WO1997020037A1

WO1997020037A1 - Antimicrobial compositions

Info

Publication number: WO1997020037A1
Application number: PCT/US1996/018962
Authority: WO
Inventors: Novis W. Smith
Original assignee: Dr. Novis Smith And Company, Inc.
Priority date: 1995-11-28
Filing date: 1996-11-26
Publication date: 1997-06-05
Also published as: AU1084597A

Abstract

The invention provides antimicrobial compositions which contain a phenol complex with a film forming complex of a polycarboxylic acid and a microbicide containing at least two quaternary and/or amine sites. The composition can include a film forming lactone or lactam which is complexed with a phenol.

Description

ANTIMICROBIAL COMPOSITIONS

Field of the Invention

The present invention relates to antimicrobial compositions comprising novel phenol containing film forming complexes of antifungal or antimicrobial compounds or other functional compounds. More particularly, there is provided compositions with novel complexes which render the same antimicrobial activity as the unreacted smaller molecule but are more hypoallergenic, have slower release and longer lasting. The complexes are especially useful in killing or deactivating microorganisms on contact and preventing growth of colonies over longer periods of time . Background of the Invention

There is a need to provide a safe and effective means for preventing viral, fungal and bacterial growth which can be used on or near a person's body without adverse effects on the user. There is a further need to provide preparations which will inhibit and/or prevent the growth of disease or odor causing viruses, bacteria and f ngus.

There is a further need to provide longer lasting protection against infectious diseases caused by viruses and bacteria. New strains of viruses and bacteria are developing which are resistant to antibiotics. Therefore, it has become important as a defense to kill or deactivate them before infection.

Compositions that contain only phenol compounds, which are initially highly effective, quickly evaporate and provide no after treatment protection against regrowth. Previously, hexachlorophene was widely used in many preparations to kill bacteria on contact and to prevent growth of bacteria and fungus. Hexachlorophene was included in deodorant compositions, talcum preparations, foot powders, and the like. However, the hexachlorophene when used in direct contact with skin was absorbable. Prolonged exposure to hexachlorophene was considered as being hazardous so that it was withdrawn from use in such compositions.

There is a need to provide film forming compositions which are used on or near body parts for preventing bacterial and fungal growth which does not adversely affect the user.

French Patent No. 2,695,297 discloses a method of disinfecting comprising using a composition containing citric acid, diaminetetraacetic acid and a polymeric biguanide salt.

Japanese Patent Publication No. 1989-22824, discloses a medicament for external use that is fungicidal and exhibits an antibacterial spectrum. The medicament comprises quaternary ammonium salts of polymeric carboxylic acid compounds which are sparingly soluble in water. However, the active component is utilized for its ability to permeate into the cutaneous stratum corneum so that such use cannot be continuous and without medical supervision.

U.S. Patent No. 4,332,763 to Hempel et al discloses the uεe of a quaternary ammonium polymer obtained by the reaction of dimethyl sulphate with a mixed polymer of vinyl pyrrolidone and dimethylamino ethylmethacrylate. However, the quaternary ammonium cation of this polymer is leachable and the polymer is slightly soluble so that polymer cannot be used in compositions which contact skin or where long term use is required.

U.S. Patent No 3,872,128 to Byck, which is herein incorporated by reference, discloses anti-microbial ammonium polymer salts which are prepared from carboxyl-containing a- olefm polymers and quaternary ammonium salts. The polymers are used to form solid polymeric articles for hospitals and patient care The compounds do not form antimicrobial films.

U.S. Patent No. 4,946,672 to Gilbs discloses a disinfectant comprising a biguanide, citric acid and other components

U.S. Patent No. 3,404,134 to Rees, which is herein incorporated by reference discloses a process for crosslinking copolymers of alpha olefin and alpha, beta ethylenically unsaturated carboxylic acid units . The copolymers are crosslinked utilizing diamine cations. None of the diamine cations are stated as being anti-microbial . Furthermore, the polymers are used to make molded articles and sheet material.

The term "polycarboxylic acid" is intended to mean carboxylic acid compounds having 2-4 carboxylic acid groups or anhydrides which reacted behave as polycarboxylic acids or salts thereof . Summary of the Invention

The invention provides novel antimicrobial film forming compositions containing complexes which are formed between polycarboxylic acids and non-benzyl containing functional biocides, fungicides, and anti-viral agents having at least two quaternary ammonium or amine site, or the salts thereof The reactions between these functional compounds and the carboxylic acid causes at least two of the quaternary ammonium or amme or combination of quaternary ammonium or amme molecules to coordinate or complex per molecule of polycarboxylic acid to form a higher molecule weight compound. These nigher molecular weight species possess the full activity of the smaller unreacted functional molecule and do not penetrate the skin. Preferably, the functional compound has two quaternary ammonium or amme sites or a mixture thereof . It has been surprisingly found that these complexes further form complexes with phenols so as to provide a longer term of antimicrobial activity of the phenol

When the complex with the phenol compound s placed an alkanol as a carrier, there is a multiplicity of antimicrobial activity. The alkanol provides the first antimicrobial action, after the alkanol evaporates, the phenol is in greater concentration so as to provide the second antimicrobial activity. After the phenol is released, the film formmg complex continues its activity and retards colonization of microbes.

Advantageously, the antimicrobial film is enhanced when a film forming nitrogen contammg lactam or lactone is mcluded. The phenol activity is further prolonged when a complex is formed between the lactam or lactone and a phenol .

It is therefore an object of the invention to provide a phenol containing long lasting anti-microbial composition.

It is a further object of the invention to provide an anti¬ microbial composition having a broad spectrum of anti-microbial activity. Description of the Preferred Embodiment

In accordance with the present mvention there is provided novel compositions which contain a plurality of complexes including one formed between polycarboxylic acids and a non- benzyl containing functional biocides, fungicides, herbicides, pesticides, nematicides and microbicides, all having at least two sites which are quaternary ammonium, amine, a mixture thereof, and/or the salts thereof . There is a further complex formed with a phenol and a lactone or lactam.

The reaction between these functional or useful compoundε containing the quaternary and/or amine sites and polycarboxylic acids causes at least two functional molecules to coordinate or complex (react) per molecule of polycarboxylic acid. This forms a higher molecular weight molecule. These higher molecular weight species possess the full activity of the smaller unreacted functional molecule but are more hypoallergenic . The formation of these simple but larger complexes has the effect of creating a slower release type of functional compound and the phenol. Therefore, a larger lasting effect is achieved with these complexes without having to use the microbial or other type of biocidal agent or herbicide in higher doses or frequent doses.

A preferred antimicrobial compound used in the invention has the general formula:

!^■ f'

R - N₊ - (CH₂)_y - N₊ - R

I I

X^' X^" wherein

X is halogen; y is an integer of 1 to 6;

R is hydrogen or an alkyl of 1-15 carbon atoms; and

Rj is hydrogen or lower alkyl . A preferred antimicrobial compound which is used in the mvention is sold by Witco Corp. of Dublin, Ohio under the trademark ADOGEN (N^J^ N¹ - pentamethyl, N^tallow alkyl-1, 3 propanamme diammonium chloride; N-tallow pentamethyl propane diammonium chloride) .

Benzyl containing antimicrobial compounds are environmentally not suitable.

The use of known phenolic compounds such as phenol or 0- phenylphenol which is used m an amount of about 0.1 to 10% by weight of composition provides a broad spectrum of kill m combmation with the complexes of the invention.

The use of the high amounts of phenol compound is particularly useful for compositions that are sprayed into air ducts and vents which are considered as sources for the spread of disease. The phenol not only provides its own antimicrobial activity but improves the antimicrobial capabilities of the film formmg complex. The phenol helps to make the film tacky so that the composition adheres to surfaces which are moist or dirty. This feature is especially useful in installations where there is no cleaning or maintenance of the ducts or vents. The phenol further picks up moisture from the air so as to keep the film tacky for longer periods of time. The tacky film holds m the phenol and provides a slow release of phenolic vapors.

After the phenol has evaporated, the film complex of the mvention not only provides a surface which prevents regrowth of viruses, bacteria and fungus but still retains the antimicrobial activity of the base quaternary compound. Polycarboxylic acids useful in the invention contain 2-4 carboxylic acid groups and include: succinic, acrylic, carboxymethyl cellulose, methacrylic, ethacrylic, ltacomc, maleic, fumaric, citric, oxalic, phthaiic, tartaπc, and the like. The salts thereof with anions such as citrates, tartrates, succmates, fumarates, maleates, malonates, alates, phthalates, etc can be used. Maleic anhydride and other anhydrides are considered acids for the purposes of the present invention. The succinic acid is the most preferred complexing agent .

The complex with a polycarboxylic acid and quaternary ammonium compound of the invention can be generally prepared as follows :

A solution of the polycarboxylic acid m water or water- alcohol is formed either as the ammonium or sodium salt with ammonium or sodium hydroxide, respectively. The anti-microbial compound is dissolved in water or a water soluble solvent . The molecular ratio of anti-microbial compound to sodium or ammonium carboxylate groups m the acid or mixture of acids is adjusted to one or less than one by varying the quantity of solution to be added to the acid solution. The appropriate amounts of the two solutions are mixed with stirring. The complex forms quickly. This complex can be treated with a phenol compound added directly mto spray compositions, powder compositions, etc for control and the killing of microorganisms. The solubility of the complex can be adjusted to soluble or to precipitate it out as a dispersion usually by the use of different phenols.

Any of the phenolic compounds which are antimicrobial can be used It is preferable to use two different phenols so as to have a broader spectrum of antimicrobial activity. Preferred phenols are O-phenylphenol (Dowcil sold by The Dow Chemical Company) , paratertiary a yl phenol and phenol . The chlorinated phenols can also be used but they are environmentally unacceptable.

The complexes are soluble in water or alcohol . Alcohols as a group possess many desirable features for disinfecting. However, pure alcohol is not as effective as a mixture of alcohol and water The preferred alcohols are methyl, ethyl and isopropyl alcohol .

The addition of nitrogen containing film forming lactones and lactams together with a phenol to make a complex between the two has been found to provide a longer lasting film which maintains the phenol over longer periods of time. The most preferred lactones and lactams are polyvinyl pyridine, polyvinyl pyrrolidone and their derivatives.

A suitable complex is formed between polyvinyl pyridine and O-phenylphenol .

The phenol complex of the phenol with the antimicrobial compound is generally used m a ratio with the phenol complex of the lactone or lactam is 0.1:1 to 1:1.

The followmg examples are illustrative of the invention but are not to be construed as to limiting the scope thereof in any manner. The percentages disclosed herem relate to percentages by weight unless otherwise stated. Example I

Step A. The following ingredients were mixed:

Ingredients Wt %

Methyl alcohol 74 . . 5 Succinic acid 2 . . 5 Phenol (90%) 5 . . 5 Adogen 4 , . 0 Water 10 . 0

A complex is formed between succinic acid and Adogen and the phenol and Adogen complex.

Step B. To the mixture of Step A were added the following:

Ingredients Wt %

O-phenylphenol 1.5

Polyvinyl pyridine 2.0

100.0

The combination of Step A alone is suitable for use as an antimicrobial composition. However, the combination of Steps A and B provide a composition having a broad spectrum of antimicrobial activity which lasts for at least 28 days.

The pH of the mixture was 6.5. In lieu of methyl alcohol, water may be utilized especially when the composition is to be used in vents and ducts. Additional phenol may be added so that the resulting film is tacky for use in the vents and ducts.

Claims

What Is Claimed Is:

1. A film forming composition comprising: a) a complex of a polycarboxylic acid and non-benzyl contammg antimicrobial compound having at least two quaternary ammonium and/or amme sites or a combination thereof n admixture with a phenol ; and b) a carrier selected from the group consisting of alkanol, water and mixture thereof

2. The composition of claim 1 wherein said carrier comprises alcohol and water.

3 The composition of claim 1 including a complex of a nitrogen contammg film formmg lactone or lactam and a phenol

4. A film formmg composition of claim 1 comprising- a) the admixture of an antimicrobial complex of compound of the formula :

wherem X is halogen; y is an integer of 1 to 6 ;

R is hydrogen or an alkyl of 1-15 carbon atoms; and R_x is hydrogen or lower alkyl, with a polycarboxylic acid having 2 to 4 carboxylic acid groups; b) about 0.1 to 10% by weight of a phenol, and c) a carrier selected from the group consisting of a lower alkanol and water.

5. The composition of claim 4 including a complex formed by a nitrogen containing film formmg lactone or lactam which is complexed with a phenol .

6. The composition of claim 5 wherein said lactam is polyvinyl pyridine

7. The composition of claim 6 wherein said phenol is 0- phenylphenol .

8 The composition of claim 5 wherein said lactone is polyvinyl pyrrolidone

9. The composition of claim 4 wherein said polycarboxylic acid is selected from the group consistmg of succinic, citric and isophthalic

10. A film forming anti-microbial composition which comprises the admixture of : a) a polycarboxylic acid; b) ^^ ¹ - pentamethyl, N'-tallow alkyl 1,3- propanamme diammonium chloride; c) phenol; d) a lower alkanol; and e) O-phenylphenol and polyvinyl pyridine complex