DE2110602C3 - Process for the production of ampholytic compounds, their use as antimicrobial surface-active substances and washing, cleaning and disinfecting agents containing them Hoechst AG, 6000 Frankfurt - Google Patents

Description

in which R ^{1 is} an alkyl or alkenyl radical having 8 to 18 carbon atoms, R ² and R ^{3 are} hydrogen or the radical of the formula II

CH-COOY

CH ₁ -CONH,

(U)

where at least one of the radicals R ² or R ^{j is} a radical of the formula 11 and Y 2c is hydrogen or an alkali metal ion and ν is 2 or 3, characterized in that an N-alkyl- or an N-alkenyl-alkylenediamine is used of the general formula III

R ¹ - NH- (CH ₂ I ₁ NH ₂

(111)

in which R ¹ and ν have the meanings mentioned, is reacted in an aqueous or aqueous-alcoholic phase with maleic acid half-amide or its salts in a manner known per se.

2. The method according to claim 1, characterized in that that the N-alkyl- or N-alkenyl-alky'.enediamine of the general formula Hl with the • \ mmonium salt of maleic acid half-amide. _v;

3. Use of the compounds prepared according to claim 1 as antimicrobial surface-active Substances.

4. Detergents, cleaning agents and disinfectants, characterized by a content of after Claim 1 produced compounds.

5. Washing, cleaning and disinfecting agent! according to claim 4. characterized in that you Content of compounds of the general formula (1) is 0.1 to 10 percent by weight. 4s

The present invention relates to the subject matter specified in the claims. The one according to claim Compounds produced in 1 retain their antimicrobial activity, i. H. their effectiveness towards mushrooms, ray mushrooms. Bacteria and viruses even in the presence of surface-active cleaning agents.

The known surface-active compounds. which have good cleaning properties usually have no antimicrobial effect. On the other hand, certain agents have cationic activity. such as, for example, quaternary ammonium compounds, which are effective against certain types of bacteria, only idle cleaning processes. Bacteria and fungus can be combated at the same time as cleaning, so far two separate treatments have generally been necessary, namely normal washing and then separate treatment of the washed goods with an antimicrobial agent in a suitable physical form. z. B. as a solution or dispersion.

In many cases it would be more practical and effective if the cleaning agent and the antimicrobial agent could be used simultaneously or if both effects were combined in a single preparation. Such attempts have already been made, but they did not lead to satisfactory results (cf. KH W a 11 hä u -ser, H. Schmidt, Sterilization, Disinfection, Conservation, Chemotherapy, 1967, pages 233-234).

One reason for the previous failures can be seen, among other things, in a disruptive interaction that occurs between most of the antimicrobial agents on the one hand and the soap or the synthetic detergent raw material on the other. This incompatibility shows up either in a reduced detergency of the surface-active agent or in the partial or complete ineffectiveness of the antimicrobial agent or in both aspects.

Striking examples of such mutual interference are preparations containing anionic detergent surfactants, including soaps and non -soap compounds, as well as heretofore known antimicrobial agents. In these cases , the cleaning effect of the anionic cleaning agent is generally less good than when it is used alone, and the effect of the antimicrobial agent is also significantly less than when it is used alone. A similar interaction also occurs with preparations that are non-ionic. contain cationic and amphoteric surfactants .

Recently, some antimicrobial agents compatible with certain detergents have become available, such as: B. bromosalicylanilide and carbanilide, soaps and synthetic detergents have an inhibiting or killing effect against gram-positive bacteria such as Staphylococcus aureus. Bact. ammoniagenes. Lactobacillus casei give. However, it lacks still appropriate means that are compatible with soap and cleaning products and give them a significant effect even against resistant Gram-negative bacteria such as Escherichia coli, Proteus mirabilis, Pscudomonas aeruginosa and against fungi such as Candida albic.ms.

To date, it is not possible to predict how a given antimicrobial agent will appear in a detergent preparation will behave. Some of the numerous unknowns that influence the behavior of the Means can have, inter alia. the complex nature of the detergent preparation itself, the existing one Dirt, the diversity of the tissues, and the different ionogenicity of the connections.

Suitable antimicrobial agents are particularly suitable for use in detergent preparations wanted to be used for washing clothes. Here, it is desirable that after washing a certain amount of the disinfectant remains as a residue on the fabric, so that a longer lasting effect is achieved. Antibacterial agents are therefore desirable when washing laundry, that can be used in a washing solution that remain on the tissue and multiply prevent bacteria and / or fungi and the development of body odor on the tissue. One such laundering treatment is particularly advantageous for undergarments, especially when the adherent antimicrobial agent 'also against gram-negative bacteria

rien is effective. Antibacterial agents compatible with soaps and synthetic detergents also find use in the field of deodorant and cosmetic soaps. Here, it is desirable that the active compound has adhesiveness to human skin so that a residue of the agent remains on the skin after a washing treatment and can serve to inhibit the bacterial flora which decomposes sweat with the simultaneous generation of odor.

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

ι

N- (CH ₂ I _x -NH

! ι

I j

R ² R- '

(D

in which R ^{1 is} an alkyl or alkenyl radical mi! 8 to 18 carbon atoms, one of the radicals R- and R * is the remainder of the formula II

CH-COOY

CH-, ■ - CONH,

111)

and the other of the radicals R ² and R ³ also denotes the radical of the formula U or hydrogen and Y denotes hydrogen or an alkali metal ion and ν denotes 2 or 3, excellent antimicrobially active surface-active substances are which their antimicrobial vj effectiveness even in the presence of other surface-active detergents and cleaning agents.

The lipophilic group R ^{1 of} the new ampholytes is saturated or unsaturated, straight-chain 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 or N-alkynylalkylenediamines of the general formula -to

R ¹ -NH- (CH ₂ ), - NH ₂

in which R ¹ and ν have the meanings given above, with maleic acid albamide. The reaction is carried out in the aqueous or aqueous-alcoholic phase, expediently at elevated temperature in order to accelerate the reaction for 4s. The salts, especially the alkali or ammonium salts, of maleic acid half-amide can also be used for the reaction. be used. The reaction is preferably carried out with the ammonium salt 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 ss potassium salt dos maleic acid half-amides are formed in the reaction with the diamine, the compounds of general formula I in the form of the corresponding alkali metal / e. which, if desired, can be converted into the inner salts by the S.uire / ugaruhis / um pli value of the isoelectric punkws.

A particular advantage of the ampholus according to the present invention is that it retains its antimicrobial active wedge even in the presence of anionic, cationic and non-ionic surface-active substances and also in the presence of organic and inorganic odorous substances. The Ampholite can be added to detergents and cleaning agents as well as fabric softeners or used together with them.

Surface-active substances and also builders that are used for the production of detergents and cleaning agents and that are used together with the new ampholytes according to the invention can be used, are, for. ß. listed in Schwarz, Perry, Berch, "Surface-active agents and detergents". Volume Il (1958), pages 25-138 and 288-317. The detergents and cleaning agents can also contain optical brighteners, perborates and Contain enzymes without impairing the antimicrobial effect of the ampholytes. Also by other conventional additives and diluents such as perfumes, dyes, fluorescent agents, foam promoting and foam inhibiting agents and auxiliaries the advantageous effect of the ampholytes according to the invention is not diminished against sedimentation

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 depends primarily on the desired antimicrobial effectiveness of the detergent or cleaning agent. The quantities used are generally 0.1-10 %, based on the weight of the detergent and cleaning agent or fabric softener. The preferred concentration range of the amnholytes is, however, between 0.5 and ^r i percent by weight, based on the weight of the detergent or cleaning agent. For the upper limit of the amount of ampholytes according to the invention used, economic considerations and, if appropriate, also oil solubility properties are decisive. As expected, an increase in the application concentration increases the antimicrobial effectiveness of the detergent and cleaning agent.

The ampholytes according to the invention can be used in soaps. Washing or cleaning preparations after one Any method can be incorporated, provided that it is evenly distributed throughout the mass is ensured. This shows a good compatibility of the ampholytes according to the invention with the the above-mentioned soaps and non-soap detergents and cleaning agents in the form of bars, Liquids, flakes. Granules and the like by the ampholyte is also under the influence of sunlight no discoloration of the soaps. Detergent or cleaning agent causes. The ampholytes of the invention are the well-known antimicrobial additives based on bisphenolic compounds think.

Another surprising advantage in using the ampholytes according to the invention is also. that they are used when washing or rinsing textiles /. B. containing wool or cotton with ampholytes Laundry detergents or dishwashing detergents noun to the Pull up textiles. This gives the textiles an amimicrobial protection that lasts for a long time remains echoed.

To test the antimicrobial effectiveness aul Textile goods are served by üewebeschut / versurh. This essentially consists in the fact that one First wash the samples with a normal wash liquor; and then in an aqueous solution with a

Fabric softener, which contains the antimicrobial agents, after treatment, dries the samples and puts them on nutrient agar. to which the bacteria used for the test are added. After a short time, the material samples are removed again and the agar plates are ^{incubated at 37 °} C. for 24 hours. With antibacterial effectiveness, no bacterial growth is found on the contact surfaces or in their vicinity.

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

The following examples serve to explain the present invention without affecting it Examples limited. The quantitative data mean. : s unless expressly stated otherwise, Parts by weight and the percentages are percentages by weight.

B is ρ ie 1 1 ^ ₀

A) Internal salts:

A solution of 52.8 Gewichlsteilen the ammonium salt of monomaleamide (prepared from maleic anhydride and gaseous ammonia in chloroform) in 200 parts by weight of water with 53 parts by weight coconut fatty propylenediamine (having a basic nitrogen content of 10.6%) of 2 ¹ /: for long hours 92 ° C stirred. Ammonia is evolved during the conversion. The liquid is concentrated under reduced pressure (rotary evaporator) by distilling off water. The pasty residue is dried in a vacuum cabinet at a temperature of approx. 50 ° C. The compound mixture A) is obtained in a yield of 108 g

R ¹ - N CH ₂ - CH, - CH ₂ - NH

A) CH COOH CH - COOH

I I

CH ₂ -CONH, CH ₂ -CONH ₂ > o

R ¹ - C ₈ to Cie-alkyl radical corresponding to the chain distribution of the coconut fatty acid (7% C ₈ , 6% C, _o , 51% C _{] 2,} 19% Ci _4, 8% C ₁₆ and 9% C ₁₈ ).

as a yellowish solid substance that turns into a fine Powder can be ground.

The acid number is 230 (calc. 227) and the basic nitrogen content is 6.1% (calc. 5.66%).

The pH of the 1% pure solution in water is at 5.5 (poientiomeinsch). <«>

Sodium Salts:

Will be in the implementation with otherwise the same Working method instead of 52.8 weights Ammotiiumsalzes von Maleinsüurehalbamid ~> 4.7 Gewichixleile des Natnumsal / es des Malemsa.iiehalb- (^ amides are used, the above-mentioned compound mixture () is not obtained in the form of the internal S.il/e but as N a ι; iii: nsal / e

B) A mixture of 132 parts by weight of the ammonium salt of maleic acid half-amide. 274 parts by weight of coconut fat propylenediamine (with a content of basic nitrogen of 10.2%) and 500 parts by weight of water at 83 ° C. for 3 hours touched. The solution, which can be diluted with water, is concentrated in vacuo and the residue then dried in a vacuum cabinet at 50-60 ° C. The yellowish obtained in a yield of 389 g Solid substance (B) consisting of a mixture of the compounds of the general formulas

R ¹ - NHCH ₂ -CH, -CH ₂ -NH-CH-COOH

CH ₂ CONH ₂
and

R '- N - CH, - CH ₂ -CH, NH-CH -COOH
CH ₂ -CONH,

(Ri ₌ C ₈ to Cix-alkyl radical according to the press grant of coconut fatty acid)

considered, whereby the proportion of Bi predominates, is in water brightly soluble.

C) 132 parts by weight of the ammonium salt of maleic acid half-amide in 1000 parts by weight of water and 381 parts by weight of N-tallow fatty propylenediamine (m, i a basic nitrogen content of 7.3%) are 31/2 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 are and can be used as such, or they can be converted into powder form by drying. The light yellow product (C) obtained in a yield of 496 g, which is a mixture of the compounds of the general Formulas

R ¹ NHCH ₂ -CH ₂ -CH ₂ -NH-Ch COOH

CH, - CONH, and

R ¹ - N -CH, - CH, -CH ₂ NlL

CH COOH

CKL (ONlL

(Ri = Cu to de-Kohfenwasserstoffrest corresponding to the chain distribution of the tallow fatty acid, 1% Ci;, 3 ° <i> C ₁ , 31% C, 35% Ci, and 30% C ₁₈ unsaturated),
with a predominant proportion of Ci, has a basic nitrogen content of 5.7% (calc. 5.64%) and an acidity of 111/112 (calc. 113).

D) In the reaction, with otherwise the same procedure, instead of 381 parts by weight of tallow fatty tiropylenediamine, 172 parts by weight of N- (n-octyl) -ethyleneamine can be used, a yellowish product (D) being obtained in a yield of 287 g , which is a mixture of compounds of the formulas

CH, (CH ₂ ) - NH-CH, CH ₂ NH CIl COOH

i \\ _z CONH ₂
and

CH, (CH,) -

CH CC) OH
CH ₂ CONH,

with a predominant proportion of Di represents.

Show the good surfactant properties of ampholytes according to the present invention to the investigations made with the product A as an example of these compounds, their Results are summarized in Table I.

The antimicrobial effectiveness of the ampholytes according to the invention is surprisingly diverse. The ampholytes are bacteriostatically and bactericidally effective against gram-positive and gram-negative organisms. However, they are also fungistatically effective. The good bacteriostatic and fungistatic activity of the ampholytes according to the invention is demonstrated on the basis of the data compiled in Table II. The results of these investigations show the surprisingly broad spectrum of antimicrobial activity of the ampholytes according to the invention in comparison with typical, known surface-active ampholytes 1 and 11 (cf. H. Schmidt. KHWallhäuser. Sterilization, Disinfection. Preservation. Chemotherapy. Stuttgart [1967]. Pages 234-236 ).

Comparative product 1 :

CH,
R - CONH - CH ₂ - CH ₂ - N - CH ₂ - COOH

CH ₃

R = C ₈ to Ci8-alkyl radical corresponding to the chain distribution of the coconut fatty acid

Table 11 Minimal inhibitory concentration

Comparative product II:
(H,
KN CH

cn,

COOH

R = Cx to C'iK-alkyl radical corresponding to the Keuenverleilung the coconut maker

Table 1

Application properties of the product A

concentration I'onipc- Newed r.; Ic! I i ei t Ii r DlN -33 901 (Sec.) 1 g / l in water of 50 C 85 O dH 1 g / l in water of 7OC 38 0 ^: dH concentration Tempe Schaimiuene after rature DIN 53 902 (cm foam) (5 min. Hitting) 1 g / l in water of 40 C 240 O dH concentration Tempe Cotton laundry in rature Laundcrometer (% Brightening) Test fabric with Standard soiling (WFK) lg / 1 + 2 g / l 80 ° C 63 Sodium tripoly phosphate in what ser from O dH concentration Temperature Delicates for wool in ratu- Launderometer (% Brightening) Test fabric with .Standard soiling (WFK) lg / 1 + 2 g / l 2O ⁰ C 79 Sodium tripoly phosphate in what water of 15 ° dH

Type of germ Strept faecium E.COÜ Proteus Pseudom. Cand. albican: Staph. aureus MD8b 055 mirabilis aeruginosa SG 54 40 - // ml 80 y / ml 5 mg / ml 80 y / ml 60 y / ml Product A. 32 y / ml 63 y / ml 42 y / mi 5 mg / ml 32 y / ml 63 y / ml Product B 10 y / ml 12.5 y / ml 12.5 y / ml > 10 mg / ml 62.5 y / ml - Product C 12.5 - // ml - ineffective ineffective ineffective 65 y / ml Comparison 1 160y / m1 - 10 mg / ml 10 mg / ml ineffective 65 y / ml Comparison 11 80 v / ml 709 624/141

ίο

Table 111 concentration !:. coil 055 Proteus mirub. Ps. Aeruginosa Cand. albicans Bactericidal Kcimari 350 y / ml
IbO y / ml > 10 mg / ml
5 mg / ml 1.25 mg / ml
350 y / ml 1.25 mg / ml
625 y / ml Staph. aiirous ineffective
ineffective ineffective
ineffective ineffective
ineffective ineffective
ineffective j50 y / ml
J50 y / ml ineffective
ineffective ineffective
ineffective ineffective
Ib mg / ml 1.25 mg / ml
350 y / ml Product A.
5 '
15 ' ineffective
ineffective Comparison I.
5
15 ' 15b y / ml
1 5b y / ml Comparison Il
5 '
15 '

The test results were obtained from a Serial dilution test received based on the "Guidelines for Testing Chemical Disinfectants" (Gustav Fischer-Verlag. Stuttgart [1969]). published by the German Society for Hygiene and Microbiology.

The minimum inhibitory concentration (MIC) is determined in these examinations. This is the minimum concentration found in the serial dilution test in weight units per cubic centimeter of test solution of a ¹ "antimicrobial substance, in which no growth of the organisms tested can be detected any more.

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

Example 2

A synthetic heavy duty detergent with a granular structure consists of the following components:

8.00% secondary alkanesulfonate sodium (average 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 The remainder to 100 percent by weight water

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 was added.

In solutions of 0.3 g per liter of the pure detergent mixture (without the disinfecting component), the minimum inhibitory concentration of the ampholyte according to the invention was determined by the method specified above and compared with the MH K values measured for the detergent alone. It was found that the heavy duty detergent practically did not impair the antimicrobial effectiveness of Amphoiyts product A. The results of the - <> investigations are summarized in Table IV.

Table IV

Minimum inhibitory concentration (y / ml) in the presence of heavy duty detergents

Kciinan

Product α detergent
alone alone

Product A in detergent solution of 03 g / l

St. faecalis
MD8b
E. coli 055

78.2
15b

1250
1250

156 313

The same tests were carried out with coarse detergents of the above composition , which, however, instead of 8.0% de; secondary alkanesulfonate sodium

a) 8.00% of a mixture of equal parts of sodium salts of a prior vOlefinsulfonats 15 to IS carbon atoms and the secondary Alkansul Fonats and

b) 8.00% sodium dodecylbenzenesulfonate
contains.

In both cases there was no impairment antimicrobial effectiveness of the inventive egg Ampholytes detected by the detergent.

Example 3

A mild detergent consists of the following components:

10.00% of an adduct of 8 moles of ethy

lenoxide to 1 mole of coconut fatty alcohol 10.00% of an adduct of 5 moles of ethy

lenoxide to 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

The wash is given an antimicrobial setting center! an addition of an amphoiyts according to the invention to be measured according to the desired effectiveness z. B. Product A.

In the same way as in Example 2, in solution « of 5 g per liter of the pure mild detergent dii

Ha ^ P

minimum inhibitory concentration for the * product A determined and the values for the detergent alone and for product A alone. The values obtained are summarized in Table V.

Tubelle V

Minimum inhibitory concentration () '/ ml)

Kcimart

Product A.

Mild detergent

Product A in mild detergent solution
of 5 g / l

St. faecalis 78.2 5000 19.6 MD8b E. coli 055 156 ineffective 313

The results show that the addition of an ampholyte according to the invention produces an excellent The anti-microbial effectiveness of the mild detergent is maintained, with the effect of the ampholyte opposite Str. Faecalis MD 8 b is increased by the ingredients of the mild detergent.

Example 4

A fabric softener has the following composition:

Distearyl dimethyl ammonium chloride

of an adduct of 12 moles of ethylene oxide and 1 mole of oleyl alcohol

optical brightening agents

Perfume oil

0.05%

The rest is 100% water

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

In the same way as in Example 3 was in solutions 0.3 g per liter of the pure fabric softener is the minimum inhibitory concentration of the invention Ampholytes determined and with the values for the fabric softener alone and the ampholyte alone compared. The results are given in Table VI. They show that the anti-microbial effectiveness the components of the fabric softener are not impaired.

Table Vl

Minimum inhibitory concentration () '/ ml)

Keimari

Product A fabric softener alone

Product A in fabric softener solution of 0.3 g / l

St. faecalis 80
MD8b

1250

156

Example 5 It becomes a liquid foot wash with the following

Composition made;

30.0% of an addition test for 10 moles of ethylene oxide to 1 mole of coconut fatty alcohol

0.2% perfume and dyes

1.0% of product A
The rest is 100% water

Due to the fungicidal effectiveness of the ampholyte, the foot wash shows excellent results Effect against athlete's foot. The antimicrobial effect of the ampholyte is due to the other components of the foot wash is not affected.

Example 6

A mild detergent that contains a compound mixture according to the invention as a detergent and antimicrobial Contains substance has the following composition:

12% Product A. 8th% an addition compound of 8 moles of ethy lenoxide to 1 mole of coconut fatty alcohol 40% Sodium tripolyphosphate 5% Sodium silicate 10% Calcined soda 2% Carboxymethyl cellulose 23% Sodium sulfate

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

Claims (1)

'i "C claims: 1. Process for the preparation of compounds of the general formula I. R ¹ -Ν - (CH,), - NH j! R ² R- ' (I)