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Publication numberUS3003915 A
Publication typeGrant
Publication dateOct 10, 1961
Filing dateDec 11, 1959
Publication numberUS 3003915 A, US 3003915A, US-A-3003915, US3003915 A, US3003915A
InventorsPaul M. Borick
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Method of destroying lactobacilli em-
US 3003915 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

United States Patent fifice 3,003,915 Patented Oct. 10, 1961 3,003,915 METHOD OF DESTROYING LACTOBACILLI EM- MONO (TETRADECYLAMINE) MALO- Paul M. Borick, Cranford, N.J., and Martin Daniel Bratt, Edgewood, Md., assignors to Bristol-Myers Company, New York, N.Y., a corporation of Delaware No Drawing. Filed Dec. 11, 1959, Ser. No. 858,857 1 Claim. (Cl. 167-22) This application relates to germicidal compositions and more particularly to germicidal compositions containing amine salts of malonic acid. The germicidal salts of this invention have the generic formula:

1 R-IYI (C 31340 4) wherein R is an alkyl radical having from about 12 to about 16 carbon atoms; R is hydrogen or an alkyl radical having from 1 to 6 carbon atoms; R is hydrogen or an alkyl radical having from 1 to 6 carbon atoms and n is 1 or 2.

Most germicides suffer from a variety of defects such as: specificity to only certain types of microorganisms; inactivation when in contact with organic matter; inactivation with hard water, i.e., Water containing relatively high concentrations of calcium or magnesium salts; having a narrow pH sensitivity; having an odor; or causing a discoloration of clothing and other materials with which the germicide comes in contact. Thus, penicillin, sulfonamides and certain antibiotics are specific to gram positive bacteria. Other germicides such as fatty acids, salts of fatty acids, salicylates and benzoates are specific to the fungi. The fatty acids also have a very perceptible odor. Germicides such as gentian violet and copper-8- quinolinolate impart a color to germicidal compositions and materials which come in contact with the compositions such as clothing. Only a limited number of germicides are effective against gram negative bacteria and only a few of the germicides which are effective against the gram negative bacteria possess a broad germicidal spectmm.

It has now been found that the malonic acid salts of certain alkyl amines have good activity against a wide variety of microorganisms such as the gram positive bacteria, gram negative bacteria and the various fungi. In addition, these salts are not inactivated by organic matter or hard water. They do not possess an undesirable perceptible odor; do not cause discoloration of clothing; and are active over a broad pH range, e.g., pH of 2 to 12.

The amines employed for producing the germicidal salts of this invention are alkyl amines and can be primary, secondary or tertiary amines wherein one alkyl chain contains from about 12 to about 16 carbon atoms and preferably 14 carbon atoms. The remaining valences of the nitrogen atom of the alkyl amine reactant are satisfied by hydrogen or alkyl radicals containing from 1 to 6 carbon atoms. Amine salts of malonic acid with less than about 12 carbon atoms, e.g., 7 or 8 carbon atoms in the long chain alkyl group of the amine portion of the salt are irritating to the skin and do not possess the high germicidal activity of those having 12 to 16 carbon atoms in the alkyl chain. Amine salts with more than about 16 carbon atoms, such as 22 carbon atoms, do not have the high order of activity of the shorter chain alkyl radicals containing about 12 to 16 carbon atoms. Illustrative of the germicidal salts there can be mentioned: mono (dodecylamine) m'alonate; di (dodecylamine) malonate; mono (tridecylamine) malonate;

mono (tetradecylamine) malonate; di (tetradecylamine) malonate; mono (pentadecylamine) malonate; di (pentadecylamine) malonate; mono (hexadecylamine) malonate; di (hexadecy-lamine) malonate; mono (N,N-dimethyldodecylamine) malonate; di (N,N-dimethyldodecylamine) malonate; mono (N,Ndiethyltetradecylamine) malonate; di (diethyltetradecyl-amine) malonate; mono ('N-ethyl-N-propyl-tetradecylamine) malonate; di (N-methyltetradecylamine) malonate; and di (N,N-dibutylpentadecylamine) malonate. The germicidal salts employed are those wherein either one or both of the two carboxylic acid groups of the dibasic acid have been neutralized. Of course, compositions which contain a mixture of the salts can also be employed. The chemical formula for mono (tetradecylamine) malonate and di (tetradecylamine) malonate respectively, can be represented as: C H NH -HOOC-CH COOH and (C H NH 'HOOC-CH --COOH. For convenience, in the nomenclature of these salts, the portion of the salt possessing the amine compound is referred to as the amine portion of the salt, e.g., in the case of the mono (tetradecylarnine) vmalonate it is the portion to the left of the bonding dot. The chemical formula for the mono and di (tetradec-ylamine) malonate can also be expressed respectively as The germicidal salts of this invention can be prepared by simply dissolving malonic acid and the amine in an organic polar solvent at room temperature. Heating the mixture of polar solvent, amine and dibasic acid at slightly elevated temperatures such as 40 C. to 60 C. aids in solubilizing the mixture. The salts can be precipitated from their solution in the polar solvent by cooling the solution to a temperature of about 1 to 10 C. or adding ether to the solution. The solid germicidal salts are then recovered from the reaction medium by conventional means such as by filtration.

EXAMPLE 1 This example shows the preparation of mono (tetradecylamine) malonate. The salt was prepared by mixing solutions of 0.1 mol of tetradecylamine (C H N) and 0.105 mol of malonic acid (C H O in'jafrninimum quantity of ethanol as a solvent at room temperature. The slight excess of acid was used to prevent formation of the di (tetradecylamine) salt. The salt precipitated upon addition of ether (about ten times asmuch ether was added as compared to the ethanol used as a solvent). The reaction mixture was then filtered to recover the salt. The salt was subsequently recrystallized from acetone. The yield of mono (tetradecylamine) malonate was about 84% based on the amine reactant. The salt was white in color and had a melting point of 95.5 C. to 97 0.; molecular weight of 309 (calc. 317) and nitrogen analysis of 4.4% (calc. 4.4%

The germicidal salts of this invention can be used in their pure form for their germicidal activity or preferably by formulating germicidal compositions wherein the germicidal salts are used in germicidally etfective amounts such as from about 0.05% to about 5% of the entire composition and preferably from about 0.1% to 1% with the remaining or major portion of the composition comprising conventional germicidal adjuv-ants or carriers. Thus, they can be formulated as solutions, suspensions, emulsions, or powders with the conventional carriers.

The germicidal compositions of the invention may also take the form of preparations suitable -for dispensing as aerosols, liquids or foams from conventional, resilientwalled or pressurized containers. For such purposes, the compounds may be incorporated in non-solvent suspensions or emulsions or they may be dissolved in suitable solvents as an alcohol, acetone or the like. If these are to be dispensed from pressurized containers, conventional propellants may be used such as the various haloalkanes, hydrocarbon gases, nitrogen, carbon dioxide, etc. When desired, film-forming materials can also be incorporated in the compositions. The film-forming materials can be the self-supporting type of film-formers such as cellulose derivatives, natural or synthetic lacquers, etc. or they can be selected from non-self-supporting film-forming materials such as silicones.

The germicidal compounds of the invention can also be formulated for use in the form of powders. Conventional pulverulent carriers can be utilized such as starch, talc, etc. For example, a suitable antimycotic powder can be prepared in accordance with the following formulation.

The germicidal activities of certain of the contemplated compounds are illustrated and compared to those of some closely related substances in Table 1, wherein the activities are given, in milligrams percent (mg. as the minimum concentration necessary to inhibit growth of the microorganisms against which the compounds were tested. (One mg. percent=1 mg. of the compound being tested per 100 ml. of solutlon or parts per million).

Table 1 Mono Mixed Mono Mono (tetratetra- (tetra- (lauryl Tetradeclydecyldecyltrisdecylamine) amine amine) methylamine iumarate malomalonate amine) palmitate mates 1 malonate S. aureus 1. 25 0. 6 0.3 0. St. f 1. 0.3 0. 6 1. 25 20 2.5 0.6 0.3 1.25 20 L 1. 25 0. 07 0.0015 0. 15 1. 25 0. 3 0. 07 0. 6 1. 25 1. 25 10 10 5.0 10 20 0.6 0.15 0.6 0.6 20 0.6 0.3 0.3 0.15 10 10 5.0 10 10 20 A. aeragenes 10 0. 6 1. 25 5 20 L. delbrueckii 0.07 0.0015 0.0015 0. 3 10 M. gypseum 0. 3 0.3 20 0.3 20 T. mentagrophytes. 0.3 0.6 1.25 25 20 SJU hose 10 0.6 1.25 2.5 20 S. (11 us 0.6 0.15 0.3 0.15 20 B. ammoniaqenes" 0. 6 0. 07 0.3 1.25 20 P. ovale 0. 3 0. 15 1. 25 0.15 20 1 The mixture contained about equal parts of the mono and di (tetradeeylamine) malonate.

It can be seen from the data of Table 1 thatthe malonate salts are highly effective germicides, particularly against gram negative organisms and lactobacilli. Also, it can be seen from Table 1 that the amine salts of the malonates are more effective than the amine salts of closely related compounds such as palmitic acid or fumaric acid. H

The germicidal salts of this invention canalsobe employed as preservatives and antifungal agents by incorporating them in materials normally susceptible to attack by microorganisms. Illustratively they can. be incorporated in paints, e.g., antifouling marine paints, as well as in adhesives and textile sizes. They can also be incorporated in articles of molded plastic materials, such as synthetic resins, cellulose derivatives and the like whereby they confer on the molded articles a rcsistance to attack by various microorganisms such as the fungi. The salts of this invention can also be used as fungicidal agents on garden plants, such as tomatoes, wherein they can be admixed with conventional carriers such as talc and applied to plants.

What is claimed is:

A method for inhibiting the growth of lactobacilli which comprises applying to said lactobacilli a germicidally effective quantity of mono (tetradecylamine) malonate.

References Cited in the file of this patent UNITED STATES PATENTS 1,873,732 Adams Aug. 23, 1932 2,218,181 Searle Oct. 15, 1940 2,779,741 Cross n Jan. 29, 1957 OTHER REFERENCES King: US. Dept. Agr., Handbook No. 69, page 221 (May 1954).

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US1873732 *Dec 28, 1928Aug 23, 1932Abbott LabBactericide applicable to acid-fast bacteria
US2218181 *Jun 15, 1939Oct 15, 1940Du PontPest control
US2779741 *Dec 26, 1950Jan 29, 1957Gen Aniline & Film CorpWater-soluble compositions containing water-insoluble organic amines
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3176033 *Apr 2, 1962Mar 30, 1965Roussel UclafNovel cupric pyruvate compounds and fungicidal compositions thereof
US3385755 *Jul 31, 1962May 28, 1968Rewo Chem Fab G M B HUndecylenic acid alkylolamide derivatives for controlling bacteria, fungi, and dandruff
US5843865 *Feb 6, 1997Dec 1, 1998Buckman Laboratories International, Inc.Synergistic antimicrobial compositions containing an ionene polymer and a salt of dodecylamine and methods of using the same
US6103666 *Sep 10, 1998Aug 15, 2000Buckman Laboratories International, Inc.Synergistic antimicrobial compositions containing an ionene polymer and a salt of dodecylamine and methods of using the same
U.S. Classification514/554, 562/590, 424/45
Cooperative ClassificationA61K31/205