CA2028163C - Solid antimicrobial - Google Patents
Solid antimicrobialInfo
- Publication number
- CA2028163C CA2028163C CA002028163A CA2028163A CA2028163C CA 2028163 C CA2028163 C CA 2028163C CA 002028163 A CA002028163 A CA 002028163A CA 2028163 A CA2028163 A CA 2028163A CA 2028163 C CA2028163 C CA 2028163C
- Authority
- CA
- Canada
- Prior art keywords
- carbon atoms
- radical
- value
- formula
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Abstract
A method of treating surfaces in order to eliminate microbial growth by adding an antibacterially effective amount of an organosilicon quaternary ammonium silatrane compound to the surface in order to destroy bacteria and fungi. The preferred organosilicon quaternary ammonium silatrane compound has the formula (see fig. I) wherein R1, R2, R3 and R4, each represent a hydrogen atom or a methyl, ethyl, propyl or butyl radical.
Description
~ ~ 2 ~ ~ 3 ~ ~ ~
.~
..,_ SOLID ANTIMICROBIAL
An antimicrobial is an agent that destroys or inhibits the growth of microorganisms. The major classes of microorganisms are bacteria, fungi including mold and mildew, yeasts and algae. Microorganisms can be found in the air, the waters, the human body, soil, wastes and on all surfaces.
The organisms are deposited from the air, food and drink spills, dust, dirt and tracked in soil and from human excreta such as sweat, urine and feces. Organisms grow and multiply when there is available a nutrient source of food such as dirt, organic or inorganic material and living tissue. For growth and multiplication, organisms also require warm temperatures and moisture. When these conditions exist, microorganisms thrive and flourish. Microbial growth, however, leads to many problems such as unpleasant odors ranging from stale to musty and mildew-like, to putrid and foul smelling, resembling ammonia. The growths also produce unsightly stains, discoloration and deterioration of many surfaces and materials in which they come into contact. A
more serious disadvantage of microbial growth is the production of pathogenic microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of disease, infection and disorders.
Antimicrobial agents are chemical compositions that are used to prevent such microbiological contaminations by inhibiting, killing and/or removing them and neutralizing their effects of deterioration, defacement, odor, disease or other negative effects. Particular areas of application of antimicrobial agents and compositions are, for example, ~_ -2 cosmetics, disinfectants, sanitizers, wood preservation, food, animal feed, cooling water, metalworking fluids, hospital and medical uses, plastics and resins, petroleum, pulp and paper, textiles, latex, adhesives, leather and hides and paint slurries. In the area of medical applications, antimicrobials are often used as powders, in lotions, creams, ointments and/or delivered in a variety of solvents or directly as over-the-counter or ethical drugs to alleviate, mediate, cure and/or protect people or other animals from disease or cosmetic conditions. Of the diverse categories of antimicrobial agents and compositions, quaternary ammonium compounds represent one of the largest of the classes of antimicrobial agents in use. At low concentrations, quaternary ammonium type antimicrobial agents are bacteriostatic, fungistatic, algistatic, sporostatic and tuberculostatic. At medium concentrations they are bactericidal, fungicidal, algicidal and viricidal against lipophilic viruses.
The "unbound" antimicrobials of the prior art are not the equivalent of the "bound" antimicrobial organosilanes of the present invention because the unbound antimicrobials do not perform substantially the same function, in substantially the same way, to produce substantially the same results, as do the bound silanes of the present invention.
The function differs because the bound antimicrobial is permanent whereas the unbound types are easily washed away or rubbed from the surface. The compounds of the present invention are not only durable but retain their antimicrobial activity after some ten laundering cycles and only slightly diminish in their activity after as many as twenty-five laundering cycles. The bound silanes of the present invention retain an effective kill level of microorganisms.
The manner in which the bound silane functions differs from ,_ -3- ~ 3 the unbound types, since the bound silane attaches itself to the surface to which it is applied, whereas the unbound types are mere coatings which are not substantive. This is significant since the silane antimicrobial will continue to prevent reinfestation and enables one to utilize the intrinsic antimicrobial activity of the silane treated surface to kill transient microbes, long after the unbound types of antimicrobials have been depleted of their activity.
Further, the bound silanes of the present invention destroy, reduce and inhibit the growth and multiplication of bacteria, fungi and other pathogenic microorganisms, by the disruption of cell membranes, a mechanism absent from conventional unbound antimicrobial materials. The results produced by the bound silanes are not the same as the results produced by the unbound types since the bound silanes provide a prolonged antimicrobial activity and continue to kill and inhibit the proliferation of potentially destructive microorganisms, versus mere temporary and superficial protection offered by the unbound category of material.
Among the numerous attempts to alleviate the problems of microorganisms on surfaces some have involved the use of soaps, detergents and surface cleaners. The treatments, however, have for the most part included an unbound category of antimicrobial which is not actually bonded to the surface sought to be treated and, therefore, is consumed by the microorganisms, with the result that the unbound antimicrobial is depleted and washed away during routine cleansing. As this diffusion continues, the concentration of the active ingredient becomes diluted below effective levels, with the result that the microorganisms sought to be inhibited, adapt and build up a tolerance, becoming immune to what was once an effective treatment dose. Such unbound diffusible antimicrobials have therefore been found to be 2 ~ r~ 3 limited in their ability to offer broad spectrum control of microorganisms, in contrast to the bound type of antimicrobial which remains chemically attached to the surface to which it is applied providing for a surface that prevents recolonization by the microflora associated therewith. Diffusing types of antimicrobials also often suffer from the propensity to transfer percutaneously, giving rise to sensitization and irritation immunological responses and raising serious questions as to their ultimate fate within the body and body systems.
Bound antimicrobials kill organisms on contact and continue to kill organisms without being diffused or leached from the surface. Thus, the bound antimicrobial leaves behind an effective level of active ingredient and is able to control a broad spectrum of microorganisms including gram negative and gram positive bacteria, mold, mildew, fungi, yeast and algae. The compounds of the present invention have been found to be more effective at reducing the number of microorganisms and inhibiting microbially generated odors, than conventional organotin compounds and other organic quaternary ammonium compounds. The silanes of the present invention when delivered from simple water solutions immobilize on surfaces and bond thereto to provide a coating of immobilized antimicrobial, unlike conventional materials.
The class of organofunctional silane antimicrobials referred to above are compounds whose methoxy, ethoxy, propoxy and butoxy silanes are stabilized by their corresponding solvents. To maximize the stability of these compounds, the solvents must be present. Disadvantages of this are, but not limited to, associated toxicities, odors, flammability and difficulties in formulating with other useful materials.
In the present invention, this bound characteristic of organic solvent borne organosilicon quaternary ammonium compounds is maintained when water delivered, as well as their capabilities of performing at effective kill levels beyond prior art types of compositions, is taken advantage of in the treatment of surfaces, in order to reduce or substantially eliminate the incidence of microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of such microbes and the problems they cause such as deterioration, defacement, odors and health problems of plants and animals. All of this is accomplished from the easily derived solid forms represented by the silatranes, eliminating the need for solvents and the associated problems of solvents.
This invention relates to a composition and method of treating a surface harboring microorganisms in order to combat the microorganisms by destroying the microorganisms or by preventing proliferation of the microorganisms to numbers that would be destructive to the surface sought to be treated and protected or whose body parts or metabolic products can give rise to odors, defacement or negatively affect other life forms. The method includes reacting an alkanolamine with an organosilicon quaternary ammonium compound to form a silatrane compound in the form of a solid particulate powder, dissolving the silatrane powder in an aqueous medium to form an antimicrobially active solution of the silatrane powder and applying the solution in an antimicrobially effective amount to the surface sought to be treated and protected, the organosilicon quaternary ammonium compound being an organo-silane having the formula selected from the group consisting of -6~ 3 Y SiR''N~R'''R''''RV~
.~
..,_ SOLID ANTIMICROBIAL
An antimicrobial is an agent that destroys or inhibits the growth of microorganisms. The major classes of microorganisms are bacteria, fungi including mold and mildew, yeasts and algae. Microorganisms can be found in the air, the waters, the human body, soil, wastes and on all surfaces.
The organisms are deposited from the air, food and drink spills, dust, dirt and tracked in soil and from human excreta such as sweat, urine and feces. Organisms grow and multiply when there is available a nutrient source of food such as dirt, organic or inorganic material and living tissue. For growth and multiplication, organisms also require warm temperatures and moisture. When these conditions exist, microorganisms thrive and flourish. Microbial growth, however, leads to many problems such as unpleasant odors ranging from stale to musty and mildew-like, to putrid and foul smelling, resembling ammonia. The growths also produce unsightly stains, discoloration and deterioration of many surfaces and materials in which they come into contact. A
more serious disadvantage of microbial growth is the production of pathogenic microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of disease, infection and disorders.
Antimicrobial agents are chemical compositions that are used to prevent such microbiological contaminations by inhibiting, killing and/or removing them and neutralizing their effects of deterioration, defacement, odor, disease or other negative effects. Particular areas of application of antimicrobial agents and compositions are, for example, ~_ -2 cosmetics, disinfectants, sanitizers, wood preservation, food, animal feed, cooling water, metalworking fluids, hospital and medical uses, plastics and resins, petroleum, pulp and paper, textiles, latex, adhesives, leather and hides and paint slurries. In the area of medical applications, antimicrobials are often used as powders, in lotions, creams, ointments and/or delivered in a variety of solvents or directly as over-the-counter or ethical drugs to alleviate, mediate, cure and/or protect people or other animals from disease or cosmetic conditions. Of the diverse categories of antimicrobial agents and compositions, quaternary ammonium compounds represent one of the largest of the classes of antimicrobial agents in use. At low concentrations, quaternary ammonium type antimicrobial agents are bacteriostatic, fungistatic, algistatic, sporostatic and tuberculostatic. At medium concentrations they are bactericidal, fungicidal, algicidal and viricidal against lipophilic viruses.
The "unbound" antimicrobials of the prior art are not the equivalent of the "bound" antimicrobial organosilanes of the present invention because the unbound antimicrobials do not perform substantially the same function, in substantially the same way, to produce substantially the same results, as do the bound silanes of the present invention.
The function differs because the bound antimicrobial is permanent whereas the unbound types are easily washed away or rubbed from the surface. The compounds of the present invention are not only durable but retain their antimicrobial activity after some ten laundering cycles and only slightly diminish in their activity after as many as twenty-five laundering cycles. The bound silanes of the present invention retain an effective kill level of microorganisms.
The manner in which the bound silane functions differs from ,_ -3- ~ 3 the unbound types, since the bound silane attaches itself to the surface to which it is applied, whereas the unbound types are mere coatings which are not substantive. This is significant since the silane antimicrobial will continue to prevent reinfestation and enables one to utilize the intrinsic antimicrobial activity of the silane treated surface to kill transient microbes, long after the unbound types of antimicrobials have been depleted of their activity.
Further, the bound silanes of the present invention destroy, reduce and inhibit the growth and multiplication of bacteria, fungi and other pathogenic microorganisms, by the disruption of cell membranes, a mechanism absent from conventional unbound antimicrobial materials. The results produced by the bound silanes are not the same as the results produced by the unbound types since the bound silanes provide a prolonged antimicrobial activity and continue to kill and inhibit the proliferation of potentially destructive microorganisms, versus mere temporary and superficial protection offered by the unbound category of material.
Among the numerous attempts to alleviate the problems of microorganisms on surfaces some have involved the use of soaps, detergents and surface cleaners. The treatments, however, have for the most part included an unbound category of antimicrobial which is not actually bonded to the surface sought to be treated and, therefore, is consumed by the microorganisms, with the result that the unbound antimicrobial is depleted and washed away during routine cleansing. As this diffusion continues, the concentration of the active ingredient becomes diluted below effective levels, with the result that the microorganisms sought to be inhibited, adapt and build up a tolerance, becoming immune to what was once an effective treatment dose. Such unbound diffusible antimicrobials have therefore been found to be 2 ~ r~ 3 limited in their ability to offer broad spectrum control of microorganisms, in contrast to the bound type of antimicrobial which remains chemically attached to the surface to which it is applied providing for a surface that prevents recolonization by the microflora associated therewith. Diffusing types of antimicrobials also often suffer from the propensity to transfer percutaneously, giving rise to sensitization and irritation immunological responses and raising serious questions as to their ultimate fate within the body and body systems.
Bound antimicrobials kill organisms on contact and continue to kill organisms without being diffused or leached from the surface. Thus, the bound antimicrobial leaves behind an effective level of active ingredient and is able to control a broad spectrum of microorganisms including gram negative and gram positive bacteria, mold, mildew, fungi, yeast and algae. The compounds of the present invention have been found to be more effective at reducing the number of microorganisms and inhibiting microbially generated odors, than conventional organotin compounds and other organic quaternary ammonium compounds. The silanes of the present invention when delivered from simple water solutions immobilize on surfaces and bond thereto to provide a coating of immobilized antimicrobial, unlike conventional materials.
The class of organofunctional silane antimicrobials referred to above are compounds whose methoxy, ethoxy, propoxy and butoxy silanes are stabilized by their corresponding solvents. To maximize the stability of these compounds, the solvents must be present. Disadvantages of this are, but not limited to, associated toxicities, odors, flammability and difficulties in formulating with other useful materials.
In the present invention, this bound characteristic of organic solvent borne organosilicon quaternary ammonium compounds is maintained when water delivered, as well as their capabilities of performing at effective kill levels beyond prior art types of compositions, is taken advantage of in the treatment of surfaces, in order to reduce or substantially eliminate the incidence of microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of such microbes and the problems they cause such as deterioration, defacement, odors and health problems of plants and animals. All of this is accomplished from the easily derived solid forms represented by the silatranes, eliminating the need for solvents and the associated problems of solvents.
This invention relates to a composition and method of treating a surface harboring microorganisms in order to combat the microorganisms by destroying the microorganisms or by preventing proliferation of the microorganisms to numbers that would be destructive to the surface sought to be treated and protected or whose body parts or metabolic products can give rise to odors, defacement or negatively affect other life forms. The method includes reacting an alkanolamine with an organosilicon quaternary ammonium compound to form a silatrane compound in the form of a solid particulate powder, dissolving the silatrane powder in an aqueous medium to form an antimicrobially active solution of the silatrane powder and applying the solution in an antimicrobially effective amount to the surface sought to be treated and protected, the organosilicon quaternary ammonium compound being an organo-silane having the formula selected from the group consisting of -6~ 3 Y SiR''N~R'''R''''RV~
3-al and Ra 0,b~ xa Ra wherein, in each formula, Y is R or RO where each R is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
a has a value of O, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms:
R''', R'''' and Rv are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH20H, -CH20H and -(CH2)XNHC(O)R , vi wherein x has a value of from 2 to 10 and R
is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
The treatment can be applied in the form of an emulsion including water, the silatrane and a water immiscible liquid which is a polysiloxane selected from the group consisting of polysiloxanes having the general formula R'3SiO(R''2SiO)W(R'''QSiO)2SiRp,3 and (R'R''SiO)y wherein R' is an alkyl radical of 1 to 3 carbon atoms, phenyl, an alkoxy radical having the formula R''''O-, wherein R'''' is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
R'' is an alkyl radical of 1 or 2 carbon atoms or the phenyl 2~2~
,......
- ~ -7-group; R''' has the same meaning as R''; Q is a substituted or unsubstituted radical composed of carbon and hydrogen or carbon, hydrogen and oxygen or carbon, hydrogen and sulfur or carbon, hydrogen and nitrogen; w has a value of from 1 to 500; z has a value of 1 to 25 and y has a value of 3 to 5.
The most preferred organosilane quaternary ammonium compound for use in preparing the silatranes in accordance with the method of the present invention is 3-(trimethoxy-silyl) propyldimethyloctadecyl ammonium chloride (TMS) of the formula ~ CH3 CH3-0-Si-cH2-cH2-cH2-1 C18H37 The invention is also directed to compounds prepared in accordance with the above described method.
~ mmonium compounds in which all of the hydrogen atoms on nitrogen have been substituted by alkyl groups are called quaternary ammonium salts. These compounds may be represented in a general sense by the formula:
[R4-1+ R2]x~
The nitrogen atom includes four covalently bonded substituents that provide a cationic charge. The R groups can be any organic substituent that provides for a carbon and nitrogen bond with similar and dissimilar R groups. The counterion X is typically halogen. Use of quaternary ammonium compounds is based on the hydrophilic portion of the molecule which bears a positive charge. Since most surfaces are negatively charged, solutions of these cationic surface active agents are readily absorbed to the negatively charged surface. This affinity for negatively charged surfaces is exhibited by a compound hereinafter referred to as "TMS" which is 3-(trimethoxysilyl)propyldimethyl-octadecyl ammonium chloride of the formula:
CH3-o-si-cH2-cH2-cH2-N~-cl8H37 Cl~
In the presence of moisture, this antimicrobial agent imparts a durable, wash resistant, broad spectrum biostatic surface antimicrobial finish to a substrate. The organosilicon quaternary ammonium compound is leach resistant, nonmigrating and is not consumed by micro-organisms. It is effective against gram positive and gram negative bacteria, fungi, algae, yeasts, mold, rot and mildew. The silicone quaternary ammonium complex provides durable, bacteriostatic, fungistatic and algistatic surfaces.
The silanes useful in preparing the silatranes in accordance with this invention have the general formula (R0)3 aSiR''N~R'''R''''RVX~ and (R0)3 aliR'N ~ X~
It should be noted that generically, these materials are quaternary ammonium salts of silanes. Most of the silanes falling within the scope of this invention are known silanes and references disclosing such silanes are numerous. One such reference, United States Patent No. 4,259,103, issued to James R. Malek and John L. Speier, on March 31, 1981, discusses the use of such silanes to render the surfaces of certain substrates antimicrobial.
British Patent No. 1,433,303, issued to Charles A. Roth shows the use of fillers treated with certain silanes to be used in paints and the like to give antimicrobial effects.
Numerous other publications have disclosed such silanes, namely, A. J. Isquith, E. A. Abbott and P. A.
Walters, Applied Microbiology, December, 1972, pages 859-863;
P. A. Walters, E. A. Abbott and A. J. Isquith, Applied Microbiology, 25, No. 2, p. 253-256, February 1973 and E. A.
Abbott and A. J. Isquith, United States Patent No. 3,794,736 issued February 26, 1974, U.S. Patent No. 4,406,892, issued September 27, 1983, among others.
For purposes of this invention, the silanes can be used neat or they can be used in solvent or aqueous-solvent solutions. When the silanes are used neat, the inventive process is preferably carried out in a system in which some small amount of water is present. If it is not possible to have a system with some small amount of water present, then a water soluble or water-dispersable, low molecular weight hydrolyzate of the silane may be used. What is important is the fact that the durability of any effect produced by the silane as part of a product requires that the silane molecule react with a surface to a certain e~tent. The most reactive species, as far as the silanes are concerned, is the -SiOH
~li~! ~
-10- ~n ~ 3 that is formed by the hydrolysis of the alkoxy groups present on the silane. The -SiOH groups tend to react with the surface and bind the silanes to the surface. It is believed by the inventor that even though the prime mode of coupling to the surface system is by the route described above, it is also believed by the inventor that the alkoxy groups on the silicon atom may also participate in their own right to bind to the surface.
Preferred for this invention is a reactive surface containing some small amount of water. By "reactive", it is meant that the surface must contain some groups which will react with some of the silanols generated by hydrolysis of the silanes of this invention.
R in the silanes of this invention are alkyl groups of 1 to 4 carbon atoms. Thus, useful as R in this invention are the methyl, ethyl, propyl and butyl radical. In the above formula RO can also be R. T can also be hydrogen thus indicat~ng the silanol form, i.e. the hydrolyzate. The value of a is O, 1 or 2 and R' is a methyl or ethyl radical.
Because of the presence of these alkyl radicals, the prior art teaches that these materials must be stabilized with a corresponding solvent. Thus, methoxy groups require methanol and ethoxy groups require ethanol, for example.
R'' for purposes of this invention is an alkylene group of 1 to 4 carbon atoms. Thus, R" can be alkylene groups such as methylene, ethylene, propylene and butylene.
R''', R'''' and R~ are each independently selected from a group which consists of alkyl radicals of 1 to 18 carbons, -CH2C6H5, -CH2CH20H, -CH20H and -(CH2)xNHC(O)R . x has a value of from 2 to 10 and RVl is a perfluoroalkyl radical having from 1 to 12 carbon atoms. X is chloride, bromide, fluoride, iodide, acetate or tosylate.
2 ~
Preferred for this invention are the silanes of the general formula (RO)3_aSiR N R'''R''''RVX~
R'a is methyl or ethyl; a has a value of zero; R'' is propylene;
R''' is methyl or ethyl; R'''' and Rv are selected from alkyl groups containing 1 to 18 carbon atoms wherein at least one such group is larger than eight carbon atoms and x is either chloride, acetate or tosylate.
As indicated above, most of these silanes are known from the literature and methods for their preparation are known as well. See, for example, U.S. Patent No. 4,282,366, issued August 4, 1981; U.S. Patent No . 4,394,378, issued July 19, 1983 and U.S. Patent No. 3,661,963 issued May 9, 1972, among others.
Specific silanes within the scope of the invention are represented by the formulae:
(CH30)3Si(CH2)3N (CH3)2C18H37 (CH30)3Si(CH2)3N (CH3)2C18H37 3~)3Si(CH2)3N (CloH2l)2cH3cl-~
3~)3Si(cH2)3N (ClOH2l)2cH3Br-, ( H30)3Si(CH2)3N (cH3)3cl, (cH3o)3sicH2cH2cH2p (C6H5)3 (CH30)3sicH2cH2cH2P (C6H5)3B
(CH30)3sicH2cH2cH2p+(cH3)3cl (CH30)3sicH2cH2cH2P (C6H13)3C
(CH3)3Si(cH2)3N (cH3)2cl2H25 ( H3)3Si(CH2)3N (CloH2l)2cH3cl-, 3)3Si(CH2)3N (CH3)2C18H37Cl-(CH30)3Si(CH2)3N (CH3)2C4H9 (c2H5o)3si(cH2)3N (CH3)2C18H37 (cH3o)3si(cH2)3N (CH3)2CH2C6 5 (CH3~)3Si(cH2)3N(cH3 )2CH2CH2 0/~ xa (H0)3Si(CH2)3 30)3Si(CH2)3N~ X~
3 )3 (CH2)3N (CH3)2(cH2)3NHc(O)(cF2)6cF3 (CH3O)3Si(cH2)3N (C2H5)3 The water immiscible liquids or volatiles as used in the emulsions of the present invention, are silicone oils which are highly volatile and low in viscosity and molecular weight. For example, there may be employed trimethylsiloxy endblocked polydimethylsiloxanes, cyclic siloxanes such as dimethylsiloxane cyclic tetramer and phenylmethyl fluids such as linear polyphenylmethylsiloxanes. Preferred for this invention are those silicone oils having a viscosity at 25~C.
ranging from about 0.65 cs. to about 1000 cs. A particularly preferred range is from about 0.65 cs. to about 20 cs., although those silicone oils of viscosities of 50 cs. and 350 cs. can be employed. These silicone oils are more particularly described and set forth in detail in U.S. Patent No. 4,631,273, issued December 23, 1986, and assigned to Dow Corning Corporation. Such silicone oils are siloxanes which are low molecular weight cyclics and polysiloxanes having the general formula R 3SiO(R 2Si~)w(R QSiO)2SiRp,3 and (R'R''SiO) wherein R' is an alkyl radical of 1 to 3 carbon atoms, phenyl, an alkoxy radical having the formula R''''O-, wherein R'''' is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
R'' is an alkyl radical of 1 or 2 carbon atoms or the phenyl group; R''' has the same meaning as R''; Q is a substituted B
or unsubstituted radical composed of carbon and hydrogen or carbon, hydrogen and oxygen or carbon, hydrogen and sulfur or carbon, hydrogen and nitrogen; w has a value of from 1 to 500; z has a value of 1 to 25 and y has a value of 3 to 5.
The organosilane silatrane may also be employed in accordance with the present invention in the form of a microemulsion containing the silatrane. Such microemulsions and their preparation are described in applicants' U.S. Patent No; 4,842,766 issued June 27, 1989, and assigned to the same assignee as the present application. Solutions with particle sizes less than 0.150 microns are disclosed which are either oil-in-water or water-in-oil microemulsions including the silatrane and at lease one surfactant.
Various procedures are employed in order to test the organosilanes of the present invention. For example, the presence of the chemical on a substrate can be determined by complexing a standarized solution of bromophenol blue in water the quaternary nitrogen of the organosilane and recording the color change spectrophotometrically. Results of this test can be used in order to determine whether the organosilane has bound itself to a particular surface. Such a test procedure is set forth below.
The anion of an aqueous sodium salt of bromophenol blue can be complexed with the cation of polymerized silanes of this invention while on a substrate. The blue colored 2a~3 ~ ~
. ,~
complex, substantive to a water rinse, is qualitatively indicative of the presence of the cation on the substrate thus indicating the extent of antimicrobial agent on a given substrate. A comparison of the intensity of retained blue color to a color standard is used as a check to determine if the treatment has been applied properly.
One method consists of preparing a 0.02 to 0.04 weight percent solution of bromphenol blue in distilled water. This solution is made alkaline using a few drops of saturated Na2C03 solution per 100 milliliters of the solution. Two to three drops of this solution are placed on the treated substrate and allowed to stand for two minutes.
The substrate is then rinsed with copious amounts of tap water and the substrate is observed for a blue stain and it is compared to a color standard.
For a spectrophotometric determination, the following test is used. The sodium salt of bromphenol blue is depleted from a standard solution by complexing with the cations on a treated substrate. The change in bromphenol blue concentration is determined spectrophotometrically or by comparison with color standards whereby the level of substrate treatment by the cationic silane is determinable.
The method consists of preparing a 0.02 weight percent standard solution of bromphenol blue in distilled water. It is made alkaline with a few drops of saturated Na2C03 solution per 100 milliliters of bromphenol blue solution. The color of this solution is purple. The blank solution is adjusted to yield a 10 to 12% transmittance reading when measured in 1 cm cells using a spectrophotometer set at 589 nm by the following method. Fill a container 3/4 full of distilled water and add 2 ml of the 0.02% standard bromphenol blue solution for every 50 ml of distilled water.
Add 0.5 ml of a 170 Triton~ X-100 surfactant (manufactured by Rohm and Haas, Philadelphia, PA, USA) aqueous solution for every 50 ml of water. Mix and, using the spectrophotometer, determine the maximum absorbance. Adjust the upper zero to 100% transmittance with distilled water. Check the percent transmittance of the working bromphenol blue solution at the maximum absorbance setting. Adjust the blank solution to 10 to 12% transmittance with either water or bromphenol blue standard solution as necessary.
The samples of treated substrate can be tested by placing 0.5 gram samples of the substrate standards in a flask large enough for substantial agitation of the sample and the test solution. Add 50 ml of the working solution.
Agitate for 20 minutes on a wrist-action shaker. Fill the test curvette with the test solution. Centrifuge if particulate matter is present. Measure the % transmittance at the wavelength set forth above. The transmittance is compared against a standard curve prepared by preparing several substrate samples of known concentration of the cationic silane. For example, samples containing a known amount of cationic silane at, for example, 0%, 0.25%, 0.50%, 0.75% and 1% are read spectrophotometrically and a curve is plotted.
The antimicrobial activity of a treated surface is normally evaluated by sh~ki ng a sample weighing 0.75 grams in a 750,000 to 1,500,000 count Klebsiella pneumoniae suspension for a one hour contact time. The suspension is serially diluted, both before and after contact and cultured. The number of viable organisms in the suspensions is determined.
The percent reduction based on the original count is determined. The method is intended for those surfaces having a reduction capability of 75 to 100% for the specified contact time. The results are reported as the percent reduction. Media used in this test are nutrient broth, catalog No. 0003-01-6 and tryptone glucose extract agar, catalog No. 0002-01-7 both available from Difco laboratories, Detroit, Michigan, U.S.A. The microorganism used is Klebsiella pneumoniae American Type Culture Collection; Rockville, Md. U.S.A., catalog No. 4352. The procedure used for determining the zero contact time counts is carried out by utilizing two sterile 250 ml. screw-cap Erlenmeyer flasks for each sample. To each flask is added 70 ml of sterile buffer solution. To each flask is added, aseptically, 5 ml of the organism inoculum. The flasks are capped and placed on a wrist action shaker. They are shaken at maximum speed for 1 minute. Each flask is considered to be at zero contact time and is immediately subsampled by transferring 1 ml of each solution to a separate test tube containing 9 ml of sterile buffer. The tubes are agitated with a vortex mixer and then 1 ml of each solution is transferred to a second test tube containing 9 ml of sterile buffer. Then, after agitation of the tubes, 1 ml of each tube is transferred to a separate sterile petri dish.
Duplicates are also prepared. Sixteen ml of molten (42~C.) tryptone glucose extract agar is added to each dish. The dishes are each rotated ten times clockwise and ten times counterclockwise. The dishes are then incubated at 37~C for 24 to 36 hours. The colonies are counted considering only those between 30 and 300 count as significant. Duplicate samples are averaged. The procedure used for determining the bacterial count after 1 hour is essentially the same as that used to determine the count at the zero contact time. The only difference is that pour plating is performed at the 10~
and 10 1 dilutions as well as at the 10 2 dilution. "Percent reduction" is calculated by the formula 2~
B+C
%R = 2 - A 100 B+C
where A is the count per milliliter for the flask containing the treated substrate; B is zero contact time count per milliliter for the flask used to determine "A" before the addition of the treated substrate and C is zero contact time count per milliliter for the untreated control substrate.
The foregoing "Shake Flask Test" measures antimicrobial substrate activity. An alternative test sometimes employed is the "Agar Plate Graphing Technique"
which again affords a measure of antimicrobial substrate activity, in which treated swatches of fabric are placed on agar impregnated with Klebsiella pneumoniae. Antimicrobial activity is measured by the existence of a zone of inhibition and diffusability in the agar. Immobilized antimicrobials will not show a zone.
It is also possible to measure antimicrobial solution activity and this is performed in accordance with the procedures of the "Minimum Inhibitory Concentration Test (MIC)" in which the level of chemical required to inhibit the growth of microorganisms in a system is determined, typically employing organisms such as Staphylococcus aureus, Klebsiella pneumoniae and Asper~illus ni~er.
The following examples illustrate the concepts of the present invention.
Example I
A white powder antimicrobial solid was prepared by the reaction of 118.9 grams of 3-(trimethoxysilyl) propyldimethyl octadecyl ammonium chloride and 142 grams of methanol with 14.9 grams of triethanolamine in a solvent mixture of 9 grams isobutanol and 50 grams of toluene. These materials were heated and refluxed with stirring.
Over a period of three hours, the methanol solvents and water were distilled off and the mixture cooled. A white solid representing 84% of theoretical yield was obtained after vacuum filtration.
While the foregoing example employs triethanolamine as a reactant to produce the silatrane reaction product, any alkanolamine is appropriate.
Example II
The Shake Flask antimicrobial test explained above was employed in order to determine antimicrobial activity.
Cotton fabric was treated with one percent by weight of the white powder in a water solution. Both ten and thirty minute soaks provided a reduction of 100 percent in comparison to a reduction of 64.8 percent for a control, indicating excellent antimicrobial activity for the organosilane silatrane composition of the present invention.
Example III
There was heated and stirred for three hours a mixture including 118.4 grams of 3-(trimethoxysilyl) propyldimethyl octadecyl ammonium chloride, 141 grams of methanol, 14.9 grams of triethanolamine and fifty grams of toluene. The mixture was dried in a forced air oven at about 200~C. to yield a yellow-white powder. The powder was washed three times with acetone resulting in a dry white powder material.
A ladder series of concentration calculated as fully hydrolyzed 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride were prepared using the triethanolamine silatrane of 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride (I) and 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride (II), the ladder being composed of 0.09, 0.1., 0.25, 0.50 and 1.00% by weight active on cotton and polyester fabrics. Treatment was accomplished by wet weight pick up from tap water solutions of the test compounds. The fabrics were dried and tested by the following procedures:
A. Dynamic Shake Flask Antibacterial Test - Klebsiella pneumonia Gram (-) and Staphylococcus Aureus Gram (+).
Standard procedure.
B- Bromophenol blue Spectrophotometric Analytical Test.
0.5g test fabric used in standard procedure.
C. A above after 2 grams of the test fabric were rinsed in 200 ml of 40~C deionized water for 20 minutes, squeezed dry and oven dryed at 100~C.
D. B above per C.
E. Zone of Inhibition 1- zTrypticase Soy Agar, 1 7/8" fabric circle placed on lawn of Klebsiella pneumoniae (24 hour broth culture diluted 1:100 in sterile deionized water phosphate buffer, 1 ml spread on plate as lawn) or Staphylococcus aureus (prepared as above).
Readings after 48 hours incubation at 37~C.
2. Saborauds Dextro~e Agar, 1 7/8" fabric circle placed on agar and inoculated with a spore suspension with "Triton~ X-100 wetting agent of AsPer~illus ni~er.
Readings were made for total coverage after 21 days incubation at 30~C.
F. Zone of Inhibition Run as E with samples per C.
The test results are shown in the Tables that follow.
2 ~8 ~ ;3 The evidence of a leaching component that gives a zone of inhibition is clear from tests E and F showing a zone before rinse and no zone after rinse and from tests A and C
where the activity against the test organisms is measurably reduced after rinsing. The durability of the antimicrobial as the silane quaternary amine as the monomer or as delivered from the hydrolysis of the silatrane is seen clearly from tests E and F, surface growth of A. niger profile the same and tests B and D showing analytical equivalence from rinsed/nonrinsed silane/silatrane comparisons and tests A and C showing identical minimal activity profiles silane/silatrane.
The silatrane of triethanolamine and 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride provides a water soluble solid delivery form of 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride that provides a durable antimicrobial surface after a rinse protocol and provides for a leaching antimicrobial before rinsing. Upon contact with water, the silatrane reverts to TMS and triethanolamine.
TABLE I
Analytical and Antimicrobial Tests - Silatrane Sample A. DsF-~ntih~ctprial B. BPB-Analytical C. DSF (Rin~ed) D. BPB (Rinsed) E. Zone of Inhibition P. Zone of Inhibition (Rinsed) % Reduction X T- r~i~sion % r- Lion X TransDission mm mm K.pneunoniae S.aureus K.pneumoniae S.aureus K.pneuDoniae S.aureus A.niger K.l ~P S.aureus A.niger mD Surface DD Surface Active Ingredient Growth Gro~th (Silatrane) XCovered 7.Covered 21 days 21 days Fabric : Cotton 0.00% 16 32 11.0 19 26 11.0 0 0 0 100 0 0 0 100 0.10% 46 64 12.5 38 32 12.5 0 0 0 75 0 0 0 80 0.25% 98 100 21.0 94 84 23.0 1 3 0 50 0 0 0 40 0.50% 99.99 100 58.0 99.9 99.9 73.0 2 7 0 0 0 0 o 0 1.00% 100 100 68.0 100 100 81.0 4 8 1 0 0 0 0 0 Fabric : Polyester o.00% 0 3 11.0 0 4 11.0 0 0 0 lO0 0 0 0 100 0.10% 28 35 12.0 41 28 13.0 0 0 0 75 0 0 0 80 0.25% 92 100 27.0 86 96 36.0 0 2 0 10 0 0 0 20 0.507O 97 100 61.0 93 100 64.0 l 4 0 0 0 0 o 0 1.00% 100 100 75.0 100 100 78.0 3 6 l 0 0 0 0 o Analytical Blank - - 11.0 11.0 TABLE II
Analytical and Anti~icrobial Tests - TMS
Sample A. DSP-Antih~ct~rial B. BPB-Analytical C. DSP (Rinsed) D. BPB (Rinsed) E. Zone of Inhibition P. Zone of Inhibition (Rinsed) X Reduction % Transmission % Reduction X Transmission mm mm K.pneumoniae S.aureus K.pneumoniae S.aureus K.~ S.aureus A.niger K.pneumoniae S.aureus A.niger mmSurface mmSurface Active Ingredient Growth Growth (Silatrane) 7.Covered XCovered 21 days 21 days Pabric : Cotton 0.00% 22 38 11.0 18 29 11.0 0 0 0 100 0 0 0 100 0.10% 63 65 13.5 55 48 12.5 0 0 0 70 0 0 0 75 0.25% 72 84 28.0 83 90 23.0 0 0 0 25 0 0 0 30 0.50% 99.9 100 63.0 99.5 100 58.0 0 0 0 0 0 0 o 0 1.00% 100 100 72.0 100 100 75.0 0 0 0 o 0 0 o 0 Pabric : Polyester 0.00% 0 2 11.0 0 3 11.0 0 0 0 100 0 0 0 100 0.10% 48 52 16.0 32 28 14.0 0 0 0 50 0 0 0 50 0.25% 98 99.99 34.0 96 98.6 29.0 0 0 0 0 o 0 0 0 0.50% 100 99.99 74.0 100 100 65.0 0 0 0 0 o 0 0 0 1.00% 100 100 86.0 100 100 82.0 0 0 o 0 0 0 o 0 Analytical Blank - - 11.0 - - 11.0 - - - - - - - -~'~
S~
The organosilane quaternary ammonium silatrane compound produced in the foregoing examples is shown in the following formula N(CRlR2CR3R40)3Si-CH2-CH2-CH2-11 'C18H37Cl wherein Rl, R2, R3 and R4, each represent a hydrogen atom or a methyl, ethyl, propyl or butyl radical.
The genus of the organosilane silatrane compounds of the present invention is shown below and, in each formula, the radicals indicated therein are as previously defined above.
N(CRlR2CR R 0)3SiR''N~R'''R''IrRvX
N(CRlR2CR R 0)3SiRI'N ~ X~
Regarding the activity of the compounds of the present invention, such compounds have been found to be effective against a number of microorganisms, such as "BACTERIA'': Gram (-); Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeru~inosa, Pseudomonas fluorescens, Proteus mirabilis, Proteus vul~aris, Salmonella typhi, Salmonella typhimurium, Salmonella cholera suis, Enterobacter cloacae, Enterobacter aero~enes, Mor~anella mor~anii, Aeromonas hydrophila, Citrobacter freundii, Citrobacter deversus, Serratia marcescens, Serratia liquifaciens, ~anthomonas campestris, Acinetobacter calcoaceticus; Gram (~): Staphylococcus aureus, - - - - , ....
2 ~ g 3 ~ ~ 3 Staphylococcu~ epidermidis, Streptococcus mutans, Streptococcus pyoRenes, Streptococcus fecalis, Micrococcus lutea, Bacillus sp. (vegetative cell); "Fungi": Aspergillus niger, AsperRillus flavus, Aspergillus sydowi, AsperRillus versicolor, AsperRillus terreus, Penicillium chryso~enum, Penicillium variabile, Penicillium funiculosum, Penicillium pinophilum, Poria placenta, Aureobasidium pullulans, Gloeophyllum trabeum, Chaetomium globosum, Trichoderma viride, Trichophyton menta~rophytes; "Fungi" (yeasts):
Candida albicans, Candida pseudotropoicalis, Saccharomyces cerevisiae.
It will be apparent from the foregoing that many other variations and modifications may be made in the compounds, compositions and methods described herein without departing substantially from the essential features and concepts of the present invention. Accordingly, it should be clearly understood that the forms of the invention described herein are exemplary only and are not intended as limitations on the scope of the present invention.
a has a value of O, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms:
R''', R'''' and Rv are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH20H, -CH20H and -(CH2)XNHC(O)R , vi wherein x has a value of from 2 to 10 and R
is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
The treatment can be applied in the form of an emulsion including water, the silatrane and a water immiscible liquid which is a polysiloxane selected from the group consisting of polysiloxanes having the general formula R'3SiO(R''2SiO)W(R'''QSiO)2SiRp,3 and (R'R''SiO)y wherein R' is an alkyl radical of 1 to 3 carbon atoms, phenyl, an alkoxy radical having the formula R''''O-, wherein R'''' is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
R'' is an alkyl radical of 1 or 2 carbon atoms or the phenyl 2~2~
,......
- ~ -7-group; R''' has the same meaning as R''; Q is a substituted or unsubstituted radical composed of carbon and hydrogen or carbon, hydrogen and oxygen or carbon, hydrogen and sulfur or carbon, hydrogen and nitrogen; w has a value of from 1 to 500; z has a value of 1 to 25 and y has a value of 3 to 5.
The most preferred organosilane quaternary ammonium compound for use in preparing the silatranes in accordance with the method of the present invention is 3-(trimethoxy-silyl) propyldimethyloctadecyl ammonium chloride (TMS) of the formula ~ CH3 CH3-0-Si-cH2-cH2-cH2-1 C18H37 The invention is also directed to compounds prepared in accordance with the above described method.
~ mmonium compounds in which all of the hydrogen atoms on nitrogen have been substituted by alkyl groups are called quaternary ammonium salts. These compounds may be represented in a general sense by the formula:
[R4-1+ R2]x~
The nitrogen atom includes four covalently bonded substituents that provide a cationic charge. The R groups can be any organic substituent that provides for a carbon and nitrogen bond with similar and dissimilar R groups. The counterion X is typically halogen. Use of quaternary ammonium compounds is based on the hydrophilic portion of the molecule which bears a positive charge. Since most surfaces are negatively charged, solutions of these cationic surface active agents are readily absorbed to the negatively charged surface. This affinity for negatively charged surfaces is exhibited by a compound hereinafter referred to as "TMS" which is 3-(trimethoxysilyl)propyldimethyl-octadecyl ammonium chloride of the formula:
CH3-o-si-cH2-cH2-cH2-N~-cl8H37 Cl~
In the presence of moisture, this antimicrobial agent imparts a durable, wash resistant, broad spectrum biostatic surface antimicrobial finish to a substrate. The organosilicon quaternary ammonium compound is leach resistant, nonmigrating and is not consumed by micro-organisms. It is effective against gram positive and gram negative bacteria, fungi, algae, yeasts, mold, rot and mildew. The silicone quaternary ammonium complex provides durable, bacteriostatic, fungistatic and algistatic surfaces.
The silanes useful in preparing the silatranes in accordance with this invention have the general formula (R0)3 aSiR''N~R'''R''''RVX~ and (R0)3 aliR'N ~ X~
It should be noted that generically, these materials are quaternary ammonium salts of silanes. Most of the silanes falling within the scope of this invention are known silanes and references disclosing such silanes are numerous. One such reference, United States Patent No. 4,259,103, issued to James R. Malek and John L. Speier, on March 31, 1981, discusses the use of such silanes to render the surfaces of certain substrates antimicrobial.
British Patent No. 1,433,303, issued to Charles A. Roth shows the use of fillers treated with certain silanes to be used in paints and the like to give antimicrobial effects.
Numerous other publications have disclosed such silanes, namely, A. J. Isquith, E. A. Abbott and P. A.
Walters, Applied Microbiology, December, 1972, pages 859-863;
P. A. Walters, E. A. Abbott and A. J. Isquith, Applied Microbiology, 25, No. 2, p. 253-256, February 1973 and E. A.
Abbott and A. J. Isquith, United States Patent No. 3,794,736 issued February 26, 1974, U.S. Patent No. 4,406,892, issued September 27, 1983, among others.
For purposes of this invention, the silanes can be used neat or they can be used in solvent or aqueous-solvent solutions. When the silanes are used neat, the inventive process is preferably carried out in a system in which some small amount of water is present. If it is not possible to have a system with some small amount of water present, then a water soluble or water-dispersable, low molecular weight hydrolyzate of the silane may be used. What is important is the fact that the durability of any effect produced by the silane as part of a product requires that the silane molecule react with a surface to a certain e~tent. The most reactive species, as far as the silanes are concerned, is the -SiOH
~li~! ~
-10- ~n ~ 3 that is formed by the hydrolysis of the alkoxy groups present on the silane. The -SiOH groups tend to react with the surface and bind the silanes to the surface. It is believed by the inventor that even though the prime mode of coupling to the surface system is by the route described above, it is also believed by the inventor that the alkoxy groups on the silicon atom may also participate in their own right to bind to the surface.
Preferred for this invention is a reactive surface containing some small amount of water. By "reactive", it is meant that the surface must contain some groups which will react with some of the silanols generated by hydrolysis of the silanes of this invention.
R in the silanes of this invention are alkyl groups of 1 to 4 carbon atoms. Thus, useful as R in this invention are the methyl, ethyl, propyl and butyl radical. In the above formula RO can also be R. T can also be hydrogen thus indicat~ng the silanol form, i.e. the hydrolyzate. The value of a is O, 1 or 2 and R' is a methyl or ethyl radical.
Because of the presence of these alkyl radicals, the prior art teaches that these materials must be stabilized with a corresponding solvent. Thus, methoxy groups require methanol and ethoxy groups require ethanol, for example.
R'' for purposes of this invention is an alkylene group of 1 to 4 carbon atoms. Thus, R" can be alkylene groups such as methylene, ethylene, propylene and butylene.
R''', R'''' and R~ are each independently selected from a group which consists of alkyl radicals of 1 to 18 carbons, -CH2C6H5, -CH2CH20H, -CH20H and -(CH2)xNHC(O)R . x has a value of from 2 to 10 and RVl is a perfluoroalkyl radical having from 1 to 12 carbon atoms. X is chloride, bromide, fluoride, iodide, acetate or tosylate.
2 ~
Preferred for this invention are the silanes of the general formula (RO)3_aSiR N R'''R''''RVX~
R'a is methyl or ethyl; a has a value of zero; R'' is propylene;
R''' is methyl or ethyl; R'''' and Rv are selected from alkyl groups containing 1 to 18 carbon atoms wherein at least one such group is larger than eight carbon atoms and x is either chloride, acetate or tosylate.
As indicated above, most of these silanes are known from the literature and methods for their preparation are known as well. See, for example, U.S. Patent No. 4,282,366, issued August 4, 1981; U.S. Patent No . 4,394,378, issued July 19, 1983 and U.S. Patent No. 3,661,963 issued May 9, 1972, among others.
Specific silanes within the scope of the invention are represented by the formulae:
(CH30)3Si(CH2)3N (CH3)2C18H37 (CH30)3Si(CH2)3N (CH3)2C18H37 3~)3Si(CH2)3N (CloH2l)2cH3cl-~
3~)3Si(cH2)3N (ClOH2l)2cH3Br-, ( H30)3Si(CH2)3N (cH3)3cl, (cH3o)3sicH2cH2cH2p (C6H5)3 (CH30)3sicH2cH2cH2P (C6H5)3B
(CH30)3sicH2cH2cH2p+(cH3)3cl (CH30)3sicH2cH2cH2P (C6H13)3C
(CH3)3Si(cH2)3N (cH3)2cl2H25 ( H3)3Si(CH2)3N (CloH2l)2cH3cl-, 3)3Si(CH2)3N (CH3)2C18H37Cl-(CH30)3Si(CH2)3N (CH3)2C4H9 (c2H5o)3si(cH2)3N (CH3)2C18H37 (cH3o)3si(cH2)3N (CH3)2CH2C6 5 (CH3~)3Si(cH2)3N(cH3 )2CH2CH2 0/~ xa (H0)3Si(CH2)3 30)3Si(CH2)3N~ X~
3 )3 (CH2)3N (CH3)2(cH2)3NHc(O)(cF2)6cF3 (CH3O)3Si(cH2)3N (C2H5)3 The water immiscible liquids or volatiles as used in the emulsions of the present invention, are silicone oils which are highly volatile and low in viscosity and molecular weight. For example, there may be employed trimethylsiloxy endblocked polydimethylsiloxanes, cyclic siloxanes such as dimethylsiloxane cyclic tetramer and phenylmethyl fluids such as linear polyphenylmethylsiloxanes. Preferred for this invention are those silicone oils having a viscosity at 25~C.
ranging from about 0.65 cs. to about 1000 cs. A particularly preferred range is from about 0.65 cs. to about 20 cs., although those silicone oils of viscosities of 50 cs. and 350 cs. can be employed. These silicone oils are more particularly described and set forth in detail in U.S. Patent No. 4,631,273, issued December 23, 1986, and assigned to Dow Corning Corporation. Such silicone oils are siloxanes which are low molecular weight cyclics and polysiloxanes having the general formula R 3SiO(R 2Si~)w(R QSiO)2SiRp,3 and (R'R''SiO) wherein R' is an alkyl radical of 1 to 3 carbon atoms, phenyl, an alkoxy radical having the formula R''''O-, wherein R'''' is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
R'' is an alkyl radical of 1 or 2 carbon atoms or the phenyl group; R''' has the same meaning as R''; Q is a substituted B
or unsubstituted radical composed of carbon and hydrogen or carbon, hydrogen and oxygen or carbon, hydrogen and sulfur or carbon, hydrogen and nitrogen; w has a value of from 1 to 500; z has a value of 1 to 25 and y has a value of 3 to 5.
The organosilane silatrane may also be employed in accordance with the present invention in the form of a microemulsion containing the silatrane. Such microemulsions and their preparation are described in applicants' U.S. Patent No; 4,842,766 issued June 27, 1989, and assigned to the same assignee as the present application. Solutions with particle sizes less than 0.150 microns are disclosed which are either oil-in-water or water-in-oil microemulsions including the silatrane and at lease one surfactant.
Various procedures are employed in order to test the organosilanes of the present invention. For example, the presence of the chemical on a substrate can be determined by complexing a standarized solution of bromophenol blue in water the quaternary nitrogen of the organosilane and recording the color change spectrophotometrically. Results of this test can be used in order to determine whether the organosilane has bound itself to a particular surface. Such a test procedure is set forth below.
The anion of an aqueous sodium salt of bromophenol blue can be complexed with the cation of polymerized silanes of this invention while on a substrate. The blue colored 2a~3 ~ ~
. ,~
complex, substantive to a water rinse, is qualitatively indicative of the presence of the cation on the substrate thus indicating the extent of antimicrobial agent on a given substrate. A comparison of the intensity of retained blue color to a color standard is used as a check to determine if the treatment has been applied properly.
One method consists of preparing a 0.02 to 0.04 weight percent solution of bromphenol blue in distilled water. This solution is made alkaline using a few drops of saturated Na2C03 solution per 100 milliliters of the solution. Two to three drops of this solution are placed on the treated substrate and allowed to stand for two minutes.
The substrate is then rinsed with copious amounts of tap water and the substrate is observed for a blue stain and it is compared to a color standard.
For a spectrophotometric determination, the following test is used. The sodium salt of bromphenol blue is depleted from a standard solution by complexing with the cations on a treated substrate. The change in bromphenol blue concentration is determined spectrophotometrically or by comparison with color standards whereby the level of substrate treatment by the cationic silane is determinable.
The method consists of preparing a 0.02 weight percent standard solution of bromphenol blue in distilled water. It is made alkaline with a few drops of saturated Na2C03 solution per 100 milliliters of bromphenol blue solution. The color of this solution is purple. The blank solution is adjusted to yield a 10 to 12% transmittance reading when measured in 1 cm cells using a spectrophotometer set at 589 nm by the following method. Fill a container 3/4 full of distilled water and add 2 ml of the 0.02% standard bromphenol blue solution for every 50 ml of distilled water.
Add 0.5 ml of a 170 Triton~ X-100 surfactant (manufactured by Rohm and Haas, Philadelphia, PA, USA) aqueous solution for every 50 ml of water. Mix and, using the spectrophotometer, determine the maximum absorbance. Adjust the upper zero to 100% transmittance with distilled water. Check the percent transmittance of the working bromphenol blue solution at the maximum absorbance setting. Adjust the blank solution to 10 to 12% transmittance with either water or bromphenol blue standard solution as necessary.
The samples of treated substrate can be tested by placing 0.5 gram samples of the substrate standards in a flask large enough for substantial agitation of the sample and the test solution. Add 50 ml of the working solution.
Agitate for 20 minutes on a wrist-action shaker. Fill the test curvette with the test solution. Centrifuge if particulate matter is present. Measure the % transmittance at the wavelength set forth above. The transmittance is compared against a standard curve prepared by preparing several substrate samples of known concentration of the cationic silane. For example, samples containing a known amount of cationic silane at, for example, 0%, 0.25%, 0.50%, 0.75% and 1% are read spectrophotometrically and a curve is plotted.
The antimicrobial activity of a treated surface is normally evaluated by sh~ki ng a sample weighing 0.75 grams in a 750,000 to 1,500,000 count Klebsiella pneumoniae suspension for a one hour contact time. The suspension is serially diluted, both before and after contact and cultured. The number of viable organisms in the suspensions is determined.
The percent reduction based on the original count is determined. The method is intended for those surfaces having a reduction capability of 75 to 100% for the specified contact time. The results are reported as the percent reduction. Media used in this test are nutrient broth, catalog No. 0003-01-6 and tryptone glucose extract agar, catalog No. 0002-01-7 both available from Difco laboratories, Detroit, Michigan, U.S.A. The microorganism used is Klebsiella pneumoniae American Type Culture Collection; Rockville, Md. U.S.A., catalog No. 4352. The procedure used for determining the zero contact time counts is carried out by utilizing two sterile 250 ml. screw-cap Erlenmeyer flasks for each sample. To each flask is added 70 ml of sterile buffer solution. To each flask is added, aseptically, 5 ml of the organism inoculum. The flasks are capped and placed on a wrist action shaker. They are shaken at maximum speed for 1 minute. Each flask is considered to be at zero contact time and is immediately subsampled by transferring 1 ml of each solution to a separate test tube containing 9 ml of sterile buffer. The tubes are agitated with a vortex mixer and then 1 ml of each solution is transferred to a second test tube containing 9 ml of sterile buffer. Then, after agitation of the tubes, 1 ml of each tube is transferred to a separate sterile petri dish.
Duplicates are also prepared. Sixteen ml of molten (42~C.) tryptone glucose extract agar is added to each dish. The dishes are each rotated ten times clockwise and ten times counterclockwise. The dishes are then incubated at 37~C for 24 to 36 hours. The colonies are counted considering only those between 30 and 300 count as significant. Duplicate samples are averaged. The procedure used for determining the bacterial count after 1 hour is essentially the same as that used to determine the count at the zero contact time. The only difference is that pour plating is performed at the 10~
and 10 1 dilutions as well as at the 10 2 dilution. "Percent reduction" is calculated by the formula 2~
B+C
%R = 2 - A 100 B+C
where A is the count per milliliter for the flask containing the treated substrate; B is zero contact time count per milliliter for the flask used to determine "A" before the addition of the treated substrate and C is zero contact time count per milliliter for the untreated control substrate.
The foregoing "Shake Flask Test" measures antimicrobial substrate activity. An alternative test sometimes employed is the "Agar Plate Graphing Technique"
which again affords a measure of antimicrobial substrate activity, in which treated swatches of fabric are placed on agar impregnated with Klebsiella pneumoniae. Antimicrobial activity is measured by the existence of a zone of inhibition and diffusability in the agar. Immobilized antimicrobials will not show a zone.
It is also possible to measure antimicrobial solution activity and this is performed in accordance with the procedures of the "Minimum Inhibitory Concentration Test (MIC)" in which the level of chemical required to inhibit the growth of microorganisms in a system is determined, typically employing organisms such as Staphylococcus aureus, Klebsiella pneumoniae and Asper~illus ni~er.
The following examples illustrate the concepts of the present invention.
Example I
A white powder antimicrobial solid was prepared by the reaction of 118.9 grams of 3-(trimethoxysilyl) propyldimethyl octadecyl ammonium chloride and 142 grams of methanol with 14.9 grams of triethanolamine in a solvent mixture of 9 grams isobutanol and 50 grams of toluene. These materials were heated and refluxed with stirring.
Over a period of three hours, the methanol solvents and water were distilled off and the mixture cooled. A white solid representing 84% of theoretical yield was obtained after vacuum filtration.
While the foregoing example employs triethanolamine as a reactant to produce the silatrane reaction product, any alkanolamine is appropriate.
Example II
The Shake Flask antimicrobial test explained above was employed in order to determine antimicrobial activity.
Cotton fabric was treated with one percent by weight of the white powder in a water solution. Both ten and thirty minute soaks provided a reduction of 100 percent in comparison to a reduction of 64.8 percent for a control, indicating excellent antimicrobial activity for the organosilane silatrane composition of the present invention.
Example III
There was heated and stirred for three hours a mixture including 118.4 grams of 3-(trimethoxysilyl) propyldimethyl octadecyl ammonium chloride, 141 grams of methanol, 14.9 grams of triethanolamine and fifty grams of toluene. The mixture was dried in a forced air oven at about 200~C. to yield a yellow-white powder. The powder was washed three times with acetone resulting in a dry white powder material.
A ladder series of concentration calculated as fully hydrolyzed 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride were prepared using the triethanolamine silatrane of 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride (I) and 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride (II), the ladder being composed of 0.09, 0.1., 0.25, 0.50 and 1.00% by weight active on cotton and polyester fabrics. Treatment was accomplished by wet weight pick up from tap water solutions of the test compounds. The fabrics were dried and tested by the following procedures:
A. Dynamic Shake Flask Antibacterial Test - Klebsiella pneumonia Gram (-) and Staphylococcus Aureus Gram (+).
Standard procedure.
B- Bromophenol blue Spectrophotometric Analytical Test.
0.5g test fabric used in standard procedure.
C. A above after 2 grams of the test fabric were rinsed in 200 ml of 40~C deionized water for 20 minutes, squeezed dry and oven dryed at 100~C.
D. B above per C.
E. Zone of Inhibition 1- zTrypticase Soy Agar, 1 7/8" fabric circle placed on lawn of Klebsiella pneumoniae (24 hour broth culture diluted 1:100 in sterile deionized water phosphate buffer, 1 ml spread on plate as lawn) or Staphylococcus aureus (prepared as above).
Readings after 48 hours incubation at 37~C.
2. Saborauds Dextro~e Agar, 1 7/8" fabric circle placed on agar and inoculated with a spore suspension with "Triton~ X-100 wetting agent of AsPer~illus ni~er.
Readings were made for total coverage after 21 days incubation at 30~C.
F. Zone of Inhibition Run as E with samples per C.
The test results are shown in the Tables that follow.
2 ~8 ~ ;3 The evidence of a leaching component that gives a zone of inhibition is clear from tests E and F showing a zone before rinse and no zone after rinse and from tests A and C
where the activity against the test organisms is measurably reduced after rinsing. The durability of the antimicrobial as the silane quaternary amine as the monomer or as delivered from the hydrolysis of the silatrane is seen clearly from tests E and F, surface growth of A. niger profile the same and tests B and D showing analytical equivalence from rinsed/nonrinsed silane/silatrane comparisons and tests A and C showing identical minimal activity profiles silane/silatrane.
The silatrane of triethanolamine and 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride provides a water soluble solid delivery form of 3-trimethoxysilylpropyl dimethyloctadecyl ammonium chloride that provides a durable antimicrobial surface after a rinse protocol and provides for a leaching antimicrobial before rinsing. Upon contact with water, the silatrane reverts to TMS and triethanolamine.
TABLE I
Analytical and Antimicrobial Tests - Silatrane Sample A. DsF-~ntih~ctprial B. BPB-Analytical C. DSF (Rin~ed) D. BPB (Rinsed) E. Zone of Inhibition P. Zone of Inhibition (Rinsed) % Reduction X T- r~i~sion % r- Lion X TransDission mm mm K.pneunoniae S.aureus K.pneumoniae S.aureus K.pneuDoniae S.aureus A.niger K.l ~P S.aureus A.niger mD Surface DD Surface Active Ingredient Growth Gro~th (Silatrane) XCovered 7.Covered 21 days 21 days Fabric : Cotton 0.00% 16 32 11.0 19 26 11.0 0 0 0 100 0 0 0 100 0.10% 46 64 12.5 38 32 12.5 0 0 0 75 0 0 0 80 0.25% 98 100 21.0 94 84 23.0 1 3 0 50 0 0 0 40 0.50% 99.99 100 58.0 99.9 99.9 73.0 2 7 0 0 0 0 o 0 1.00% 100 100 68.0 100 100 81.0 4 8 1 0 0 0 0 0 Fabric : Polyester o.00% 0 3 11.0 0 4 11.0 0 0 0 lO0 0 0 0 100 0.10% 28 35 12.0 41 28 13.0 0 0 0 75 0 0 0 80 0.25% 92 100 27.0 86 96 36.0 0 2 0 10 0 0 0 20 0.507O 97 100 61.0 93 100 64.0 l 4 0 0 0 0 o 0 1.00% 100 100 75.0 100 100 78.0 3 6 l 0 0 0 0 o Analytical Blank - - 11.0 11.0 TABLE II
Analytical and Anti~icrobial Tests - TMS
Sample A. DSP-Antih~ct~rial B. BPB-Analytical C. DSP (Rinsed) D. BPB (Rinsed) E. Zone of Inhibition P. Zone of Inhibition (Rinsed) X Reduction % Transmission % Reduction X Transmission mm mm K.pneumoniae S.aureus K.pneumoniae S.aureus K.~ S.aureus A.niger K.pneumoniae S.aureus A.niger mmSurface mmSurface Active Ingredient Growth Growth (Silatrane) 7.Covered XCovered 21 days 21 days Pabric : Cotton 0.00% 22 38 11.0 18 29 11.0 0 0 0 100 0 0 0 100 0.10% 63 65 13.5 55 48 12.5 0 0 0 70 0 0 0 75 0.25% 72 84 28.0 83 90 23.0 0 0 0 25 0 0 0 30 0.50% 99.9 100 63.0 99.5 100 58.0 0 0 0 0 0 0 o 0 1.00% 100 100 72.0 100 100 75.0 0 0 0 o 0 0 o 0 Pabric : Polyester 0.00% 0 2 11.0 0 3 11.0 0 0 0 100 0 0 0 100 0.10% 48 52 16.0 32 28 14.0 0 0 0 50 0 0 0 50 0.25% 98 99.99 34.0 96 98.6 29.0 0 0 0 0 o 0 0 0 0.50% 100 99.99 74.0 100 100 65.0 0 0 0 0 o 0 0 0 1.00% 100 100 86.0 100 100 82.0 0 0 o 0 0 0 o 0 Analytical Blank - - 11.0 - - 11.0 - - - - - - - -~'~
S~
The organosilane quaternary ammonium silatrane compound produced in the foregoing examples is shown in the following formula N(CRlR2CR3R40)3Si-CH2-CH2-CH2-11 'C18H37Cl wherein Rl, R2, R3 and R4, each represent a hydrogen atom or a methyl, ethyl, propyl or butyl radical.
The genus of the organosilane silatrane compounds of the present invention is shown below and, in each formula, the radicals indicated therein are as previously defined above.
N(CRlR2CR R 0)3SiR''N~R'''R''IrRvX
N(CRlR2CR R 0)3SiRI'N ~ X~
Regarding the activity of the compounds of the present invention, such compounds have been found to be effective against a number of microorganisms, such as "BACTERIA'': Gram (-); Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeru~inosa, Pseudomonas fluorescens, Proteus mirabilis, Proteus vul~aris, Salmonella typhi, Salmonella typhimurium, Salmonella cholera suis, Enterobacter cloacae, Enterobacter aero~enes, Mor~anella mor~anii, Aeromonas hydrophila, Citrobacter freundii, Citrobacter deversus, Serratia marcescens, Serratia liquifaciens, ~anthomonas campestris, Acinetobacter calcoaceticus; Gram (~): Staphylococcus aureus, - - - - , ....
2 ~ g 3 ~ ~ 3 Staphylococcu~ epidermidis, Streptococcus mutans, Streptococcus pyoRenes, Streptococcus fecalis, Micrococcus lutea, Bacillus sp. (vegetative cell); "Fungi": Aspergillus niger, AsperRillus flavus, Aspergillus sydowi, AsperRillus versicolor, AsperRillus terreus, Penicillium chryso~enum, Penicillium variabile, Penicillium funiculosum, Penicillium pinophilum, Poria placenta, Aureobasidium pullulans, Gloeophyllum trabeum, Chaetomium globosum, Trichoderma viride, Trichophyton menta~rophytes; "Fungi" (yeasts):
Candida albicans, Candida pseudotropoicalis, Saccharomyces cerevisiae.
It will be apparent from the foregoing that many other variations and modifications may be made in the compounds, compositions and methods described herein without departing substantially from the essential features and concepts of the present invention. Accordingly, it should be clearly understood that the forms of the invention described herein are exemplary only and are not intended as limitations on the scope of the present invention.
Claims (6)
1. A method of treating a surface harboring microorganisms in order to combat the microorganisms by destroying the microorganisms or by preventing proliferation of the microorganisms to numbers that would be destructive to the surface sought to be treated and protected, comprising reacting an alkanolamine with an organosilicon quaternary ammonium compound to form a silatrane compound in the form of a solid particulate powder, dissolving the silatrane powder in an aqueous medium to form an antimicrobially active solution of the silatrane powder and applying the solution in an antimicrobially effective amount to the surface sought to be treated and protected, the organosilicon quaternary ammonium compound being an organosilane having the formula selected from the group consisting of and wherein, in each formula, Y is R or RO where each R is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
a has a value of 0, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
a has a value of 0, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
2. A method as claimed in claim 1 wherein the organosilicon compound has the formula wherein each R is an alkyl radical of 1 to 4 carbon atoms or hydrogen; a has a value of 0, 1 or 2; R' is a methyl or ethyl radical; R'' is an alkylene group of 1 to 4 carbon atoms;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
3. A method as claimed in claim 1 wherein the organosilicon compound has the formula wherein R is an alkyl radical of 1 to 4 carbon atoms or hydrogen; a has a value of 0, 1 or 2; R' is a methyl or ethyl radical; R'' is an alkylene of 1 to 4 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
4. A solid antimicrobial composition comprising the reaction product of an alkanolamine and at least one organosilicon quaternary ammonium compound, the organosilicon quaternary ammonium compound being an organosilane having the formula selected from the group consisting of and wherein, in each formula, Y is R or RO where each R is an alkyl radical of 1 to 4 carbon atoms or hydrogen;
a has a value of 0, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms ;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
a has a value of 0, 1 or 2;
R' is a methyl or ethyl radical;
R'' is an alkylene group of 1 to 4 carbon atoms ;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, -CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
5. A composition as claimed in claim 4 wherein the organosilicon compound has the formula wherein each R is an alkyl radical of 1 to 4 carbon atoms or hydrogen; a has a value of 0, 1 or 2; R' is a methyl or ethyl radical; R'' is an alkylene group of 1 to 4 carbon atoms;
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
R''', R'''' and R v are each independently selected from a group consisting of alkyl radicals of 1 to 18 carbon atoms, -CH2C6H5, -CH2CH2 0H, CH2 0H and -(CH2)xNHC(O)R vi, wherein x has a value of from 2 to 10 and R vi is a perfluoroalkyl radical having from 1 to 12 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
6. A composition as claimed in claim 4 wherein the organosilicon compound has the formula wherein R is an alkyl radical of 1 to 4 carbon atoms or hydrogen; a has a value of 0, 1 or 2; R' is a methyl or ethyl radical; R'' is an alkylene of 1 to 4 carbon atoms; and X is chloride, bromide, fluoride, iodide, acetate or tosylate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/431,415 US5064613A (en) | 1989-11-03 | 1989-11-03 | Solid antimicrobial |
| US431,415 | 1989-11-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2028163A1 CA2028163A1 (en) | 1991-05-04 |
| CA2028163C true CA2028163C (en) | 1999-01-26 |
Family
ID=23711846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002028163A Expired - Lifetime CA2028163C (en) | 1989-11-03 | 1990-10-22 | Solid antimicrobial |
Country Status (3)
| Country | Link |
|---|---|
| US (2) | US5064613A (en) |
| JP (1) | JP3311745B2 (en) |
| CA (1) | CA2028163C (en) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5180578A (en) * | 1987-01-30 | 1993-01-19 | Colgate-Palmolive Company | Antibacterial antiplaque anticalculus oral composition |
| US5145596A (en) * | 1989-08-07 | 1992-09-08 | Dow Corning Corporation | Antimicrobial rinse cycle additive |
| US5064613A (en) * | 1989-11-03 | 1991-11-12 | Dow Corning Corporation | Solid antimicrobial |
| DE4293451T1 (en) * | 1991-09-13 | 1994-09-08 | Gillette Canada | Polymer particles for dental applications |
| US5290541A (en) * | 1992-06-18 | 1994-03-01 | The Procter & Gamble Company | Methods for making oral compositions |
| US5292528A (en) * | 1992-06-19 | 1994-03-08 | Sunstar Kabushiki Kaisha | Oral Composition |
| US5936703A (en) * | 1993-10-13 | 1999-08-10 | Nof Corporation | Alkoxysilane compound, surface processing solution and contact lens |
| US5731037A (en) * | 1995-09-06 | 1998-03-24 | Kansai Paint Co., Ltd. | Pollution-preventing process |
| US5959014A (en) * | 1996-05-07 | 1999-09-28 | Emory University | Water-stabilized organosilane compounds and methods for using the same |
| US6632805B1 (en) * | 1996-05-07 | 2003-10-14 | Emory University | Methods for using water-stabilized organosilanes |
| US5954869A (en) | 1997-05-07 | 1999-09-21 | Bioshield Technologies, Inc. | Water-stabilized organosilane compounds and methods for using the same |
| US6762172B1 (en) | 1997-07-17 | 2004-07-13 | Nova Biogenetics, Inc. | Water-stabilized organosilane compounds and methods for using the same |
| US6113815A (en) * | 1997-07-18 | 2000-09-05 | Bioshield Technologies, Inc. | Ether-stabilized organosilane compositions and methods for using the same |
| US6088854A (en) * | 1998-06-30 | 2000-07-18 | Brownrigg; Elizabeth Ann | Lateral body-supporting pillow |
| AU3887500A (en) | 1999-03-16 | 2000-10-04 | Coating Systems Laboratories, Inc. | Antimicrobial skin preparations containing organosilane quaternaries |
| KR20020042919A (en) * | 2000-12-01 | 2002-06-08 | 박재준 | A Manufacturing Method of Water Coating-remedy for Infraed-rayes, Antibiosis and Perfume |
| US7151139B2 (en) * | 2001-04-23 | 2006-12-19 | Massachusetts Institute Of Technology | Antimicrobial polymeric surfaces |
| US9089407B2 (en) | 2001-04-23 | 2015-07-28 | Massachusetts Institute Of Technology | Antibacterial coatings that inhibit biofilm formation on implants |
| US6712976B2 (en) | 2001-09-13 | 2004-03-30 | Abtech Industries, Inc. | Dual-action decontamination system |
| US6787682B2 (en) | 2001-11-05 | 2004-09-07 | Hollister Incorporated | Absorbent foam wound dressing |
| US6905711B1 (en) | 2002-05-02 | 2005-06-14 | Smart Anti-Microbial Solutions, Llc | Antimicrobial agents, products incorporating said agents and methods of making products incorporating antimicrobial agents |
| SE0400073D0 (en) * | 2003-04-04 | 2004-01-14 | Appear Sweden Hb | Antibacterial material |
| CA2525865A1 (en) * | 2003-05-22 | 2004-12-09 | Coating Systems Laboratories, Inc. | Antimicrobial quaternary ammonium organosilane coatings |
| US9764264B2 (en) | 2003-05-22 | 2017-09-19 | Coating Systems Laboratories, Inc. | Ballast water treatment systems |
| US9364572B2 (en) | 2003-05-22 | 2016-06-14 | Coating Systems Laboratories, Inc. | Static fluid disinfecting systems and related methods |
| US20050211635A1 (en) * | 2004-03-24 | 2005-09-29 | Yeh Eshan B | Anti-microbial media and methods for making and utilizing the same |
| US7585426B2 (en) * | 2004-03-26 | 2009-09-08 | Arrowstar, Llc | Compositions and methods for imparting stain resistance, liquid repellency, and enhanced antimicrobial activity to an article and articles thereof |
| GB2415948A (en) * | 2004-07-03 | 2006-01-11 | Ebac Ltd | Bottled liquid dispenser |
| US7686878B2 (en) * | 2005-03-10 | 2010-03-30 | Momentive Performance Materials, Inc. | Coating composition containing a low VOC-producing silane |
| US20080213394A1 (en) * | 2005-03-11 | 2008-09-04 | Tullo Louis J | Polymer-Based Antimicrobial Agents, Methods of Making Said Agents, and Products Incorporating Said Agents |
| JP2008534714A (en) | 2005-03-22 | 2008-08-28 | バイオセーフ インク． | Method for making solvent-free, silicone-containing quaternary ammonium-containing polymer antibacterial agents with excellent and durable antibacterial properties |
| US9714371B2 (en) | 2005-05-02 | 2017-07-25 | Trican Well Service Ltd. | Method for making particulate slurries and particulate slurry compositions |
| GB2465914B (en) * | 2005-05-02 | 2010-08-25 | Trican Well Service Ltd | Method for making transportable aqueous slurries by particulate hydrophobicization |
| US20070163964A1 (en) * | 2005-11-07 | 2007-07-19 | Williamson J K | Methods and compositions for filtration media |
| AU2006325820B2 (en) | 2005-12-12 | 2013-02-14 | Allaccem, Inc. | Methods and systems for preparing antimicrobial films and coatings |
| US7759408B2 (en) * | 2005-12-21 | 2010-07-20 | Bausch & Lomb Incorporated | Silicon-containing monomers end-capped with polymerizable cationic hydrophilic groups |
| US7622512B2 (en) * | 2005-12-21 | 2009-11-24 | Bausch & Lomb Incorporated | Cationic hydrophilic siloxanyl monomers |
| US20070161769A1 (en) * | 2006-01-06 | 2007-07-12 | Schorzman Derek A | Polymerizable silicon-containing monomer bearing pendant cationic hydrophilic groups |
| US7960447B2 (en) * | 2006-04-13 | 2011-06-14 | Bausch & Lomb Incorporated | Cationic end-capped siloxane prepolymer for reduced cross-link density |
| CN101627092A (en) * | 2006-11-08 | 2010-01-13 | 麻省理工学院 | Make the polymeric coatings of virus and inactivation of bacteria |
| US20080152540A1 (en) * | 2006-12-22 | 2008-06-26 | Bausch & Lomb Incorporated | Packaging solutions |
| NZ579785A (en) * | 2007-02-21 | 2012-06-29 | Allaccem Inc | Bridged polycyclic compound based compositions for the inhibition and amelioration of disease |
| EP2147077A4 (en) | 2007-04-26 | 2011-04-06 | Trican Well Service Ltd | Control of particulate entrainment by fluids |
| US7691917B2 (en) | 2007-06-14 | 2010-04-06 | Bausch & Lomb Incorporated | Silcone-containing prepolymers |
| US8153618B2 (en) * | 2007-08-10 | 2012-04-10 | Allaccem, Inc. | Bridged polycyclic compound based compositions for topical applications for pets |
| US8153617B2 (en) * | 2007-08-10 | 2012-04-10 | Allaccem, Inc. | Bridged polycyclic compound based compositions for coating oral surfaces in humans |
| US8188068B2 (en) * | 2007-08-10 | 2012-05-29 | Allaccem, Inc. | Bridged polycyclic compound based compositions for coating oral surfaces in pets |
| US20090074833A1 (en) * | 2007-08-17 | 2009-03-19 | Whiteford Jeffery A | Bridged polycyclic compound based compositions for controlling bone resorption |
| US8648127B2 (en) * | 2008-06-02 | 2014-02-11 | The Boeing Company | Self decontaminating chemical and biological agent resistant coating |
| US20100016270A1 (en) * | 2008-06-20 | 2010-01-21 | Whiteford Jeffery A | Bridged polycyclic compound based compositions for controlling cholesterol levels |
| US20100004218A1 (en) * | 2008-06-20 | 2010-01-07 | Whiteford Jeffery A | Bridged polycyclic compound based compositions for renal therapy |
| CA2690768A1 (en) | 2010-01-21 | 2011-07-21 | Trican Well Services Ltd. | Compositions and methods for enhancing fluid recovery for hydraulic fracturing treatments |
| GB201209229D0 (en) * | 2012-05-25 | 2012-07-04 | Epistem Ltd | Nucleic acid extraction |
| MX2015013714A (en) * | 2013-03-26 | 2016-08-18 | Qore Systems LLC | Static fluid disinfecting systems and related methods. |
| USRE49528E1 (en) | 2013-04-26 | 2023-05-16 | Biointeractions Ltd. | Bioactive coatings |
| CN110776610A (en) | 2013-04-26 | 2020-02-11 | 生物相互作用有限公司 | Bioactive coating |
| CA2889374A1 (en) | 2014-04-25 | 2015-10-25 | Trican Well Service Ltd. | Compositions and methods for making aqueous slurry |
| CA2856942A1 (en) | 2014-07-16 | 2016-01-16 | Trican Well Service Ltd. | Aqueous slurry for particulates transportation |
| RU2676089C1 (en) | 2014-11-04 | 2018-12-26 | ЭЛЛАЙД БИОСАЙНС, Инк. | Composition and method of creation of self-distinctive surface |
| US10993441B2 (en) | 2014-11-04 | 2021-05-04 | Allied Bioscience, Inc. | Antimicrobial coatings comprising organosilane homopolymers |
| US10980236B2 (en) | 2014-11-04 | 2021-04-20 | Allied Bioscience, Inc. | Broad spectrum antimicrobial coatings comprising combinations of organosilanes |
| US10258046B2 (en) * | 2014-11-04 | 2019-04-16 | Allied Bioscience, Inc. | Antimicrobial coatings comprising quaternary silanes |
| CA2880646A1 (en) | 2015-01-30 | 2016-07-30 | Trican Well Service Ltd. | Composition and method of using polymerizable natural oils to treat proppants |
| WO2016130837A1 (en) | 2015-02-11 | 2016-08-18 | Allied Bioscience, Inc. | Anti-microbial coating and method to form same |
| US10117435B2 (en) | 2015-02-27 | 2018-11-06 | Nano Photo Sciences, LLC | Composition containing an organosilane and a photocatalyst, and methods of treating flowering plants infected with a bacterial disease using the composition |
| GB201513492D0 (en) | 2015-07-30 | 2015-09-16 | Arcis Biotechnology Holdings Ltd | Method and composition |
| JP6925705B2 (en) * | 2017-03-09 | 2021-08-25 | 株式会社川島織物セルコン | Functional fibers, manufacturing methods for functional fibers, and functional agents |
| WO2019212718A1 (en) * | 2018-05-02 | 2019-11-07 | Allied Bioscience, Inc. | Antimicrobial coatings comprising quaternary silanes |
| TWI686399B (en) * | 2018-07-05 | 2020-03-01 | 國立中央大學 | Amphoteric dual ion material with nitrogen silicon tricyclic ring and antifouling base material containing it |
| AU2019360154A1 (en) * | 2018-10-18 | 2021-05-27 | Topikos Pharmaceutical Company, Inc. | Organosilanes for the treatment of infections |
| JP2022552017A (en) * | 2019-10-18 | 2022-12-14 | トピコス ファーマシューティカルズ インコーポレイテッド | antibacterial organosilane |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3560385A (en) * | 1968-11-01 | 1971-02-02 | Dow Corning | Method of lubricating siliceous materials |
| GB1321616A (en) * | 1969-10-27 | 1973-06-27 | Dow Corning Ltd | Organosilicon compounds and process |
| US3730701A (en) * | 1971-05-14 | 1973-05-01 | Method for controlling the growth of algae in an aqueous medium | |
| US3860709A (en) * | 1971-09-29 | 1975-01-14 | Dow Corning | Method of inhibiting the growth of bacteria and fungi using organosilicon amines |
| BE789399A (en) * | 1971-09-29 | 1973-03-28 | Dow Corning | INHIBITION OF THE GROWTH OF BACTERIA AND FUNGI USING SILYLPROPYLAMINES AND DERIVATIVES THEREOF |
| GB1386876A (en) * | 1971-10-04 | 1975-03-12 | Dow Corning | Bactericidal and fungicidal composition |
| BE791134A (en) * | 1971-11-12 | 1973-05-09 | Dow Corning | PROCESS AND FILTER TO INHIBIT GROWTH |
| US3865728A (en) * | 1971-11-12 | 1975-02-11 | Dow Corning | Algicidal surface |
| CA1010782A (en) * | 1973-02-20 | 1977-05-24 | Charles A. Roth | Articles exhibiting antimicrobial properties |
| US4048206A (en) * | 1975-04-22 | 1977-09-13 | Mikhail Grigorievich Voronkov | Process for the production of 1-organylsilatranes and carbofunctional derivatives thereof |
| US4005028A (en) * | 1975-04-22 | 1977-01-25 | The Procter & Gamble Company | Organosilane-containing detergent composition |
| US4055637A (en) * | 1975-08-15 | 1977-10-25 | Mikhail Grigorievich Voronkov | Medicinal preparation for healing wounds and treating dermatites using 1-(chloromethyl)silatrane |
| DE2542534C3 (en) * | 1975-09-24 | 1979-08-02 | Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler, 6000 Frankfurt | Process for the preparation of sulfur-containing organosilicon compounds |
| JPS5938957B2 (en) * | 1976-08-31 | 1984-09-20 | 味の素株式会社 | Synthesis method of silatrane derivatives |
| US4161518A (en) * | 1977-12-29 | 1979-07-17 | Minnesota Mining And Manufacturing Company | Compositions and methods for inhibiting plaque formation |
| US4259103A (en) * | 1979-03-12 | 1981-03-31 | Dow Corning Corporation | Method of reducing the number of microorganisms in a media and a method of preservation |
| US4282366A (en) * | 1979-11-06 | 1981-08-04 | International Paper Company | Organosilicon quaternary ammonium antimicrobial compounds |
| US4406892A (en) * | 1979-11-06 | 1983-09-27 | International Paper Company | Organosilicon quaternary ammonium antimicrobial compounds |
| JPS57193573A (en) * | 1981-05-22 | 1982-11-27 | Mitsubishi Burlington | Anti-bacterial carpet and method |
| US4394378A (en) * | 1981-07-08 | 1983-07-19 | Klein Stewart E | 3-(Trimethoxysilyl) propyldidecylmethyl ammonium salts and method of inhibiting growth of microorganisms therewith |
| US4467013A (en) * | 1981-10-09 | 1984-08-21 | Burlington Industries, Inc. | Bioactive water and alcohol-repellant medical fabric |
| US4615882A (en) * | 1982-09-27 | 1986-10-07 | Stockel Richard F | Disinfectant solution for contact lens |
| US4472327A (en) * | 1983-01-31 | 1984-09-18 | Neefe Charles W | Method of making hydrogel cosmetic contact lenses |
| GB8314500D0 (en) * | 1983-05-25 | 1983-06-29 | Procter & Gamble Ltd | Cleaning compositions |
| US4504541A (en) * | 1984-01-25 | 1985-03-12 | Toyo Boseki Kabushiki Kaisha | Antimicrobial fabrics having improved susceptibility to discoloration and process for production thereof |
| US4557854A (en) * | 1984-03-02 | 1985-12-10 | Dow Corning Corporation | Detergent compositions containing insoluble particulates with a cationic surface treatment |
| US4631297A (en) * | 1984-03-12 | 1986-12-23 | Dow Corning Corporation | Antimicrobially effective organic foams and methods for their preparation |
| US4564456A (en) * | 1984-06-01 | 1986-01-14 | Dow Corning Corporation | Method of treating water to inhibit corrosion and diminish mineral deposition |
| US4682992A (en) * | 1984-06-25 | 1987-07-28 | Potters Industries, Inc. | Microbicidal coated beads |
| JPS62500014A (en) * | 1984-08-24 | 1987-01-08 | ペアソン、グレン エ−． | Powder flame retardant and its manufacturing method |
| US4721511A (en) * | 1984-10-05 | 1988-01-26 | W. R. Grace & Co. | Leach resistant antimicrobial fabric |
| US4567039A (en) * | 1984-10-12 | 1986-01-28 | Revlon, Inc. | Hair conditioning composition and method |
| US4631273A (en) * | 1984-11-05 | 1986-12-23 | Dow Corning Corporation | Aqueous emulsions using cationic silanes |
| JPS61148285A (en) * | 1984-12-21 | 1986-07-05 | Toray Silicone Co Ltd | Solid material treating agent composition |
| US4772593A (en) * | 1985-07-01 | 1988-09-20 | The Dow Chemical Company | Alkoxysilane compounds in the treatment of swine dysentery |
| JPS6281393A (en) * | 1985-10-04 | 1987-04-14 | Sumitomo Chem Co Ltd | Triorganotin silatrane derivative, production thereof, insecticide, acaricide and fungicide containing same as active ingredient |
| JPS62184126A (en) * | 1986-02-04 | 1987-08-12 | 帝人株式会社 | Polyamide yarn having built-in antibacterial property applied thereto and its production |
| US4781974A (en) * | 1986-04-23 | 1988-11-01 | James River Corporation | Antimicrobially active wet wiper |
| US4842766A (en) * | 1987-02-17 | 1989-06-27 | Dow Corning Corporation | Silane microemulsions |
| US4822667A (en) * | 1988-03-04 | 1989-04-18 | Precision Fabrics Group | Woven medical fabric |
| US4847088A (en) * | 1988-04-28 | 1989-07-11 | Dow Corning Corporation | Synergistic antimicrobial composition |
| US5064613A (en) * | 1989-11-03 | 1991-11-12 | Dow Corning Corporation | Solid antimicrobial |
-
1989
- 1989-11-03 US US07/431,415 patent/US5064613A/en not_active Expired - Lifetime
-
1990
- 1990-10-22 CA CA002028163A patent/CA2028163C/en not_active Expired - Lifetime
- 1990-11-02 JP JP29555590A patent/JP3311745B2/en not_active Expired - Fee Related
-
1991
- 1991-04-08 US US07/681,585 patent/US5359104A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP3311745B2 (en) | 2002-08-05 |
| JPH03188006A (en) | 1991-08-16 |
| CA2028163A1 (en) | 1991-05-04 |
| US5359104A (en) | 1994-10-25 |
| US5064613A (en) | 1991-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2028163C (en) | Solid antimicrobial | |
| US5013459A (en) | Opthalmic fluid dispensing method | |
| US4908355A (en) | Skin treatment method | |
| EP0415540B1 (en) | Antimicrobial rinse cycle additive | |
| AU2004243046B2 (en) | Antimicrobial quaternary ammonium organosilane coatings | |
| EP0339957B1 (en) | A synergistic antimicrobial composition | |
| US4921701A (en) | Antimicrobial water soluble substrates | |
| AU619547B2 (en) | Method of treating tinea pedis and related dermatophytic infections | |
| US5073298A (en) | Antimicrobial antifoam compositions and methods | |
| US5169561A (en) | Antimicrobial antifoam compositions and methods | |
| EP0877027A2 (en) | Water-stabilized organosilane compounds and methods for using the same | |
| JPH0214741A (en) | Composition and method for anti-germ ultraadsorbent | |
| CA1331333C (en) | Antimicrobial antifoam compositions and methods | |
| US5169625A (en) | Antimicrobial water soluble substrates | |
| KR20150120656A (en) | Composition of non-volative antibacterial agents for fabrics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |