Germicidal, disinfecting and antiseptic compositions containing certain alkoxy aliphatic amine compounds

A germicidal, disinfecting and antiseptic composition comprising alkoxy aliphatic amine derivatives of the formula (I) or (II) and an organic or inorganic compound capable of blocking metals. The composition can be used in germicides, disinfectants, cosmetics, domestic sundries and city water, and to remove the microbial pollution and other contamination problems in industrial processes.

The present invention relates to a non-medical germicidal, disinfecting and 
antiseptic composition which is extremely effective. More particularly, 
this invention relates to a germicidal, disinfecting and antiseptic 
composition comprising an alkoxy aliphatic amine derivative and an organic 
or inorganic compound capable of blocking metals wherein the activity of 
the alkoxy amines is greatly strengthened by the presence of the metal. 
The composition can be applied as a germicide, disinfectant, cosmetic, 
domestic sundry and to city water sources such as water reservoirs or 
circulating water. The composition can further be used to solve microbial 
pollution problems and other pollution problem industrial processes. 
Drugs for controlling or eradicating the reproduction of harmful 
microorganisms, particularly germicides, disinfectants and antiseptics 
which are used under usual environmental circumstances must be very safe 
to such higher level organisms as human beings. Further, such drugs should 
possess broad spectrum antibacterial characteristics and substantial 
potency at low concentrations, as well as being soluble in many compounds 
and complexes thereof and having excellent adaptability to systems to be 
sterilized, disinfected and preserved against decay. 
Typical germicides, disinfectants and antiseptics which are used in social 
environments include inorganic metal agents, organometal agents such as 
organic mercury agents and organotin agents, aromatic phenol derivatives 
represented by phenol, halogenated derivatives thereof and long-chain 
alkylammonium halides known as reversed soaps. 
These organic metal agents have possessed broad spectrum antibacterial 
characteristics and strong germicidal or bacteriostatic action. However, 
it is known from the organomercury agents that such compounds possess 
substantial toxicity to high level organisms, particularly to mammals and 
can be the source of severe disorders. Organic tin agents analogous to 
organic mercury agents pose many of the same problems and questions as the 
mercury compounds. Currently, because of their problems with the 
conventional organometal reagents, their use is being restricted or 
prohibited, and they have lost their superiority as drugs. 
Phenolic derivatives have been widely used as antibacterial substances, but 
they have, in general, narrow spectrum antibacterial properties and 
exhibit effects only at high concentrations. But at high concentrations 
these compounds are a source of irritability to higher level organisms and 
they possess unpleasant odors. In order to surmount these defects, many 
phenolic derivatives have been provided and in particular, halogenated 
derivatives have been advocated. However, pentachlorophenol (PCP), for 
example, has a high toxicity (LD.sub.50 ; 29.0 mg/kg) in the human body 
and it has been demonstrated that it easily attacks the mucous membrane, 
the spleen and the like, and induces pharyngitis, bronchitis and pneumonia 
upon inhalation. Because of these problems, the use of the halogenated 
phenol is prohibited. Polychlorobiphenyl (PCB), a halogenated aromatic 
compound, has been used for a long time as a heat medium, however, it has 
been proven that when the compound is inhaled by mammals, that it has a 
violently toxic effect and is a cause of diseases in the internal organs. 
On the other hand, these compounds are not decomposed by natural 
environmental conditions and accumulate and widely pollute the natural 
world. 
As is generally known, aromatic phenolic agents are, in general, inactive 
to gram-negative bacteria, such as those of the Pseudomonas group 
(Pseudomonas aeruginosa is an example of this group) which bring bacterial 
impediments to articles of commerce composed of long-chain hydrocarbon 
compounds such as cosmetics and domestic sundries. Accordingly, these 
agents are insufficient to prevent bacterial impediments. 
Of the aromatic phenolic compounds, p-phenylphenol, salicyclic acid, 
p-hydroxybenzoic acid ester and benzoic acid derivatives are relatively 
safe and have been widely used. However, they possess hydrophobic 
properties and are only slightly soluble in water in which medium the 
antiseptic effects are exerted. Accordingly, in order to obtain the 
desired germicidal effect, several to several ten times the additional 
amounts are required, depending upon the system to be used, and depending 
upon the amount dissolved in the aqueous system. In fact, an amount added 
of 0.5% is insufficient to prevent bacterial pollution in emulsion systems 
of hydrocarbon derivatives and water. 
In fact, when slightly soluble antibacterial agents are added to cosmetic 
emulsion systems, domestic sundries and the like containing long-chain 
hydrocarbonyl derivatives, these antibacterial agents frequently separate 
from the system, or destroy the properties of the product and severely 
damage the intended function and form of the article. For this reason, 
water-soluble alkaline salts of carboxylic acids, such as benzoic acid and 
salicylic acid are used, but they exhibit substantially reduced 
antibacterial effects in comparison with the corresponding acid form. 
Accordingly, amounts of the salts of several times the amounts of the free 
acids are required. The existence of an electrolyte often exerts a harmful 
influence on the stability of an emulsion system. For this reason, limited 
amounts of electrolyte are desired and consequently, the use of these 
alkaline salts is severely limited. 
Of the reversed soaps which are widely known to be readily soluble in water 
and are known to exert significant antibacterial effects at low 
concentration, are typically the long-chain alkylbenzyldimethylammonium 
halides, which as is commonly known, are widely used as germicides, 
disinfectants and antiseptics in hospitals, food processing factories and 
dining halls for sanitary reasons. However, the reversed soaps cause 
problems because of their irritability and toxicity properties and are 
ill-fitted for the systems in which bubbling must be avoided, such as 
industrial water, reservoir water and circulating water for the reason of 
strong surface-activity ability. On the other hand, when the reversed 
soaps are used as antiseptics for emulsified articles, such as non-ionic 
emulsified cosmetics and domestic sundries, they take on a physiochemical 
form in which they cannot exert their expected antibacterial action 
because they are taken into the emulsion system because of their 
surface-active ability. Further, they change the emulsion system and tend 
to severely damage the properties and the form of the articles, and are 
accordingly ill-fitted for the emulsified articles. For this reason, 
scrupulous care must be taken when reversed soaps are used. Of the 
amphoteric surface active agents having superior safety which have been 
developed to overcome the defects of reversed soaps is a typical 
antibacterial agent, dodecylpolyaminoethylalanine, which also possesses 
the same unavoidable defect as the reversed soaps because of its 
surface-active ability. 
In view of the various defects possessed by the existing antibacterial 
agents, an intensive investigation was started for novel antibacterial 
agents which do not possess the above-mentioned defects, and as a result, 
form the basis of a novel germicidal, disinfecting and antiseptic 
composition which improved the defects of the conventional antibacterial 
agents and is thus characterized by improved safety, broader spectrum 
antibacterial activity, lower concentration at which inhibitory action on 
bacterial growth is exerted and do not possess the various defects of 
cationic or amphoteric antibacterial agents having surface-active 
abilities. From the intensive investigation, the present invention has 
been developed. 
Accordingly, this invention provides a germicidal, disinfecting and 
antiseptic composition comprising an alkoxy aliphatic amine derivative 
represented by the following formula (I) 
##STR1## 
wherein R.sub.1 represents an alkyl or alkenyl group having 8 to 18 carbon 
atoms, R.sub.2 represents a hydrogen atom or an alkyl group having 1 to 3 
carbon atoms, R.sub.3 represents a hydrocarbonyl group having 2 to 3 
carbon atoms, X represents a hydrogen atom or a hydroxy group and n is an 
integer of 1 or 2, or by formula (II) 
##STR2## 
wherein R.sub.1 -R.sub.3, X and n are the same as defined above, R.sub.4 
represents a hydrocarbonyl group having 2 to 3 carbon atoms and m is 0 or 
an integer of 1 or 2, and an organic or inorganic compound capable of 
blocking metals. 
The alkoxy aliphatic amine derivatives of formulae (I) and (II) which are 
constituents of the composition of this invention, have broad spectrum 
antibacterial activity and exhibit inhibitory effects on bacterial growth 
at low concentrations, and at the same time, are water-soluble because of 
the alcoholic hydroxy groups. 
In connection with safety, the toxicity of the composition is as low as the 
anionic surface active agents used as cleansers, and is only of mild 
irritability to the skin. Further, the surface-active ability of these 
derivatives is extremely poor in comparison with cationic and amphoteric 
surface active agents. These compounds are soluble in emulsified articles 
because of the non-ionic long-chain aliphatic portions of the molecules. 
Accordingly, they can be combined in articles without destroying the 
properties of the articles. Also, they exert an antiseptic effect on city 
water supplies such as reservoir water and circulating water at low 
concentration without bubbling. In the event that cleansing is necessary, 
these compounds may be used in combination with various surface-active 
agents without loss of their antibacterial activity. 
However, alkoxy aliphatic amine derivatives of the formula (I) or (II), 
independently, exhibit only extremely weak germicidal effects on the 
bacteria of the Pseudomonas group such as Pseudomonas aeruginosa. Such 
bacteria are the sources of severe microbial pollution in articles of 
manufacture and various city water supplies. For this reason, when they 
are used as germicides and disinfectants, they must be applied in high 
concentrations. Accordingly, the benefits as described above may actually 
decrease. 
According to an embodiment of the present invention, the coexisting 
presence of an organic or inorganic compound capable of blocking metals 
greatly enhances the antimicrobial activity of the alkoxy aliphatic amine 
derivatives of formula (I) or (II) against the Pseudomonas group. The 
increased activity cannot be attained by the alkoxy aliphatic amine 
derivatives alone. Accordingly, the present composition possesses superior 
germicidal, disinfecting and antiseptic effects. 
Suitable organic and inorganic compounds capable of blocking metals in the 
present composition include organic compounds such as ethylenediamine 
tetraacetic acid and salts thereof (EDTA), nitriloacetic acid and salts 
thereof (NTA), malonic acid and salts thereof, citric acid and salts 
thereof, DL-aspartic acid and salts thereof, acetylacetone, 
8-hydroxyquinoline, o-phenanthroline and the like; and inorganic compounds 
such as polyphosphoric acids such as tripolyphosphoric acid, 
pyrophosphoric acid and metaphosphoric acid and salts thereof. 
Salts of the compounds described above include, in general, salts of the 
alkali metals such as sodium and potassium. 
The ratio of the compounds capable of blocking metals to the alkoxy 
aliphatic amine derivatives depends upon the amount of the alkoxy 
aliphatic amine derivative to be used. The amount to be used of alkoxy 
aliphatic amines less, the amount to be used of the compounds capable of 
blocking metals larger, and vice versa. 
For example, the ratio of disodium ethylenediamine tetra-acetate (EDTA-2Na) 
to N,N-bis(2-hydroxyethyl)laurylamine is as follows: 
______________________________________ 
The amount of Ratio of EDTA-2Na to 
n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
______________________________________ 
10 ppm 280 mole % 
20 ppm 140 mole % 
50 ppm 55 mole % 
100 ppm 30 mole % 
1000 ppm 3 mole % 
10000 ppm 0.2 mole % 
______________________________________ 
The germicidal, disinfecting and antiseptic composition of the present 
invention may be used in combination with non-ionic, cationic and 
amphoteric surface-active agents without loss of antimicrobial activity 
when a cleansing is necessary. 
Having generally described the invention, a further understanding can be 
obtained by reference to certain specific examples which are provided 
herein for purposes of illustration only and are not intended to be 
construed as limiting unless otherwise specified. 
An estimation of the germicidal effect of the present invention was 
conducted as follows: 
To 10 ml of a sterile saline solution or broth of the present composition 
having a fixed concentration was inoculated 1 ml of a broth of various 
microorganisms cultivated for three successive generations. After the 
mixture was cultivated in a thermostat at 30.degree. C. for a given time, 
the amount of one platinum loop was withdrawn from the liquid to be 
tested, which was used to inoculate the broth. The resulting mixture was 
cultivated at 30.degree. C. for 48 hours. At this time, the germicidal 
effect of the resulting broth was measured by using a turbidimeter. 
EXPERIMENT 1 
(1) Germicidal potency of n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
alone against Pseudomonas aeruginosa 
Table 1 
__________________________________________________________________________ 
Germicidal potency** 
Test Concentration 
Contact time 
Compounds ppm 60 minutes 
120 minutes 
180 minutes 
__________________________________________________________________________ 
##STR3## 10,000 1,000 100 
+ + + 
+ + + 
+ + + 
__________________________________________________________________________ 
**expression of germicidal potency . . . 
+: non-germicidal 
-: germicidal 
(2) Germicidal potency of n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
in the existence of 1 mM EDTA-2Na against Pseudomonas aeruginosa 
Table 2 
__________________________________________________________________________ 
Germicidal potency 
Test Concentration 
Contact time 
Compounds ppm 2.5 (min.) 
5 (min.) 
10 (min.) 
15(min.) 
__________________________________________________________________________ 
##STR4## 100 50 20 10 
- .+-. + + 
- - - + 
- - - + 
- - - + 
__________________________________________________________________________ 
(3) germicidal potency of n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
in the existence of 0.1 mM EDTA-2Na against Pseudomonas aeruginosa 
Table 3 
______________________________________ 
Concen- Germicidal potency 
tration Contact time (minutes) 
Test compounds (ppm) 2.5 5 10 15 
______________________________________ 
##STR5## 100 50 20 10 
.+-. + - .+-. + + 
- - - - - + 
______________________________________ 
experiment 2 
germicidal potency of n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 in 
the existence of various metal-blocking compounds against Pseudomonas 
aeruginosa 
Table 4 
______________________________________ 
##STR6## 
Concentration (ppm) Germicidal potency 
Metal-blocking compounds 
Contact time (minutes) 
Concentration (mM) 2.5 5.0 10 5 
______________________________________ 
10 mM 1000 - - - - 
Nitrilotriacetic 
1.0 1000 + + + + 
acid-trisodium 100 + + + + 
salt (NTA-3Na) 1000 + + + + 
0.1 100 + + + + 
10 + + + + 
10 1000 - - - - 
1.0 1000 + + + + 
Sodium citrate 100 + + + + 
1000 + + + + 
0.1 100 + + + + 
10 + + + + 
10 1000 - - - - 
1.0 1000 + + + + 
o-phenanthroline 100 + + + + 
1000 + + + + 
0.1 100 + + + + 
10 + + + + 
10 1000 - - - - 
Sodium 1.0 1000 - - - - 
tripolyphosphate 100 - - - - 
1000 - - - - 
0.1 100 - - - - 
10 + + + + 
______________________________________ 
EXPERIMENT 3 
Germicidal potency of n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 in 
the existence of various metal-blocking compounds against Escherichia coli 
and Proteus vulgaris 
Table 5 
__________________________________________________________________________ 
##STR7## Germicidal potency Escherichia coliProteus vulgaris 
Concentration (ppm) Contact time 
Contact time 
Metal-blocking compounds 
(minutes) 
(minutes) 
Concentration (mM) 5 10 15 
5 10 15 
__________________________________________________________________________ 
1000 
- - - - - - 
n-C.sub.12 H.sub.25 N(CH.sub.2 CH.sub.2 OH).sub.2 
100 
- - - - - - 
10 
+ + + + + - 
10 mM 
1000 
- - - - - - 
Disodium ethylenediamine 
1 100 
- - - - - - 
tetraacetate (EDTA-2Na) 
0.1 10 
- - - - - - 
Trisodium 10 1000 
- - - - - - 
nitrilotriacetate 
1 100 
- - - - - - 
(NTA-3Na) 0.1 10 
- - - - - - 
10 1000 
- - - - - - 
Sodium citrate 
1 100 
- - - - - - 
0.1 10 
- - - - - - 
10 1000 
- - - - - - 
Sodium malonate 
1 100 
- - - - - - 
0.1 10 
- - - - - - 
10 1000 
- - - - - - 
Sodium asparatate 
1 100 
- - - - - - 
0.1 10 
+ - - + + - 
10 1000 
- - - - - - 
Acetylacetone 
1 100 
- - - - - - 
0.1 10 
- - - - - - 
10 1000 
- - - - - - 
8-hydroxyquinoline 
1 100 
- - - - - - 
0.1 10 
+ - - - - - 
10 1000 
- - - - - - 
o-phenanthroline 
1 100 
- - - - - - 
0.1 10 
- - - - - - 
10 1000 
- - - - - - 
Sodium tripolyphosphate 
1 100 
- - - - - - 
0.1 10 
- - - - - - 
__________________________________________________________________________ 
EXPERIMENT 4 
Germicidal concentrations of the test compounds in 5 minutes-contact in the 
existence of 1.0 mM EDTA-2Na 
Table 6 
__________________________________________________________________________ 
Germicidal concentration (ppm) 
Staphylo- Pseudo- 
coccus 
Bacillus 
Escherichia 
Proteus 
monas 
Test compounds aereus 
subtilis 
coli vulgaris 
aeruginosa 
__________________________________________________________________________ 
n-C.sub.12 H.sub.25 NHCH.sub.2 CH.sub.2 OH 
&lt;10 &lt;10 &lt;10 &lt;10 20 
##STR8## &lt;10 &lt;10 &lt;10 &lt;10 40 
##STR9## &lt;10 &lt;10 &lt;10 &lt;10 20 
##STR10## &lt;10 &lt;10 &lt;10 &lt;10 25 
##STR11## &lt;10 &lt;10 &lt;10 &lt;10 35 
##STR12## &lt;10 &lt;10 &lt;10 &lt;10 60 
##STR13## &lt;10 &lt;10 &lt;10 &lt;10 30 
##STR14## &lt;10 &lt;10 &lt;10 &lt;10 40 
##STR15## &lt;10 &lt;10 &lt;10 &lt;10 60 
##STR16## &lt;10 &lt;10 &lt;10 &lt;10 60 
__________________________________________________________________________ 
experiment 5 
germicidal potency of commercial germicides in the existence of 1.0 mM 
EDTA-2Na against Pseudomonas aeruginosa 
Table 7 
______________________________________ 
Germicidal potency 
Coexistance of 
Germicides alone 
EDTA 
Contact time Contact time 
Test Compounds (minutes) (minutes) 
Concentration (ppm) 
5 15 60 5 15 30 60 
______________________________________ 
100000 + + + - + - - - 
50000 + + + + + + + + 
25000 + + + + + + + + 
10000 + + + + + + + + 
Sodium benzoate 
5000 + + + + + + + + 
2500 + + + + + + + + 
1000 + + + + + + + + 
500 + + + + + + + + 
250 + + + + + + + + 
100 + + + + + + + + 
100000 - - - - - - - - 
50000 + + - - + + - - 
25000 + + + + + + + - 
10000 + + + + + + + + 
Sodium salicylate 
5000 + + + + + + ++ 
2500 + + + + + + + + 
1000 + + + + + + + + 
500 + + + + + + + + 
250 + + + + + + + + 
100 + + + + + + + + 
______________________________________ 
EXPERIMENT 6 
Germicidal potency of various metal-blocking compounds against Pseudomonas 
aeruginosa 
Table 8 
______________________________________ 
Germicidal potency 
Concentra- 
in 30 minutes- 
Metal-blocking compounds 
tion (mM) contact 
______________________________________ 
Disodium ethylenediamine 
tetraacetate 10 + 
Trisodium nitrilotriaacetate 
10 + 
Sodium citrate 10 + 
Sodium malonate 10 + 
Sodium DL-asparatate 
10 + 
Acetylacetone 10 + 
8-hydroxyquinoline 
10 + 
o-phenanthroline 
10 + 
Sodium tripolyphosphate 
10 + 
______________________________________ 
EXPERIMENT 7 
Germicidal potency test in water and broth in 5 minutes-contact 
Table 9 
__________________________________________________________________________ 
Maximum dilution at which germicidal effect 
is manifested 
Pseudomonas 
aeruginosa 
Escherichia coli 
Proteus vulgaris 
Germicides Water 
Broth 
Water 
Broth 
Water 
Broth 
__________________________________________________________________________ 
##STR17## &lt;100 
&lt;100 
25,000 
20,000 
30,000 
25,000 
##STR18## 50,000 
7,500 
100,000 
75,000 
100,000 
80,000 
EDTA-2Na 0.5mM(0.016%) 
##STR19## 35,000 
1,500 
50,000 
40,000 
64,000 
55,000 
NaOCl 10,000 
200 
10,000 
200 
15,000 
300 
__________________________________________________________________________