Indian Patents. 262864:"QUATERNARY AMINE ACRYLATE COPOLYMER AND A PROCESS OF PREPARATION THEREOF"

Title of Invention	"QUATERNARY AMINE ACRYLATE COPOLYMER AND A PROCESS OF PREPARATION THEREOF"
Abstract	A quaternary amine acrylate based non- brittle copolymeric system with broad spectrum antimicrobial activity by contact killing in few minutes without releasing bioactive agents has been developed.

Full Text	Field of the invention The present invention relates to quaternary amine acrylate based contact killing antimicrobial copolymers with broad-spectrum antimicrobial activity without releasing any bioactive agents and can be used for wide number of applications Background and prior art Disinfection of drinking water continues to be a challenging problem and more so in a developing and over-populated country like India, where majority of population resides m rural and slum areas and do not have access to safe potable drinking water The efficacy of many of the disinfection systems is still based on actual release of bioactive agents like iodine, chlorine, silver etc in drinking water Physiological effects due to long-term ingestion of bioactive agents, even though at ppm levels, could be an issue Hence, feasibility of incorporating the bioactive agents permanently in the system for killing bacteria on contact without releasing bioactive agents in water will be the best approach There is a keen interest m materials capable of killing harmful microorganisms Such materials could be used to coat the surfaces of common objects touched by people in everyday life (eg door knobs, children's toys, computer keyboards) to render them antiseptic and unable to transmit bacterial infections Hence materials can be impregnated with antimicrobial agents such as antibiotics, quaternary ammonium compounds, silver ions or lodme that are released gradually into the surrounding solution over time and kill microorganisms therem Although these strategies have verified in aqueous solution containing bacteria, they would not expected to be effective against airborne bacteria in the absence of a liquid medium, this situation is especially true for release - based materials which are also liable to become impotent when the leaching antibacterial is exhausted Quaternary amine acrylate (QAA) have a large variety of usage areas from cosmetics to clothes softeners but especially they are known to be good disinfectants Quaternary amine acrylate's antibacterial ability is resulted from their amphillic structure and surfactant property, which was first reported by Dogmak The antimicrobial action of the AA is based on theu damaging surfactant like interaction with the membrane (cytoplasmic) of bacteria resulting the loss of the membrane permeability At convenient concentrations, they can cause cell leakage and the death of the cell Quaternary structures are effective on both gram positive and gram-negative bacteria, but they have a stronger antibacterial effect on positive once, since gram negatives have an extra protective membrane Quaternary compounds are widely used because of their non-toxic and non-lrritant property QAA are not affected from the protein concentration of the environment and don't loose their affectivity on bacteria over the course of tune The effectiveness of the agent against microorganisms is directly related to its area of contact with the microorganism's medium A new concept of contact type of disinfection by iodine based resm formed by adsorption of iodine on a strong alkaline amon-exchange resin has been patented by Liwang He claimed that lodme resin could remove and kill more than 99 9% of E coh, S aureus and C albicans in water at 25°C and pH 6 5 Another Quaternary ammonium exchange resm binding tri-iodide or penta iodide was reported for their ability to disinfect water containing L pneumophile Results mdicated that the lodmated resms are stable demand release disinfectants There was no residual iodine detected by amperometric titration When an aqueous suspension containing 2 7xl09 cfu of L pneumophile per ml was passed through tn-iodinated resins less than 0 004% were recovered No viable cells were detected by direct platmg from a suspension of 2 3 X109 cfu per ml eluted through penta-lodmated resins (>99 999% reduction m viability) but, bactericidal active agents concentration decreases with time Another researcher Ranuci et al synthesized new polymeric disulphides containing t-amino groups m their main chain They were prepared by polyoxidauon of 3,6-dimethyl-3,6-diazoctane-l,8 dithiol and 3,10-dimethyl 3,10-diazadodecane-l,12-dinol respectively They were then quaterrused with methyl iodide and benzyl bromide and the resulting quaternary ammonium polymers were preliminary tested for antimicrobial activity against E coh, P aeruginosa and S aureus Groups like thiocyanates have also been tried to covalently immobilized on a biomaterial surface by Nirmala etal in presence of a phase transfer catalyst in aqueous media leadmg to the nucleophilic substitution of chlorine by thiocyanates on the PVC surface It was found that the thiocyanate groups have bactericidal properties and remains effective against S aureus and S epidermis even after immobilization on PVC surface Similarly Tiller etal synthesized poly(4-vinyl-N-alkylpyridiruum bromide) which was covalently attached to glass slides to create a surface that kills airborne bacteria on contact The antibacterial properties were assessed by spraying aqueous suspension of bacterial cells on the surface followed by air drying and counting the number of cells remaining viable cells Recently Lee etal reported a permanent, non-leaching antibacterial surface which they have grown directly on the surfaces of glass and paper using atom transfer radical polymerization (ATRP) But above mentioned modified surface were found to loose properties with time because of less extent of quatermsation and also due to surface erosion The prior arts WO9940791, US6264936, US6126931, US5575917, WO03064412, US2004062744, WO0185813, US6039940, US6448305 and WO0228927 describe contact killing polymer, but there polymers have the limitation of surface modification and they require higher contact time to kill bacteria completely and the surface loose its activity because of erosion of surface active polymeric layer Object of the invention The primary objective of the present invention is to develop a polymer with a antimicrobial property Another object of the invention is to develop quaternary amine acrylate based non-brittle hydrophilic and flexible copolymeric systems with broad spectrum of antimicrobial activities by contact killing in few minutes without releasing any bioactive agents Another object of the invention is to develop hydrophilic, porous, non-brittle and flexible polymeric matrix, which is easy to handle and has long shelf life Yet another object of the present invention is to provide material, which gets easily integrated into conventional equipments and devices Still another object of the present invention is to obtain the product, which imparts no residual odor and undesirable taste when used for water disinfection application Further object of the present invention is to develop a system where no sophisticated instrumentation or control is required while handling it Summary of the invention The present invention relates to a quaternary amine acrylate based contact killing antimicrobial copolymers with broad-spectrum antimicrobial activity without releasmg any bioactive agents The present invention also relates to method of using for water disinfection and in medical applications by coating them onto biomedical devices like sutures, catheters, mcorporation mto dental/bone cement formulations to impart permanent contact killing antimicrobial properties to them to prevent microbial infection Brief description of figures Figure 1 FTIR Spectra of Quatermsed EGDMA-piperazme ammonium iodide Figure 2 Structural formula Quatermsed EGDMA-piperazine ammonium iodide Figure 3 1H-NMR Spectra of Quatermsed EGDMA-piperazine ammonium iodide Figure 4 HEMA-QAA copolymer tube formed by redox bulk polymerization Figure 5 Crossed-linked pattern of HEMA-QAA co-polymer Figure 6 FTIR Spectra of poly (HEMA-co-Q AA) Figure 7 Structural formula of poly (HEMA-co-QAA) Figure 8 Effect of QAA concentration on thermal stability & contact angle values of co polymer Figure 9 Effect of QAA concentration on pore size of co-polymer Figure 10 Comparison of iodine release from various polymeric systems Figure 11 Anti-microbial activity of QAA co-polymers by zone inhibition against E coh Figure 12 Effect of QAA concentration against E coh Figure 13 Anti-microbial activity of QAA co-polymer* (20g) filled in polyester cloth Detailed Description of the Invention Accordingly, the present invention relates to a Quaternary Amine Acrylate Copolymer of Formula 1, having the structure, (Structure Removed) wherein A is A,Z are acrylate monomer in m and n proportions, wherein B is a cyclic or acyclic amine, wherein R is a hydrocarbon and, wherein X is a halide An embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1 wherein the acrylate A is selected from a di or tri acrylate Another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the di- and tri- acrylate A is selected from a group compnsmg ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprising vmyl monomers Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the vinyl monomer is selected from a group compnsmg methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA) Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the cyclic amine is selected from a group comprising of piperazrne Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the hydrocarbon is selected from a group compnsmg of CI to C15 Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the halide is selected from a group comprising of iodine, bromide and chloride A further embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1, (Formula Removed) Formula 1 the said process comprising the steps of, a) esterifying 0 5-2 moles of diols or triols with excess of substituted or unsubstituted acrylic or methacryhc acid in the presence of acid catalyst and inhibitors, in a solvent, at a temperature m the range of 80-100 deg C to obtain an acrylic monomer with at least four functionality b) reacting 0 5-1 5 moles of secondary amines with acrylate monomer of step (a) with 1 5-3 5 moles to obtain amine acrylate with functionality in the range of 4-16 with Nitrogen content in the range of 1-12, in presence of 20-30 % (w/w) alcohol at a temperature of 20-40 deg C for 6-10 hrs c) quaternizrng the amine acrylate of step (b) with alkyl hakde hydrocarbon cham of C1-C15 to obtam Quaterruzed Amine Acrylates,and d) polymerizing the Quaterruzed AA of step ( c) m the range of 10-60% with double bond containing functional vinylic monomers using a initiator, optionally along with a suspending agent, to obtain Quaterruzed Amine Acrylate-Copolymer Another embodiment of the present mvention relates to the process for preparing quaterruzed amine acrylate copolymers represented by the Formula lwherern the acrylate A is selected from a group compnsmg of di or tri acrylate Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula 1, wherem the di-and tri- acrylate A is selected from a group compnsmg of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprising vinyl monomers Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the vmyl monomer is selected from a group compnsmg methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA) Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula 1, wherem the cyclic amine is selected from a group comprising of piperazine Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula l,wherern the acyclic amine is selected from a group comprising of ethylene diamine, dimethylamme, hexylamine and diethyl amine Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the hydrocarbon group is selected from selected from a group comprising of CI to C15 Yet another embodiment of the present mvention relates to the process for preparing Quatermzed amine acrylate copolymers represented by the Formula 1, wherein the halide is selected from a group compnsmg of iodine, bromide and chloride Yet another embodiment of the present mvention relates to the process for preparing Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the catalyst m step(a) is selected from a group comprising of sulphuric acid and methane sulphomc acid (1-2)% Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the inhibitor in step (d) is selected from a group comprising of hydroqumone and other derivatives (0 15-0 35%) Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the solvent m step(a) is selected from a group comprising of toluene, cyclohexane, benzene and xylene Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherein the initiator m step (d) is selected from a group compnsmg of redox initiator and peroxide initiator Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the redox initiator is a formulation of Ammonium Persulfate (APS) in the range of 0 4-0 8% and N,N,N ,N'-tetramethylene diamine (TEMED) in the range of 0 4-0 8% Yet another embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1, wherem the peroxide initiator is selected from a group comprising of Azobisisobtyromtrile (AIBN), benzoyl peroxide (BPO) and dimethyl paratoluidrne (DPMT) Yet another embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1, wherein the suspending agent is selected from a group compnsmg of sodium polyacrylate (0 8-2 0%) of total monomer used Yet another embodiment of the present invention relates to the process for preparmg Quaternized amine acrylate copolymers represented by the Formula 1, wherem the functional vinyhc monomer Z is selected from a group compnsmg of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), styrene and n-butyl methacrylate (n-BMA) A further embodiment of the present invention relates to a pharmaceutical antimicrobial composition, said composition compnsmg of a Quaternary Amine Acrylate Copolymer of Formula 1 and a pharmaceutically acceptable substance and optionally the said composition bemg coated onto a medical device such as herein described, wherem Quaternized Amine Acrylate Copolymer is present in the said pharmaceutical acceptable material m the ratio of 1 6 _ (Formula Removed) Formula 1 Another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the acrylate A is selected from a selected from a group comprismg of di- or tri- acrylate Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the di- and tri- acrylate is selected from a group comprismg of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprismg vmyl monomers Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the vmyl monomer is selected from a group comprismg methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA) Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the cyclic amine is selected from a group comprismg of piperazme Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimethylanune and diethyl amine Yet another embodiment of the present invention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the hydrocarbon group is selected from a group comprising carbon atoms of number 1 to 15 Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the hahde is selected from a group compnsmg of iodine, bromide and chloride Yet another embodiment of the present invention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the pharmaceutical acceptable substance is selected from a group compnsmg of dental cement and bone cement formulation Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the medical device is selected from a group compnsmg of sutures and catheters Yet another embodiment of the present invention relates to a pharmaceutical antimicrobial composition of Formula 1, with water for a period in the range of 2-10 minutes In accordance with the object of the mvention, the present mvention provides a quaternary amine acrylate based non- brittle co-polymeric system with broad spectrum antimicrobial activity by contact killing in few minutes without releasing bioactive agents has been developed In addition to this, they are double bond containing reactive monomers and by usmg chemical initiator or plasma radiation or gamma radiation they can be coated onto various articles mtroducmg long term and stable antimicrobial properties These quaternary amine acrylate polymers have wide range of applications as water disinfectant for potable drinking water, m dental/bone cement formulations and polymerized onto various biomedical devices to impart permanent antimicrobial properties In an embodiment of the present mvention required synthesis of quaterruzed ammonium iodide monomer which is planned m three steps m which the desired reactive acrylate is synthesized and arrunauon is done usmg secondary amine (Michael's addition) followed by its quatermsation with desired alkyl iodide (hydrocarbon chain length varying C-l to C-15) In an embodiment of the present invention provides a process of synthesis of reactive acrylate monomer, in which various reactive di, tri, tetra terminal double bonded functional monomers are synthesized by esterification of 0 9-1 2 mole of di,tn,tetra functional alcohol with excess of acrylic acid and methacrylic acid using dean-stark apparatus In still another embodiment acid catalyst like sulphuric acid, methane sulphomc acid (1-2%) as catalyst, hydroqumone and other derivatives (0 15-0 35%) as inhibitor and 15-35% solvent (toulene, cyclohexane, xylene) is used The amount of catalyst, inhibitor and solvent are taken w/w percentage of total monomer The reaction is carried out m heavy paraffm oil bath at 75-105° C at 180-220 rpm for 4-7 hrs The reaction is stopped when calculated amount of water is collected in the arm of dean stark apparatus In yet another embodiment of the invention provides the synthesis of amine acrylate 1-2 mole of secondary amine (piperazine, diethyl amine/dimethyl amine) and excess of synthesized reactive diacrylate /triacrylate (2 9-3 2 moles) and 25-30% (w/w of total monomer) methanol /chloroform/ethanol are taken as solvent The reaction is carried out at 25-35°C for 5-8 hrs at 180-200 rpm using mechanical stirrer The product obtamed is kept at 30°C in vacuum oven till residual solvent was evaporated and stored at 4°C To introduce more nitrogen content in the oligomer cham 1-2 mole of triacrylate was reacted with 2-4 moles of piperazine/ diethyl amine/dimethyl amine then obtained product (1-2 mole) was reacted with 3-4 mole of diacrylate under the same condition as mentioned before To further increase the number of nitrogen instead of reacting with diacrylate it is further reacted with excess of triacrylate and then amrnated with secondary amine In still yet another embodiment of the invention the quaterrusation of amine acrylates containing number of nitrogen varying from 1-12 (1 ,2, 6, 12 ) is carried out using alkyl iodide (hydrocarbon cham length varying C-l to C-15) (1 0-1 4eq/amine) The reaction is refluxed for 2-3 hrs Still another embodiment of the invention m which copolymerization of QAA by bulk polymerization (tube form) is carried out m which vinylic monomers like 2-hydroxyethyl methacrylate (HEMA) ,methyl methacrylate (MMA), N-vmyl pyrrohdone (NVP),n-butyl methacrylate (n-BMA) are copolymerized with QAA containing number of nitrogen varying from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 4- 0 8%, TEMED 0 4-0 8% ) in an aqueous solution The formulation consisted of variable percentage of HEMA/MMA/NVP/n-BMA (52-87%), QAA (0,5,20,40%), distilled water (10%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration In another embodiment of the invention quaterrusation after copolymerisation of amine acrylate by bulk polymerization (tube form) is carried out in which vinylic monomers like 2-hydroxyethyl methacrylate (HEMA) ,methyl methacrylate (MMA), N-vmyl pyrrohdone (NVP), n-butyl methacrylate (n-BMA) are copolymerized with amine acrylates containing number of nitrogen varying from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 4-0 8% , TEMED 0 4-0 8% ) m an aqueous solution The formulation consisted of variable percentage of HEMA/MMA/NVP/n-BMA (52-87%), QAA (0, 5, 20, 40%), distilled water (8-10%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration Still another embodiment of the invention where quaternisation after copolymerisation of amine acrylate by suspension polymerization (beads form) is carried out in which 20-30% two vinylic monomers 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), n-butyl methacrylate (n-BMA) and 40-60% of amine acrylate containing number of nitrogen varying from 1 to 12 (1,2,6) are copolymerised usmg suspension polymerization technique Azobisisobutyromtrile (AIBN)/benzoyl peroxide (BPO) (0 4-0 8% of total monomer) as an initiator and sodium polyacrylate (0 8-2 0 % of total monomer) as suspending agent Water is taken as solvent and the ratio of total monomer and water is 1 3 to 1 5 The reaction temperature is mamtamed at 60-80° C at 180-220 rpm for 3-5hrs The beads obtained are quatermsed using alkyl iodide (hydrocarbon chain length varymg C-l to C-15) (1-1 4eq/amine) The copolymer synthesized in tube form and sharp, small holes are made in the tube or if beads are used then they are filled in polypropylene tube with fine holes at regular interval and is then stirred for 3-5 minutes if the initial bacterial count is 100 cfu/100ml and was then plated and viable cells are counted using colony counter Quaternary amine acrylate can be used for various applications they can be coated onto various medical devices like sutures and catheters because of the presence of reactive functional groups at the end of synthesized acrylate cham using plasma/ gamma radiations They can also be mcorporated into dental/bone cement formulation 5-15% of methylmethacrylate (MMA) monomer in 12 ratio of monomer and PMMA powder generally used for bone cement formulation if replaced by quaternary amine acrylate provides a composition which shows no cytotoxicity and antimicrobial property The polymerization is carried out by redox initiator system using 0 6-0 9% of benzoyl peroxide and 0 65-85% of dimethyl paratouhdine (DPMT) Examples The present invention is illustrated by the following examples, which are set forth to illustrate the present invention and are not to be construed as limiting thereof The synthesis of quaterruzed ammonium iodide monomer is planned m three steps m which the desired reactive acrylate was synthesized and arrunation is done using secondary amine (Michael's addition) followed by its quatermsation with desired alkyl iodide (hydrocarbon cham length varying C-l to C-15) Example 1 Preparation of reactive acrylate monomer Various reactive di, tri, tetra terminal double bonded functional monomers are synthesized by esterification of 1 05 mole of di,tn,tetra functional alcohol with excess of acrylic acid and methacryhc acid using dean-stark apparatus Acid catalyst like sulphuric acid /methane sulphonic acid (1 4%) as catalyst, hydroquinone and derivatives (015%) as inhibitor and 22% solvent ( toulene ,cyclohexane, xylene) was used The amount of catalyst, inhibitor and solvent are taken w/w percentage of total monomer The reaction is carried out in heavy paraffin oil bath at 95° C at 200 rpm for 5 hrs The reaction was stopped when calculated amount of water is collected m the arm of dean stark apparatus The acid value of the obtained product is determined by titrating with ale KOH which is standardized using oxalic acid and cresol red as mdicator The product is first given wash with chilled 50 ml distill water and then depending on the acid value ,the product is washed several times by slowly addmg 5% NaHCO3 solution with continuous stirring to remove the un-reacted acid and to remove the inhibitor The process is repeated till the acid value reached below 1 0 Finally the product obtamed is washed with 50ml of distilled water The product obtamed is vacuum distilled at 95° C with 110 ppm of inhibitor and stored at 4° C Example 2 Preparation of amine acrylate 1 03 mole of secondary amine (piperazme, diethyl amine,dimethyl amine) and excess of synthesized reactive diacrylate /triacrylate (3 02 moles) and 28 % (w/w of total monomer) methanol is taken as solvent The reaction is carried out at 32°C for 6hrs at 220 rpm usmg mechanical stirrer The product obtamed is kept at 30°C m vaccum oven till residual solvent is evaporated and stored at 4°C Example 3 Preparation of quaternised amine acrylate Quatermsation of synthesized amine acrylates containing number of nitrogen varying from 1-12 (1,2, 6,12 ) is carried out usmg alkyl iodide (hydrocarbon cham length varying C-l to C-15) (1 2eq/amine) The reaction is refluxed for 2-3 hrs Figures 1-3 shows the FTIR spectra, structural formula and 1H NMR spectra of Quaternised EGDMA-piperazme ammonium iodide respectively Example 4 Preparation of QAA copolymer by bulk polymerization (tube form) for water disinfection 2-hydroxyethyl methacrylate (HEMA) is copolymenzed with QAA containing number of nitrogen varying from 1-12 (1, 2, 6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 65%, TEMED 0 65%) in an aqueous solution The formulation consisted of variable percentage of HEMA (52-87%), QAA (0, 5, 20, 40%), distilled water (8%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration The reaction mixture is then poured in a polypropylene mould with an inner diameter of 5mm Within time span of 5-20 minute a polymeric tube is obtamed and it is immersed into distilled water at room temperature Figure 4 reveals the HEMA-QAA co-polymer tube formed by redox bulk polymerization Example 5 Preparation of quatemtsation after copolymensation of amine acrylate by bulk polymerization (tube form) for water disinfection 2-hydroxyethyl methacrylate (HEMA) was copolymenzed with amine acrylates containing number of nitrogen varymg from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 65%, TEMED 0 65%) m an aqueous solution The formulation consisted of variable percentage of HEMA (42-87%), amine acrylate (0,5,20,40,50%), distilled water (8%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration The reaction mixture is then poured in a polypropylene mould with an inner diameter of 5mm Within time span of 5-20 minute a polymeric tube is obtamed and it is immersed into distilled water at room temperature The copolymer obtained is then quaterrused using alkyl iodide (hydrocarbon cham length varymg C-l to C-15) (1 3eq/amine) The reaction is refluxed for 2-3 hrs Figure 5 the pattern of cross linking of the said co-polymer FTIR spectra and structural formula are shown m the Figures 6 and 7 respectively Studies were carried out to assess the role of QAA concentration on thermal stability and contact angle values of co-polymer and pore size of the same The results are shown m 8 and 9 respectively Example 6 Preparation of quaternisation after co-polymerisation of amine acrylate by suspension polymerization (beads form) for water disinfection 26% of 2-hydroxyethyl methacrylate (HEMA), 26% of methyl methacrylate and 48% of amine acrylate containing number of nitrogen varymg from lto 12 (1,2,6) are copolymenzed usmg suspension polymerization technique Azo-bisisobutyronitrile (AIBN), benzoyl peroxide (BPO) (0 65% of total monomer) as an initiator and sodium poly aery late (13% of total monomer) as suspending agent Water is taken as solvent and the ratio of total monomer and water is 13 upto 15 The reaction temperature is maintained at 70° C and stirred at 220 rpm for 3hrs The beads obtamed are washed several times with boiling distilled water to get rid of residual monomer if left The beads obtamed are then quaterrused usmg alkyl iodide (hydrocarbon cham length varymg C-l to C-15) (1 2eq/amine) The reaction is refluxed for 2-3 hrs Agam the washing is done with boiling distilled water to remove loosely bound alkyl iodide on the surface of copolymer A closer scrutiny of Figure 10 reveals that the co-polymer of the present invention does not release lodme in water, while other conventional anh-mirobial filters release iodine in water Example 7 Methods for using quaternary amine acrylate for water disinfection (for a glass of water) The copolymer synthesized in tube form (weighing 20g) and sharp, small holes are made in the tube or if beads (20 g) are used then they were filled in polypropylene tube with fine holes at regular mterval and is then stirred for few mmutes if the initial bacterial count is 100 cfu/l00ml of Ecoh and for different copolymers containing variable amount of nitrogen content are used and after the treatment with different copolymers the aliquot of treated water is taken and plated onto the luna agar plate and incubated at 37°C for overnight and the contact time of killing against various microorganisms is noted 2x10s nos of viable cells per ml of E coll was filled in synthesized antimicrobial polymeric tube containing varymg cone of QAA and contact killing property of polymer was studied at different time interval by colony count method Figure 12 shows that the polymer of the present invention is very effective against E coli Within less than 10 mmutes bacterial count goes down to zero Example 8 Methods for using Quaternary amine acrylate in medical application Quaternary amine acrylate can be used for various applications they can be coated onto various medical devices like sutures and catheters because of the presence of reactive functional groups at the end of synthesized acrylate chain usmg plasma/gamma radiations They can also be incorporated mto dental/bone cement formulation 15% of methylmethacrylate (MMA) monomer in 1 2 ratio of monomer and PMMA powder generally used for bone cement formulation if replaced by quaternary amine acrylate provides a composition which shows no cytotoxicity and antimicrobial property The polymerization is carried out by redox initiator system usmg 0 8% of benzoyl peroxide and 0 85% of dimethyl paratoulidine (DPMT) Example 9 Interpretation of the results (Table Removed) In all the system 20 g of copolymer is taken to treat a glass of water, which is contaminated, with the bacterial count of 100 cfu/100ml and the contact time of killing is noted and after the treatment no viable cells are present m the treated water Example 10 QUATERNARY AMINE ACRYLATE (QAA) MONOMER SYNTHESIS The monomer Synthesis was carried out m two steps Step I Animation of diacrylate using piperazine (Structure Removed) Step II- Quaternization of amine acrylate using n-alkyl iodide using C-8 (Structure Removed) Quaternized EGDMA-piperazine octyl ammonium iodide (QAA) 3 moles of ethylene glycol dimethacrylate was reacted with 1 mole of piperazine in the presence of methanol at 200 rpm at a temperature condition of 30-35 ° C for 6-8 hrs to obtain piperazine bis (ethylene glycol dimethacrylate) QAA This QAA was reacted with hahdes and subsequently quatermzed at 200 rpm, at temperature conditions 85-90 ° C for 2-3 hrs Advantages The following are the advantageous features associated with quaternary amine acrylate based copolymer used for wide number of applications 1 Requires short contact time to kill microbes 2 No release of bioactive agents 3 Non-brittle and flexible polymeric matrix 4 Hydrophihc and porous matrix 5 Imparts no residual odor, undesirable taste when used for water disinfection 6 Bactericidal effect with broad spectrum antimicrobial activities 7 Easily integrated mto conventional equipments and devices 8 Effective over wide range of microorganisms 9 Long shelf life 10 Safe to handle, chemically stable 11 No sophisticated instrumentation or controls required We claim, 1. A Quaternary Amine Aerylate Copolymer of Formula 1, having the structure, (Formula Removed) Formula 1 wherein A,Z are acrylate monomer in m and n proportions, wherein B is a cyclic or acyclic amine, wherein R is a hydrocarbon and, wherein X is a halide. wherein m is in a range of 35-45% of the Quaternary Amine Acrylate Copolymer. 2. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1 wherein the acrylate A is selected from a di or tri acrylate. 3. A Quaternary Amine Acrylate Copolymer, as claimed in claim 2, wherein the di-and tri- acrylate is selected from a group comprising ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate. 4. A Quaternary Amine Acrylate Copolymer of, as claimed in Claim 1, wherein the Z is a Vinyl Monomer. 5. A Quaternary Amine Acrylate Copolymer , as claimed in claim 1, wherein the vinyl monomer is selected from a group comprising methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA). 6. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1, wherein the cyclic amine is selected from a group comprising of piperazine. 7. A Quaternary Amine Acrylate Copolymer ,as claimed in claim 6, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dirnethylamine,hexylamine and diethyl amine. 8. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1, wherein the hydrocarbon is selected from a group comprising of carbon atoms of number 1 to 15. 9. A Quaternary Amine Acrylate Copolymer (QAA-CP), as claimed in claim 1, wherein the halide is selected from a group comprising of iodine, bromide and chloride. 10. A process for preparing Quaternized amine acrylate copolymers represented by Formula 1, the said process comprising the steps of, Formula 1 (Formula Removed) wherein A,Z are acrylate monomer in m and n proportions, wherein B is a cyclic or acyclic amine, wherein R is a hydrocarbon and, wherein X is a halide. wherein m is in a range of 35-45% of the Quaternary Amine Acrylate Copolymer. a. esterifying 0.5-2 moles of diols or triols with excess substituted or substituted acrylic acid in the presence of acid catalyst and inhibitors, in a solvent, at a temperature in the range of 80-100 deg C to obtain an acrylic monomer with at least four functionality. b. reacting 0.5-1.5 moles of secondary amines with acrylate monomer of step (a) with 1.5-3.5 moles to obtain amine acrylate with functionality in the range of 4-16 with Nitrogen content in the range of 1-12, in presence of 20-30 % (w/w) alcohol at a temperature of 20-40 ° C for 6-10 hrs. c. quaternizing the amine acrylate of step (b) with alkyl halide hydrocarbon chain of C1-C15 to obtain Quaternized Amine Acrylates,and d. polymerizing the QAA of step (c) in the range of 10-60% with double bond containing functional vinylic monomers using a initiator, optionally along with a suspending agent, to obtain QAA-CP. 11. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10 wherein the acrylate A is selected from a group comprising of di or tri acrylate. 12. A process for preparing a Quaternary Amine Acrylate Copolymer ,as claimed in claim 10, wherein the di- and tri- acrylate is selected from a group comprising of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate. 13. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the cyclic amine is piperazine. 14. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimethylamine, hexylamine and diethyl amine. 15. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the hydrocarbon group is selected from selected from a group comprising of carbon atoms of number 1 to 15. 16. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the halide is selected from a group comprising of iodine, bromide and chloride. 17. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the catalyst in step(a) is selected from a group comprising of sulphuric acid and methane sulphonic acid in the range of 1-2 %. 18. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the inhibitor in step (d) is selected from a group comprising of hydroquinone and other derivatives in the range of 0.15-0.35%. 19. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the solvent in step (a) is selected from a group comprising of toluene, cyclohexane, benzene and xylene. 20. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the initiator in step (d) is selected from a group comprising of redox initiator and peroxide initiator. 21. A process for preparing a Quaternary Amine Acrylate Copolymer ,as claimed in claim 18, wherein the redox initiator is a formulation of Ammonium Persulfate (APS) in the range 0.4-0.8% and N,N,N',N'-tetramethylenediamine (TEMED) in the range 0.4-0.8%. 22. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 20, wherein the peroxide initiator is selected from a group comprising of Azobisisobtyronitrile (AIBN), benzoyl peroxide (BPO) and dimethyl paratoluidine (DPMT). 23. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the suspending agent is selected from a group comprising of sodium polyacrylate in the range of 0.8-2.0% of total monomer used. 24. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the functional vinylic monomer Z is selected from a group comprising of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), styrene and n-butyl methacrylate (n-BMA). 25. A pharmaceutical antimicrobial composition, said composition comprising of a Quaternary Amine Acrylate Copolymer of Formula 1 Formula 1 (Formula Removed) wherein A,Z are acrylate monomer in m and n proportions, wherein B is a cyclic or acyclic amine, wherein R is a hydrocarbon and, wherein X is a halide. wherein m is in a range of 35%-45% of the Quaternary Amine acrylate Copolymer. and a pharmaceutically acceptable substance and optionally the said composition being coated onto a medical device such as herein described, wherein Quaternized Amine Acrylate Copolymer is present in the said pharmaceutical acceptable material in the ratio of 1:6. 26. A pharmaceutical antimicrobial composition of Formula 1 as claimed in claim 25, wherein the acrylate is selected from a selected from a group comprising of di- or tri- acrylate. 27. A pharmaceutical antimicrobial composition as claimed in claim 26, wherein the di- and tri- acrylate is selected from a group comprising of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate. 28. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the cyclic amine is selected from a group comprising of piperazine. 29. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimemylarnine and diethyl amine. 30. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the hydrocarbon group is selected from a group comprising of carbon atoms of number 1 to 15. 31. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the halide is selected from a group comprising of iodine, bromide and chloride. 32. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the pharmaceutical acceptable substance is selected from a group comprising of dental cement and bone cement formulation. 33. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the medical device is selected from a group comprising of sutures and catheters. 34. A method of disinfecting water from microbes, said method comprising contacting Quaternary Amine Acrylate Copolymer of Claim 1 with water for a period in the range of 2-10 minutes. 35. A Quaternary Amine Acrylate Copolymer, a process of preparation thereof, a pharmaceutical antimicrobial composition, and a method for disinfecting water, substantially as herein described and illustrated.

Full Text

Field of the invention
The present invention relates to quaternary amine acrylate based contact killing antimicrobial copolymers with broad-spectrum antimicrobial activity without releasing any bioactive agents and can be used for wide number of applications
Background and prior art
Disinfection of drinking water continues to be a challenging problem and more so in a developing and over-populated country like India, where majority of population resides m rural and slum areas and do not have access to safe potable drinking water The efficacy of many of the disinfection systems is still based on actual release of bioactive agents like iodine, chlorine, silver etc in drinking water Physiological effects due to long-term ingestion of bioactive agents, even though at ppm levels, could be an issue Hence, feasibility of incorporating the bioactive agents permanently in the system for killing bacteria on contact without releasing bioactive agents in water will be the best approach There is a keen interest m materials capable of killing harmful microorganisms Such materials could be used to coat the surfaces of common objects touched by people in everyday life (eg door knobs, children's toys, computer keyboards) to render them antiseptic and unable to transmit bacterial infections Hence materials can be impregnated with antimicrobial agents such as antibiotics, quaternary ammonium compounds, silver ions or lodme that are released gradually into the surrounding solution over time and kill microorganisms therem Although these strategies have verified in aqueous solution containing bacteria, they would not expected to be effective against airborne bacteria in the absence of a liquid medium, this situation is especially true for release - based materials which are also liable to become impotent when the leaching antibacterial is exhausted
Quaternary amine acrylate (QAA) have a large variety of usage areas from cosmetics to clothes softeners but especially they are known to be good disinfectants Quaternary amine acrylate's antibacterial ability is resulted from their amphillic structure and surfactant property, which was first reported by Dogmak The antimicrobial action of the
AA is based on theu damaging surfactant like interaction with the membrane (cytoplasmic) of bacteria resulting the loss of the membrane permeability At convenient concentrations, they can cause cell leakage and the death of the cell Quaternary structures are effective on both gram positive and gram-negative bacteria, but they have a stronger antibacterial effect on positive once, since gram negatives have an extra protective membrane Quaternary compounds are widely used because of their non-toxic and non-lrritant property QAA are not affected from the protein concentration of the environment and don't loose their affectivity on bacteria over the course of tune The effectiveness of the agent against microorganisms is directly related to its area of contact with the microorganism's medium
A new concept of contact type of disinfection by iodine based resm formed by adsorption of iodine on a strong alkaline amon-exchange resin has been patented by Liwang He claimed that lodme resin could remove and kill more than 99 9% of E coh, S aureus and C albicans in water at 25°C and pH 6 5 Another Quaternary ammonium exchange resm binding tri-iodide or penta iodide was reported for their ability to disinfect water containing L pneumophile Results mdicated that the lodmated resms are stable demand release disinfectants There was no residual iodine detected by amperometric titration When an aqueous suspension containing 2 7xl09 cfu of L pneumophile per ml was passed through tn-iodinated resins less than 0 004% were recovered No viable cells were detected by direct platmg from a suspension of 2 3 X109 cfu per ml eluted through penta-lodmated resins (>99 999% reduction m viability) but, bactericidal active agents concentration decreases with time Another researcher Ranuci et al synthesized new polymeric disulphides containing t-amino groups m their main chain They were prepared by polyoxidauon of 3,6-dimethyl-3,6-diazoctane-l,8 dithiol and 3,10-dimethyl 3,10-diazadodecane-l,12-dinol respectively They were then quaterrused with methyl iodide and benzyl bromide and the resulting quaternary ammonium polymers were preliminary tested for antimicrobial activity against E coh, P aeruginosa and S aureus Groups like thiocyanates have also been tried to covalently immobilized on a biomaterial surface by Nirmala etal in presence of a phase transfer catalyst in aqueous media leadmg
to the nucleophilic substitution of chlorine by thiocyanates on the PVC surface It was found that the thiocyanate groups have bactericidal properties and remains effective against S aureus and S epidermis even after immobilization on PVC surface Similarly Tiller etal synthesized poly(4-vinyl-N-alkylpyridiruum bromide) which was covalently attached to glass slides to create a surface that kills airborne bacteria on contact The antibacterial properties were assessed by spraying aqueous suspension of bacterial cells on the surface followed by air drying and counting the number of cells remaining viable cells Recently Lee etal reported a permanent, non-leaching antibacterial surface which they have grown directly on the surfaces of glass and paper using atom transfer radical polymerization (ATRP)
But above mentioned modified surface were found to loose properties with time because of less extent of quatermsation and also due to surface erosion
The prior arts WO9940791, US6264936, US6126931, US5575917, WO03064412, US2004062744, WO0185813, US6039940, US6448305 and WO0228927 describe contact killing polymer, but there polymers have the limitation of surface modification and they require higher contact time to kill bacteria completely and the surface loose its activity because of erosion of surface active polymeric layer
Object of the invention
The primary objective of the present invention is to develop a polymer with a antimicrobial property
Another object of the invention is to develop quaternary amine acrylate based non-brittle hydrophilic and flexible copolymeric systems with broad spectrum of antimicrobial activities by contact killing in few minutes without releasing any bioactive agents
Another object of the invention is to develop hydrophilic, porous, non-brittle and flexible polymeric matrix, which is easy to handle and has long shelf life
Yet another object of the present invention is to provide material, which gets easily integrated into conventional equipments and devices
Still another object of the present invention is to obtain the product, which imparts no residual odor and undesirable taste when used for water disinfection application
Further object of the present invention is to develop a system where no sophisticated instrumentation or control is required while handling it
Summary of the invention
The present invention relates to a quaternary amine acrylate based contact killing antimicrobial copolymers with broad-spectrum antimicrobial activity without releasmg any bioactive agents The present invention also relates to method of using for water disinfection and in medical applications by coating them onto biomedical devices like sutures, catheters, mcorporation mto dental/bone cement formulations to impart permanent contact killing antimicrobial properties to them to prevent microbial infection
Brief description of figures
Figure 1 FTIR Spectra of Quatermsed EGDMA-piperazme ammonium iodide
Figure 2 Structural formula Quatermsed EGDMA-piperazine ammonium iodide
Figure 3 1H-NMR Spectra of Quatermsed EGDMA-piperazine ammonium iodide
Figure 4 HEMA-QAA copolymer tube formed by redox bulk polymerization
Figure 5 Crossed-linked pattern of HEMA-QAA co-polymer
Figure 6 FTIR Spectra of poly (HEMA-co-Q AA)
Figure 7 Structural formula of poly (HEMA-co-QAA)
Figure 8 Effect of QAA concentration on thermal stability & contact angle values of co
polymer
Figure 9 Effect of QAA concentration on pore size of co-polymer
Figure 10 Comparison of iodine release from various polymeric systems
Figure 11 Anti-microbial activity of QAA co-polymers by zone inhibition against E coh
Figure 12 Effect of QAA concentration against E coh
Figure 13 Anti-microbial activity of QAA co-polymer* (20g) filled in polyester cloth
Detailed Description of the Invention
Accordingly, the present invention relates to a Quaternary Amine Acrylate Copolymer of
Formula 1, having the structure,
(Structure Removed)
wherein A is A,Z are acrylate monomer in m and n proportions,
wherein B is a cyclic or acyclic amine,
wherein R is a hydrocarbon and,
wherein X is a halide An embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1 wherein the acrylate A is selected from a di or tri acrylate
Another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the di- and tri- acrylate A is selected from a group compnsmg ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate
Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprising vmyl monomers
Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the vinyl monomer is selected from a group compnsmg methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA)

Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the cyclic amine is selected from a group comprising of piperazrne
Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the hydrocarbon is selected from a group compnsmg of CI to C15
Yet another embodiment of the present invention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherein the halide is selected from a group comprising of iodine, bromide and chloride
A further embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1,
(Formula Removed)
Formula 1
the said process comprising the steps of,
a) esterifying 0 5-2 moles of diols or triols with excess of substituted or unsubstituted acrylic or methacryhc acid in the presence of acid catalyst and inhibitors, in a solvent, at a temperature m the range of 80-100 deg C to obtain an acrylic monomer with at least four functionality
b) reacting 0 5-1 5 moles of secondary amines with acrylate monomer of step (a) with 1 5-3 5 moles to obtain amine acrylate with functionality in the range of 4-16 with Nitrogen content in the range of 1-12, in presence of 20-30 % (w/w) alcohol at a temperature of 20-40 deg C for 6-10 hrs
c) quaternizrng the amine acrylate of step (b) with alkyl hakde hydrocarbon cham of C1-C15 to obtam Quaterruzed Amine Acrylates,and
d) polymerizing the Quaterruzed AA of step ( c) m the range of 10-60% with double bond containing functional vinylic monomers using a initiator, optionally along with a suspending agent, to obtain Quaterruzed Amine Acrylate-Copolymer
Another embodiment of the present mvention relates to the process for preparing quaterruzed amine acrylate copolymers represented by the Formula lwherern the acrylate A is selected from a group compnsmg of di or tri acrylate
Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula 1, wherem the di-and tri- acrylate A is selected from a group compnsmg of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate
Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprising vinyl monomers
Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the vmyl monomer is selected from a group compnsmg methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA)
Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula 1, wherem the cyclic amine is selected from a group comprising of piperazine
Yet another embodiment of the present mvention relates to the process for preparmg Quaterruzed amine acrylate copolymers represented by the Formula l,wherern the acyclic amine is selected from a group comprising of ethylene diamine, dimethylamme, hexylamine and diethyl amine
Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the hydrocarbon group is selected from selected from a group comprising of CI to C15
Yet another embodiment of the present mvention relates to the process for preparing Quatermzed amine acrylate copolymers represented by the Formula 1, wherein the halide is selected from a group compnsmg of iodine, bromide and chloride
Yet another embodiment of the present mvention relates to the process for preparing Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the catalyst m step(a) is selected from a group comprising of sulphuric acid and methane sulphomc acid (1-2)%
Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the inhibitor in step (d) is selected from a group comprising of hydroqumone and other derivatives (0 15-0 35%)
Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the solvent m step(a) is selected from a group comprising of toluene, cyclohexane, benzene and xylene
Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherein the initiator m step (d) is selected from a group compnsmg of redox initiator and peroxide initiator
Yet another embodiment of the present mvention relates to the process for preparmg Quatermzed amine acrylate copolymers represented by the Formula 1, wherem the redox
initiator is a formulation of Ammonium Persulfate (APS) in the range of 0 4-0 8% and N,N,N ,N'-tetramethylene diamine (TEMED) in the range of 0 4-0 8%
Yet another embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1, wherem the peroxide initiator is selected from a group comprising of Azobisisobtyromtrile (AIBN), benzoyl peroxide (BPO) and dimethyl paratoluidrne (DPMT)
Yet another embodiment of the present invention relates to the process for preparing Quaternized amine acrylate copolymers represented by the Formula 1, wherein the suspending agent is selected from a group compnsmg of sodium polyacrylate (0 8-2 0%) of total monomer used
Yet another embodiment of the present invention relates to the process for preparmg Quaternized amine acrylate copolymers represented by the Formula 1, wherem the functional vinyhc monomer Z is selected from a group compnsmg of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), styrene and n-butyl methacrylate (n-BMA)
A further embodiment of the present invention relates to a pharmaceutical antimicrobial composition, said composition compnsmg of a Quaternary Amine Acrylate Copolymer of Formula 1 and a pharmaceutically acceptable substance and optionally the said composition bemg coated onto a medical device such as herein described, wherem Quaternized Amine Acrylate Copolymer is present in the said pharmaceutical acceptable material m the ratio of 1 6 _
(Formula Removed)
Formula 1
Another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the acrylate A is selected from a selected from a group comprismg of di- or tri- acrylate
Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the di- and tri- acrylate is selected from a group comprismg of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate
Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the Z is selected from a group comprismg vmyl monomers
Yet another embodiment of the present mvention relates to Quaternary Amine Acrylate Copolymer of Formula 1, wherem the vmyl monomer is selected from a group comprismg methyl methacrylate (MMA), N-vmyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA)
Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the cyclic amine is selected from a group comprismg of piperazme
Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimethylanune and diethyl amine
Yet another embodiment of the present invention relates to a pharmaceutical antimicrobial composition of Formula 1, wherem the hydrocarbon group is selected from a group comprising carbon atoms of number 1 to 15
Yet another embodiment of the present mvention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the hahde is selected from a group compnsmg of iodine, bromide and chloride
Yet another embodiment of the present invention relates to a pharmaceutical antimicrobial composition of Formula 1, wherein the pharmaceutical acceptable substance is selected from a group compnsmg of dental cement and bone cement formulation
Yet another embodiment of the present mvention relates to a pharmaceutical
antimicrobial composition of Formula 1, wherem the medical device is selected from a
group compnsmg of sutures and catheters
Yet another embodiment of the present invention relates to a pharmaceutical
antimicrobial composition of Formula 1, with water for a period in the range of 2-10
minutes
In accordance with the object of the mvention, the present mvention provides a quaternary amine acrylate based non- brittle co-polymeric system with broad spectrum antimicrobial activity by contact killing in few minutes without releasing bioactive agents has been developed In addition to this, they are double bond containing reactive monomers and by usmg chemical initiator or plasma radiation or gamma radiation they can be coated onto various articles mtroducmg long term and stable antimicrobial properties These quaternary amine acrylate polymers have wide range of applications as water disinfectant for potable drinking water, m dental/bone cement formulations and polymerized onto various biomedical devices to impart permanent antimicrobial properties
In an embodiment of the present mvention required synthesis of quaterruzed ammonium iodide monomer which is planned m three steps m which the desired reactive acrylate is synthesized and arrunauon is done usmg secondary amine (Michael's addition) followed by its quatermsation with desired alkyl iodide (hydrocarbon chain length varying C-l to C-15)
In an embodiment of the present invention provides a process of synthesis of reactive acrylate monomer, in which various reactive di, tri, tetra terminal double bonded functional monomers are synthesized by esterification of 0 9-1 2 mole of di,tn,tetra functional alcohol with excess of acrylic acid and methacrylic acid using dean-stark apparatus
In still another embodiment acid catalyst like sulphuric acid, methane sulphomc acid (1-2%) as catalyst, hydroqumone and other derivatives (0 15-0 35%) as inhibitor and 15-35% solvent (toulene, cyclohexane, xylene) is used The amount of catalyst, inhibitor and solvent are taken w/w percentage of total monomer The reaction is carried out m heavy paraffm oil bath at 75-105° C at 180-220 rpm for 4-7 hrs The reaction is stopped when calculated amount of water is collected in the arm of dean stark apparatus
In yet another embodiment of the invention provides the synthesis of amine acrylate 1-2 mole of secondary amine (piperazine, diethyl amine/dimethyl amine) and excess of synthesized reactive diacrylate /triacrylate (2 9-3 2 moles) and 25-30% (w/w of total monomer) methanol /chloroform/ethanol are taken as solvent The reaction is carried out at 25-35°C for 5-8 hrs at 180-200 rpm using mechanical stirrer The product obtamed is kept at 30°C in vacuum oven till residual solvent was evaporated and stored at 4°C To introduce more nitrogen content in the oligomer cham 1-2 mole of triacrylate was reacted with 2-4 moles of piperazine/ diethyl amine/dimethyl amine then obtained product (1-2 mole) was reacted with 3-4 mole of diacrylate under the same condition as mentioned before To further increase the number of nitrogen instead of reacting with diacrylate it is further reacted with excess of triacrylate and then amrnated with secondary amine
In still yet another embodiment of the invention the quaterrusation of amine acrylates containing number of nitrogen varying from 1-12 (1 ,2, 6, 12 ) is carried out using alkyl iodide (hydrocarbon cham length varying C-l to C-15) (1 0-1 4eq/amine) The reaction is refluxed for 2-3 hrs
Still another embodiment of the invention m which copolymerization of QAA by bulk polymerization (tube form) is carried out m which vinylic monomers like 2-hydroxyethyl methacrylate (HEMA) ,methyl methacrylate (MMA), N-vmyl pyrrohdone (NVP),n-butyl methacrylate (n-BMA) are copolymerized with QAA containing number of nitrogen varying from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 4-
0 8%, TEMED 0 4-0 8% ) in an aqueous solution The formulation consisted of variable
percentage of HEMA/MMA/NVP/n-BMA (52-87%), QAA (0,5,20,40%), distilled water
(10%) The APS and TEMED concentrations are expressed as weight percentages of total
monomer concentration
In another embodiment of the invention quaterrusation after copolymerisation of amine acrylate by bulk polymerization (tube form) is carried out in which vinylic monomers like 2-hydroxyethyl methacrylate (HEMA) ,methyl methacrylate (MMA), N-vmyl pyrrohdone (NVP), n-butyl methacrylate (n-BMA) are copolymerized with amine acrylates containing number of nitrogen varying from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 4-0 8% , TEMED 0 4-0 8% ) m an aqueous solution The formulation consisted of variable percentage of HEMA/MMA/NVP/n-BMA (52-87%), QAA (0, 5, 20, 40%), distilled water (8-10%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration Still another embodiment of the invention where quaternisation after copolymerisation of amine acrylate by suspension polymerization (beads form) is carried out in which 20-30% two vinylic monomers 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), n-butyl methacrylate (n-BMA) and 40-60% of amine acrylate containing number of nitrogen varying from 1 to 12 (1,2,6) are copolymerised usmg suspension polymerization technique Azobisisobutyromtrile (AIBN)/benzoyl peroxide (BPO) (0 4-0 8% of total monomer) as an initiator and sodium polyacrylate (0 8-2 0 % of total monomer) as suspending agent Water is taken as solvent and the ratio of total monomer and water is
1 3 to 1 5 The reaction temperature is mamtamed at 60-80° C at 180-220 rpm for 3-5hrs The
beads obtained are quatermsed using alkyl iodide (hydrocarbon chain length varymg C-l
to C-15) (1-1 4eq/amine)
The copolymer synthesized in tube form and sharp, small holes are made in the tube or if beads are used then they are filled in polypropylene tube with fine holes at regular interval and is then stirred for 3-5 minutes if the initial bacterial count is 100 cfu/100ml and was then plated and viable cells are counted using colony counter
Quaternary amine acrylate can be used for various applications they can be coated onto various medical devices like sutures and catheters because of the presence of reactive functional groups at the end of synthesized acrylate cham using plasma/ gamma radiations They can also be mcorporated into dental/bone cement formulation 5-15% of methylmethacrylate (MMA) monomer in 12 ratio of monomer and PMMA powder generally used for bone cement formulation if replaced by quaternary amine acrylate provides a composition which shows no cytotoxicity and antimicrobial property The polymerization is carried out by redox initiator system using 0 6-0 9% of benzoyl peroxide and 0 65-85% of dimethyl paratouhdine (DPMT)
Examples
The present invention is illustrated by the following examples, which are set forth to illustrate the present invention and are not to be construed as limiting thereof
The synthesis of quaterruzed ammonium iodide monomer is planned m three steps m which the desired reactive acrylate was synthesized and arrunation is done using secondary amine (Michael's addition) followed by its quatermsation with desired alkyl iodide (hydrocarbon cham length varying C-l to C-15)
Example 1
Preparation of reactive acrylate monomer
Various reactive di, tri, tetra terminal double bonded functional monomers are synthesized by esterification of 1 05 mole of di,tn,tetra functional alcohol with excess of acrylic acid and methacryhc acid using dean-stark apparatus Acid catalyst like sulphuric acid /methane sulphonic acid (1 4%) as catalyst, hydroquinone and derivatives (015%) as inhibitor and 22% solvent ( toulene ,cyclohexane, xylene) was used The amount of
catalyst, inhibitor and solvent are taken w/w percentage of total monomer The reaction is carried out in heavy paraffin oil bath at 95° C at 200 rpm for 5 hrs The reaction was stopped when calculated amount of water is collected m the arm of dean stark apparatus The acid value of the obtained product is determined by titrating with ale KOH which is standardized using oxalic acid and cresol red as mdicator The product is first given wash with chilled 50 ml distill water and then depending on the acid value ,the product is washed several times by slowly addmg 5% NaHCO3 solution with continuous stirring to remove the un-reacted acid and to remove the inhibitor The process is repeated till the acid value reached below 1 0 Finally the product obtamed is washed with 50ml of distilled water The product obtamed is vacuum distilled at 95° C with 110 ppm of inhibitor and stored at 4° C
Example 2
Preparation of amine acrylate
1 03 mole of secondary amine (piperazme, diethyl amine,dimethyl amine) and excess of synthesized reactive diacrylate /triacrylate (3 02 moles) and 28 % (w/w of total monomer) methanol is taken as solvent The reaction is carried out at 32°C for 6hrs at 220 rpm usmg mechanical stirrer The product obtamed is kept at 30°C m vaccum oven till residual solvent is evaporated and stored at 4°C
Example 3
Preparation of quaternised amine acrylate
Quatermsation of synthesized amine acrylates containing number of nitrogen varying from 1-12 (1,2, 6,12 ) is carried out usmg alkyl iodide (hydrocarbon cham length varying C-l to C-15) (1 2eq/amine) The reaction is refluxed for 2-3 hrs Figures 1-3 shows the FTIR spectra, structural formula and 1H NMR spectra of Quaternised EGDMA-piperazme ammonium iodide respectively
Example 4
Preparation of QAA copolymer by bulk polymerization (tube form) for water disinfection
2-hydroxyethyl methacrylate (HEMA) is copolymenzed with QAA containing number of nitrogen varying from 1-12 (1, 2, 6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 65%, TEMED 0 65%) in an aqueous solution The formulation consisted of variable percentage of HEMA (52-87%), QAA (0, 5, 20, 40%), distilled water (8%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration The reaction mixture is then poured in a polypropylene mould with an inner diameter of 5mm Within time span of 5-20 minute a polymeric tube is obtamed and it is immersed into distilled water at room temperature Figure 4 reveals the HEMA-QAA co-polymer tube formed by redox bulk polymerization
Example 5
Preparation of quatemtsation after copolymensation of amine acrylate by bulk
polymerization (tube form) for water disinfection
2-hydroxyethyl methacrylate (HEMA) was copolymenzed with amine acrylates containing number of nitrogen varymg from 1-12 (1,2,6, 9 combination of 6 and 12 N) with by a redox initiator (APS 0 65%, TEMED 0 65%) m an aqueous solution The formulation consisted of variable percentage of HEMA (42-87%), amine acrylate (0,5,20,40,50%), distilled water (8%) The APS and TEMED concentrations are expressed as weight percentages of total monomer concentration The reaction mixture is then poured in a polypropylene mould with an inner diameter of 5mm Within time span of 5-20 minute a polymeric tube is obtamed and it is immersed into distilled water at room temperature The copolymer obtained is then quaterrused using alkyl iodide (hydrocarbon cham length varymg C-l to C-15) (1 3eq/amine) The reaction is refluxed for 2-3 hrs Figure 5 the pattern of cross linking of the said co-polymer FTIR spectra and structural formula are shown m the Figures 6 and 7 respectively Studies were carried out to assess the role of QAA concentration on thermal stability and contact angle values of co-polymer and pore size of the same The results are shown m 8 and 9 respectively
Example 6
Preparation of quaternisation after co-polymerisation of amine acrylate by suspension
polymerization (beads form) for water disinfection
26% of 2-hydroxyethyl methacrylate (HEMA), 26% of methyl methacrylate and 48% of amine acrylate containing number of nitrogen varymg from lto 12 (1,2,6) are copolymenzed usmg suspension polymerization technique Azo-bisisobutyronitrile (AIBN), benzoyl peroxide (BPO) (0 65% of total monomer) as an initiator and sodium poly aery late (13% of total monomer) as suspending agent Water is taken as solvent and the ratio of total monomer and water is 13 upto 15 The reaction temperature is maintained at 70° C and stirred at 220 rpm for 3hrs The beads obtamed are washed several times with boiling distilled water to get rid of residual monomer if left The beads obtamed are then quaterrused usmg alkyl iodide (hydrocarbon cham length varymg C-l to C-15) (1 2eq/amine) The reaction is refluxed for 2-3 hrs Agam the washing is done with boiling distilled water to remove loosely bound alkyl iodide on the surface of copolymer A closer scrutiny of Figure 10 reveals that the co-polymer of the present invention does not release lodme in water, while other conventional anh-mirobial filters release iodine in water
Example 7
Methods for using quaternary amine acrylate for water disinfection (for a glass of water) The copolymer synthesized in tube form (weighing 20g) and sharp, small holes are made in the tube or if beads (20 g) are used then they were filled in polypropylene tube with fine holes at regular mterval and is then stirred for few mmutes if the initial bacterial count is 100 cfu/l00ml of Ecoh and for different copolymers containing variable amount of nitrogen content are used and after the treatment with different copolymers the aliquot of treated water is taken and plated onto the luna agar plate and incubated at 37°C for overnight and the contact time of killing against various microorganisms is noted 2x10s nos of viable cells per ml of E coll was filled in synthesized antimicrobial polymeric tube containing varymg cone of QAA and contact killing property of polymer was studied at different time interval by colony count method Figure 12 shows that the polymer of the present invention is very effective against E coli Within less than 10 mmutes bacterial count goes down to zero
Example 8
Methods for using Quaternary amine acrylate in medical application
Quaternary amine acrylate can be used for various applications they can be coated onto various medical devices like sutures and catheters because of the presence of reactive functional groups at the end of synthesized acrylate chain usmg plasma/gamma radiations
They can also be incorporated mto dental/bone cement formulation 15% of methylmethacrylate (MMA) monomer in 1 2 ratio of monomer and PMMA powder generally used for bone cement formulation if replaced by quaternary amine acrylate provides a composition which shows no cytotoxicity and antimicrobial property The polymerization is carried out by redox initiator system usmg 0 8% of benzoyl peroxide and 0 85% of dimethyl paratoulidine (DPMT)
Example 9
Interpretation of the results
(Table Removed)
In all the system 20 g of copolymer is taken to treat a glass of water, which is contaminated, with the bacterial count of 100 cfu/100ml and the contact time of killing is noted and after the treatment no viable cells are present m the treated water
Example 10
QUATERNARY AMINE ACRYLATE (QAA) MONOMER SYNTHESIS
The monomer Synthesis was carried out m two steps
Step I Animation of diacrylate using piperazine
(Structure Removed)
Step II- Quaternization of amine acrylate using n-alkyl iodide using C-8
(Structure Removed)
Quaternized EGDMA-piperazine octyl ammonium iodide (QAA)
3 moles of ethylene glycol dimethacrylate was reacted with 1 mole of piperazine in the presence of methanol at 200 rpm at a temperature condition of 30-35 ° C for 6-8 hrs to obtain piperazine bis (ethylene glycol dimethacrylate) QAA This QAA was reacted with
hahdes and subsequently quatermzed at 200 rpm, at temperature conditions 85-90 ° C for 2-3 hrs
Advantages
The following are the advantageous features associated with quaternary amine acrylate based copolymer used for wide number of applications
1 Requires short contact time to kill microbes
2 No release of bioactive agents
3 Non-brittle and flexible polymeric matrix
4 Hydrophihc and porous matrix
5 Imparts no residual odor, undesirable taste when used for water disinfection
6 Bactericidal effect with broad spectrum antimicrobial activities
7 Easily integrated mto conventional equipments and devices
8 Effective over wide range of microorganisms
9 Long shelf life
10 Safe to handle, chemically stable
11 No sophisticated instrumentation or controls required

We claim,
1. A Quaternary Amine Aerylate Copolymer of Formula 1, having the structure,
(Formula Removed)
Formula 1
wherein A,Z are acrylate monomer in m and n proportions,
wherein B is a cyclic or acyclic amine,
wherein R is a hydrocarbon and,
wherein X is a halide.
wherein m is in a range of 35-45% of the Quaternary Amine Acrylate
Copolymer.
2. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1 wherein the acrylate A is selected from a di or tri acrylate.
3. A Quaternary Amine Acrylate Copolymer, as claimed in claim 2, wherein the di-and tri- acrylate is selected from a group comprising ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate.
4. A Quaternary Amine Acrylate Copolymer of, as claimed in Claim 1, wherein the Z
is a Vinyl Monomer.
5. A Quaternary Amine Acrylate Copolymer , as claimed in claim 1, wherein the vinyl monomer is selected from a group comprising methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), 2-hydroxyethyl methacrylate (HEMA), n-butyl methacrylate (n-BMA).
6. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1, wherein the cyclic amine is selected from a group comprising of piperazine.
7. A Quaternary Amine Acrylate Copolymer ,as claimed in claim 6, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dirnethylamine,hexylamine and diethyl amine.
8. A Quaternary Amine Acrylate Copolymer, as claimed in claim 1, wherein the hydrocarbon is selected from a group comprising of carbon atoms of number 1 to 15.
9. A Quaternary Amine Acrylate Copolymer (QAA-CP), as claimed in claim 1, wherein the halide is selected from a group comprising of iodine, bromide and chloride.
10. A process for preparing Quaternized amine acrylate copolymers represented by Formula 1, the said process comprising the steps of,
Formula 1
(Formula Removed)
wherein A,Z are acrylate monomer in m and n proportions, wherein B is a cyclic or acyclic amine, wherein R is a hydrocarbon and, wherein X is a halide.
wherein m is in a range of 35-45% of the Quaternary Amine Acrylate
Copolymer.
a. esterifying 0.5-2 moles of diols or triols with excess substituted or
substituted acrylic acid in the presence of acid catalyst and inhibitors, in a
solvent, at a temperature in the range of 80-100 deg C to obtain an acrylic
monomer with at least four functionality.
b. reacting 0.5-1.5 moles of secondary amines with acrylate monomer of step
(a) with 1.5-3.5 moles to obtain amine acrylate with functionality in the
range of 4-16 with Nitrogen content in the range of 1-12, in presence of 20-30 % (w/w) alcohol at a temperature of 20-40 ° C for 6-10 hrs.
c. quaternizing the amine acrylate of step (b) with alkyl halide hydrocarbon
chain of C1-C15 to obtain Quaternized Amine Acrylates,and
d. polymerizing the QAA of step (c) in the range of 10-60% with double bond
containing functional vinylic monomers using a initiator, optionally along
with a suspending agent, to obtain QAA-CP.
11. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in
claim 10 wherein the acrylate A is selected from a group comprising of di or tri
acrylate.
12. A process for preparing a Quaternary Amine Acrylate Copolymer ,as claimed in claim 10, wherein the di- and tri- acrylate is selected from a group comprising of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate.
13. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the cyclic amine is piperazine.
14. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimethylamine, hexylamine and diethyl amine.
15. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the hydrocarbon group is selected from selected from a group comprising of carbon atoms of number 1 to 15.
16. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the halide is selected from a group comprising of iodine, bromide and chloride.
17. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the catalyst in step(a) is selected from a group comprising of sulphuric acid and methane sulphonic acid in the range of 1-2 %.
18. A process for preparing a Quaternary Amine Acrylate Copolymer of Formula l,as claimed in claim 10, wherein the inhibitor in step (d) is selected from a group comprising of hydroquinone and other derivatives in the range of 0.15-0.35%.
19. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the solvent in step (a) is selected from a group comprising of toluene, cyclohexane, benzene and xylene.
20. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the initiator in step (d) is selected from a group comprising of redox initiator and peroxide initiator.
21. A process for preparing a Quaternary Amine Acrylate Copolymer ,as claimed in claim 18, wherein the redox initiator is a formulation of Ammonium Persulfate (APS) in the range 0.4-0.8% and N,N,N',N'-tetramethylenediamine (TEMED) in the range 0.4-0.8%.
22. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 20, wherein the peroxide initiator is selected from a group comprising of Azobisisobtyronitrile (AIBN), benzoyl peroxide (BPO) and dimethyl paratoluidine (DPMT).
23. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the suspending agent is selected from a group comprising of sodium polyacrylate in the range of 0.8-2.0% of total monomer used.
24. A process for preparing a Quaternary Amine Acrylate Copolymer, as claimed in claim 10, wherein the functional vinylic monomer Z is selected from a group comprising of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), N-vinyl pyrrolidine (NVP), styrene and n-butyl methacrylate (n-BMA).
25. A pharmaceutical antimicrobial composition, said composition comprising of a Quaternary Amine Acrylate Copolymer of Formula 1
Formula 1 (Formula Removed)
wherein A,Z are acrylate monomer in m and n proportions,
wherein B is a cyclic or acyclic amine,
wherein R is a hydrocarbon and,
wherein X is a halide.
wherein m is in a range of 35%-45% of the Quaternary Amine acrylate
Copolymer. and a pharmaceutically acceptable substance and optionally the said composition being coated onto a medical device such as herein described, wherein Quaternized Amine Acrylate Copolymer is present in the said pharmaceutical acceptable material in the ratio of 1:6.
26. A pharmaceutical antimicrobial composition of Formula 1 as claimed in claim 25, wherein the acrylate is selected from a selected from a group comprising of di- or tri- acrylate.
27. A pharmaceutical antimicrobial composition as claimed in claim 26, wherein the di- and tri- acrylate is selected from a group comprising of ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethyl propane triacrylate, dipropylene glycol diacrylate, pentaerythrytol tetracrylate.
28. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the cyclic amine is selected from a group comprising of piperazine.
29. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the acyclic amine is selected from a group comprising of ethylene diamine, dimemylarnine and diethyl amine.
30. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the hydrocarbon group is selected from a group comprising of carbon atoms of number 1 to 15.
31. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the halide is selected from a group comprising of iodine, bromide and chloride.
32. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the pharmaceutical acceptable substance is selected from a group comprising of dental cement and bone cement formulation.
33. A pharmaceutical antimicrobial composition as claimed in claim 25, wherein the medical device is selected from a group comprising of sutures and catheters.
34. A method of disinfecting water from microbes, said method comprising contacting Quaternary Amine Acrylate Copolymer of Claim 1 with water for a period in the range of 2-10 minutes.
35. A Quaternary Amine Acrylate Copolymer, a process of preparation thereof, a pharmaceutical antimicrobial composition, and a method for disinfecting water, substantially as herein described and illustrated.

Documents:

2525-del-2005-Abstract-(13-08-2014).pdf

2525-del-2005-abstract.pdf

2525-del-2005-Claims-(13-08-2014).pdf

2525-del-2005-claims.pdf

2525-del-2005-Correspondence Others-(10-09-2013).pdf

2525-del-2005-Correspondence Others-(13-08-2014).pdf

2525-del-2005-Correspondence Others-(19-08-2014).pdf

2525-del-2005-correspondence-others.pdf

2525-del-2005-description (complete).pdf

2525-del-2005-Drawings-(13-08-2014).pdf

2525-del-2005-drawings.pdf

2525-del-2005-form-1.pdf

2525-DEL-2005-Form-18.pdf

2525-del-2005-Form-2-(13-08-2014).pdf

2525-del-2005-form-2.pdf

2525-del-2005-form-3.pdf

2525-del-2005-form-5.pdf

2525-del-2005-GPA-(19-08-2014).pdf

Cover letter.pdf

Petition 137-for Form 1.pdf

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Patent Number

262864

Indian Patent Application Number

2525/DEL/2005

PG Journal Number

39/2014

Publication Date

26-Sep-2014

Grant Date

20-Sep-2014

Date of Filing

16-Sep-2005

Name of Patentee

INDIAN INSTITUTE OF TECHNOLOGY

Applicant Address

HAUZ KHAS, NEW DELHI-110016, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	SUPRIYA PUNYANI	CENTRE FOR BIOMEDICAL ENGINEERING, IIT, HAUZ KHAS, NEW DELHI-110016, INDIA.
2	HARPAL SINGH	CENTRE FOR BIOMEDICAL ENGINEERING, IIT, HAUZ KHAS, NEW DELHI-110016, INDIA.

PCT International Classification Number

C08F 226/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA