IL29956A - Disinfectant compositions - Google Patents

Description

DISINFECTANT COMPOSITIONS This invention relates to compositions of matter and the processes of treatment for disinfecting and for killing or disabling the growth of micro organisms.

Numerous proposals have been made in the past to provide disinfectant compositions for killing or controlling microorganisms which involved the complexing of iodine with various compounds which have the property of liberating the iodine for its disinfecting properties under conditions of use. These compositions are generally referred to in . · the art as iodophor s, and their disinfectant and germicidal activity is derived essentially from the free iodine which they liberate.

Characteristics of these iodophor compositions include their positive reaction to the starch-iodine test and their progressive loss of iodine from aqueous solution. For example, if an aqueous solution of such an iodophor is boiled, all of the iodine is very soon lost by volatilization.

Many different types of compositions or complexes of iodine have been disclosed in the prior art. In some cases the resulting iodine complexes or iodophors are more or less unstable and liberate the iodine in aqueous solution. Examples of materials which have been used in the past in an attempt to form a complex of iodine having anti-microbial activity include ethylene oxide condensates other anionic sulfonate-type detergents or surface-active agents. It is further known that lower alkyl monoethers of ethylene glycol will promote the formation of an iodophor complex. Other compounds used to f orm iodophor complexes include quaternary compounds such as hexamethylene tetramine. Further examples of anionic-iodine complexes which have previously been disclosed include iodine complexes with alkanoyl taurates which are a group of anionic sulfonated amino compounds. All of the above-referred-to complexing agents or carriers for iodine result in the production of the usual iodophors which are capable of liberating iodine in solution, and their products are made and used for their germicidal activity.

It is also known to be possible to make stable complexes of iodine which do not yield any quantity of free iodine in aqueous solution, which will not show a positive reaction in the starch-iodine test and do not lose iodine when their aqueous solution is boiled.

These known stable complexes of iodine, however, with one exception, have been found to possess very little or no germicidal or antimicrobial activity. This known exception consists in a new type of disinfectant, composition comprising iodine together with an ampholytic germicidal amine sulphonate complexed with a non-ionic surfact nt such as an alkyl phenol-ethylene oxide condensation product. These comparatively new compositions are not iodophors but constitute or contain stable iodine containing complexes which will not respond to the starch/iodine test and are disinfectants in their own right. They have a much wider range of utility than iodophors especially in vivo.

The present invention relates to a new class of halogen-ampholytic amino sulfonate-nonionic surface-active agent - glycol The new class of iodine-amphol tic amino sulfonate-nonionic surface-active agent - glycol complexes of this invention are again not iodophors as commonly known and described, they do not show the starch-iodine reaction, they do not lose iodine even from boiling aqueous solutions but nevertheless have disinfectant or anti-microbial activity superior to that of the known exception just referred to. In particular the complexes of the present invention have a much higher activity per unit weight or volume.

The ampholytic amino sulfonates which can be used according to this invention exhibit some germicidal or disinfectant activity alone and include the various salts of N-lauryl (amino sulfonic) beta amino butyric acid which have been commercially available under the trade name Siposan D. Other amino sulphonates which may be used are the higher alkyl amino alkane sulphonates such as the dodecyl and tetradecyl amino ethane sulphonates, and mixtures thereof, such as may be prepared from commercially available higher alkyl amines by known procedures. The above amine sulfonates belong to a class of surface-active agents known as ampholytes or ampholytics, and can be generally designated as higher alkylamino sulfonates or higher alkylamino alkane sulfonates. Other long chain alJslamino alkane sulfonates could be substituted for the above dodecyl and tetradecyl amino ethane sulfonate mixture. The dodecyl (12 carbon atoms) and the tetradecyl (14 carbon atoms) amino alkane sulfonates, for example, could be used independently if desired. The exact range of the number of carbon atoms which can be used for the alkyl group, i.e. below 12 and above 14 carbon atoms, is not known but this could readily be determined by routine experimentation. Similarly, the exact number of carbon atoms which can be contained in the alkane portion of the compound, i. e. , below 2 and above 2, is not known but this also could be readily determined by routine experimentation.

Various aryl or aromatic amino sulfonates can also be used including the reaction product of tetraethoxynonyl phenol, glycerol and amino sulfonic acid, such as dodecyl amino sulfonic acid. Other aromatic or aryl amino sulfonates could possibly be substituted for the above tetraethoxynonyl phenol amino sulfonate so long as they are ampholytic and possess the necessary properties to produce the stable halogen or iodine complexes having the disinfectant properties in accordance with this invention. The number of carbon atoms of the aryl radical or alkyl-aryl radical which can be employed, either higher or lower, has not been determined, but this could be determined by routine experimentation.

The ampholytic higher alkylamino sulfonates of this invention may be prepared by known methods such as by condensing an alkyl amine with an alkyl sulfonic acid, or with amino sulfonic acid to give the amino sulfonate, e .g. N-lauryl amine amino sulfonate.

For example, an ampholytic higher alkylamino sulfonate which can be used according to this invention can be prepared by mixing 100 parts of ethyl alcohol with 410 parts of dodecyl amine in a · suitable vessel and heating the mixture to approximately 50°C , A stream of air is then blown through stabilized sulphur trioxide held at about 80°C. and the resulting gas containing sulphur trioxide passed into the mixture of ethyl alcohol and dodecyl amine below the surface thereof. The quantity of sulphur trioxide used is sufficient to supply approximately 1.1 moles of sulphur trioxide per mole of ethyl alcohol. The temperature of the reaction in this particular example should preferably be held under about 55°C . and the reaction mixture agitated for about one hour to complete the reaction. The product is then neutralized with a suitable base such as ammonia, ethyl amine or ethanol amine to form the corresponding salt. The product produced from this process is probably a mixture of products, but nonetheless quite suitable for the purposes of this invention for complexing iodine in conjunction with the nonionic surface-active agent.

A more purified ampholytic higher alkylamino sulfonate which is also useful in accordance with this invention can be made by mixing 240 parts of dodecyl amine in a suitable vessel equipped with a stirrer, and the temperature raised to about 40° C. 100 parts of ethane sulfonic acid are then slowly added and the temperature preferably kept below about 50°C. during the reaction. The reaction mixture is stirred for approximately one hour to complete the reaction.

As previously discussed, other aryl and higher alkylamino sulfonates can be used according to this invention so long as they are ampholytic and are capable of forming the advantageous stable iodine complex exhibiting germicidal or anti-microbial activity in accordance with this invention.

The ampholytic nonyl phenol amino sulfonate referred to above can also be prepared by processes well known in the art. One advantageous method of preparing the ampholytic nonyl phenol amino sulfonate involves placing 800 parts of tetraethoxynonyl phenol or the nonyl ratio of another alcohol and 100 parts of glycerol in a suitable vessel and efficiently stirring the mixture together. The temperature of the mixture is raised to 90°C. Nitrogen is then blown into the reaction vessel and when substantially all of the air has been displaced, amino sulfonic acid, typically dodecyl amino sulfonic acid, is slowly added thereto over a period of three hours. The quantity added should be sufficient to supply approximately 1.1 moles of the amino sulfonic acid per mole of tetraethoxynonyl phenol. The reaction mixture is finally agitated at a temperature of about 115°C. for one hour. Using this particular process, the nonyl phenol amino sulfonate is obtained directly in the form of the ammonium salt due to the use of the amino sulfonic acid as the sulfonating agent.

The various amino sulfonates discussed above may be used as such or as the alkali metal, alkaline earth metal salts, e.g. , sodium, potassium, calcium, magnesium salts, or ammonium salts.

The halogen used can be iodine, bromine, chlorine or fluorine, and the properties of the various end complexes produced in accordance with this invention will of course vary depending upon the particular halogen employed. Iodine is the most advantageous halogen.

Various well-known nonionic surface-active agents can be used in conjunction with the ampholytic amino sulfonates and the halogens to form the stable complex of this invention. To date, no nonionic surface-active agent has been found which cannot be used to form the new class of disinfectant compositions according to this invention.

Examples of the more advantageous nonionic surface-active agents, which may be characterized as complexing aids, include the nonionic ethylene oxide condensate-type surface-active agents such as the polyethoxylate of alkyl phenols in which the alkyl group contains from about 7 to 11 carbon atoms and the condensate contains about 9 to 17 ethylene oxide units. Dimethylnonyl polyethoxylate, marketed under the name of Tergitol S-9, has been found to be particularly advantageous. The numeral 9 indicates the presence of 9 ethylene oxide units, but it is understood that many more ethylene oxide units can be present, even up to 20 to 30 ethylene oxide units.

Further examples of nonionic surface-active agents which can be used in conjunction with the ampholytic amino sulfonate compounds are the nonionic betaines such as the N-alkyl betains, for example, N-lauryl betaine. Again it is advantageous to use betaines in which the alkyl group is of higher molecular weight, for example, those containing 9 to 14 carbon atoms.

It is particularly advantageous to use higher molecular weight nonionic ethylene oxide condensation products containing 9 or more moles of ethylene oxide since it has been found that this results in a novel complex which is less irritating and less toxic particularly when the complex is to be used for oral administration to animals.

The glycol which forms an essential part of the stable complex of this invention preferably has at least three, and may have upto twelve carbon atoms. . The expression "glycol" will be understood to include the condensed glycols, or ether glycols, that is to say the polyalkylene glycols such as triethylene glycol, O-C H.-OH. Of the alkylene glycols, 1 : 2- propylene glycol is 2 d preferred but 1 : 3 propylene glycol, and diethylene and triethylene glycols may be used in the same way and in equivalent amounts. The function of the glycol is to stablize the resulting cage complex and the lower its molecular weight the better.

Although the exact mechanism is not known, it is quite clear that the nonionic surface-active agent and glycol actually enter into the molecular structure of the resulting stable halogen complex and become an integral part thereof . It is believed that the ampholytic germicidal nt to th r with the l col and the nonionic urface-active a ent form agent and 1 mole of glycol.

The novel complexes of this invention are in general semi-solid or viscous liquids and their colour, odour, and taste will depend on the particular halogen employed. Where iodine is employed, the complexes have a deep yellowish-brown colour, a distinctive penetrating odour, and a slightly bitter taste. They are in general heavier than water; they show no iodine reaction with starch at room temperature or at slightly elevated temperatures, at least up to 100°C. ; they show no loss of iodine on heating up to 100°C. and in general no loss on heating up to 200°C. In the presence of long chain organic anions, on the contrary, the novel iodine-containing complexes of this invention are disrupted with the liberation of iodine. One specific agent which will disrupt the novel complexes of this invention is dodecylbenzene sulfonic acid.

Mixtures of various different ampholytic amino sulfonates as well as mixtures of various different nonionic surface-active agents can of course be used in accordance with this invention. Mixtures of the various halogens could also be used if desired.

As previously discussed, the novel halogen complexes of this invention have the same or better disinfectant or germicidal properties as the known iodophors and can be used in the same manner. The novel complexes of this invention can further be diluted with water (especially if containing excess non-ionic surface-active agent) and are effective against both gram-negative and gram-positive organisms, fungi and viruses. They have the advantage that the halogen, particularly iodine, while retaining its germicidal function and extending the lethal spectrum of the ampholytic germicidal amino sulfonates, can be fully complexed and are thus rendered non-irritating, non-tainting, and non-staining. Further it becomes possible to use numerous perfumes previously unstable in the presence of a simple iodine solution.

The novel complexes of this invention can be applied in known manners for the purposes of disinfecting hospitals, animal living quarters such as stalls, pens, kennels, etc. This type of use is best effected by diluting the complex with a suitable amount of water and discharging it through a conventional aerosol container.

The complexes of this invention can also be used for topical application to animals and humans at the concentration required or desired by incorporating it into suitable and known carriers to form solutions or creams so long as the carrier does not adversely affect the disinfectant properties or the stability of the complex.

The complexes of this invention have also been used orally and fed to animals. This can be best accomplished by adsorbing onto a suitable powder such as silica powder and mixing with the animal feed. It can also be given to animals by incorporation into drinking water.

The complexes have been adsorbed onto silica powder and mixed with animal feed and fed to chickens, turkeys, and pigs without any noticeable toxic effects.

The of the iodine complexes produced according to this invention is about 3 to 4 g. per kilo in male albino rats of the Wistar strain. Kidneys of the surviving rats after treatments were indis-tinguishable histologically from those of the untreated control rats.

Livers of the surviving rats were substantially normal except for a slight increase in the number of centrilobular fat droplets and slight necrosis.

The production of the novel complexes of this invention is particularly simple. All that is required is to mix the components together, namely, the ampholytic amino sulfonate, the nonionic surface-active agent, and the glycol and then incorporate the halogen, maintaining the mixture at a moderately elevated temperature with agitation. The purpose of the agitation is merely to insure that the reagents are kept in intimate contact with each other during the formation of the complex.

The proportions of the ampholytic amino sulfonate, the non-ionic surface-active agent, and the halogen are not critical although the reaction proportions appear to be specific since any excess iodine will remain at the bottom of the reaction vessel while any excess ampholytic amino sulfonate will remain as a separate phase at the top of the reaction mixture. Any excess nonionic surface-active agent appears to remain as a dilutent in the reaction mixture without adversely affecting the formation or properties of the novel antimicrobial complexes. An example of specific proportions which can be used as a guide where the nonionic surface-active agent is nonyl phenol polyethoxylate such as the sodium salt, is one part of halogen such as iodine, 2 1/2 - 3 parts of the amino sulfonate produced according to the procedure beginning on page 4, line 17, and continuing over to page 5, line 6, (preferably 5 .- 6 parts in the form of a 50 percent aqueous dispersion or solution) 3«6 parts of the nonyl phenol polyethoxylate and 1 part of propen - 1:2 - diol. The parts are by weight. With these proportions the iodine and the ampholyte are substantially completely complexed together with the nonyl phenol as a dilutent in the final product. It is understood, however, that these proportions will vary depending upon the particular ampholyte and nonionic surface-active agent used« The preferred procedure for making the novel complexes is to first mix the ampho lytic amino sulfonate, glycol and the non-ionic surface-active agent in a suitable vessel furnished with heating and stirring means and heating the mixture to about 70°C. to 75°C. while stirring until a clear solution results, after which the halogen, such as iodine, is charged in and the agitation continued for a sufficient time to insure dissolution. Usually approximately 30 minutes will be required to complete the complexing reaction, but this will vary to some extent depending upon the nature of the agitation, the temperature used, as well as the specific ingredients employed in making the complexes. Generally, continued agitation, even for several hours, will not have any adverse effects in the production of the complexes. After the reaction has been completed, the mixture is allowed to cool. The end product may be diluted with water, preferably distilled water, free from interfering cations such as calcium or magnesium, to a standard or desired concentration, de-pending upon the end use desired of the product. Any addition of water, whether it be for the purpose of diluting to a predetermined desired concentration or merely for the purpose of making good water loss during the reaction, should be deferred until the reaction is complete.

The following example illustrates compositions in accordance with the invention: Example (the ammonia salt) were mixed with 3.6 5 parts of nonyl phenol pol ethoxylate (Na salt), 1 part of 1:2 propylene glycol and 0.6 parts of an ethylene oxide condensation product (about 3 moles ethylene oxide) of the ampholyte, and were heated to 70-75°C. with stirring until the solution became clear. One part of iodine was then added to the clear solution and agitation continued 10 for about 30 minutes until substantially complete dissolution of the iodine and the complexing of the reactants were completed. -The complex is then cooled and can be diluted with distilled water to the concentration desired. Parts are by weight, taking iodine as 1. The above disinfectant composition was tested and found successful for the 15 controlling and killing of numerous microorganisms, including Pseudomonas pyocyanea, as well as Staph¾.ococcus strains, as well as various fungi and viruses.

The other halogens, namely, chlorine, bromine, and fluorine can be substituted for the iodine such compositions also have germicidal activity, but iodine is preferred.

The pH of the complexes of this invention is preferably retained on the acid side such as a pH between 5 and 6, but the invention is not limited thereto. In some instances the pH can be higher or lower, depending on the particular materials used to form the complex and the particular materials used in conjunction therewith or additives for the complex. In some instances the pH can be fairly highly alkaline and buffered back to an acid pH or to a pH of about 7.5.

Claims (9)

C L A I M S I An antimicrobial

1. / A composition comprising a complex of an ampholytic organo amino sulfonate, a nonionic surface-active agent, a glycol and a halogen.

2. The composition of claim 1 in which the halogen is iodine . gbyxxikxxtf-KX ¾¾ togescxx iocioddxKX 1 K

3. The composition of claim 4c in which the ampholytic organo amino sulfonate contains an alkyl group having between about 12 and 14 carbon atoms. 3 6ς

4. The composition of claim |c in which the nonionic surface- active agent is an ethylene oxide condensation product. 4 ¾

5. . The composition of claim %. in which the ethylene oxide condensation product contains an alkyl group having from about 7 to 11 carbon atoms and between about 9 and 17 ethylene oxide units. 5 3θς

6. The composition of claim 5. in which the nonionic surface- active agent is n-octyl phenol ethylene oxide condensate. 2 -φς

7. The composition of claim £ in which the surface-active agent is an ampholytic N-alkyl betaine. 1 xli¾t

8. The composition of claim 2 in which the halogen is at least one member of the group consisting of iodine, chlorine, bromine and fluorine . 1 -4i.

9. The composition according to claim $ in which the glycol contains from 3 to 8 carbon atoms. 1 li c 1 0. The composition according to claim ¾5 in which the glycol is selected from the group consisting of 1 : 2 propylene glycol, 1 i 3 propylene glycol and trimethylene glycol. £% 1 1 . A complex of 1 mole of nonionic surface-active agent, 1 mole of ampholytic germicidal agent, 1 mole of a glycol and 1 equivalent of iodine . 14x 1 2 . The method of disinfecting which comprises applying to the ' area to be disinfected a composition according to "claim x 2. ¾ .· 1 3. The method of controlling the growth of micro-organisms in .animals which comprises orally administering thereto a composition according to claim 4ςχ 2 . AGENT FOR APPLICANTS Tel-Aviv, dated 6th May, 1968