CA2754820A1 - Biodelivery systems - Google Patents
Biodelivery systems Download PDFInfo
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- CA2754820A1 CA2754820A1 CA2754820A CA2754820A CA2754820A1 CA 2754820 A1 CA2754820 A1 CA 2754820A1 CA 2754820 A CA2754820 A CA 2754820A CA 2754820 A CA2754820 A CA 2754820A CA 2754820 A1 CA2754820 A1 CA 2754820A1
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- Prior art keywords
- biocide
- composition
- biodelivery
- biofilm
- liposome
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/50—Treatment of water, waste water, or sewage by addition or application of a germicide or by oligodynamic treatment
-
- 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
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/26—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests in coated particulate form
- A01N25/28—Microcapsules or nanocapsules
-
- 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
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
Abstract
A biodelivery system has been found which increases the efficiency and effectiveness of introducing anti microbial compounds into complex biofilm matrices through the use of liposome carriers, thereby removing the biofouling in industrial wa-ter bearing s\ stems, including piping, heat exchanges, condensers, filtration s> stems and fluid storage tanks According to one embodiment of the invention, antimicrobial compound containing liposomes are added to water systems prone to biofouling and biofilm formation The liposomes, being similar in composition to microbial membranes or cells, are readily incorporated into the existing biofilm Once the antimicrobial compound containing liposomes become entrained with the biofilm matrix, the decomposition or disintegration of the liposome proceeds Thereafter the biocidal core is released to react directly with the biofilm encased microorganisms. Upon the death of the organisms, the matrix decomposes and thereby results in reduced fouling of the water bear-ing system, resulting in increased heat transfer, increased flux, less deposit of colloidal and particulate solids and dissolved organ-ics on the surface of the microfiltration membrane, thereby reducing the frequency and duration of the membrane cleaning and ul-timate replacement
Description
BIOD :LIVERY SYSTEMS
11' ieki of the Invention [0001] The field of the invention generally relates to hiodelÃve.Ã r: systems for pro siding products or compounds, such as chemicals, to industrial systems, The invention also .relates to compositions for use in a. targeted delivery of said compositions to bacterial biofllms various environments.
Background of the invention [0002] l3actefl'al biofilms exist in natural, medical, and industrial environments.
The biofilms offer a selective advantage to microorganisms to ensure the microorganisms' survival or to allow them a certain time to exist in a dormant state until suitable growth conditions arise. infortunately, this selective advantage poses serious threat's to heaaltla, or to the e.{ :iciency and lifetime of: industrial systems. The biofil.ms must be minimized or destroyed to improve the efficiency of industrial systems, or remove the potential health threats.
11' ieki of the Invention [0001] The field of the invention generally relates to hiodelÃve.Ã r: systems for pro siding products or compounds, such as chemicals, to industrial systems, The invention also .relates to compositions for use in a. targeted delivery of said compositions to bacterial biofllms various environments.
Background of the invention [0002] l3actefl'al biofilms exist in natural, medical, and industrial environments.
The biofilms offer a selective advantage to microorganisms to ensure the microorganisms' survival or to allow them a certain time to exist in a dormant state until suitable growth conditions arise. infortunately, this selective advantage poses serious threat's to heaaltla, or to the e.{ :iciency and lifetime of: industrial systems. The biofil.ms must be minimized or destroyed to improve the efficiency of industrial systems, or remove the potential health threats.
[0003] I I:a7.ny industrial or commercial operations rely on large quantities of x~w,ater for various reasons, such as for cooling systems, or said systems may produce large quantities ofwaÃstec-ater, which result in the creation of biohlms that need to be treated.
These industries include, but are not limited to, a ;riceÃlture, petroleum, oil drilling oil pipelines, oil. storage. gas drilling, gas pipelines. gas storage. chemical, pharmaceutical, mining, metal plating, textile, papermakin4g, brewing, food and beverage processing, and semiconductor industries. In these operations, naturally occurring biof lmÃs are continuously produced and often accumulate on numerous structural or equipment surfaces or on natural or biological surfaces. In industrial settings, the presence of these biofilms causes a decrease in the efficiency of industrial machiner-,, requires increased maintenance and presents potential health hazards, An example is the surfaces of water cooling towers which become increasingly coated with inicrobially produced bio.fllin slime Which constricts Water flow and reduces heat exchange capacity Specifically' in flowing or stagnant water, biollms can cause serious problems, including pipeline blockages, corrosion of equipment by growth of underfiln n ricrobes and the growth of potentially harmful pathogenic bacteria. Water cooling tower biofilms may form a harbor or reservoir that perpetuates growth. of pathogenic nricroorganisi s such as Legioncllca pica anolpl ilea.
These industries include, but are not limited to, a ;riceÃlture, petroleum, oil drilling oil pipelines, oil. storage. gas drilling, gas pipelines. gas storage. chemical, pharmaceutical, mining, metal plating, textile, papermakin4g, brewing, food and beverage processing, and semiconductor industries. In these operations, naturally occurring biof lmÃs are continuously produced and often accumulate on numerous structural or equipment surfaces or on natural or biological surfaces. In industrial settings, the presence of these biofilms causes a decrease in the efficiency of industrial machiner-,, requires increased maintenance and presents potential health hazards, An example is the surfaces of water cooling towers which become increasingly coated with inicrobially produced bio.fllin slime Which constricts Water flow and reduces heat exchange capacity Specifically' in flowing or stagnant water, biollms can cause serious problems, including pipeline blockages, corrosion of equipment by growth of underfiln n ricrobes and the growth of potentially harmful pathogenic bacteria. Water cooling tower biofilms may form a harbor or reservoir that perpetuates growth. of pathogenic nricroorganisi s such as Legioncllca pica anolpl ilea.
[0004] Another example of industrial systems are those systems that are found in the .food and beverage industries. Food preparation lines are routinely plagued by blofilni build-up both on the machinery and on the food product where bioflms often include potential pathogens, Industrial biofilmrs, such as those found in the food industry, are complex assemblages of insoluble polysaccharide-rich hiopolyrmers, which are produced and elaborated by surface dwelling micrroorganisms. More particularly, biofilms or microbial slimes are composed of polysaccharides, proteins and lipopolysaccharides extruded from certain microbes that allow them to adhere to solid surfaces in contact with water environments and form persistent colonies of sessile bacteria that thrive within a protective film. The film may allow anaerobic species to gro'~w~, producing acidic or corrosive conditions. To control these problems, processes and rntirnicrobial products are needed to control the formation and growth ofbiofilms. Control ofbiof lms involves the prevention of microbial attachment and/or the removal of existing b:ic.f:ilms from surfaces. While removal in many contexts is accomplished by short cleansing treatments With highly caustic or oxidizing agents the most common l y used mater ials to control biof lms are biocides and dispersants, In t S. patent no. 5,4I 1.,666 a method of removing a biofilm or preventing buildup of a biollm on a solid substrate is taught, that comprises a combination of at least two hiologicallv produced enzymes, such as an acidic or alkaline protease and a glucoarnylase or alpha amylase and at least one surfactant. U. S.
patent no. 6,759,040 teaches a method for preparing biofrlm degrading, multiple specificity, hydrolytic enzyme mixtures that are targeted to remove specific biofiirns.
[0006] U.S. patent no. 6,267 89, relates to a method of inhibiting l iotilm formation in commercial and industrial water systems by adding one or more plant oils to the system. However., although the biocides are e.1edive in controlling dispersed microorganism suspensions, i.e. planktonic microbes-, biocides do :riot work well a against sessile microbes, the basis of biolrars. This is due to the fact that biocides have difficulty penetrating the poivsacchande/protein slime layers surrounding the microbial l cells.
Thicker biofilms see little penetration of biocides and poor biocide efficacy, is the result.
One known. method of trying to better control biof-ilms has been the addition of dispersants and wetting agents to biocide compositions to enhance biocide eflica.cy.
Biodispersants r ray= operate to keep planktonic microbes sufficiently dispersed so that they do not agglomerate or achieve the local densities necessary to initiate the extracellular processes responsible for anchoring to a surface, or initiating film- or colony,-torrrrirrgmechanisms As components in biocidal treatment formulations, these biodispersants have helped in opening channels in the.. biofilm to allow better permeability ofthe toxic agents and to better disperse the microbial aggregates and clumps that have been ~w~eakened and released from the surfaces. However, biodispersants have proven to be more effective in preventing initial biofil:.m formation than in removing existing biofilms. In many cases, the activity of biodispersants has been responsible for only ?5 to 30% biornass removal from biofouled surfaces, even when used in conjunction with a biocida.l agent.
[0006] Therefore, a clear need still exists for an efficient and effective means for delivering antimicrobial compounds that are better able to penetrate existing bioh Ims and biofilm matrices, and more effective in killing microorganisms contained within a biofilm matrix, thus killing and eliminating bicf'tlm, as well as preventing future formation nor-buildup ofbiofilm, in systems, such as industrial systems. Decreasing the fouling of rnicroiltration sy=stems, and providing less frequent cleaning and/or replacement which.
would enhance the overall frlt.ration process. are also needs which should be addressed.
Summary of the Invention [0007] A biodeliver, system has been found which increases the efficiency and effectiveness of introducing antimicrobial compounds into complex biofilm matrices, through the use of liposome carriers, which can be used in natural, medical and industrial applications. hi industrial application,,,, the delivery system can minimize or eliminate fouling in industrial sy sterns, including, but not limited to. aqueous systems, such as piping, heat exchangers, condensers, filtration systems and media, and fluid storage tanks.
[0008] According to one embodiment of the invention, liposorrres containing an antimicrobial agent, such as a hydrophilic biocide, are added to a water system prone to biofouling and bioilrrr formation. The liposonaes, being similar in composition to the outer surface of the microbial cell wall structure or to the material on which the microbes feed, are readily incorporated into the microbes present in the existing biof (rn. Once the liposornes become entrained with the biofilm matrix, digestion, decomposition or degradation of the l peascarrre proceeds, releasing the ant microbial agent, or biocidal aqueous core reacts locally with the biofilm- encased microorganisms. 1. Iron the death of the organisms, the polysa cch,rricle?,protein matrix cannot be replenished and decomposes and thereby results in reduced bin fouling of the water bearing system.
Depending on the particular system involved, this bioflnr removal or destruction therefore results in increased heat transfer (industrial heat exchanger), increased flux (filter or filtration membrane), less deposit of colloidal and particulate solids and dissolved organics on the surface of the rnicrofiltra.tion membrane, thereby reducing the frequency and duration of the membrane cleaning and ultimate replacement, or general reduction of corrosive surface conditions in pipelines, tanks, vessels or other industrial equipment-[0009] An alternate embodiment of the invention provides for a delivery system of actives into a natural, medical or industrial system, which can be chosen from the group consisting o.f'anti-cor-.rosion treatments, pesticides for agriculture and commercial home uses, food additives and preservatives, chemical and biological detection, color and flavor enhancement, odor control and aquatic pest managerraent.
[0010] The various features of.noveltvr that characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invent. on, its operating advantages and benefits obtained by its uses, reference is made to the accompanying drawings and descriptive matter. The accompany ing draaxv,ings are intended to show examples of the invention The drawings are not intended as showing the limits of all of the ways the invention can be made and used. Changes to and substitutions of the various components of the invention can of course be rnaade. The invention resides as well in sub-combinations and sub-systems of the elements described, and in methods of using them.
Brief Description of the Drawings [0011] Refer now to the figures, which are meant to be exemplar, and not l:imitirrw, and wherein like elements are numbered alike, and not all numbers are repeated in every figure for clant-y of the illustration.
[0012] Fig. I is chart setting forth results obtained from an isothiazolin according to one embodiment of the invention, [0013] H& 2 is chart setting forth further results obtained from an isothiazolin according to one embodiment of the invention.
[0014] Fig. 3 is chart setting forth results obtained from an isothiazolin according to one embodiment of the invention.
[0015] pig 4 is chart setting forth results obtained from a substituted nitnlopropionamide according to one emb xli r .meat of the inventory.
[0016] Figs. 5 and 6 are charts setting .forth results obtained from an amrrroniurn salt according to embodiments of the invention.
[0017] Figs. 7 and are charts setting forth results obtained from a substituted propanediol biocide according to embodiments of the invention.
[0018] Fig. 9 .is chart settin4g forth results obtained from a phosphonium salt according to one embodiment of the invention.
Detailed Description of the Invention [0019] Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly vary without resulting in a. change in the basic .function to which it is related.
Accordingly, a value modified by a term or terms, such as "aboutf", is not limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value. Range limitations may be combined andior interchanged, and such ranges are identified and include all the sub-ranges included herein unless context or language indicates otherwise.
Other than in the operating examples or where otherwise indicated, all numbers or expressions referring to quantities of ingredients, reaction conditions and the like, used in the specification and the claims, are to be understood as modified in all instances by the ter n ;about".
[0020] As used herein, the terms "comprises," "comprising," "includes, "including," "has," "having' or any other var.ation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article or apparatus that comprises a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such process, .,Method article or apparatus.
L0021] A. delivery system has been found which increases the efficiency and effectiveness of introducing antimicrobial compounds into complex bicafrlm matrices through the use of liposo.. me carriers. which can. be used in natural, medical and industrial applications. Ill. industrial. applications, the delivery system can minimize or eliminate fouling in industrial systems, including, but not limited to, aqueous systems, such as cooling towers, piping, heat exclangers, condensers, filtration systems and media, and fluid storage tanks.
[0022] According to one embodiment of the invention, liposo..mes containing a biocidal or antimicrobial agent or compound are added to an industrial. system prone to biofouling and biofilna formation_ The liposomes, being similar in conapositic:.n to microbial membranes or cells, are readily incorporated into the existing biofilna. Once the antic microbial c ampound-containing liposora-les diffuse into, adsorb or otherwise become entrained with the biofilm matrix, the microorganisms existing within the biofilm matrix will ingest the, liposorte structure, resulting in the decomposition or disintegration of the l:iposome inside the intracellular matrix of the .rmmicroorganis.m, thereby releasing the antinnic:robial compound into the intracellular rnrat ix of the microorganisar.r., ultimately resulting; in the death of the microorganism. That is lipid decomposition and biocide release can be programmed to occur by making the lipid matrix sensitive to pl-1, redox potential. Ca concentration, or other changes. Thereafter the biocidal component that may be concentrated in the aqueous core of the liposome or in the lipid membrane portion of the liposome, is released to react directly with the biofilm-encased nmicroor<ganismms Thus, rather than adding a biocide at high levels to the bulk water system, a small quantity of liposome-encased biocide is taken rip by the biofil.rr or by free (planktonic) organisms, and degradation of the liposome releases the biocide locally in or at the target organisms or their film matrix .niche. The biocide thus attains a high concentration locally to kill the target organisms, and upon the death of the organisms, the polysaccharide/protein matrix that forms the biofilrrr cannot be maintained OF
regenerated and decomposes, and thereby results in reduced fouling of the water bearing system, resulting in increased heat transfer., increased flux, less deposit of colloidal and particulate solids and dissolved organics on the surface of the microfiltration membrane:
thereby reducing the frequency and duration of the membrane cleaning and ultimate replacement or other benefits.
[0023] Liposornes, or lipid bodies, are systems in which lipids are added to an aqueous buffer to forma vesicles, structures that enclose a volume. The l poso:rrres may be comprised of lipids selected from the group consisting of phospholipids, lcthicin, phosphatidyl choline, glycolipid, tfli<glyceride, sterol, fatty acid, sphingolipid, or combinations thereof.
[0024] More specifically; liposomes are microscopic vesicles, most commonly composed of phospholipids and water. The liposorares may be made from phospholipids derived from various sources, including, but not limited to soybeans and eggs.
When properly mixed, the phospholipids arrange themselves into a bilayer or multi layers, very similar to a cell membrane, surrounding an aqueous volume core. l_ iposernyes can be produced to carry various compounds or chemicals Within the aqueous cores or the desired compounds can be formulated in a suitable carrier to enter the lipid layer(s).
Liposomes can be produced in various sizes and may be manufactured in submicron to multiple micron diameters. The Iiposc.mes may be manufactured by several known _7-processes. Such processes include, but are not limited to, controlled evaporation, extrusion, injection, microfluid processors and rotor-stator mixers. Liposomes can be produced in diameters ranging from about 10 naanomete:rs to greater than about. 1.5 micrometers. When produced in sizes from about 100 manometers to about 2 micrometer sizes the liposomes are very similar in size and composition to most microbial. cells. The biocide or antimicrobial compound contai.ni.ng-hposomes should be produced in sizes that mimic bacterial cells, for example, from about 005 to about 15 l,t, or alternately, about 0. 1 to 10.0 p..
[0025] In one embodiment, effective amounts of the biocide containing liposome is introduced into an industrial system. which is prone to biof'ouling and biofilm.
formation, or can be introduced into systems drat already exhibit signs of biofouling or biofilm formation. The effective amount will vary according to the antimicrobial compound or biocide, and the aqueous system to which it is added, but one embodiment provides from about 0.01 ppm to about 100 ppm, with an alternative of from about 0.05 to about 50 ppm, alternately from about 0.05 to about 5.0 The l.iposomes, being similar in composition to microbial membranes, or cell walls, are readily incorporated into the existing biofÃlm and become entrained within the biofÃlm .matrix. Tae liposomes containing biocides have improved penetration of the biofilm matrix, due to similarity in composition acrd str .rcture with tyre hiof'rlm. Once the liposomare :is incorporated o.r entrained within the existing biofilm matrix, the liposome will begin to disintegrate.
Upon the deco decomposition or programmed disintegration of the liposonae, the biocidal compound contained within the aqueous core of the liposome is released to react directly with the biofilna encased microorganisms, resulting in their demise. Upon the death of t:he or gani swim s, the poly sa .achari de/protei ra matrix will rapidly decompose, treei n g the surface from contaminating microbes.
[0026] A principal feature of one embodiment of the present invention is that the liposonies constitute extremely small ydropbobic'bodies that may readily survive in and disperse in systems, such as for example, aqueous or natural systems, and yet will adsorb to or penetrate a hiofi [in and preferentially target or be targeted by the microbes that inhabit, constitute or sustain the biofilm. As such, the liposomes deliver a biocidaal. agent directly to the microbes or biof lmra, resulting in effective locally biocidal level of activity, _8-without requiring that the industrial system as a. whole sustain a. high dose Thus, here conventional bioflm treatment may require dosing with a bulb biocidal chemical at a certain level, delivery via liposome may be dosed at levels an order of niagYnitude or more lower in the aqueous system, yet still achieve, or build Lip to a level that effectively controls or removes biofilm. This lower level of biocide concentration has positive.
effects on the environment due to the efficacy resulting from the delivery system.
Addit:ionaal.ly~, depending upon the particular systeni that is being treated, an embodiment provides for flexibility iii where the liposomes are actually delivered into the system. If there is one particular area in a system that is prone to biofilm creation, the delivery of the liposomes may be delivered to that particular portion or point of the system. such that the delivery of the biodelivery composition is to a targeted location, and not necessarily privy to or exposed to the entire system. As smaller doses of the liposonie containing biocides are needed due to the efficacy of the biocides in this format, an entire system of process need :not be ..flooded with or treated with biocides.
[0027] Indeed, while the terms "antimicrobial- or "biocide" or "biocidal" have been employed to describe the agent carried by the liposome, these agents need not be the highly bioactive materials normally understood by those terms, but may include a number of relatively harmless materials that become highly effective simply by virtue of their highly localized release. Thus, for example, surfactants or harmless ammonium or phosphonium halide salts, when released locally, may affect the normal action of extracellular colony-forming secretions, and are to be included as a antiniicrobiaal or biocidal agents for purposes of the invention, and the same mechanism may be employed to deliver other treatment chemicals to the targeted biofilin sites.
[0028] Aqueous systems that can be treated by this method include, but are not limited to, potable and non-potable water distribution systems, cooling towers, boiler systems, showers, aquaria, sprinklers, spas, cleaning baths, air washers, paasteudzers, air conditioners, fluid transporting pipelines, storage tanks, ion exchange resins, food and beverage processing lines, metalworking fluid baths, coal and mineral slurries, metal leaching fluids, wastev water treatment facilities, mollusk control, pulp and papermaking operations, acid mine drainage, or any application prone to biofouling by microbial species. Application such as oil drilling,, oil storage tanks or oil pipelines., where b:iof:ilins form in stagnant or t pooled aqueous sumps or lenses along the conduitsystem, may also be effectively treated.
[0029] Additional applications for liposome delivery of a treatment chemical comprise natural, medical and industrial systems, such as, but not limited to anti-corrosion treatments for equipment generally, delivery of hormone, vitamin or antioxidant treatments or antibiotic and gene therapies for medical or veterinary. pur-lposes, delivery of pesticides for agriculture:. and commercial home uses, effective formulations of food additives and presenvatives, targeted delivery for chemical and biological detection sysÃems, color and flavor enhancement, odor control, fungicides, rodenticides, insecticides, mildew control and aquatic pest management.
[0030] Various biocides, for example non-oxidizing biocides, can be incorporated into the liposome, which would be effective, The use c f certain biocides has shown the efficacy of this delivery system versus inclusion of biocides in the industrial systems wherein the biocide is outside of the liposome delivery system. The level or concentration of biocides is measured in active levels, to provide consistency across various forms of the same biocide, [001] One embodiment of the invention calls for the use of isothiazolin-3-one biocides. These isothiazolin- 3-one liposome formulations are more effective at killing and removing biofzlms when compared to the same isothiazolin-3-one compounds at the same active concentrations, which are introduced into systems, but not incorporated in lipos(nnaes, as the liposonre containing biocides readily penetrate the microbial biokilnrs and are highlyy, eff= ctiye at destroying the bioflrmrr matrix. This lipo om.e delivery method may comprise 5wclrlcaro- -methyl- rise tlaircali.rti- -cane acrd - et:lrr:l- -iscati is c~lin- -one, but any substituted isotbiazolin-_)-one based biocide can be made significantly more effective when delivered in a liposome biodeliv ery system or composition.
[0032] An example of an isothiazoli.n-3-cane compound is _10-lsothiazolin-3-one ' V_~
X.. ' N -- R
Where:
R = H, Cl, Br, I. C,H'n+2) X = H, CI, Br, 1, CnH{ ,+2 Y = H, CI, Br, 1, CnHtn+2 [0033] For an embodiment of'liposomes comprising isotlriazolin, the active range is from about 0.02 to about 10.0 actives, and alternately from about 0.03 to about 5.5 active.
[0034] 1.n alternate embodiment of the invention provides for liposomes produced that incorporate the biocide a substituted ni.trilopropiona.mide, for example DUNPA. The DB:NP.A liposome formulation targets and eliminates higher levels of biofiln when compared to the same D 3NPA compound at the sane active concentration that is not incorporated into liposome delivery systems. The liposome biocide readily penetrates the microbial biofilm and is highly effective at destroying the biof.lm cells and associated slime complex. This liposonre delivery method has been proven with 2,2-dibrorno-3-nitrilo-propiona.mide, but it is believed that any substituted nitrilcopropionaanide biocide active could be made sigill ficall tly more effective when delivered in a liposome format. Non-limiting examples of substituted nitrilopropionamide are shown. below Also, another possibility from the family of nitrilopropionan.ide compounds comprises :DBNlP A, 2,2,dibro..mmo-3-n-rit:rilopr-op ornarm-ride, is also shown.
3-Nitrilopropionamide .1 x2 0 NC
y1 ''2 NH2 Where:
X1 =F,CI,Br,1,CH3,H
X2 = F, C1, Br, 1,CH3.H
Y., = F, Cl, Br, 1, CH3, H
Y2 = F, CI, Br, 1, CH3, H
2. -D bromo-3-nitric propionamide (DBNPA) H B r {
NC
H Br NH2 [0035] For an embodiment of lilroscames comprising nitifloproplonamide, the active. range is from abo. t 0,2 . to about 25 actives, and alternately from about 0.5 to about 12.5 actives.
[0036] A further embodiment of the invention provides for liposomes that are produced which incorporate cl. arternary ammonium salts, such as the cationic surfactant and biocide aikyi diÃnethyl-benzyl ammonium chloride (ADE ' [_' Qurat). :t1 BA
C type quats are one form of ammonium salts that may be used as abiocide in the liposonle del:iveryr system, but any substituted quaternary ammonium salt hiocide active, such as for example dialkyl dimethyl clua:ts, can be more effective when delivered in a liposome format. 'Non-limiting examples of quaternary ammonium salts are shown with.
the following general formula.-ADBAC I DIALKYL QUATS
I
I
R
Where Rr = 'taHi2Frr'E where n = 1 - 20 R2 + R3 = CfaHc2,+r), where n = 1 -R4. Cfl ,2 +1), where n = 1 - 20 H
-U GH CH
Hf C1, Br, 1, I C 3, CH3OS a [0037] For an embodiment oflipcasomes comprising anamo.nium salts, the active range is from about 2.0 to about 2-50 actives, and alternately from about 4.0 to about 125 acfi es.
[0038] Astrrrt.her embodiment of the nveatican., comprises substituted propanediol biocide actives, such as for example, 2-bromo,2-nitro, ], 3,propane-diol (l3NPD active, a representative of the substituted propanediol class of compounds.
Examples of substituted propanediol compounds:
Substituted Propanediols y Where:
X = CI, Br, I, NO2. O3H, OH
Y = Cl, Br, 1, N02, S03H, OH
Example:
Bronopol (BNPD) = 2--bromo- -nitre-prepanedical = -brc e-2-nitre -l3-propanediol Br HOH2C +CH20H
[0039] [`. ective amounts of a substituted propanediol biocide incorporated into the liposome would include from about 1.0 to about 100 biocide actives, or altemately about 2 5 to about 8.0 biocide actives.
[0040] A. f urtlaer embodiment cat` tlae :invention , l:ipr~asonres produced drat.
incorporate the biocide phosphonium salts for example the cationic surfactant and biocide tributyltetradecyl plaosphonium chloride (TTPC). The TTPC' Iiposome fibrniulation targets and eliminates higher levels ofbiofilm when compared to the same. TTPC
compound at the same active concentration that is not incorporated into liposome delivery systems. The liposome biocide .readily penetrates the microbial biofilm and is highly effective at destroying the biofil.m cells and associated slime corammplex. This liposome delivery method has been proven with TT`l'K, but any phosphoniurn salts biocide active could be made significantly more effective when delivered in a liposome format. Non-liraiting examples of phosphoniun salts are shown as:
Substituted Phosphon um Salts I
I
Rol Where:
RI CH3, CH9CH, CfHi2,,+1 ) where n R2, R3. R4 = CH3, CH 0H, C,H(2,+,) where n = 2 - 5 X = Cl, Br, 1, NO2, SO4, HCI
Examples:
Bellaeide 350 (Tetradeeyl tributyl phesphonium chloride) C~H
Cr4Hc P C4H9 Cl CA
THPS (Tetrakis hydroxyrnethyl phosphonium sulfate) CN..; N-P-CH CH S0$
CH OH
[0041] Effective amounts of a plrospl>oniu salt biocide incorporated into the liposon e would include from about 1 .0 to about 1.00 biocide acÃives, or alternately about 1.5 to about 50.0 biocide actives [0042] Liposor res of the present invention may be created as multi-layer bodies.
in which one or more additional layers are provided to enhance the stability of the l:iposomes or to effectuate a programmed release of the underlying lipid body and contents. Thus, this technology may be used to encapsulate medicines for intracorpoaal delivery, such that the additional layers may include a protective layer that is hydrolyzed or otherwise breaks down over time to provide a sustained release or longer lifetime of the r,rrnderlyyin. lipcosorsme. Such additional layer may additionally or alternatively include an encapsulating polymer that selectively breaks down when the multi-layer liposome encounters a low-pl--H environment, like the corrosive high acidity environment that rnay develop beneath a biof`rl..m. A. layer may also be compounded to be vulnerable to sulfur fixing bacteria, causing the liposome to specifically release its biocide in proximity to these corrosive organisms often present in a waste or pipeline system.
Furthermore, several such layers may be employed to assure a sufficient lifetime of the liposome, prefe:raably on the order of several days as well as an ability to target a specific niche or environment in the biofilm. This assures that the liposomes will effectively encounter the target organisms or bio.film colonies and deliver their biocides thereto. The lipid material itself may be treated to provide enhanced resistance to hydrolysis or decay, or the added layers may be tuned of various harderaable or cross-linkable oils or polymers.
[0043] An alternate embodiment of the invention provides for a. biodelivery<
composition for delivering at least one antimicrobial composition into a biotilm present in an industrial system, wherein the biofilrn comprises at least one microorganism species; b) the biodelivery composition comprises a liposome structure containing at least one lipid or phospholipid type component, and c) the liposome structure encapsulates at least one antimicrobial composition.
[0044] A further embodiment provides for the targeted delivery of biocide actives into an industrial system, such as an industrial aqueous system, by introducing into said system an effective amount of said biocides in a critical area of said system, By targeting ,in area,, and entry at a specific point in a process, the eft caacy of the liposome system provides for a noteworthy impact on the environment as well as the cost of maintaining a ay=steam, as the entire system does not need to be flooded with biocides, only the specific area of interest.
[0045] The invention will now be described with respect, to certain examples that are merely representative of the invention and should not be construed as limiting thereof EXAMPLES
[0046] The invention is illustrated in the following nonlir citing examples, which are provided for the purpose of representation, and are not to be construed as limiting the scrape of the :invention. All parts and percentages in the examples are by weight unless indicated otherwise.
Example 1 [4047] Three batches of liposomes (150 nanometers averagr diameter) were created that incorporated an isothiazolin biocide, Kat-hon`r= r (available from Rohr-Haas, :Philadelphia, PA) as the active ingredient. The liposomes were than.
placed in microtiter plates that had microbial biofilnis coating them. The microbe inhibiting efficacy of the isothiazolin liposomes was then compared with non-liposomal ise)thiazcalina biocide when Lused at. the sarmae :isothia.zolin conacentra.tionas. The liposonaes containing isothiazolin penetrated the bioflrn and inhibited the hiotilm organisms much r tore effectively than the non--liposonial isothiazolin solution.
[0448] The .results are shown in Tables 1, 2 and 3 below and in Figs. 1, 2 and 3.
The non-liposomal isothiazolin is listed as Kathon av, each of the liposome samples were made by three different technicians and are referred to by code. The tables and charts show the. concentration of the. isothiazolin versus the percent inhibition of the biot lm. It is clear from both the tables and the figures that in all three trials, the liposomal isothiazolin formulations exhibited more effective biofilin killing)] removal efficiency than the isothiazolin control (listed as Kathon av) in every liposonie concentration that was tested. 'Elie liposome carrier is highly effective at delivering biocide to the bioilrn at low isothiazol.iaa. concentrations, thus providing better biofilm control at much reduced i sothiazolin concentrations (reduced toxicity and cost performance).
.
Table 1 Concentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW GT Kathon av 0016 21 29.9 7.9 0.93 0.031 29.7 34.1 28.7 10.9 0.0625 26.8 31 31.4 14.5 0.125 31.7 38.3 26.5 11.3 0.25 18.6 32.9 37.9 6.7 --------------- ----------------- ------0.5 37,4 32.4 37.5 9.0 -------- --------- -------- -------- ---- ---- ----------------------------------------- ----------------------------------------- ------------------------------------------1 42.9 50.3 44.8 17.9 2 48.6 53.1 54.4 37.9 Table 2 oncentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW T Kathon av -------- -------- -- -- ----- -------- -----0016 15.7 21.1 10.2 0.93 ------------------------------------------------------------ ----------------------------------------- ----------------------------------------- ----------------------------------------- ------------------------------------------0.031 27.3 31.3 26.1 10.9 0.0625 21.6 30.5 25.8 14.5 --------------------------- -------------------------------- ------------------------------------------ ---- -0.125 26.7 35.1 29.6 11.3 0.25 24.6 36,6 33.4 6.7 0.5 32.6 34,6 31.8 9.0 1 36.6 43.9 35.9 17.9 2 45.3 45.1 48.3 37.9 Table 3 Concentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW GT Kathon av 0016 10.4 123 12.4 0.93 10.031 24.9 28.4 23.5 10.9 -- ----- -----------------------------------------U625 16.3 30 221 14.5 0.125 21.E 31.9 32.7 11.3 0.25 33.5 40.2 28.8 6.7 --------------- ----------------- ------0.5 277 36.7 26.0 9.0 -------- --------- -------- -------- ---- ----- ----------------------------------------- ----------------------------------------- ------------------------------------------1 30.3 37.3 26.9 17.9 2 42.0 37,0 42.1 37.9 Example 2 [0049] One batch of liposomes (150 manometers average diameter) was created that incorporated a substituted nitrilopropionamide ocide as the active ingredient. The liposo.mes were then placed in :Ã Ãacrcatiter plates that had microbial hiof lms coating them.
The microbe inhibiting efficacy of the substituted nitrilopropfonamidc liposomes was then compared with non=-liposonaal substituted r itrilopr-opionanide biocide when used at the same n trilopropionamide concentrations. The liposoines containing Substituted nitrflopropionam:ide, particularly 1).BN:PA,, penetrated the b1ofilyn and inhibited the biofilm organisms ..much more effectively than the nova-fliposomal substituted nitrilopropionannide solution.
[0060] The results are shown in Table 4 below and in Fig 4- The table a7.nd.
Chart show the concentration of the substituted nitrilopropionamide versus the percent inhibition of the hiotil.m. It is clear from both the table and the figure that the liposomal substituted .nitrilol)ral-iarrart ide f rrrrulation exhibited more effective biofilni killing,"
removal efficiency than the substituted nitrilopropionaride control in every liposome concentration that was tested.
Table 4 "
""
oncentratior DBNPA liposome DBNPA
0.39 29.9 17.9 ------------------------------------------------------- --------------------------------------------------------------- ----------------------------------------------------------------------------Q.B - -------- ---- 38.6 23.3 1.56 62.1 35.3 3.13 79.7 66.5 6,25 85.6 80.3 12.5 97.6 89.3 ------- -------- -------- ------- -- -------- -------- ---------Example 3 [0051] Two batches of lilaosoames (150 nanometers average diameter) were created that incorporated an annnoniuna silt biocide as the active ingredient, specifically a quaternary ammonium salt, 50% allkyl,d: methyl-benzvi amnion: um chloride (ADBAC).
The liposones were then placed in microliter plates that had microbial biofilms coating thenp. The microbe inhibiting efficacy of the A[).AÃ` liposomes was then compared with non -liposomal ADBAC biocide when used at the same BAC`: concentrations, The liposomes containing ADBAC penetrated the biolilm and inhibited the biofilm organisms much more effectively than the non-liposomal ADBAC solution.
[0052] The results are shown in Tables 5 and 6 below and in Figs 5 and 6. The table and chart show, the concentration of ADBAC'. versus the percent inhibition of the biofilna. It is clear from both the table and the figure that the liposonlal ADBAC
formulations were as good as or more effective in biofilni killing! removal efficiency than the ADBAC control in even., liposome concentration that was tested.
iConcentraton 50% ADBAC Quat 50%AD AC Quat liposome 3.9 17 15 -------------------- -- - ---------------------------------------------------------------------------15.6 65 47 31.3 69 52 -------------------------------- 62.5 ------- --------------------------------------------------------------------------------------- ----------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------Soo 98 97 Table 6 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Concentration 50% ADBAC Quat 50% ADBAC Quat lipe one ----3.9 7 3 7.3 15 7 15.6 40 19 -------------------------------------------------------------------------------------------------------------------------------------- 31.3 48 62.5 61 40 ---------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------- ----------------------------------------------------------------------------[Example 4 [0053] Two batches of liposomes (1.50 nanorY eters average diameter) were created that incorporated a substituted propanediol biocide as the active ingredient, specifically a b:r-onopol. The Iiposo.mes were then placed in .microtiter plates that had microbial bioti:laars coating them. The microbe inhibiting efficacy of the bronopol liposonaes was then compared with non--liposomal bronopol biocide when used at the same bronopol concentrations. The liposomes containing bronopol penetrated the biofllm and inhibited the bio.him organ isn s much more effectively than the 11011-liposomal bronropol solution.
[0054] The results are shown in Tables 7 and 8 below and in Figs 7 ,and S. The table and chart show the concentration of bronopol versus the percent inhibition of the blot lm, lt. is clear #rcart tae tla the table and tlr figure tlatat tlrc lil c sc r rrrl larrarrc ta<al formulations were as good as or more effective in biotilra killing/ removal efficiency than the br-onopol control in every l:iposomrre concentration that was tested.
Table 7 ----------------------- ------- -------------------------------------------- ---------------------------------------------------------------------------- ----------------------------------------------------------------------------oncentration Bronopol liposorn Bronopol 0,625 0 0 1.25 5 0 - ----------------------------2. 19 ------------------------------------------------------------------------------------------------------------------------------------------------------ -------------------------------------------------------------------------------------------------------------------------------------------------------------- -------- ------- -------------------------------- --- -------- ----`T'able 4 Concentration Bronopol liposome ronopol 0.78 0 0 1.6 4 0 ------------------------------------------------------ ------------------------------------------------------------------------- ----------------------------------------------------------------------a 18 3 12.5 21 5 Example 5 [Ã3065] One batch of liposomes (150 narnorneters average diameter) was created that incorporated a phosphonium salt biocide, Bellacide 3SOT r WA, Tucker, GA) as the active ingredient. The liposomes were then placed in microtiter plates that had microbial biolilr-rms coating them. The microbe inhibiting efficacy of the ph.osphoniur-rm salt liposomes was then compared with non-liposomal phosphonium salt biocide when used at the same concentrations. The liposomes containing phosphonium salt penetrated the biotilm and inhibited the biohlm orga.nisrns much r-nore effectively than the non-liposomal phosphonium salt solution.
[0056] The results are shown M. Table 9 below and in Fig 9. The table and chart show the concentration of the phosphonium salt versus the percent inhibition of the biotalm_ It is clear from both the table and the figure that the liposornal phosphornium salt formulation exhibited equal or more effective biofil m killing./ removal efficiency than the phosphonium salt control in every liposome concentration that was tested.
Table 9 Concentration Belleclde 350 Boone à Bellacide 350 ------------------------------------------------------- ---------------155 6.6 0 3.13 14.5 0 6,25 14.9 0 ------- -------- -------- ------- -------------------------------- --------- ------1 .5 23.8 8 --------- ------- --------- ---------25 21.6 ------- -------- -------- -------- --------- -------- -------- -------- -------- ------- -- -------- -------- ---------[0057] While the present invention has been described with references to preferred embodiments, various changes or substitutions may be made on these embodiments by those ordinarily skilled in the art pertinent to the present invention with out departing from the technical scope of the present invention. 'T'herefore, the technical scope of the present :invention encompasses not only those embodiments described above., but also all that fall within the scope of the appended claims.
patent no. 6,759,040 teaches a method for preparing biofrlm degrading, multiple specificity, hydrolytic enzyme mixtures that are targeted to remove specific biofiirns.
[0006] U.S. patent no. 6,267 89, relates to a method of inhibiting l iotilm formation in commercial and industrial water systems by adding one or more plant oils to the system. However., although the biocides are e.1edive in controlling dispersed microorganism suspensions, i.e. planktonic microbes-, biocides do :riot work well a against sessile microbes, the basis of biolrars. This is due to the fact that biocides have difficulty penetrating the poivsacchande/protein slime layers surrounding the microbial l cells.
Thicker biofilms see little penetration of biocides and poor biocide efficacy, is the result.
One known. method of trying to better control biof-ilms has been the addition of dispersants and wetting agents to biocide compositions to enhance biocide eflica.cy.
Biodispersants r ray= operate to keep planktonic microbes sufficiently dispersed so that they do not agglomerate or achieve the local densities necessary to initiate the extracellular processes responsible for anchoring to a surface, or initiating film- or colony,-torrrrirrgmechanisms As components in biocidal treatment formulations, these biodispersants have helped in opening channels in the.. biofilm to allow better permeability ofthe toxic agents and to better disperse the microbial aggregates and clumps that have been ~w~eakened and released from the surfaces. However, biodispersants have proven to be more effective in preventing initial biofil:.m formation than in removing existing biofilms. In many cases, the activity of biodispersants has been responsible for only ?5 to 30% biornass removal from biofouled surfaces, even when used in conjunction with a biocida.l agent.
[0006] Therefore, a clear need still exists for an efficient and effective means for delivering antimicrobial compounds that are better able to penetrate existing bioh Ims and biofilm matrices, and more effective in killing microorganisms contained within a biofilm matrix, thus killing and eliminating bicf'tlm, as well as preventing future formation nor-buildup ofbiofilm, in systems, such as industrial systems. Decreasing the fouling of rnicroiltration sy=stems, and providing less frequent cleaning and/or replacement which.
would enhance the overall frlt.ration process. are also needs which should be addressed.
Summary of the Invention [0007] A biodeliver, system has been found which increases the efficiency and effectiveness of introducing antimicrobial compounds into complex biofilm matrices, through the use of liposome carriers, which can be used in natural, medical and industrial applications. hi industrial application,,,, the delivery system can minimize or eliminate fouling in industrial sy sterns, including, but not limited to. aqueous systems, such as piping, heat exchangers, condensers, filtration systems and media, and fluid storage tanks.
[0008] According to one embodiment of the invention, liposorrres containing an antimicrobial agent, such as a hydrophilic biocide, are added to a water system prone to biofouling and bioilrrr formation. The liposonaes, being similar in composition to the outer surface of the microbial cell wall structure or to the material on which the microbes feed, are readily incorporated into the microbes present in the existing biof (rn. Once the liposornes become entrained with the biofilm matrix, digestion, decomposition or degradation of the l peascarrre proceeds, releasing the ant microbial agent, or biocidal aqueous core reacts locally with the biofilm- encased microorganisms. 1. Iron the death of the organisms, the polysa cch,rricle?,protein matrix cannot be replenished and decomposes and thereby results in reduced bin fouling of the water bearing system.
Depending on the particular system involved, this bioflnr removal or destruction therefore results in increased heat transfer (industrial heat exchanger), increased flux (filter or filtration membrane), less deposit of colloidal and particulate solids and dissolved organics on the surface of the rnicrofiltra.tion membrane, thereby reducing the frequency and duration of the membrane cleaning and ultimate replacement, or general reduction of corrosive surface conditions in pipelines, tanks, vessels or other industrial equipment-[0009] An alternate embodiment of the invention provides for a delivery system of actives into a natural, medical or industrial system, which can be chosen from the group consisting o.f'anti-cor-.rosion treatments, pesticides for agriculture and commercial home uses, food additives and preservatives, chemical and biological detection, color and flavor enhancement, odor control and aquatic pest managerraent.
[0010] The various features of.noveltvr that characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invent. on, its operating advantages and benefits obtained by its uses, reference is made to the accompanying drawings and descriptive matter. The accompany ing draaxv,ings are intended to show examples of the invention The drawings are not intended as showing the limits of all of the ways the invention can be made and used. Changes to and substitutions of the various components of the invention can of course be rnaade. The invention resides as well in sub-combinations and sub-systems of the elements described, and in methods of using them.
Brief Description of the Drawings [0011] Refer now to the figures, which are meant to be exemplar, and not l:imitirrw, and wherein like elements are numbered alike, and not all numbers are repeated in every figure for clant-y of the illustration.
[0012] Fig. I is chart setting forth results obtained from an isothiazolin according to one embodiment of the invention, [0013] H& 2 is chart setting forth further results obtained from an isothiazolin according to one embodiment of the invention.
[0014] Fig. 3 is chart setting forth results obtained from an isothiazolin according to one embodiment of the invention.
[0015] pig 4 is chart setting forth results obtained from a substituted nitnlopropionamide according to one emb xli r .meat of the inventory.
[0016] Figs. 5 and 6 are charts setting .forth results obtained from an amrrroniurn salt according to embodiments of the invention.
[0017] Figs. 7 and are charts setting forth results obtained from a substituted propanediol biocide according to embodiments of the invention.
[0018] Fig. 9 .is chart settin4g forth results obtained from a phosphonium salt according to one embodiment of the invention.
Detailed Description of the Invention [0019] Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly vary without resulting in a. change in the basic .function to which it is related.
Accordingly, a value modified by a term or terms, such as "aboutf", is not limited to the precise value specified. In at least some instances, the approximating language may correspond to the precision of an instrument for measuring the value. Range limitations may be combined andior interchanged, and such ranges are identified and include all the sub-ranges included herein unless context or language indicates otherwise.
Other than in the operating examples or where otherwise indicated, all numbers or expressions referring to quantities of ingredients, reaction conditions and the like, used in the specification and the claims, are to be understood as modified in all instances by the ter n ;about".
[0020] As used herein, the terms "comprises," "comprising," "includes, "including," "has," "having' or any other var.ation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article or apparatus that comprises a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such process, .,Method article or apparatus.
L0021] A. delivery system has been found which increases the efficiency and effectiveness of introducing antimicrobial compounds into complex bicafrlm matrices through the use of liposo.. me carriers. which can. be used in natural, medical and industrial applications. Ill. industrial. applications, the delivery system can minimize or eliminate fouling in industrial systems, including, but not limited to, aqueous systems, such as cooling towers, piping, heat exclangers, condensers, filtration systems and media, and fluid storage tanks.
[0022] According to one embodiment of the invention, liposo..mes containing a biocidal or antimicrobial agent or compound are added to an industrial. system prone to biofouling and biofilna formation_ The liposomes, being similar in conapositic:.n to microbial membranes or cells, are readily incorporated into the existing biofilna. Once the antic microbial c ampound-containing liposora-les diffuse into, adsorb or otherwise become entrained with the biofilm matrix, the microorganisms existing within the biofilm matrix will ingest the, liposorte structure, resulting in the decomposition or disintegration of the l:iposome inside the intracellular matrix of the .rmmicroorganis.m, thereby releasing the antinnic:robial compound into the intracellular rnrat ix of the microorganisar.r., ultimately resulting; in the death of the microorganism. That is lipid decomposition and biocide release can be programmed to occur by making the lipid matrix sensitive to pl-1, redox potential. Ca concentration, or other changes. Thereafter the biocidal component that may be concentrated in the aqueous core of the liposome or in the lipid membrane portion of the liposome, is released to react directly with the biofilm-encased nmicroor<ganismms Thus, rather than adding a biocide at high levels to the bulk water system, a small quantity of liposome-encased biocide is taken rip by the biofil.rr or by free (planktonic) organisms, and degradation of the liposome releases the biocide locally in or at the target organisms or their film matrix .niche. The biocide thus attains a high concentration locally to kill the target organisms, and upon the death of the organisms, the polysaccharide/protein matrix that forms the biofilrrr cannot be maintained OF
regenerated and decomposes, and thereby results in reduced fouling of the water bearing system, resulting in increased heat transfer., increased flux, less deposit of colloidal and particulate solids and dissolved organics on the surface of the microfiltration membrane:
thereby reducing the frequency and duration of the membrane cleaning and ultimate replacement or other benefits.
[0023] Liposornes, or lipid bodies, are systems in which lipids are added to an aqueous buffer to forma vesicles, structures that enclose a volume. The l poso:rrres may be comprised of lipids selected from the group consisting of phospholipids, lcthicin, phosphatidyl choline, glycolipid, tfli<glyceride, sterol, fatty acid, sphingolipid, or combinations thereof.
[0024] More specifically; liposomes are microscopic vesicles, most commonly composed of phospholipids and water. The liposorares may be made from phospholipids derived from various sources, including, but not limited to soybeans and eggs.
When properly mixed, the phospholipids arrange themselves into a bilayer or multi layers, very similar to a cell membrane, surrounding an aqueous volume core. l_ iposernyes can be produced to carry various compounds or chemicals Within the aqueous cores or the desired compounds can be formulated in a suitable carrier to enter the lipid layer(s).
Liposomes can be produced in various sizes and may be manufactured in submicron to multiple micron diameters. The Iiposc.mes may be manufactured by several known _7-processes. Such processes include, but are not limited to, controlled evaporation, extrusion, injection, microfluid processors and rotor-stator mixers. Liposomes can be produced in diameters ranging from about 10 naanomete:rs to greater than about. 1.5 micrometers. When produced in sizes from about 100 manometers to about 2 micrometer sizes the liposomes are very similar in size and composition to most microbial. cells. The biocide or antimicrobial compound contai.ni.ng-hposomes should be produced in sizes that mimic bacterial cells, for example, from about 005 to about 15 l,t, or alternately, about 0. 1 to 10.0 p..
[0025] In one embodiment, effective amounts of the biocide containing liposome is introduced into an industrial system. which is prone to biof'ouling and biofilm.
formation, or can be introduced into systems drat already exhibit signs of biofouling or biofilm formation. The effective amount will vary according to the antimicrobial compound or biocide, and the aqueous system to which it is added, but one embodiment provides from about 0.01 ppm to about 100 ppm, with an alternative of from about 0.05 to about 50 ppm, alternately from about 0.05 to about 5.0 The l.iposomes, being similar in composition to microbial membranes, or cell walls, are readily incorporated into the existing biofÃlm and become entrained within the biofÃlm .matrix. Tae liposomes containing biocides have improved penetration of the biofilm matrix, due to similarity in composition acrd str .rcture with tyre hiof'rlm. Once the liposomare :is incorporated o.r entrained within the existing biofilm matrix, the liposome will begin to disintegrate.
Upon the deco decomposition or programmed disintegration of the liposonae, the biocidal compound contained within the aqueous core of the liposome is released to react directly with the biofilna encased microorganisms, resulting in their demise. Upon the death of t:he or gani swim s, the poly sa .achari de/protei ra matrix will rapidly decompose, treei n g the surface from contaminating microbes.
[0026] A principal feature of one embodiment of the present invention is that the liposonies constitute extremely small ydropbobic'bodies that may readily survive in and disperse in systems, such as for example, aqueous or natural systems, and yet will adsorb to or penetrate a hiofi [in and preferentially target or be targeted by the microbes that inhabit, constitute or sustain the biofilm. As such, the liposomes deliver a biocidaal. agent directly to the microbes or biof lmra, resulting in effective locally biocidal level of activity, _8-without requiring that the industrial system as a. whole sustain a. high dose Thus, here conventional bioflm treatment may require dosing with a bulb biocidal chemical at a certain level, delivery via liposome may be dosed at levels an order of niagYnitude or more lower in the aqueous system, yet still achieve, or build Lip to a level that effectively controls or removes biofilm. This lower level of biocide concentration has positive.
effects on the environment due to the efficacy resulting from the delivery system.
Addit:ionaal.ly~, depending upon the particular systeni that is being treated, an embodiment provides for flexibility iii where the liposomes are actually delivered into the system. If there is one particular area in a system that is prone to biofilm creation, the delivery of the liposomes may be delivered to that particular portion or point of the system. such that the delivery of the biodelivery composition is to a targeted location, and not necessarily privy to or exposed to the entire system. As smaller doses of the liposonie containing biocides are needed due to the efficacy of the biocides in this format, an entire system of process need :not be ..flooded with or treated with biocides.
[0027] Indeed, while the terms "antimicrobial- or "biocide" or "biocidal" have been employed to describe the agent carried by the liposome, these agents need not be the highly bioactive materials normally understood by those terms, but may include a number of relatively harmless materials that become highly effective simply by virtue of their highly localized release. Thus, for example, surfactants or harmless ammonium or phosphonium halide salts, when released locally, may affect the normal action of extracellular colony-forming secretions, and are to be included as a antiniicrobiaal or biocidal agents for purposes of the invention, and the same mechanism may be employed to deliver other treatment chemicals to the targeted biofilin sites.
[0028] Aqueous systems that can be treated by this method include, but are not limited to, potable and non-potable water distribution systems, cooling towers, boiler systems, showers, aquaria, sprinklers, spas, cleaning baths, air washers, paasteudzers, air conditioners, fluid transporting pipelines, storage tanks, ion exchange resins, food and beverage processing lines, metalworking fluid baths, coal and mineral slurries, metal leaching fluids, wastev water treatment facilities, mollusk control, pulp and papermaking operations, acid mine drainage, or any application prone to biofouling by microbial species. Application such as oil drilling,, oil storage tanks or oil pipelines., where b:iof:ilins form in stagnant or t pooled aqueous sumps or lenses along the conduitsystem, may also be effectively treated.
[0029] Additional applications for liposome delivery of a treatment chemical comprise natural, medical and industrial systems, such as, but not limited to anti-corrosion treatments for equipment generally, delivery of hormone, vitamin or antioxidant treatments or antibiotic and gene therapies for medical or veterinary. pur-lposes, delivery of pesticides for agriculture:. and commercial home uses, effective formulations of food additives and presenvatives, targeted delivery for chemical and biological detection sysÃems, color and flavor enhancement, odor control, fungicides, rodenticides, insecticides, mildew control and aquatic pest management.
[0030] Various biocides, for example non-oxidizing biocides, can be incorporated into the liposome, which would be effective, The use c f certain biocides has shown the efficacy of this delivery system versus inclusion of biocides in the industrial systems wherein the biocide is outside of the liposome delivery system. The level or concentration of biocides is measured in active levels, to provide consistency across various forms of the same biocide, [001] One embodiment of the invention calls for the use of isothiazolin-3-one biocides. These isothiazolin- 3-one liposome formulations are more effective at killing and removing biofzlms when compared to the same isothiazolin-3-one compounds at the same active concentrations, which are introduced into systems, but not incorporated in lipos(nnaes, as the liposonre containing biocides readily penetrate the microbial biokilnrs and are highlyy, eff= ctiye at destroying the bioflrmrr matrix. This lipo om.e delivery method may comprise 5wclrlcaro- -methyl- rise tlaircali.rti- -cane acrd - et:lrr:l- -iscati is c~lin- -one, but any substituted isotbiazolin-_)-one based biocide can be made significantly more effective when delivered in a liposome biodeliv ery system or composition.
[0032] An example of an isothiazoli.n-3-cane compound is _10-lsothiazolin-3-one ' V_~
X.. ' N -- R
Where:
R = H, Cl, Br, I. C,H'n+2) X = H, CI, Br, 1, CnH{ ,+2 Y = H, CI, Br, 1, CnHtn+2 [0033] For an embodiment of'liposomes comprising isotlriazolin, the active range is from about 0.02 to about 10.0 actives, and alternately from about 0.03 to about 5.5 active.
[0034] 1.n alternate embodiment of the invention provides for liposomes produced that incorporate the biocide a substituted ni.trilopropiona.mide, for example DUNPA. The DB:NP.A liposome formulation targets and eliminates higher levels of biofiln when compared to the same D 3NPA compound at the sane active concentration that is not incorporated into liposome delivery systems. The liposome biocide readily penetrates the microbial biofilm and is highly effective at destroying the biof.lm cells and associated slime complex. This liposonre delivery method has been proven with 2,2-dibrorno-3-nitrilo-propiona.mide, but it is believed that any substituted nitrilcopropionaanide biocide active could be made sigill ficall tly more effective when delivered in a liposome format. Non-limiting examples of substituted nitrilopropionamide are shown. below Also, another possibility from the family of nitrilopropionan.ide compounds comprises :DBNlP A, 2,2,dibro..mmo-3-n-rit:rilopr-op ornarm-ride, is also shown.
3-Nitrilopropionamide .1 x2 0 NC
y1 ''2 NH2 Where:
X1 =F,CI,Br,1,CH3,H
X2 = F, C1, Br, 1,CH3.H
Y., = F, Cl, Br, 1, CH3, H
Y2 = F, CI, Br, 1, CH3, H
2. -D bromo-3-nitric propionamide (DBNPA) H B r {
NC
H Br NH2 [0035] For an embodiment of lilroscames comprising nitifloproplonamide, the active. range is from abo. t 0,2 . to about 25 actives, and alternately from about 0.5 to about 12.5 actives.
[0036] A further embodiment of the invention provides for liposomes that are produced which incorporate cl. arternary ammonium salts, such as the cationic surfactant and biocide aikyi diÃnethyl-benzyl ammonium chloride (ADE ' [_' Qurat). :t1 BA
C type quats are one form of ammonium salts that may be used as abiocide in the liposonle del:iveryr system, but any substituted quaternary ammonium salt hiocide active, such as for example dialkyl dimethyl clua:ts, can be more effective when delivered in a liposome format. 'Non-limiting examples of quaternary ammonium salts are shown with.
the following general formula.-ADBAC I DIALKYL QUATS
I
I
R
Where Rr = 'taHi2Frr'E where n = 1 - 20 R2 + R3 = CfaHc2,+r), where n = 1 -R4. Cfl ,2 +1), where n = 1 - 20 H
-U GH CH
Hf C1, Br, 1, I C 3, CH3OS a [0037] For an embodiment oflipcasomes comprising anamo.nium salts, the active range is from about 2.0 to about 2-50 actives, and alternately from about 4.0 to about 125 acfi es.
[0038] Astrrrt.her embodiment of the nveatican., comprises substituted propanediol biocide actives, such as for example, 2-bromo,2-nitro, ], 3,propane-diol (l3NPD active, a representative of the substituted propanediol class of compounds.
Examples of substituted propanediol compounds:
Substituted Propanediols y Where:
X = CI, Br, I, NO2. O3H, OH
Y = Cl, Br, 1, N02, S03H, OH
Example:
Bronopol (BNPD) = 2--bromo- -nitre-prepanedical = -brc e-2-nitre -l3-propanediol Br HOH2C +CH20H
[0039] [`. ective amounts of a substituted propanediol biocide incorporated into the liposome would include from about 1.0 to about 100 biocide actives, or altemately about 2 5 to about 8.0 biocide actives.
[0040] A. f urtlaer embodiment cat` tlae :invention , l:ipr~asonres produced drat.
incorporate the biocide phosphonium salts for example the cationic surfactant and biocide tributyltetradecyl plaosphonium chloride (TTPC). The TTPC' Iiposome fibrniulation targets and eliminates higher levels ofbiofilm when compared to the same. TTPC
compound at the same active concentration that is not incorporated into liposome delivery systems. The liposome biocide .readily penetrates the microbial biofilm and is highly effective at destroying the biofil.m cells and associated slime corammplex. This liposome delivery method has been proven with TT`l'K, but any phosphoniurn salts biocide active could be made significantly more effective when delivered in a liposome format. Non-liraiting examples of phosphoniun salts are shown as:
Substituted Phosphon um Salts I
I
Rol Where:
RI CH3, CH9CH, CfHi2,,+1 ) where n R2, R3. R4 = CH3, CH 0H, C,H(2,+,) where n = 2 - 5 X = Cl, Br, 1, NO2, SO4, HCI
Examples:
Bellaeide 350 (Tetradeeyl tributyl phesphonium chloride) C~H
Cr4Hc P C4H9 Cl CA
THPS (Tetrakis hydroxyrnethyl phosphonium sulfate) CN..; N-P-CH CH S0$
CH OH
[0041] Effective amounts of a plrospl>oniu salt biocide incorporated into the liposon e would include from about 1 .0 to about 1.00 biocide acÃives, or alternately about 1.5 to about 50.0 biocide actives [0042] Liposor res of the present invention may be created as multi-layer bodies.
in which one or more additional layers are provided to enhance the stability of the l:iposomes or to effectuate a programmed release of the underlying lipid body and contents. Thus, this technology may be used to encapsulate medicines for intracorpoaal delivery, such that the additional layers may include a protective layer that is hydrolyzed or otherwise breaks down over time to provide a sustained release or longer lifetime of the r,rrnderlyyin. lipcosorsme. Such additional layer may additionally or alternatively include an encapsulating polymer that selectively breaks down when the multi-layer liposome encounters a low-pl--H environment, like the corrosive high acidity environment that rnay develop beneath a biof`rl..m. A. layer may also be compounded to be vulnerable to sulfur fixing bacteria, causing the liposome to specifically release its biocide in proximity to these corrosive organisms often present in a waste or pipeline system.
Furthermore, several such layers may be employed to assure a sufficient lifetime of the liposome, prefe:raably on the order of several days as well as an ability to target a specific niche or environment in the biofilm. This assures that the liposomes will effectively encounter the target organisms or bio.film colonies and deliver their biocides thereto. The lipid material itself may be treated to provide enhanced resistance to hydrolysis or decay, or the added layers may be tuned of various harderaable or cross-linkable oils or polymers.
[0043] An alternate embodiment of the invention provides for a. biodelivery<
composition for delivering at least one antimicrobial composition into a biotilm present in an industrial system, wherein the biofilrn comprises at least one microorganism species; b) the biodelivery composition comprises a liposome structure containing at least one lipid or phospholipid type component, and c) the liposome structure encapsulates at least one antimicrobial composition.
[0044] A further embodiment provides for the targeted delivery of biocide actives into an industrial system, such as an industrial aqueous system, by introducing into said system an effective amount of said biocides in a critical area of said system, By targeting ,in area,, and entry at a specific point in a process, the eft caacy of the liposome system provides for a noteworthy impact on the environment as well as the cost of maintaining a ay=steam, as the entire system does not need to be flooded with biocides, only the specific area of interest.
[0045] The invention will now be described with respect, to certain examples that are merely representative of the invention and should not be construed as limiting thereof EXAMPLES
[0046] The invention is illustrated in the following nonlir citing examples, which are provided for the purpose of representation, and are not to be construed as limiting the scrape of the :invention. All parts and percentages in the examples are by weight unless indicated otherwise.
Example 1 [4047] Three batches of liposomes (150 nanometers averagr diameter) were created that incorporated an isothiazolin biocide, Kat-hon`r= r (available from Rohr-Haas, :Philadelphia, PA) as the active ingredient. The liposomes were than.
placed in microtiter plates that had microbial biofilnis coating them. The microbe inhibiting efficacy of the isothiazolin liposomes was then compared with non-liposomal ise)thiazcalina biocide when Lused at. the sarmae :isothia.zolin conacentra.tionas. The liposonaes containing isothiazolin penetrated the bioflrn and inhibited the hiotilm organisms much r tore effectively than the non--liposonial isothiazolin solution.
[0448] The .results are shown in Tables 1, 2 and 3 below and in Figs. 1, 2 and 3.
The non-liposomal isothiazolin is listed as Kathon av, each of the liposome samples were made by three different technicians and are referred to by code. The tables and charts show the. concentration of the. isothiazolin versus the percent inhibition of the biot lm. It is clear from both the tables and the figures that in all three trials, the liposomal isothiazolin formulations exhibited more effective biofilin killing)] removal efficiency than the isothiazolin control (listed as Kathon av) in every liposonie concentration that was tested. 'Elie liposome carrier is highly effective at delivering biocide to the bioilrn at low isothiazol.iaa. concentrations, thus providing better biofilm control at much reduced i sothiazolin concentrations (reduced toxicity and cost performance).
.
Table 1 Concentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW GT Kathon av 0016 21 29.9 7.9 0.93 0.031 29.7 34.1 28.7 10.9 0.0625 26.8 31 31.4 14.5 0.125 31.7 38.3 26.5 11.3 0.25 18.6 32.9 37.9 6.7 --------------- ----------------- ------0.5 37,4 32.4 37.5 9.0 -------- --------- -------- -------- ---- ---- ----------------------------------------- ----------------------------------------- ------------------------------------------1 42.9 50.3 44.8 17.9 2 48.6 53.1 54.4 37.9 Table 2 oncentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW T Kathon av -------- -------- -- -- ----- -------- -----0016 15.7 21.1 10.2 0.93 ------------------------------------------------------------ ----------------------------------------- ----------------------------------------- ----------------------------------------- ------------------------------------------0.031 27.3 31.3 26.1 10.9 0.0625 21.6 30.5 25.8 14.5 --------------------------- -------------------------------- ------------------------------------------ ---- -0.125 26.7 35.1 29.6 11.3 0.25 24.6 36,6 33.4 6.7 0.5 32.6 34,6 31.8 9.0 1 36.6 43.9 35.9 17.9 2 45.3 45.1 48.3 37.9 Table 3 Concentration(ppm) % inhibition % inhibition % inhibition % inhibition JIM WKW GT Kathon av 0016 10.4 123 12.4 0.93 10.031 24.9 28.4 23.5 10.9 -- ----- -----------------------------------------U625 16.3 30 221 14.5 0.125 21.E 31.9 32.7 11.3 0.25 33.5 40.2 28.8 6.7 --------------- ----------------- ------0.5 277 36.7 26.0 9.0 -------- --------- -------- -------- ---- ----- ----------------------------------------- ----------------------------------------- ------------------------------------------1 30.3 37.3 26.9 17.9 2 42.0 37,0 42.1 37.9 Example 2 [0049] One batch of liposomes (150 manometers average diameter) was created that incorporated a substituted nitrilopropionamide ocide as the active ingredient. The liposo.mes were then placed in :Ã Ãacrcatiter plates that had microbial hiof lms coating them.
The microbe inhibiting efficacy of the substituted nitrilopropfonamidc liposomes was then compared with non=-liposonaal substituted r itrilopr-opionanide biocide when used at the same n trilopropionamide concentrations. The liposoines containing Substituted nitrflopropionam:ide, particularly 1).BN:PA,, penetrated the b1ofilyn and inhibited the biofilm organisms ..much more effectively than the nova-fliposomal substituted nitrilopropionannide solution.
[0060] The results are shown in Table 4 below and in Fig 4- The table a7.nd.
Chart show the concentration of the substituted nitrilopropionamide versus the percent inhibition of the hiotil.m. It is clear from both the table and the figure that the liposomal substituted .nitrilol)ral-iarrart ide f rrrrulation exhibited more effective biofilni killing,"
removal efficiency than the substituted nitrilopropionaride control in every liposome concentration that was tested.
Table 4 "
""
oncentratior DBNPA liposome DBNPA
0.39 29.9 17.9 ------------------------------------------------------- --------------------------------------------------------------- ----------------------------------------------------------------------------Q.B - -------- ---- 38.6 23.3 1.56 62.1 35.3 3.13 79.7 66.5 6,25 85.6 80.3 12.5 97.6 89.3 ------- -------- -------- ------- -- -------- -------- ---------Example 3 [0051] Two batches of lilaosoames (150 nanometers average diameter) were created that incorporated an annnoniuna silt biocide as the active ingredient, specifically a quaternary ammonium salt, 50% allkyl,d: methyl-benzvi amnion: um chloride (ADBAC).
The liposones were then placed in microliter plates that had microbial biofilms coating thenp. The microbe inhibiting efficacy of the A[).AÃ` liposomes was then compared with non -liposomal ADBAC biocide when used at the same BAC`: concentrations, The liposomes containing ADBAC penetrated the biolilm and inhibited the biofilm organisms much more effectively than the non-liposomal ADBAC solution.
[0052] The results are shown in Tables 5 and 6 below and in Figs 5 and 6. The table and chart show, the concentration of ADBAC'. versus the percent inhibition of the biofilna. It is clear from both the table and the figure that the liposonlal ADBAC
formulations were as good as or more effective in biofilni killing! removal efficiency than the ADBAC control in even., liposome concentration that was tested.
iConcentraton 50% ADBAC Quat 50%AD AC Quat liposome 3.9 17 15 -------------------- -- - ---------------------------------------------------------------------------15.6 65 47 31.3 69 52 -------------------------------- 62.5 ------- --------------------------------------------------------------------------------------- ----------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------Soo 98 97 Table 6 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Concentration 50% ADBAC Quat 50% ADBAC Quat lipe one ----3.9 7 3 7.3 15 7 15.6 40 19 -------------------------------------------------------------------------------------------------------------------------------------- 31.3 48 62.5 61 40 ---------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------- ----------------------------------------------------------------------------[Example 4 [0053] Two batches of liposomes (1.50 nanorY eters average diameter) were created that incorporated a substituted propanediol biocide as the active ingredient, specifically a b:r-onopol. The Iiposo.mes were then placed in .microtiter plates that had microbial bioti:laars coating them. The microbe inhibiting efficacy of the bronopol liposonaes was then compared with non--liposomal bronopol biocide when used at the same bronopol concentrations. The liposomes containing bronopol penetrated the biofllm and inhibited the bio.him organ isn s much more effectively than the 11011-liposomal bronropol solution.
[0054] The results are shown in Tables 7 and 8 below and in Figs 7 ,and S. The table and chart show the concentration of bronopol versus the percent inhibition of the blot lm, lt. is clear #rcart tae tla the table and tlr figure tlatat tlrc lil c sc r rrrl larrarrc ta<al formulations were as good as or more effective in biotilra killing/ removal efficiency than the br-onopol control in every l:iposomrre concentration that was tested.
Table 7 ----------------------- ------- -------------------------------------------- ---------------------------------------------------------------------------- ----------------------------------------------------------------------------oncentration Bronopol liposorn Bronopol 0,625 0 0 1.25 5 0 - ----------------------------2. 19 ------------------------------------------------------------------------------------------------------------------------------------------------------ -------------------------------------------------------------------------------------------------------------------------------------------------------------- -------- ------- -------------------------------- --- -------- ----`T'able 4 Concentration Bronopol liposome ronopol 0.78 0 0 1.6 4 0 ------------------------------------------------------ ------------------------------------------------------------------------- ----------------------------------------------------------------------a 18 3 12.5 21 5 Example 5 [Ã3065] One batch of liposomes (150 narnorneters average diameter) was created that incorporated a phosphonium salt biocide, Bellacide 3SOT r WA, Tucker, GA) as the active ingredient. The liposomes were then placed in microtiter plates that had microbial biolilr-rms coating them. The microbe inhibiting efficacy of the ph.osphoniur-rm salt liposomes was then compared with non-liposomal phosphonium salt biocide when used at the same concentrations. The liposomes containing phosphonium salt penetrated the biotilm and inhibited the biohlm orga.nisrns much r-nore effectively than the non-liposomal phosphonium salt solution.
[0056] The results are shown M. Table 9 below and in Fig 9. The table and chart show the concentration of the phosphonium salt versus the percent inhibition of the biotalm_ It is clear from both the table and the figure that the liposornal phosphornium salt formulation exhibited equal or more effective biofil m killing./ removal efficiency than the phosphonium salt control in every liposome concentration that was tested.
Table 9 Concentration Belleclde 350 Boone à Bellacide 350 ------------------------------------------------------- ---------------155 6.6 0 3.13 14.5 0 6,25 14.9 0 ------- -------- -------- ------- -------------------------------- --------- ------1 .5 23.8 8 --------- ------- --------- ---------25 21.6 ------- -------- -------- -------- --------- -------- -------- -------- -------- ------- -- -------- -------- ---------[0057] While the present invention has been described with references to preferred embodiments, various changes or substitutions may be made on these embodiments by those ordinarily skilled in the art pertinent to the present invention with out departing from the technical scope of the present invention. 'T'herefore, the technical scope of the present :invention encompasses not only those embodiments described above., but also all that fall within the scope of the appended claims.
Claims (35)
1. A biodelivery composition for delivering at least one antimicrobial composition into a biofilm present in an industrial system, wherein a) the biofilm comprises at least one microorganism species;
b) the biodelivery composition comprises a liposome structure containing at least one lipid or phospholipid type component; and c) the liposome structure encapsulates at least one antimicrobial composition.
b) the biodelivery composition comprises a liposome structure containing at least one lipid or phospholipid type component; and c) the liposome structure encapsulates at least one antimicrobial composition.
2. The biodelivery composition of claim 1 wherein the lipid is one member selected from the group consisting of phospholipids, lethicin, phosphatidyl choline, glycolipid, triglyceride, sterol, fatty acid, sphingolipid, or combinations thereof.
3. The biodelivery composition of claim 2 wherein the lipid is a phospholipid.
4. The biodelivery composition of claim 3 wherein the phospholipid is derived from soybeans or eggs.
5. The biodelivery composition of claim 2 wherein the lethicin is a mixture of lipids.
6. The biodelivery composition of claim 1 wherein the antimicrobial composition comprises at least one biocide.
7. The biodelivery composition of claim 6 wherein the antimicrobial composition comprises a non-oxidizing biocide.
8. The biodelivery composition of claim 6 wherein the biocide is an isothiazolin biocide.
9. The biodelivery composition of claim 8 wherein the isothiazolin biocide comprises at least one member chosen from the group consisting of 5-chloro-2-methyl-4-isothizolin-3-one, 2-methyl-4-isothiazolin-3-one, or any combinations thereof.
10. The biodelivery composition of claim 6 wherein the biocide is a substituted nitrilopropionamide.
11. The biodelivery composition of claim 10 wherein the substituted nitrilopropionamide biocide comprises 2,2-dibromo-3-nitrilo-propionamide.
12. The biodelivery composition of claim 6 wherein the biocide is a quarternary ammonium salt.
13. The biodelivery composition of claim 12 wherein the quarternary ammonium salt comprises at least one member chosen from the group consisting of alkyl,dimethyl-benzyl ammonium chloride, dialkyl dimethyl quats and combinations thereof.
The biodelivery composition of claim 6 wherein the biocide is a substituted propanediol biocide.
The biodelivery composition of claim 6 wherein the biocide is a substituted propanediol biocide.
14. The biodelivery composition of claim 6 wherein the biocide is a quarternary ammonium salt.
15. The biodelivery composition of claim 14 wherein the propanediol biocide comprises 2-bromo,2-nitro, 1,3,propane-diol.
16. The biodelivery composition of claim 6 wherein the biocide is a phosphonium salt biocide.
17. The biodelivery composition of claim 16 wherein the biocide comprises at least one member chosen from the group consisting of tributyltetradecyl phosphonium chloride, tetrakis hydroxymethyl phosphonium sulfate or any combinations thereof.
18. The biodelivery composition of claim 1 wherein the liposome structure is up to about 200 microns in diameter.
19. The biodelivery composition of claim 1 wherein the liposome structure is between about 500 nanometers to about 10 microns in diameter.
20. The biodelivery composition of claim 1 wherein the industrial system is an aqueous system.
21. The biodelivery composition of claim 20 wherein the industrial system is chosen from the group consisting of water distribution systems, cooling towers, boiler systems, showers, aquaria, sprinklers, spas, cleaning bath systems, air washers, pasteurizers, air conditioners, fluid transporting pipelines, storage tanks, ion exchange resins, food and beverage processing lines, paint spray booths, metalworking fluid baths, coal and mineral slurries, metal leaching fluids, wastewater treatment facilities, pulping and papermaking suspensions, mollusk control, acid mine drainage, oil drilling pipes, oil pipelines, oil storage tanks, gas drilling pipes, gas pipelines, or any industrial application prone to microbial induced biofilm formation or microbial induced corrosion.
22. A method for delivering an antimicrobial composition into a biofilm in an industrial system comprising the steps of:
a) forming a liposome structure which encapsulates at least one antimicrobial composition; and b) introducing an effective amount of the liposomes of a) above to an industrial system that is prone to biofouling or biofilm formation.
a) forming a liposome structure which encapsulates at least one antimicrobial composition; and b) introducing an effective amount of the liposomes of a) above to an industrial system that is prone to biofouling or biofilm formation.
23. The method of claim 22 wherein the liposome structures are introduced at from about 0.01 ppm to about 100 ppm.
24. The method of claim 22 wherein the liposome structures are introduced in the industrial system at a targeted location.
25. The method of claim 22 wherein the liposome structure comprises a biocide.
26. The method of claim 25 wherein the biocide is an isothiazolin biocide.
27. The method of claim 26 wherein the isothiazolin biocide comprises at least one member chosen from the group consisting of 5-chloro-2-methyl-4-isothizolin-3-one, 2-methyl-4-isothiazolin-3-one, or any combinations thereof.
28. The method of claim 25 wherein the biocide is a substituted nitrilopropionamide biocide.
29. The method of claim 28 wherein the substituted nitrilopropionamide biocide comprises 2,2-dibromo-3-nitrilo-propionamide.
30. The method of claim 25 wherein the biocide is a quarternary ammonium salt biocide.
31. The method of claim 30wherein the quarternary ammonium salt biocide comprises at least one member chosen from the group consisting of alkyl,dimethyl-benzyl ammonium chloride, dialkyl dimethyl quats, or any combinations thereof.
32. The method of claim 25 wherein the biocide is a propanediol biocide.
33. The method of claim 32 wherein the propanediol biocide comprises 2-bromo,2-nitro, 1,3,propane-diol.
34. The method of claim 25 wherein the biocide is a phosphonium salt biocide.
35. The method of claim 34 wherein the phosphonium salt biocide comprises at least one member chosen from the group consisting of tributyltetradecyl phosphonium chloride, tetrakis hydroxymethyl phosphonium sulfate or any combinations thereof.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/408,061 | 2009-03-20 | ||
| US12/407,953 | 2009-03-20 | ||
| US12/408,059 US20100239627A1 (en) | 2009-03-20 | 2009-03-20 | Quarternary ammonium salts delivery systems |
| US12/408,061 US20100239630A1 (en) | 2009-03-20 | 2009-03-20 | Phosphonium salts delivery systems |
| US12/408,048 | 2009-03-20 | ||
| US12/408,048 US20100239626A1 (en) | 2009-03-20 | 2009-03-20 | Propanediol delivery systems |
| US12/408,027 US20100239651A1 (en) | 2009-03-20 | 2009-03-20 | Nitrilopropionamide delivery systems |
| US12/408,059 | 2009-03-20 | ||
| US12/408,027 | 2009-03-20 | ||
| US12/407,953 US20100239650A1 (en) | 2009-03-20 | 2009-03-20 | Isothiazolin biodelivery systems |
| PCT/US2010/023973 WO2010107533A1 (en) | 2009-03-20 | 2010-02-12 | Biodelivery systems |
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| Publication Number | Publication Date |
|---|---|
| CA2754820A1 true CA2754820A1 (en) | 2010-09-23 |
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| CA2754820A Abandoned CA2754820A1 (en) | 2009-03-20 | 2010-02-12 | Biodelivery systems |
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| EP (1) | EP2408307A1 (en) |
| CN (1) | CN102355822A (en) |
| AU (1) | AU2010226257A1 (en) |
| BR (1) | BRPI1006466A2 (en) |
| CA (1) | CA2754820A1 (en) |
| MX (1) | MX2011009900A (en) |
| TW (1) | TW201036543A (en) |
| WO (1) | WO2010107533A1 (en) |
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| US20110177147A1 (en) * | 2010-01-21 | 2011-07-21 | General Electric Company | Stable biocidal delivery systems |
| EP2361502A1 (en) * | 2010-02-05 | 2011-08-31 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Active antimicrobial compositions, coatings and methods for controlling pathogenic bacteria |
| GB201200490D0 (en) | 2012-01-12 | 2012-02-22 | Univ Bath | Wound dressing |
| CA2898842C (en) | 2013-03-25 | 2021-03-16 | Kemira Oyj | Biocide formulation comprising 2,2-dibromo-3-nitrilopropionamide (dbnpa) in a micelle |
| CN108338163A (en) * | 2018-03-28 | 2018-07-31 | 陈太师 | A kind of preparation method of holding effect type Biocidal algae-killing agent |
| WO2022118313A1 (en) * | 2020-12-02 | 2022-06-09 | Bromine Compounds Ltd. | Method and composition for water treatment |
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| EP0525166B1 (en) | 1991-02-12 | 1995-08-09 | Buckman Laboratories International, Inc. | Composition and methods for removing or preventing biofilm |
| US6759040B1 (en) | 1997-09-12 | 2004-07-06 | University Of Maryland, College Park | Preparation and use of biofilm-degrading, multiple-specificity, hydrolytic enzyme mixtures |
| US6267897B1 (en) | 2000-05-04 | 2001-07-31 | Nalco Chemical Company | Method of inhibiting biofilm formation in commercial and industrial water systems |
| US7785478B2 (en) * | 2007-08-08 | 2010-08-31 | General Electric Company | Method for controlling protozoa that harbor bacteria |
| US7824557B2 (en) * | 2007-08-08 | 2010-11-02 | General Electric Company | Method for controlling microbial biofilm in aqueous systems |
-
2010
- 2010-02-12 MX MX2011009900A patent/MX2011009900A/en not_active Application Discontinuation
- 2010-02-12 CA CA2754820A patent/CA2754820A1/en not_active Abandoned
- 2010-02-12 CN CN201080012632XA patent/CN102355822A/en active Pending
- 2010-02-12 WO PCT/US2010/023973 patent/WO2010107533A1/en active Application Filing
- 2010-02-12 BR BRPI1006466A patent/BRPI1006466A2/en not_active IP Right Cessation
- 2010-02-12 EP EP10705698A patent/EP2408307A1/en not_active Withdrawn
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| CN102355822A (en) | 2012-02-15 |
| TW201036543A (en) | 2010-10-16 |
| EP2408307A1 (en) | 2012-01-25 |
| AU2010226257A1 (en) | 2011-10-06 |
| BRPI1006466A2 (en) | 2017-05-30 |
| MX2011009900A (en) | 2011-09-30 |
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