sulfoxidation of η-paraffins with 13 to 18 carbon atoms

5.00% of an adduct of 15 moles of ethylene oxide with 1 mole of tallow fatty alcohol

3.00% sodium soap
37.00 % sodium tripolyphosphate 7.00% sodium metasilicate 3.00% magnesium silicate 4.00% carboxymethyl cellulose 0.30 % of an optical brightening agent

0.15% perfume oil
20.00% sodium perborate remainder to 100% by weight water

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This detergent mixture is used for the antimicrobial setting Depending on the desired effect, 0.01 or 0.1 percent by weight of product A is added.

The minimum inhibitory concentration was found in solutions of 0.3 g per liter of the pure detergent mixture (without the disinfecting component) of the ampholyte according to the invention determined by the method given above and with that for the detergent MIC values measured alone compared. It was found that the heavy duty detergent reduced the antimicrobial effectiveness of the ampholyte Product A practically not affected. The results of the tests are shown in Table IV.

Table IV

Minimum inhibitory concentration / Jf / n] in the presence of heavy duty detergents

Type of germ Product A.
alone laundry detergent
alone Product A in wash
medium solution from
0.3 g / l St. faecalis
E. coli 78.2.
156 1250
1250 156
313

The same tests were carried out with heavy duty detergents of the above Composition carried out, which, however, took place of 8.0% of the secondary alkanesulfonate sodium

a) 8.00% of a mixture of equal parts of sodium salts of an oL -olefin sulfonate with 15 to 18 carbon atoms and the secondary alkanesulfonate and

b) 8.00% sodium dodecylbenzenesulfonate contains.

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In either case, there was no antimicrobial impairment Effectiveness of the ampholytes according to the invention determined by the detergents.

Example 3

A mild detergent consists of the following components:

10.00 % of an adduct of 8 moles of ethylene oxide and 1 mole of coconut fatty alcohol

10.00 % of an adduct of 5 moles of ethylene oxide with 1 mole of isotridecyl alcohol

40.00 % sodium tripolyphosphate

5.00 % sodium silicate
10.00 % soda calcined

2.00 % carboxymethyl cellulose
The remainder is 100 % sodium sulfate

For the antimicrobial setting, the detergent is given an additive to be measured according to the desired effectiveness Ampholytes according to the invention, e.g. B. Product A.

In the same way as in Example 2 were in solutions of 5 g per liter of the pure mild detergent determined the minimum inhibitory concentration for product A and the values for the Detergent alone and for product A alone compared. The values obtained are summarized in Table V.

Table V Minimum inhibitory concentration / ~ Mild detergent i / ml / 5 mg / ml
ineffective Product A. Product A in fine
detergent solution
of 5 g / l Type of germ 78.2 ^ / ml
156 j (/ ml 19.6 / ml
313 % / ml St. faecalis
E. coli 055

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The results show that by adding an ampholyte according to the invention, an excellent antimicrobial effectiveness of the mild detergent is obtained, the effect of the Ampholyte is partially increased by the components of the mild detergent.

Example 4 :

A fabric softener has the following composition:

6.0 % distearyl dimethyl ammonium chloride

0.5 % of an adduct of 12 moles of ethylene oxide with 1 mole of oleyl alcohol

0.5 % optical brightening agent 0.05 % perfume oil
The rest is 100% water

By adding an ampholyte according to the invention, e.g. B. Product A, this fabric softener has an excellent antimicrobial effect.

In the same way as in Example 3, the minimum inhibitory concentration was found in solutions of 0.3 g per liter of the pure fabric softener of the ampholyte according to the invention determined and with the values for compared the fabric softener alone and the ampholyte alone. The results are given in Table VI. They show that the Antimicrobial effectiveness through the ingredients of the fabric softener is not affected.

Table VI

Minimal inhibitory concentration

Type of germ

Product A.

Fabric softener alone

Product A in fabric softener solution from 0.3 g / l

St. faecalis

80 ^ / ml

1.25 mg / ml

156

ΎΊΠΠΤ

"FF

Example 5

It becomes a liquid foot wash with the following composition manufactured:

30.0 % of an adduct of 10 moles of ethylene? oxide to 1 mole of coconut fatty alcohol

0.2% perfume and dyes 1.0 % of product A, the remainder being 100 % water

Due to the fungicidal effectiveness of the ampholyte, the foot wash shows an excellent effect against athlete's foot. The.antimicrobial The effect of the ampholyte is not impaired by the other components of the foot wash.

Example 6

A mild detergent which contains the compounds according to the invention as washing-active and antimicrobial substance has the following Composition on:

12% product A.

8 % of an addition compound of 8 moles of ethylene oxide and 1 mole of coconut fatty alcohol

40 % sodium tripolyphosphate

5% sodium silicate 10 % soda calcined

2% carboxymethyl cellulose 23% sodium sulfate

A detergent of this composition showed very good washing effects in wool, polyamide, polyester and other fibers and xa reduced the germ content of the washing liquor.

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Claims (4)

Claims; in which R _{1 is} an alkyl or alkenyl radical having 8-18 carbon atoms, R ₂ and Ro are hydrogen or the radical of the formula II - <r ^H - ^C0 2 ^Y id CH ₂ - CONH ₂ mean, with at least one of the radicals R "or R_ for the remainder of the formula II and Y is hydrogen or an alkali metal ion and χ is 2 or 3. 2) Use of compounds of the formula I. ^R 2 * 3 in which R _{1 is} an alkyl or alkenyl radical having 8-18 carbon atoms, _{R 1 and R 3 are} hydrogen or the radical of the formula II - CH - CO ₂ Y " _XI) CH ₂ - CONH ₂ where at least one of the radicals R ₂ or R _{3 is} the radical of the formula II and Y is hydrogen or an alkali metal ion and χ is 2 or 3, as antimicrobial surface-active agents. 209840/1159 ■ ■ HOE 71 / F 072 - new page 19 / _ _i9 _ _211fl6 3) Detergents, cleaning agents and disinfectants, marked by a content of compounds of the general formula I. R "- ^R 2 in which R- is an alkyl or alkenyl radical with 8-18 carbon atoms, R "and R_ hydrogen or the remainder of the formula II -CH-CO ₂ Y
CH ₂ - CONH ₂ where at least one of the radicals R _{1 or R 3 is} the radical of the formula II and Y is hydrogen or an alkali metal ion and χ is 2 or 3. 4) Yiasch, cleaning and disinfecting agents according to claim 3), characterized in that their proportion of compounds of the formula I is 0.1-10% by weight. 840/1159