CA1129851A - Antimicrobial poly-alcohols and derivatives thereof - Google Patents
Antimicrobial poly-alcohols and derivatives thereofInfo
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- CA1129851A CA1129851A CA332,439A CA332439A CA1129851A CA 1129851 A CA1129851 A CA 1129851A CA 332439 A CA332439 A CA 332439A CA 1129851 A CA1129851 A CA 1129851A
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- functional derivative
- polysaccharide
- ammonium salt
- quaternary ammonium
- polyalcohol
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Abstract
ABSTRACT OF THE INVENTION
Polyalcohols and functional derivatives thereof that are chemically antimicrobially activated, methods of their prepar-ation, and finished products manufactured therewith are claimed and described. The antimicrobial entities are the esterification products of a polyalcohol or functional derivative thereof and a quaternary ammonium salt containing in direct attachment to its cationic nitrogen at least one long chain alkyl group and at alkanoic acid or alkanoic acid functional group. A variety of finished products, particularly useful in the medical/surgical field, can be manufactured with the novel entities of this inven-tion.
Polyalcohols and functional derivatives thereof that are chemically antimicrobially activated, methods of their prepar-ation, and finished products manufactured therewith are claimed and described. The antimicrobial entities are the esterification products of a polyalcohol or functional derivative thereof and a quaternary ammonium salt containing in direct attachment to its cationic nitrogen at least one long chain alkyl group and at alkanoic acid or alkanoic acid functional group. A variety of finished products, particularly useful in the medical/surgical field, can be manufactured with the novel entities of this inven-tion.
Description
~lZ~8~;1 B~CKGROUND OF THE INVENTION
This invention relates to polyalcoholic, primaril~ cellu-losicr derivatives and to their preparation, said deri~atives possessing antimicrobial activity.
Some previously known antimicrobial cellulose products are prepared by simply spraying an antimicrobial agent onto the cellulose. In these products the antimicrobial agent is not chemically incorporated into the cellulose and, as a result, antimicrobial activity is easily washed or leached out.
Quaternary ammonium salts containing long chain alkyl groups have been used in the past as antimicrobial agents in conjunction with cellulose products to impart an antimicxobial nature thereto. Howevers for varioUs reasons, these salts have, for the most part, not been readily chemically bonded lS directly to cellulose to produce cellulose derivatives which retain antimicrobial activity after repeated washings. In this con-text, the preparation of previously known antimicrobial cellulose derivatives usually requires pretreating the cellu-lose before the particular antimicrobial agent, usually a quaternary ammonium salt, can be chemically bound thereto.
For example, U.S. Patent 2,931,753 teaches an antimicrobial cellulose derivative which is a high molecular wei~ht or~anic ammonium salt of a polysaccharide carboxylic acid depicted by the formula o in which Rl is a high moleculax weight alkyl, alkenyl or alkenyl group and (~O-C-Xl) is part of one of the cyclic units of the polysaccharide anion or acid radical, Xl representing the lactol ring of this unit ~29~3S~
(usually a pyranose unit) and including the group that connects the carbonyl carbon atom o~ this acid radical to a carbon atom in the lactol ring, and this carbonyl carbon atom being either directly bonded to a carbon atom in the lactol ring as in alginic acid and peptic acid or bonded to the carbon atom in the lactol ring through the groUp (CH2 O) as in carboxyl methyl cellulose and in carboxy methyl starch or through higher alkoxy groups such as (CH2CH2O) as in carboxy ethyl cellulose and carboxyl ethyl starch. In the preparation of these antimicrobi-al derivatives, some of the hydroxyl groups of cellulose, or other polysaccharide, are converted to -O~H2COONa- to provide - host sites for a quaternary ammonium salt.
U.S. Patent 3,817,702 teaches the introduction of anion active sites on cellulosic textiles prior to addiny a cation-active microbicide such as quaternary ammonium salt. The anion-active sites are provided by reacting cellulose with the chlor ine atoms of p-N-(4,6-dichloro) s-triazinylaminobenzene-carboxy-lic acid or sulfonic acid. Thereater, the acid group is reacted with a bactericidal quaternary ammonium salt. Similar-20 ly U.S. Patent 3,5g4,221 describes treating cellulose with acid or alkali metal montmorillonite clay and a cationic germicide to provide cellulosic products which are resistant to ~acterial action ovar an extended period of time.
According to U.S. Patent 3,728,213, an antibiotic property is imparted to cellulose by the addition of a 2-(C8 C18 substan-tially straight chain) pseudourea. The antimicrobial ~e~tu~e of such cellulose derivatives can be made lon~ ting b~ in-corporating into said derivatives a normally water-soluble thermosetting wet strength resin in the thermoset state.
Heretofore, the art pertaining to cellulose~ and dexiva-tives thereof, possessing good, non-transient antimicxobi~l . . , ~ - .
~z~
activity, does not include any entity which result from chemically bonding a quaternary ammonium salt to cellulo~e, or derivative thereof by ester linkages through polyalcoholic hydroxyl groups.
. "
~L~2~851 SUMM~RY -O~ THE INVENTLON
Antimicrobially active polyalcohols and, in particular, cellulose which overcomes the problems associated wi-th pre-viously known related products have now been discovexed. The new antimicrobial entities are the esterification products o~
a polyalcoholic host ma-terial and a quatexnary ammonium salt (antimicrobial agent)containing in direct attachment to the positively charged nitrogen thereof at least one long chain alkyl group and an alkanoic acid functional group. Esters result from ester linkages between the alkanoic acid ~roups and one or more hydroxyl group5 of the host material. The new antimicrobial entities possess good antimicrobial activity which is not readily washed away upon repeated extraction with water.
Because the antimicrobial active quaternary ammonium salt is attached to the cellulose throu~h an ester linka~e of the alkanoic function, not the cationic nitro~en, antimicrobial activity is imparted to the host matexial by an antimicrobial component that is essentially and functionally identical to the unreacted salt. It is believed that this results in enhanced antimicrobial activity of the novel entities of this invenkion.
Additionally, the presence of an alkanoic acid or alkanoic acid derivative permits esterification with hydroxyl groups of the polyalcohol eliminating the requirement of modi~ying the ~ydr-oxyl groups prior to reacting with a quaternary ammonium salt.This enables the production of an antimicrobial polyalcoholic product that more closely resembles the unactivated polyalcohol.
Host materials other than cellulose may be emplo~ed with-in this invention. Basically, any host material capable o~
esterification with the alkanoic acid groups o~ the quatern~r~
~g~Sl ammonium salt are suitable. Such host materials include cellulose .iacetate, .starch, starch derivatives, rayon, rayon acetate, polyvinyl alcohol, alkyd resins, hydroxylated poly-urethanes, and other pol~alcohols.
-~a-Case 2128 1, 1~2~3S~
1 A variety o finished products can be manu~actured with the new antimicrobial entities of this,invention~ Such ~inished pxo-' ducts are particularly useful in the.~edical/~urgical field.
.. - , !
~~ _5_ 1 985~l DETAILED DESCRIPTION O~`TEIE INVENTION
Broadly, this invention relates to novel antimicrobially active pol~alcohols and ~unctional derivatives -th~reo~, ~inished products manufactured therewith, and to methods o~ their prep~
aration. The present compounds are the esterification pxoducts of a host polyalcohol or derivative thereo~ and a quaternary ammonium salt, which is an antimicrobial agent, containing in direct attachment to the positively charged nitrogen thereo~ at least one long chain alkyl group and an alkanoic acid or alkan-~ oic acid functional group. The resulting ester contains an antimicrobial component, deri~ed from the quaternar~ ammonium salt, that is ess~ntially and functionally identical to the un-reacted quaternary ammonium salt in that it is not attached to the host material through its cationic nitrogen.
Quaternary ammonium salts contribut~ the antimicrobial component of compounds of this invention and they are depicted by the formula ~ R3 -- N ( CII ~ ) n in which Rl and R2 are the same or different and each can be a straight or branched chain alkyl group of from 1 to 10 carbon atoms or a phenyl or phenyla~ group of from 7 to 10 car~on atoms; R3 is a long straight or branched chain alkyl group of from 8 to 20 carbon atoms; R4 is OH, chloride, bromider iodide or -O-~ -R5 wherein R5 is hydrogen or an alk~l group of ~rom 1 to 3 carbon atoms; n is an integer o~ ~rom l to ~; and X is a halide such as chloride, bromide, ~nd iodide, or sulfater .
s~
acetate, or the like. Pxe~erabl~, Rl and R~ are methyl; R3 contains about 18 carbon a~oms; R4 and X are halide and n is the integer 1 or 2.
-6~-';`':1 --- Case 2128 ~Z985~
The most important host materials employed in this invention are cellulose and cellulose acetate. By way o~ illustration, cel-lulose consists of anhydro~glucose unit~, connected by glycosidic linkages, each unit providing three free hydroxyl groups, one being of primary alcoholic nature (CH20H) and the other two of secondary alcoholic nature tO~) connected directly to respective carbon atoms in the lactol (pyranose) ring. Cellulosic anhydro-glucose units are depicted by the formula 0~ ~
It is believed the hydroxyl group located at the 6 position above form an ester linkage with the -~-R4 portion of the quater-nary ammonium salt.
~1 ,Oj However, it is possible additional ester linkages are formed with hydroxyls located at the 2 position, shown above. When cellulosic acetate is the host material, it is understood that acetate groups should not be present at all three hydroxyl Case 2128 li2~a851 positions of the anhydro-glucose unit. However, as the esteri~ied entities o~ this invention demonstrate good antimicrobial activity when they contain small amounts of the antimicr~bial component, the fact that some anhydro-glucose hydroxyls are not available, as in cellulose acetate, presents no problem. Similarly, other esters of this invention utilize available hydroxyls of the partic-ular host polyalcohol, or derivative thereof, involved.
Additionally, it should be pointed out that the -~-R4 portion of the quaternary ammonium salts serves only as a vehicle for est-erification and no antimicrobial activity is attributed thereto.As antimicrobial activity results from sther portions of the salt and these portions remain intact after esterification, the anti-microbial activity demonstrated by esters of this invention is similar to that of the unreacted salt.
The antimicrobial polyalcohols of this invention demonstrate antimicrobial activity when they contain as little as 0~1%, by weight, of the antimicrobial component. Optimum antimicrobial polyalcohols contain about 1% of the antimicrobial component.
Host materials suitable in preparing esters of this invention include, but are not limited tOr cellulose, cellulose acetate, rayon, rayon acetate, starch, other polysaccharides, polyvinyl alcohol, synthetic alcohols, alkyd resins, and other polyalcohols. Actually, any chemical entity containing available hydroxy groups for ester-ification with a quaternary ammonium salt containing a (~H2)~ ~-R4 radical attached to the cationic nitrogen can be employed as a hos~
material.
Quaternary ammonium salts employed in this invention are prepared by conventional methods. For example, they may be prepared by treating a tertiary amine with a chloroalkanoic acid in a suit-~ j 9~
able organic solvent such as acetonitrile. The resultingquaternary ammonium sal-t can be readily converted, i desired, to the corresponding acid halide or anh~dride.
Alternatively, a tertiary amine ~nd alkyl laatone can be reacted in a sui-table organic solven~ such as acetonitrile.
The resulting product is then treated with an acid in ethyl alcohol to provide a quaternary ammonium salt containing an alkanoic acid group which is readily converted to the correspond-ing acid halide or`anhydride.
Illustrative e~amples of tertiary amines which are suit-able for preparing quaternary ammonium salts employed in this invention are: dimethyldecyl amine; dieth~ldecyl amine; di-methyloctyl amine; dimethyllauryl amine; dimethylmyristyl amine; dimethylpalmityl amine; methyldicotyl ~mine; methyl (phenylethyl)nonyl amine; diphenyloctyl amine; methyl(phenyl-n-butyl)octylamine; n-propylisopropyllauryl amine; and methyl-phenyldecyl amine.
The method of preparing the present antimicrobial com~
pounds is not critical, and any o~ a varie~ of methods ma~ be used. Preferably, for example, pUlp is treated ~ith ~lacia~
acetic acid to activate the cellulose fibers che`mically. There after, the activated fibers are treated in situ with an above-depicted quaternary ammonium salt to provide antimicrobially active cellulosic fibers.
Alternatively, the pulp can be p~rtially es~eri~ied pXior to treating with a quaternay ammonium salt. However~ such esteri~i-cation must be monitored to prevent e~haustion o~ h~droxyl groups required for introducin~ the qua~ernary ~monium salt.
Additionally, antimicrobially active cellulose can be subjected to esterification. Such esteri~ication can be carrie~ ou~ in accordance with standard condi~ions for preparing ceIlulose _g _ `~ ,`'.-~L2~
acetate.
It will be readily apparent to those skilled in the artthat the antimicrobial esters of this invention are pxepared by standard or conventional methods and that opt~nium rsaction conditions depend upon the particular reactanks involved.
Products o~ this invention are useful as antimicrobial agents as demonstrated by their ability to retard the growth of STAPHYLOCOCCUS AUREUS. This was shown by sterili~ing capped tubes containing 0.1.g. quantities of treated pulp with ethy-lene oxide. The sterilized tubes were innoculated with 25-50 u.l. of suspension containing 10 -107 colony forming unit~ of STAPHYLOCOCCUS AUREUS and then incub~ted at ambient temperature for one or more days. 10 ml. of Nutrient Agar was added to each incubated tube followed by incubation at 35 C for 72 hours.
Turbidity, indicating growth of viable cells, was observed at 24, 48 and 72 hours. Control samples containing un reated pulp were run simultaneously with the test samples. The results shown in TABLE I, below, indicate that pulp containing 1~ anti-microbial component demonstrate good antimicrobial acti~ity.
TAB'IE'I
Microbial (STAPHYLOCOCCUS AU~EUS~ challen~e of Cellulosic Material (Pulp) treated ~ith 1~ (Chloro$ormylalk~1~oc~de-cyldimethylammonium chloride Fraction of tubes' showin~
Growth after Treatment l_Day 2 Days 3 D'~y~:
None (Control) 10/10 10/10 10/10 1% (Chloroformylmethyl) 6/8 0/10 1/10 octadecyldimethylammonium chloride 1~ (Chloroformylethyl) 9/10 3/~0 1/10 octadecyldimethylammonium chloride .j,, .
¦ Case 2128 , liZ985~
I' ,.
~, i The antimicrobial activity associ~ted with this invention demonstrates good substantivity, meaning the activity is not readily washea or leached out. This was sho.~n by extractin.~ anti-;
microbial Pulp o~ this in~ention with water ~3-4 cycles/hours) ~in a Soxhlet extractor. Following extractions the pulp was air ¦dried and then assayed, as described abo~e, for an~imicrobial jactivity. The results shown in TABLE 2, below, indicate that pulp i Icontaining 1~ antimicrobial component demonstrate good substantiv-jity.
'.~ I
j TABLE 2 Substantivit~ j Fraction showing growth after extraction for th~ indicated period , Treatment 0 hr. 1 hr. - hr. -3 hr.
~one ~control) 20/20 ¦1~ (chloroformyl 0/29 0/30 3~30 6/30 methyl~octadecyl-dimethylammonium chloride 1% (chloroformyl 0/30 0/30 2/30 1~30 ethyl)octade~yl- -dimethylammonium chloride The preparation o~ guaternar~ ammonium compounds usefùl herei is further illustrated by the following examples:
Example A
. , 1 1. 148~5g. of octadecyldimethyl amine is added to a stixriny ¦Isolution of 47.3g. of ch~oroacetic acid in 500 ml~ of acetonitrile.i I~The mixture is refluxed for 20 hours before removing the aceton~
1~ jitrile under vacuum in a rotary evaporator. The resul-ting qu~ter-nary ammonium Sa1tJ (carboxymethyl)octadecyldimethylammonium Ichloride, is heated at ~0C, under vacuum for 20 hours to remove ,any residual ace~onitrile.
11 -11 .
Case 2128 85~
This invention relates to polyalcoholic, primaril~ cellu-losicr derivatives and to their preparation, said deri~atives possessing antimicrobial activity.
Some previously known antimicrobial cellulose products are prepared by simply spraying an antimicrobial agent onto the cellulose. In these products the antimicrobial agent is not chemically incorporated into the cellulose and, as a result, antimicrobial activity is easily washed or leached out.
Quaternary ammonium salts containing long chain alkyl groups have been used in the past as antimicrobial agents in conjunction with cellulose products to impart an antimicxobial nature thereto. Howevers for varioUs reasons, these salts have, for the most part, not been readily chemically bonded lS directly to cellulose to produce cellulose derivatives which retain antimicrobial activity after repeated washings. In this con-text, the preparation of previously known antimicrobial cellulose derivatives usually requires pretreating the cellu-lose before the particular antimicrobial agent, usually a quaternary ammonium salt, can be chemically bound thereto.
For example, U.S. Patent 2,931,753 teaches an antimicrobial cellulose derivative which is a high molecular wei~ht or~anic ammonium salt of a polysaccharide carboxylic acid depicted by the formula o in which Rl is a high moleculax weight alkyl, alkenyl or alkenyl group and (~O-C-Xl) is part of one of the cyclic units of the polysaccharide anion or acid radical, Xl representing the lactol ring of this unit ~29~3S~
(usually a pyranose unit) and including the group that connects the carbonyl carbon atom o~ this acid radical to a carbon atom in the lactol ring, and this carbonyl carbon atom being either directly bonded to a carbon atom in the lactol ring as in alginic acid and peptic acid or bonded to the carbon atom in the lactol ring through the groUp (CH2 O) as in carboxyl methyl cellulose and in carboxy methyl starch or through higher alkoxy groups such as (CH2CH2O) as in carboxy ethyl cellulose and carboxyl ethyl starch. In the preparation of these antimicrobi-al derivatives, some of the hydroxyl groups of cellulose, or other polysaccharide, are converted to -O~H2COONa- to provide - host sites for a quaternary ammonium salt.
U.S. Patent 3,817,702 teaches the introduction of anion active sites on cellulosic textiles prior to addiny a cation-active microbicide such as quaternary ammonium salt. The anion-active sites are provided by reacting cellulose with the chlor ine atoms of p-N-(4,6-dichloro) s-triazinylaminobenzene-carboxy-lic acid or sulfonic acid. Thereater, the acid group is reacted with a bactericidal quaternary ammonium salt. Similar-20 ly U.S. Patent 3,5g4,221 describes treating cellulose with acid or alkali metal montmorillonite clay and a cationic germicide to provide cellulosic products which are resistant to ~acterial action ovar an extended period of time.
According to U.S. Patent 3,728,213, an antibiotic property is imparted to cellulose by the addition of a 2-(C8 C18 substan-tially straight chain) pseudourea. The antimicrobial ~e~tu~e of such cellulose derivatives can be made lon~ ting b~ in-corporating into said derivatives a normally water-soluble thermosetting wet strength resin in the thermoset state.
Heretofore, the art pertaining to cellulose~ and dexiva-tives thereof, possessing good, non-transient antimicxobi~l . . , ~ - .
~z~
activity, does not include any entity which result from chemically bonding a quaternary ammonium salt to cellulo~e, or derivative thereof by ester linkages through polyalcoholic hydroxyl groups.
. "
~L~2~851 SUMM~RY -O~ THE INVENTLON
Antimicrobially active polyalcohols and, in particular, cellulose which overcomes the problems associated wi-th pre-viously known related products have now been discovexed. The new antimicrobial entities are the esterification products o~
a polyalcoholic host ma-terial and a quatexnary ammonium salt (antimicrobial agent)containing in direct attachment to the positively charged nitrogen thereof at least one long chain alkyl group and an alkanoic acid functional group. Esters result from ester linkages between the alkanoic acid ~roups and one or more hydroxyl group5 of the host material. The new antimicrobial entities possess good antimicrobial activity which is not readily washed away upon repeated extraction with water.
Because the antimicrobial active quaternary ammonium salt is attached to the cellulose throu~h an ester linka~e of the alkanoic function, not the cationic nitro~en, antimicrobial activity is imparted to the host matexial by an antimicrobial component that is essentially and functionally identical to the unreacted salt. It is believed that this results in enhanced antimicrobial activity of the novel entities of this invenkion.
Additionally, the presence of an alkanoic acid or alkanoic acid derivative permits esterification with hydroxyl groups of the polyalcohol eliminating the requirement of modi~ying the ~ydr-oxyl groups prior to reacting with a quaternary ammonium salt.This enables the production of an antimicrobial polyalcoholic product that more closely resembles the unactivated polyalcohol.
Host materials other than cellulose may be emplo~ed with-in this invention. Basically, any host material capable o~
esterification with the alkanoic acid groups o~ the quatern~r~
~g~Sl ammonium salt are suitable. Such host materials include cellulose .iacetate, .starch, starch derivatives, rayon, rayon acetate, polyvinyl alcohol, alkyd resins, hydroxylated poly-urethanes, and other pol~alcohols.
-~a-Case 2128 1, 1~2~3S~
1 A variety o finished products can be manu~actured with the new antimicrobial entities of this,invention~ Such ~inished pxo-' ducts are particularly useful in the.~edical/~urgical field.
.. - , !
~~ _5_ 1 985~l DETAILED DESCRIPTION O~`TEIE INVENTION
Broadly, this invention relates to novel antimicrobially active pol~alcohols and ~unctional derivatives -th~reo~, ~inished products manufactured therewith, and to methods o~ their prep~
aration. The present compounds are the esterification pxoducts of a host polyalcohol or derivative thereo~ and a quaternary ammonium salt, which is an antimicrobial agent, containing in direct attachment to the positively charged nitrogen thereo~ at least one long chain alkyl group and an alkanoic acid or alkan-~ oic acid functional group. The resulting ester contains an antimicrobial component, deri~ed from the quaternar~ ammonium salt, that is ess~ntially and functionally identical to the un-reacted quaternary ammonium salt in that it is not attached to the host material through its cationic nitrogen.
Quaternary ammonium salts contribut~ the antimicrobial component of compounds of this invention and they are depicted by the formula ~ R3 -- N ( CII ~ ) n in which Rl and R2 are the same or different and each can be a straight or branched chain alkyl group of from 1 to 10 carbon atoms or a phenyl or phenyla~ group of from 7 to 10 car~on atoms; R3 is a long straight or branched chain alkyl group of from 8 to 20 carbon atoms; R4 is OH, chloride, bromider iodide or -O-~ -R5 wherein R5 is hydrogen or an alk~l group of ~rom 1 to 3 carbon atoms; n is an integer o~ ~rom l to ~; and X is a halide such as chloride, bromide, ~nd iodide, or sulfater .
s~
acetate, or the like. Pxe~erabl~, Rl and R~ are methyl; R3 contains about 18 carbon a~oms; R4 and X are halide and n is the integer 1 or 2.
-6~-';`':1 --- Case 2128 ~Z985~
The most important host materials employed in this invention are cellulose and cellulose acetate. By way o~ illustration, cel-lulose consists of anhydro~glucose unit~, connected by glycosidic linkages, each unit providing three free hydroxyl groups, one being of primary alcoholic nature (CH20H) and the other two of secondary alcoholic nature tO~) connected directly to respective carbon atoms in the lactol (pyranose) ring. Cellulosic anhydro-glucose units are depicted by the formula 0~ ~
It is believed the hydroxyl group located at the 6 position above form an ester linkage with the -~-R4 portion of the quater-nary ammonium salt.
~1 ,Oj However, it is possible additional ester linkages are formed with hydroxyls located at the 2 position, shown above. When cellulosic acetate is the host material, it is understood that acetate groups should not be present at all three hydroxyl Case 2128 li2~a851 positions of the anhydro-glucose unit. However, as the esteri~ied entities o~ this invention demonstrate good antimicrobial activity when they contain small amounts of the antimicr~bial component, the fact that some anhydro-glucose hydroxyls are not available, as in cellulose acetate, presents no problem. Similarly, other esters of this invention utilize available hydroxyls of the partic-ular host polyalcohol, or derivative thereof, involved.
Additionally, it should be pointed out that the -~-R4 portion of the quaternary ammonium salts serves only as a vehicle for est-erification and no antimicrobial activity is attributed thereto.As antimicrobial activity results from sther portions of the salt and these portions remain intact after esterification, the anti-microbial activity demonstrated by esters of this invention is similar to that of the unreacted salt.
The antimicrobial polyalcohols of this invention demonstrate antimicrobial activity when they contain as little as 0~1%, by weight, of the antimicrobial component. Optimum antimicrobial polyalcohols contain about 1% of the antimicrobial component.
Host materials suitable in preparing esters of this invention include, but are not limited tOr cellulose, cellulose acetate, rayon, rayon acetate, starch, other polysaccharides, polyvinyl alcohol, synthetic alcohols, alkyd resins, and other polyalcohols. Actually, any chemical entity containing available hydroxy groups for ester-ification with a quaternary ammonium salt containing a (~H2)~ ~-R4 radical attached to the cationic nitrogen can be employed as a hos~
material.
Quaternary ammonium salts employed in this invention are prepared by conventional methods. For example, they may be prepared by treating a tertiary amine with a chloroalkanoic acid in a suit-~ j 9~
able organic solvent such as acetonitrile. The resultingquaternary ammonium sal-t can be readily converted, i desired, to the corresponding acid halide or anh~dride.
Alternatively, a tertiary amine ~nd alkyl laatone can be reacted in a sui-table organic solven~ such as acetonitrile.
The resulting product is then treated with an acid in ethyl alcohol to provide a quaternary ammonium salt containing an alkanoic acid group which is readily converted to the correspond-ing acid halide or`anhydride.
Illustrative e~amples of tertiary amines which are suit-able for preparing quaternary ammonium salts employed in this invention are: dimethyldecyl amine; dieth~ldecyl amine; di-methyloctyl amine; dimethyllauryl amine; dimethylmyristyl amine; dimethylpalmityl amine; methyldicotyl ~mine; methyl (phenylethyl)nonyl amine; diphenyloctyl amine; methyl(phenyl-n-butyl)octylamine; n-propylisopropyllauryl amine; and methyl-phenyldecyl amine.
The method of preparing the present antimicrobial com~
pounds is not critical, and any o~ a varie~ of methods ma~ be used. Preferably, for example, pUlp is treated ~ith ~lacia~
acetic acid to activate the cellulose fibers che`mically. There after, the activated fibers are treated in situ with an above-depicted quaternary ammonium salt to provide antimicrobially active cellulosic fibers.
Alternatively, the pulp can be p~rtially es~eri~ied pXior to treating with a quaternay ammonium salt. However~ such esteri~i-cation must be monitored to prevent e~haustion o~ h~droxyl groups required for introducin~ the qua~ernary ~monium salt.
Additionally, antimicrobially active cellulose can be subjected to esterification. Such esteri~ication can be carrie~ ou~ in accordance with standard condi~ions for preparing ceIlulose _g _ `~ ,`'.-~L2~
acetate.
It will be readily apparent to those skilled in the artthat the antimicrobial esters of this invention are pxepared by standard or conventional methods and that opt~nium rsaction conditions depend upon the particular reactanks involved.
Products o~ this invention are useful as antimicrobial agents as demonstrated by their ability to retard the growth of STAPHYLOCOCCUS AUREUS. This was shown by sterili~ing capped tubes containing 0.1.g. quantities of treated pulp with ethy-lene oxide. The sterilized tubes were innoculated with 25-50 u.l. of suspension containing 10 -107 colony forming unit~ of STAPHYLOCOCCUS AUREUS and then incub~ted at ambient temperature for one or more days. 10 ml. of Nutrient Agar was added to each incubated tube followed by incubation at 35 C for 72 hours.
Turbidity, indicating growth of viable cells, was observed at 24, 48 and 72 hours. Control samples containing un reated pulp were run simultaneously with the test samples. The results shown in TABLE I, below, indicate that pulp containing 1~ anti-microbial component demonstrate good antimicrobial acti~ity.
TAB'IE'I
Microbial (STAPHYLOCOCCUS AU~EUS~ challen~e of Cellulosic Material (Pulp) treated ~ith 1~ (Chloro$ormylalk~1~oc~de-cyldimethylammonium chloride Fraction of tubes' showin~
Growth after Treatment l_Day 2 Days 3 D'~y~:
None (Control) 10/10 10/10 10/10 1% (Chloroformylmethyl) 6/8 0/10 1/10 octadecyldimethylammonium chloride 1~ (Chloroformylethyl) 9/10 3/~0 1/10 octadecyldimethylammonium chloride .j,, .
¦ Case 2128 , liZ985~
I' ,.
~, i The antimicrobial activity associ~ted with this invention demonstrates good substantivity, meaning the activity is not readily washea or leached out. This was sho.~n by extractin.~ anti-;
microbial Pulp o~ this in~ention with water ~3-4 cycles/hours) ~in a Soxhlet extractor. Following extractions the pulp was air ¦dried and then assayed, as described abo~e, for an~imicrobial jactivity. The results shown in TABLE 2, below, indicate that pulp i Icontaining 1~ antimicrobial component demonstrate good substantiv-jity.
'.~ I
j TABLE 2 Substantivit~ j Fraction showing growth after extraction for th~ indicated period , Treatment 0 hr. 1 hr. - hr. -3 hr.
~one ~control) 20/20 ¦1~ (chloroformyl 0/29 0/30 3~30 6/30 methyl~octadecyl-dimethylammonium chloride 1% (chloroformyl 0/30 0/30 2/30 1~30 ethyl)octade~yl- -dimethylammonium chloride The preparation o~ guaternar~ ammonium compounds usefùl herei is further illustrated by the following examples:
Example A
. , 1 1. 148~5g. of octadecyldimethyl amine is added to a stixriny ¦Isolution of 47.3g. of ch~oroacetic acid in 500 ml~ of acetonitrile.i I~The mixture is refluxed for 20 hours before removing the aceton~
1~ jitrile under vacuum in a rotary evaporator. The resul-ting qu~ter-nary ammonium Sa1tJ (carboxymethyl)octadecyldimethylammonium Ichloride, is heated at ~0C, under vacuum for 20 hours to remove ,any residual ace~onitrile.
11 -11 .
Case 2128 85~
2. 50g. of (carboxymethyl)octadecyldimethylammonium chloride is added to 200ml. of toluene and then 25g. of thionyl chloride is added thereto with stirring. The reaction mixture is heated at 70C for 2 hours. Thereafter, excess thionyl chloride is re-moved under aspirator vacuum before cooling the mixture to pro-vide a waxy solid precipitate. The solvent is filtered off under nitrogen using a Buchner funnel leaving the solid salt, (chloro-formylmethyl~octabecyldimethylammonium chloride.
EXAMPL~ B
lQ lo To a stirring solution of 36g. of propiolactone in 500mlO
of acetonitrile 148.8g. of octadecyldimethylamine is carefully added portionwise. After total addition, the resulting precipitateis collected by filtration and then dissolved in 500ml. of ethyl alcohol. lOOml. of concentrated hydrochloric acid is added to the ethanolic solution followed by the addition of water which precip-itates the quaternary ammonium salt, (carboxyethyl)octadecyldim-ethylammonium chloride. The salt is collected by filtration and then dried at 60C under high vacuum for 20 hours.
2. A sample of (carboxyethyl)octadecyldimethylammonium chloride is treated according to the procedure of step 2 of Example A to provide the salt, (chloroformylethyl)octadecyldimethyl ammonium chloride.
These quaternary ammonium salts and other containing, in direct attachment to the positively charged ni~rogen thereof, at least one long chain alkyl group and an alkanoic acid functional group are useful for preparing polyalcoholic derivatives of this inventionc The quaternary ammonium compounds should be added to a host material in an amount sufficient of impart antimicrobial activity thereto. The salts are used in an amount of at least 0.1%, by weight, based on the dry weight of the host material~ Amounts ~12-~ Ca~e 2128 .' ' .
~ Z9,~351 I' .
greater than O.S~are pre~erred and a~ounts o~ about 1% are es~
I pecially ~referred.
¦ The following examples further illustrate th~ present in-. vention:
EX~DLE 1 i . A mixture of 20g. of pul~ and lOg. of glacial ace~ic acid , is shaken occasionally for 1 hour before introducing l90g. o~
¦ ~lacial acetic acid, ll.Og. o~ aetic anhydride and 0.2g~ o~
sulfuric acid and then the reaction mixture is permitted to ¦ stand for 30 ~inutes. To t~e reaction mixture is added 0.2~. o [chloroormylmethvl)octadecyldimethylammonium chloride, taken ! fro.~ Exam~le A abo~e, and the reaction ~ixture is shaken frequent ,' ly for 3 hours. The well shaken mixture is filtered on a Buchner ¦. funnel a~a t~e treated pulp is collectea. The pulp is sequen-!¦ tially washed with ~tater and with acetone, and then dried at sn~c ¦ under vacuum to provide cellulose acetate containing about 1~
by weight, chemically bonded through ester link~iges to the anti-.
~icrobial comvonent depicted by the formula ~ Cl 18~37 ~ ~ - CH2~ ~ - Cl .
! _ CH3 \~'.
EXAMPLE 2 .
20g. sample of pulp is treated according to the manipula-I~. tive procedure.of Example 2, ~ubstitutin~ ~chlorofor~yle~hyljoc~a-, decyldimethyla~monium chloride, taken from Example B above, for ! ~chl~irof~rmvlmethyl)octadecyldi~ethY~ onium chloxide, ta~en rom ExamDle A above, to provide cellulose acetate con~aining 1. ' ~
i <~s~
about 1%, by weight, of the antimicrobial component depicted by the formula --~
fH3 ~18H37 ~ ~ ~ ~CH2)2 ~ Cl ~ ~3 _ which is chemicall~ bonded ~o the cell~lo$e acet~te ~hxou~h ester linkages.
Other antimicrobial comp~unds of this invention are pre-pared in analagous ashion.
The antimicrobial entities o~ this invention can be used to manufacture a variety of products having desirable anti-microbial activity~ Such products include the following:
(1) from a cellulosic host material - fabric, barrier ~abrics for medical app~ications (e.g., drapes, sur~ical and isolation gowns), coatings, diaper pulp, surgical face masks, and ~iltxa-tion media; (2) from starch host material - adhesives, surgical glove powder, wallpaper ~lue, and stabilized starch, and, ~3) from synthetic polyalcohol host material, ~dhesiv~s, paints, water thickenexs, sizing, and coatings. It is under-stood the method of manufacturing s~ch products is no~ çritical in that they can be manufactured as if the antimicrobial cQm ponent was not present.
While speci~ic examples xelatin~ ~o this in~en~ion h~ye been described, it will be evident to t~ose skilled in the ~rt that other variations within the scope of the claim~ ap~ende~
hereto are possible.
EXAMPL~ B
lQ lo To a stirring solution of 36g. of propiolactone in 500mlO
of acetonitrile 148.8g. of octadecyldimethylamine is carefully added portionwise. After total addition, the resulting precipitateis collected by filtration and then dissolved in 500ml. of ethyl alcohol. lOOml. of concentrated hydrochloric acid is added to the ethanolic solution followed by the addition of water which precip-itates the quaternary ammonium salt, (carboxyethyl)octadecyldim-ethylammonium chloride. The salt is collected by filtration and then dried at 60C under high vacuum for 20 hours.
2. A sample of (carboxyethyl)octadecyldimethylammonium chloride is treated according to the procedure of step 2 of Example A to provide the salt, (chloroformylethyl)octadecyldimethyl ammonium chloride.
These quaternary ammonium salts and other containing, in direct attachment to the positively charged ni~rogen thereof, at least one long chain alkyl group and an alkanoic acid functional group are useful for preparing polyalcoholic derivatives of this inventionc The quaternary ammonium compounds should be added to a host material in an amount sufficient of impart antimicrobial activity thereto. The salts are used in an amount of at least 0.1%, by weight, based on the dry weight of the host material~ Amounts ~12-~ Ca~e 2128 .' ' .
~ Z9,~351 I' .
greater than O.S~are pre~erred and a~ounts o~ about 1% are es~
I pecially ~referred.
¦ The following examples further illustrate th~ present in-. vention:
EX~DLE 1 i . A mixture of 20g. of pul~ and lOg. of glacial ace~ic acid , is shaken occasionally for 1 hour before introducing l90g. o~
¦ ~lacial acetic acid, ll.Og. o~ aetic anhydride and 0.2g~ o~
sulfuric acid and then the reaction mixture is permitted to ¦ stand for 30 ~inutes. To t~e reaction mixture is added 0.2~. o [chloroormylmethvl)octadecyldimethylammonium chloride, taken ! fro.~ Exam~le A abo~e, and the reaction ~ixture is shaken frequent ,' ly for 3 hours. The well shaken mixture is filtered on a Buchner ¦. funnel a~a t~e treated pulp is collectea. The pulp is sequen-!¦ tially washed with ~tater and with acetone, and then dried at sn~c ¦ under vacuum to provide cellulose acetate containing about 1~
by weight, chemically bonded through ester link~iges to the anti-.
~icrobial comvonent depicted by the formula ~ Cl 18~37 ~ ~ - CH2~ ~ - Cl .
! _ CH3 \~'.
EXAMPLE 2 .
20g. sample of pulp is treated according to the manipula-I~. tive procedure.of Example 2, ~ubstitutin~ ~chlorofor~yle~hyljoc~a-, decyldimethyla~monium chloride, taken from Example B above, for ! ~chl~irof~rmvlmethyl)octadecyldi~ethY~ onium chloxide, ta~en rom ExamDle A above, to provide cellulose acetate con~aining 1. ' ~
i <~s~
about 1%, by weight, of the antimicrobial component depicted by the formula --~
fH3 ~18H37 ~ ~ ~ ~CH2)2 ~ Cl ~ ~3 _ which is chemicall~ bonded ~o the cell~lo$e acet~te ~hxou~h ester linkages.
Other antimicrobial comp~unds of this invention are pre-pared in analagous ashion.
The antimicrobial entities o~ this invention can be used to manufacture a variety of products having desirable anti-microbial activity~ Such products include the following:
(1) from a cellulosic host material - fabric, barrier ~abrics for medical app~ications (e.g., drapes, sur~ical and isolation gowns), coatings, diaper pulp, surgical face masks, and ~iltxa-tion media; (2) from starch host material - adhesives, surgical glove powder, wallpaper ~lue, and stabilized starch, and, ~3) from synthetic polyalcohol host material, ~dhesiv~s, paints, water thickenexs, sizing, and coatings. It is under-stood the method of manufacturing s~ch products is no~ çritical in that they can be manufactured as if the antimicrobial cQm ponent was not present.
While speci~ic examples xelatin~ ~o this in~en~ion h~ye been described, it will be evident to t~ose skilled in the ~rt that other variations within the scope of the claim~ ap~ende~
hereto are possible.
Claims (37)
1. A process for preparing an antimicrobially active poly-alcohol or functional derivative therof comprising esterifying said polyalcohol or functional derivative thereof with a quater-nary ammonium salt in an amount sufficient to impart antimicrobial activity to said polyalcohol or functional derivative thereof, said quaternary ammonium salt containing an alkanoic acid or alkanoic acid functional group to provide ester linkages between said alkanoic acid or alkanoic acid functional group and hydroxy groups of said polyalcohol or functional derivative thereof, and being depicted by the formula wherein R1 and R2 are the same or different and each can be a straight or branched chain alkyl group of from 1 to 10 carbon atoms or a phenyl or phenylalkyl group of from 7 to 10 carbon atoms; R3 is a higher straight or branched chain alkyl group of from 8 to 20 carbon atoms; R4 is hydroxy, chloride, bromide, iodide or -O-?-R5 wherein R5 is hydrogen or an alkyl group of from 1 to 3 carbon atoms; n is an integer of from 1 to 4; and X is chloride, bromide, iodide, sulfate or acetate; in which the quaternary ammonium salt is used in an amount of at least 0.1% by weight based on the dry weight of the polyalcohol or functional derivative thereof.
2. The process according to Claim 1 in which the polyalcohol or functional derivative is a polysaccharide or functional derivative thereof.
3. The process according to Claim 2 in which the polysaccharide is cellulose.
4. The process according to Claim 3 in which the polysaccharide functional derivative is cellulose acetate.
5. The process according to Claim 1 in which R1 and R2 are the same or different and each is an alkyl group of from 1 to 4 carbon atoms; R3 is an alkyl group of from 15 to 20 carbon atoms; R4 and X are the same or different and each is chloride, bromide, or iodide; and n is the integer 1 or 2.
6. The process according to Claim 5 in which R1 and R2 are each methyl.
7. The process according to Claim 6 in which the quaternary ammonium salt is (chloroformylmethyl)octadecyldi-methylammonium chloride.
8. The process according to Claim 7 in which the polyalcohol or functional derivative thereof is a polysaccharide or functional derivative thereof.
9. The process according to Claim 8 in which the polysaccharide is cellulose.
10. The process according to Claim 8 in which the polysaccharide functional derivative is cellulose acetate.
11. The process according to Claim 1 in which the quaternary ammonium salt is (chloroformylethyl)octadecyldi-methylammonium chloride.
12. The process according to Claim 11 in which the polyalcohol is a polysaccharide or functional derivative thereof.
13. The process according to Claim 12 in which the polysaccharide is cellulose.
14. The process according to Claim 13 in which the polysaccharide functional derivative is cellulose acetate.
15. The process according to Claim 1 in which the quaternary ammonium salt is used in an amount greater than 0.5%.
16. The process according to Claim 15 in which the quaternary ammonium salt is used in an amount of about 1%.
17. An antimicrobial active polyalcholoic product comprising the esterification product of a polyalcohol or functional derivative thereof and a quaternary ammonium salt in an amount sufficient to impart antimicrobial activity to said polyalcohol or functional derivative thereof, said quaternary ammonium salt containing an alkanoic acid or alkanoic acid functional group, and being depicted by the formula wherein R1 and R2 are the same or different and each can be straight or branched chain alkyl group of from 1 to 10 carbon atoms, phenyl or phenylalkyl group of from 7 to 19 carbon atoms;
R3 is a higher straight of branched chain alkyl group of from 8 to 20 carbon atoms; R4 is a hydroxy, chloride, bromide, iodide or -O-?-R5 wherein R5 is hydrogen or alkyl group of from 1 to 3 carbon atoms; n is an integer of from 1 to 4; and X is chloride, bromide, iodide, sulfate or acetate; in which the quaternary ammonium salt is used in an amount of at least 0.1% by weight based on the dry weight of the polyalcohol or functional derivative thereof.
R3 is a higher straight of branched chain alkyl group of from 8 to 20 carbon atoms; R4 is a hydroxy, chloride, bromide, iodide or -O-?-R5 wherein R5 is hydrogen or alkyl group of from 1 to 3 carbon atoms; n is an integer of from 1 to 4; and X is chloride, bromide, iodide, sulfate or acetate; in which the quaternary ammonium salt is used in an amount of at least 0.1% by weight based on the dry weight of the polyalcohol or functional derivative thereof.
18. The product according to Claim 17 in which the polyalcohol or functional derivative thereof is a polysaccharide or functional derivative thereof.
19. The product according to Claim 18 in which the polysaccharide is cellulose.
20. The product according to Claim 18 in which the polysaccharide functional derivative is cellulose acetate.
21. The product according to Claim 17 in which R1 and R2 are the same or different and each can be alkyl group of from 1 to 4 carbon atoms; R3 is an alkyl group of from 15 to 20 carbon atoms; R4 is chloride, bromide, iodide or -?-R5; n is the integer 1 or 2; and X is chloride, bromide, or iodide.
22. The product according to Claim 21 in which R1 and R2 are both methyl.
23. The product according to Claim 17 in which the quaternary ammonium salt is (chloxoformylmethyl)octadecyldi-methylammonium chloride.
24. The product according to Claim 23 in which the polyalcohol or functional derivative thereof is a polysaccharide or functional derivative thereof.
25. The product according to Claim 24 in which the polysaccharide is cellulose.
26. The product according to Claim 24 in which the polysaccharide functional derivative is cellulose acetate.
27. The product according to Claim 17 in which the quaternary ammonium salt is (chloroformylethyl)octadecyldi-methylammonium chloride.
28. The product according to Claim 27 in which the polyalcohol or functional derivative thereof is a polysaccharide or functional derivative thereof.
29. The product according to Claim 28 in which the polysaccharide is cellulose.
30. The product according to Claim 28 in which the polysaccharide functional derivative is cellulose acetate.
31. Paper or fabric manufactured using the product defined in Claim 19.
32. Paper or fabric manufactured using the product defined in Claim 20.
33. Paper or fabric manufactured using the product defined in Claim 25.
34. Paper and fabric manufactured using the product defined in Claim 29.
35. Paper and fabric manufactured using the product defined in Claim 30.
36. The product according to Claim 17 in which the quaternary ammonium salt is used in an amount of greater than 0.5%
37. The product according to Claim 36 in which the quaternary ammonium salt is used in an amount of about 1%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US698179A | 1979-01-29 | 1979-01-29 | |
| US6,981 | 1979-01-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1129851A true CA1129851A (en) | 1982-08-17 |
Family
ID=21723575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA332,439A Expired CA1129851A (en) | 1979-01-29 | 1979-07-24 | Antimicrobial poly-alcohols and derivatives thereof |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1129851A (en) |
-
1979
- 1979-07-24 CA CA332,439A patent/CA1129851A/en not_active Expired
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