Cyanoacrylate-based Liquid Microbial Sealant Drape

US 20100l12036A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0112036 A1 Zhang et al. (43) Pub. Date: May 6, 2010 (54) CYANOACRYLATE-BASED LIQUID Related U.S. Application Data MICROBIAL SEALANT DRAPE (60) Provisional application No. 61/197,954, filed on Oct. (75) Inventors: Sheng Zhang, Lenoir, NC (US); 31’ 2008' Rafael R1111, H11dS011: NC (US) Publication Classification Correspondence Address: (51) Int‘ Cl‘ STRADLEY RONON STEVENS & YOUNG, LLP ‘WK 9/7” (200601) 30 VALLEY STREAM PARKWAY, GREAT VAL- ‘WK 31/215 (200601) LEY CORPORATE CENTER (52) U.S. Cl. ....................................... .. 424/443; 514/526 MALVERN, PA 19355-1481 (US) (57) ABSTRACT (73) Assignee: Adhezion Biomedical, LLC., The invention relates to methods of using compositions for Hudson, NC (U S) forming microbial sealant drapes. In particular, the invention relates to the use of compositions of combinations of (21) Appl. No.: 12/378,277 cyanoacrylates for the in situ formation of drapes that can be used in surgery to protect patients from surgical site infec- (22) Filed: Feb. 12, 2009 ti0I1S- Breakl i ne Opening channel ‘ '“’¢i',.u-v;"v*‘**’«2'(4"/ " ./4|-.. ‘ll’; 1 ._ S 0|!’ ‘V ' ' ponge ,|J M f . i I oam -A _ R . --I-—- A Liquid Sealant inside Reservoir Patent Application Publication May 6, 2010 US 2010/0112036 A1 FIGURE 1 Breakline Opening channel I -— ., -« .y - Sponge . foam Liquid Sealant inside Reservoir US 2010/0112036 A1 CYANOACRYLATE-BASED LIQUID MICROBIAL SEALANT DRAPE CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to the filing date of U.S. Provisional Application No. 61/197954 filed Oct. 31, 2008; the disclosure of which is herein incorporated by ref- erence. BACKGROUND OF THE INVENTION [0002] 1. Field of the invention [0003] The invention relates to methods of using composi- tions for forming microbial sealant drapes. In particular, the invention relates to the use of compositions of combinations of cyanoacrylates for the in situ formation of microbial seal- ant drapes that can be used in surgery to protect patients from surgical site infections. [0004] 2. Description of the PriorArt [0005] Surgical site infections (SSIs) can be classified into two categories: (1) incisional and (2) organ, which includes organs and spaces manipulated during an operation. Inci- sional infections are further divided into superficial infections and deep soft tissue-muscle and fascia infections. The Cen- ters for Disease Control and Prevention estimates that approximately 500,000 surgical site infections occur among an estimated 27 million surgical procedures conducted every year in the United States. Surgical site infections (SSI) are listed as the second most common cause of nosocomial infec- tion after urinary tract infections, which accounts for 40% of hospital-acquired infections among surgical patients. Twenty five to thirty-eight percent of all nosocomial infections among surgical patients are estimated to be incisional surgical site infections. SSI is a significant cause of surgical morbidity and mortality, occurring in 2-5% of patients having clean extra-abdominal operations and up to 20% of patients under- going intra-abdominal procedures. Patients with SSI are twice as likely to die, 60% more likely to be admitted to an Intensive Care Unit, and more than 5 times more likely to be readmitted to the hospital than patients who are not infected. Surgical site infections result in longer hospitalization and have large economic impact on patients and the health care system. Patients with surgical site infections are hospitalized an additional 7 days on average. The longer hospital stay cost an additional $3,152 on average. The average total cost for medical care during the eight weeks after hospital discharge is $5,155 for patients with surgical site infections compared with $1,773 for patients without SSIs. The total cost includes out patient visits, pharmacy, radiology services, re-hospital- ization, skill-nursing facility, home health aids, and durable equipment. [0006] The frequency of surgical site infections in patients varies from surgeon to surgeon, hospital to hospital, surgical procedure to surgical procedure and patient to patient. Surgi- cal site infections can be caused by extemal sources of con- tamination including surgical personnel, surgical environ- ment, and surgical instruments. Most SSIs are, however, caused by patient’s own normal skin flora which can enter the body through the surgical incision. The patient’s skin flora is considered as the first and foremost pathogenic source because the transmission of bacteria from skin to the incision is very eflicient. Innocuous bacterial flora on the skin may also be colonized by pathogenic organisms. The bacteria of May 6, 2010 normal skin flora can cause wound infection in the presence of foreign materials that greatly enhance the pathogenic potential of these bacteria. Therefore, bacterial contamina- tion occurs predominantly during and following surgical pro- cedures. [0007] Different methods of preventing SSIs have been developed to reduce patients’ surgical site infections. Advanced surgical techniques and skillful surgeons can reduce the duration of surgery. Operation personnel and operation room hygiene management can lower the probabil- ity of exogenous pathogens. Operations that are conducted when patients have healthy physical and psychological states may enhance patients’ immune system so that the chance of surgical infections may be considerably reduced. Thoughtful plans and careful selection of effective antibiotics can also help reduce the chance of contamination of bacteria. [0008] Topical bactericidally active or antimicrobial agents such as iodophors, chlorhexidine, and alcohol-containing products have been applied to the surgical site before surgery to kill bacteria. These agents are preoperative skin prepara- tion products, washes, surgical scrub tissues, wound cleaners, lotions and ointments.As early as 1960s, the successful use of prophylactic antibiotics was reported in a randomized, pro- spective, placebo-controlled clinical study of abdominal operations on the gastrointestinal tract. The success of anti- biotic prophylaxis was due to the appropriate patient selec- tion and wise choice of available agents. [0009] U.S. Pat. No. 4,542,012 teaches the application of antimicrobial agents by depositing antimicrobial composi- tions onto human skin to form an antiseptic film. The antimi- crobial composition is applied to the skin as a liquid solution in a fugitive solvent. After the solvent evaporates, a thin film containing antimicrobial agent is formed on the skin. [0010] U.S. Pat. No. 5,916,882 discloses a providone-io- dine alcohol gel antimicrobial skin-preparation formulation which is used to disinfect a surgical site. The pre-operative skin-preparation formulation quickly kills bacteria when applied to the surgical site. The skin-preparation formulation continues to effectively inhibit microorganism growth in the applied area for a relatively long period of time. Application of the skin-preparation formulation is controllable because the formulation does not run when applied to a patient. The antimicrobial skin-preparation formula includes iodine, alco- hol and gel. [0011] U.S. Pat. No. 6,228,354 provides a skin-preparation composition which does not harm the skin yet promotes asep- sis on the skin. The skin-preparation composition disclosed has a rapid antimicrobial activity when in a liquid form and a sustained antimicrobial activity when dry. The skin prepara- tion composition forms a water-resistant film on skin and is not readily removed when a wound or surgical site is sponged or irrigated. The antimicrobial film can be removed by rub- bing an aqueous solution having the proper pH onto the skin. This patent describes a film-forming topical antimicrobial composition that includes a broad spectrum antimicrobial agent, a water-resistant polymer system, a neutralizer, a pH sensitive polymer, and an alcohol. [0012] U.S. Pat. No. 6,488,665 discloses an antimicrobial skin-preparation delivery system used to disinfect a surgical site. The antimicrobial skin-preparation formula consists of iodine, alcohol and gel. The delivery system is composed of an antimicrobial alcohol gel formulation contained within a sealed, flexible container and a gel formulation dispenser connected to the container. A porous applicator pad with US 2010/0112036 A1 enlarged holes for passage of the gel formulation is described. The flow rate of the gel formulation is controlled by the external pressure applied to the flexible container. [0013] US Patent Publication Nos. 20040126355 and 20080102053 disclose antimicrobial skin compositions com- prised of an antimicrobial agent, water, an alcohol, and one or more pH sensitive viscosity builders. The composition’s vis- cosity is from 100 cp to 1,000 cp and the formulation com- bines the advantages of an antimicrobial agent and an alcohol. The viscosity of the formulation permits dispensing from the applicator, while preventing the solution from flowing away from the wound area. pH sensitive methacrylic polymers are used as viscosity modifiers. The preparation forms a water- resistant film that is diflicult to remove during wound irriga- tion, but can be easily removed upon completion of the pro- cedure. [0014] One of the disadvantages associated with topical application of skin preparation products is that the antimicro- bial agents are only effective for a short period of time. Bacteria that may have survived the initial application of skin preparation products can proliferate and produce a large pathogen population. In addition, appropriate antimicrobial prophylaxis is determined by many factors such as proper case selection, anti-microbial agent selection, dosing and route of administration and duration of therapy. Inappropriate use of antimicrobial agents not only increases the cost of medical health care, but also exposes the patient to potential toxicity and other risks. Moreover, many gram-positive organisms isolated from patients with surgical site infections are resistant to multiple antimicrobial agents. The problem of antimicrobial resistance in gram-positive nosocomial patho- gens has been a growing concem. [0015] In addition to the use of antimicrobial skin prepara- tion products, surgical incise drapes have also been used to help reduce the migration of germs and bacteria into the incision site. The surgical incise drape is usually a clear polymeric film with an adhesive backing on one side which is in turn covered with a release liner. Generally, the incise drape is used in conjunction with towels or surgical drapes to main- tain the surgical site as sterile and clean as possible in order to inhibit surgical site infections. A continuous or longer lasting antimicrobial effect may be obtained by combining the anti- microbial agent with a surgical incise drape. [0016] U.S. Pat. No. 3,579,628 discloses a hydrophilic acrylic film dressing which contains a composition which reacts with water to generate a bacteriostatic substance. The hydrophilic acrylic films are particularly suitable for use as occlusive dressings and for reducing bacteria. [0017] U.S. Pat. Nos. 4,310,509 and 4,323,557 disclose dermatologically acceptable compositions made of a pres- sure-sensitive surgical incise drape and a broad-spectrum antimicrobial agent which can be released from the drape placed in contact with the skin. The active broad-spectrum antimicrobial agent is polyvinylpyrrolidone-iodine complex or chlorhexidine. The antimicrobial agents are applied onto the surgical drape which is made of polymeric materials such as polyurethane, polyvinyl ethers, polyesters, or polyethyl- ene. [0018] U.S. Pat. No. 4,340,043 discloses an adhesive- coated incise drape material incorporating uniform amounts of silver sulfadiazine as an antimicrobial agent. The incise drape is made of polyurethane sheets with an adhesive layer. [0019] U.S. Pat. No. 4,643,181 discloses a surgical dress- ing or incise drape material comprising a substrate coated May 6, 2010 with an antimicrobial containing adhesive. The substrate may be a woven or knitted fabric, a nonwoven fabric, a plastic or a polymeric film. The preferred substrate in the invention is a polyurethane film. The antimicrobial is polyhexarnethylene biguanide hydrochloride, which is distributed in the adhesive as particles with a size in the range of 20 to 300 microns. [0020] U.S. Pat. No. 5,069,907 discloses a synthetic poly- meric film or fabric surgical drape having incorporated therein a broad spectrum antimicrobial agent. The drape may have an adhesive layer attached to one of its external surfaces. The preferred antimicrobial agent used is 5-chloro-2-(2,4- dichloro-phenyl)phenol. Suitable adhesives utilized include polyacrylate adhesives. [0021] U.S. Pat. No. 5,803,086 discloses adhesive coated incise drapes useful in surgical procedures. The incise drapes comprise a flexible film backed coating on one side with a dermatologically acceptable pressure sensitive adhesive (PSA) on the other side. The incise drape can be applied by two people wherein one person holds the core and a second person ur1rolls the drape by pulling on the handle protruding from the opposite end of the drape. [0022] U.S. Pat. Nos. 5,979,450; 5,985,395 and 6,742,522 provide surgical incise drapes comprising a flexible film hav- ing a major portion thereof coated with an adhesive. The incise drape has a leading edge and a trailing edge and further includes a film handle at the leading edge. Methods described include providing a drape, grasping the film handle of the drape, pulling upon the liner to remove at least a portion of the liner exposing at least a portion of the adhesive coating the major portion of the flexible film, holding the surgical incise drape in a position such that at least a portion of the adhesive is contacting the patient, and then removing portions of the liner remaining. [0023] US Patent Publication Nos. 20020002223, 20040115274 and 20080078413 disclose adhesive composi- tions containing acrylic polymers, tackifiers and a broad spec- trum antimicrobial agent. The adhesive composition is an essentially solventless composition. The antimicrobial agent utilized is diiodomethyl-p-tolylsulfone with a preferred con- centration of antimicrobial agents in the adhesive of about 0.1% to about 2% loading by weight. The antimicrobial adhe- sive composition is included in a polymeric substrate to form a surgical drape. The polymeric substrate is preferably a polyester or co-polyester sheet material. [0024] US Patent Publication No. 20050284487 discloses a draping product, which is coated with adhesive along at least one edge. The adherence strength of the adhesive is greater than 0.5 N/25 mm when applied to skin. The damage to stratum comeum of the skin covered by the adhesive is less than 30% after removal. The adhesive coating is comprised of a pressure sensitive adhesive such as silicone elastomer, a hydrogel or a soft, tacky hot melt adhesive. [0025] US Patent Publication No. 20070048356 describes an antimicrobial material composition that can be applied to material substrates. The antimicrobial composition includes a first or primary antimicrobial agent, such as polyhexameth- ylene biguanide (PHMB), a second antimicrobial agent, an anti-static agent or fluoropolymer and/ or an organic acid. The substrate may encompass both woven and nonwoven fabrics made from either natural or synthetic fibers, rubber, plastic, and other synthetic polymer materials. The composition exhibits an effective microbe-killing eflicacy within a period of about 30 minutes. US 2010/0112036 A1 [0026] In spite of the beneficial properties of conventional surgical drapes with respect to inhibition bacterial infection, there are many challenges and problems associated with the conventional surgical drapes regardless of whether they incorporate antimicrobial agents. Under certain circum- stances conventional surgical drapes may actually increase the risk of surgical site infection. Conventional surgical drapes can be lifted during surgery which results in entry of bacteria into the surgical site. The lifting of the conventional surgical drape is usually caused by failure of the adhesive to remain in contact with the patient’s skin. Attempts to increase adhesive strength may also prove disadvantageous because more force is then required to remove the drape from skin leading to damage of the skin near the surgical site. [0027] Conventional surgical drapes are normally large and difficult to apply to the patient without wrinkling the drape film. Wrinkling of the surgical drape at the surgical site may block visibility, making it difficult for the surgeon to see the incision site. In addition, the surgical drape will not prevent microorganisms from entering the incision if the drape is wrinkled. Wrinkling is especially problematic with applica- tion of the conventional surgical drapes to a non-flat skin surface such as the elbow or knee. [0028] Incorporation of antimicrobial agents into conven- tional surgical drapes may permit the antimicrobial action of the agents to last longer. Antimicrobial agents currently avail- able are, however, not effective at killing and immobilizing pathogens on the surface to which the agents are applied. The extensive use of antimicrobial products has raised concems about antimicrobial resistance to antibiotics. In addition, most antimicrobial compounds are heat labile and cannot survive radiation sterilization. This makes it difficult to pre- pare sterile surgical drapes infused with antimicrobial agents. [0029] Even though many different procedures have been applied to reduce surgical site infections, the risk of such infections still exists because of the continuing survival of skin bacteria after these treatments. Since endogenous flora on patient’s skin plays a key role in the development of surgical site infections, a simple and comprehensive solution to the problem would be to minimize endogenous bacteria at and around the surgical site. It is known that cyanoacrylate polymer film can act as a mechanical barrier to penetration by bacteria while maintaining a natural healing environment. Cyanoacrylate monomers, which polymerize on contact with tissue surface to provide a thin and flexible polymer film, have been used as tissue adhesives for several decades. Cyanoacry- late adhesives also exhibit strong bond strength and very rapid cure time. [0030] Cyanoacrylate’ properties as adhesives may also make them desirable candidates as microbial sealant drapes. Cyanoacrylate microbial sealant drapes could prevent surgi- cal site infections by overcoming the difficulties experienced by the conventional surgical drapes. U.S. Pat. No. 7,255,874 discloses that modified cyanoacrylate monomers can be used in various medical applications including wound closure, treatment of burns and abrasion and as surgical drapes. U.S. Pat. No. 5,730,994 describes methods for draping a surgical site by the in situ formation of cyanoacrylate polymer drape over skin surface. While the specification describes various cyanoacrylate monomers that can be used as surgical drapes, the preferred compositions contained only n-butyl cyanoacrylate. Furthermore, only n-butyl cyanoacrylate compositions were tested as surgical drapes. May 6, 2010 [0031] There are several shortcomings associated with using n-butyl cyanoacrylate as a surgical drape. Compared to longer chain alkyl cyanoacrylates, n-butyl cyanoacrylate is less flexible and cracks more easily after forming a polymer film. Thus a plasticizer is usually needed in the n-butyl cyanoacrylate formulation to improve flexibility. In addition, short-chain cyanoacrylates polymerize quickly and then degrade rapidly into formaldehyde and the corresponding alkyl cyanoacetate, which can cause significant histotoxicity. Polymer films of n-butyl cyanoacrylate sloughs off from skin faster than that of long alkyl chain cyanoacrylates. Skin irri- tation also occurs with the use of n-butyl cyanoacrylate. [0032] Hence, development of a cyanoacrylate-based microbial sealant drape which can immobilize the infectious microorganisms and effectively seal out the bacteria from a surgical site is desired. It is desirable to have a cyanoacrylate- based microbial sealantdrape product that can provide a um- form and flexible film. It is also desirable to develop a cyanoacrylate microbial sealant drape with significantly less tissue toxicity. Additionally, it is also desirable to develop an easy to use cyanoacrylate-based microbial sealant drape that will last a long time after the surgery to inhibit the postopera- tive surgical site infections. SUMMARY OF THE INVENTION [0033] The present invention provides cyanoacrylate- based liquid microbial sealant drape compositions compris- ing mixtures of cyanoacrylates to inhibit the surgical site infections. The liquid sealant film formed upon polymeriza- tion of the cyanoacrylate mixture prevents the spread of bac- teria by trapping and immobilizing the microorganisms on the surgical sites. The compositions of the present invention provide flexible microbial sealant drapes without the addition of plasticizers and/ or antimicrobial agents. [0034] The present invention provides a method of per- forming surgery with a lowered risk of contamination includ- ing the steps of applying a preoperative skin preparation to a surgical site, applying the microbial sealant drape composi- tion based on liquid cyanoacrylates to the surgical site, form- ing the microbial sealant film on the surgical site, making an incision through the microbial sealant film, and performing surgery. [0035] The present invention provides liquid microbial sealant drape compositions which can effectively reduce the amount of microorganisms in the surgical site. Effective immobilization of microorganisms, by liquid microbial seal- ants of the present invention, were confirmed by both in vitro and in vivo bacteria immobilization test. In vitro immobili- zation test on sterile pig skin confirms that the microbial sealant compositions of the present invention are at least 95% effective in preventing the spread of the clinically relevant bacteria on the surgical sites under a variety of usage condi- tions. In preferred embodiments of the microbial sealant com- positions of the present invention the compositions are at least 99.5% effective in preventing the spread of the clinically relevant bacteria on the surgical sites under a variety of usage conditions. In more preferred embodiments of the microbial sealant compositions of the present invention the composi- tions are at least 99.9% effective in preventing the spread of the clinically relevant bacteria on the surgical sites under a variety of usage conditions. The microbial sealant composi- tions of the present invention do not need to be used in combination with an antimicrobial surgical incise drape and may be used as a substitute for an antimicrobial surgical US 2010/0112036 A1 incise drape. The in vivo bacteria immobilization on 60 human subjects indicates that the microbial sealant composi- tions of the present invention can reduce microbial coloniza- tion by at least 99.9% within 15 minutes and maintain at least a 99.9% reduction throughout the 24 hours post treatment. [0036] The present invention provides microbial sealant drape compositions which are resistant to the passage of blood-borne pathogens using viral penetration as a test sys- tem. No viral penetration was detected for the disclosed microbial sealant film. [0037] The present invention provides a method of inhibit- ing the surgical site infections during and post the surgery. It takes days for the microbial sealant film to slough off. The disclosed cyanoacrylate liquid drape compositions are thus providing the post-surgical infection protection based on the anti-microbial property of cyanoacrylates. [0038] The present invention provides microbial sealant drape compositions which provide a desirable degradation profile. [0039] The present invention provides microbial sealant drape compositions including at least one cyanoacrylate monomer with longer alkyl chain and at least one cyanoacry- late monomer with shorter alkyl chain. The desired cyanoacrylate properties can thus be fine-tuned by combining the longer chain and shorter chain cyanoacrylates in specific ratios. Properties such as bonding strength, setting time, vis- cosity, degradability and biocompatibility can be altered depending on the specific combination of cyanoacrylates. Mixed cyanoacrylate compositions with about 60% to about 90% or more of 2-octyl cyanoacrylate are preferred for use as microbial sealants to prevent the surgical site infections. [0040] The present invention provides sterile microbial sealant drape compositions which may be sterilized by the combination of ethylene oxide exposure and E-beam irradia- tion. Sterile microbial sealant compositions sterilized in this manner provide at least a two year shelf life. [0041] The present invention provides microbial sealant drape compositions based on mixed cyanoacrylate mono- mers, which are packaged in a single use applicator. The applicator includes a compartment containing the microbial sealant composition as well as a sponge applicator tip. Cyanoacrylate-based microbial sealant composition can be readily dispensed onto the sponge applicator tip. A uniform sealing film can be formed by applying the cyanoacrylate- saturated sponge tip onto the surgical sites. [0042] The present invention provides microbial sealant drape compositions which are compatible with currently available skin preparation products, surgical incise drapes and wound closure products. [0043] The present invention provides microbial sealant drape compositions, which form flexible and tight films on the substrates so that little or no detectable cyanoacrylate residue is transferred into the incision wound by the surgical blade. [0044] The present invention provides microbial sealant drape compositions which generate less heat during the appli- cation compared to commercially available drape products comprised of 100% butyl cyanoacrylate. The average tem- perature increase of the skin after applying microbial sealant composition of the present invention is no more than about 0.25° C. [0045] The present invention provides microbial sealant drape compositions which provide a high flashpoint for safe use in the operating room or clinical surgery suite. The flash- May 6, 2010 point for the disclosed microbial sealant composition is greater than 240° F. which is greater than 100% butyl cyanoacrylate drape products. [0046] The present invention provides cyanoacrylate- based microbial sealant drape compositions which form a thin and uniform drape film on the surgical sites. The film thickness of the disclosed cyanoacrylate liquid drape compo- sitions was evaluated using optical microscope, which is less than 500 pm. [0047] The present invention provides cyanoacrylate- based microbial sealant drape compositions which has a desirable surface coverage. The average surface coverage of the drape composition disclosed in the present invention device was approximately 222.0 inch2. The average surface coverage of the drape composition disclosed in the present invention device is much larger than that of the commercial applicators with the same amount of the liquid sealant. [0048] The present invention provides cyanoacrylate- based microbial sealant drape compositions which are com- patible with lasers. The microbial sealant films do not ignite, crack, blister or peel under the intense thermal energy of the lasers so that the microbial sealant film maintains its integrity and effectiveness as a sealant on the surgical site. [0049] The present invention provides microbial sealant drape compositions which are compatible with defibrillators and electrocautery. The combined use of the disclosed micro- bial sealant composition with defibrillator and electrocautery does not affect the effectiveness of these devices. The dis- closed microbial sealant composition demonstrates desirable performance with regard to charring, plume discoloration and cleaning of the blade upon completion of the incision and coagulation procedures. No signs of ignition, blistering, cracking or peeling were observed. [0050] The present invention provides cyanoacrylate- based microbial sealant drape films which provides more resistance to water penetration by impact than the commer- cial cyanoacrylate films. The microbial sealant composition of the present invention elicited a mean value of 0.03 grams from penetration of water by impact compared to a mean value of 0.07 grams for butyl cyanoacrylate microbial sealant drapes. [0051] The present invention provides microbial sealant drape compositions which are less irritating to the skin of a patient than prior art compositions. Based on the skin irrita- tion study, the primary irritation index for the disclosed microbial sealant composition was calculated to be 0.7, while the primary irritation index for butyl cyanoacrylate drapes was calculated to be 1.4. [0052] The present invention provides microbial sealant drape compositions which are safe and biocompatible. Cyto- toxicity, genotoxicity, local irritation after implantation, and delay-type hypersensitivity of the disclosed microbial sealant compositions were evaluated based on ISO 10993, which confirmed the disclosed compositions are safe to be used as microbial sealant to inhibit the surgical site infections. BRIEF DESCRIPTION OF THE FIGURES [0053] FIG. 1 is an illustration of a preferred embodiment of the applicator for the cyanoacrylate microbial sealant drape compositions. DETAILED DESCRIPTION OF THE INVENTION [0054] The present invention provides compositions com- prising sterile mixtures of cyanoacrylates with different US 2010/0112036 A1 length alkyl chains for use as a liquid microbial sealant drape that can inhibit the surgical site infections. The drape film formed upon polymerization of the mixture of cyanoacrylates prevents the spread of microorganisms by trapping or immo- bilizing bacteria that survive on patient’s skin after common skin preparation procedures. [0055] Preferred microbial sealant drape compositions dis- closed herein include at least one cyanoacrylate with longer alkyl chain and at least one cyanocrylate with shorter alkyl chain. The longer alkyl chain cyanoacrylates are those con- taining 5 or more carbon atoms in the alkyl group, which include but are not limited to n-pentyl cyanoacrylate, iso- pentyl cyanoacrylate, n-hexyl cyanoacrylate, iso-hexyl cyanoacrylate, n-heptyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, n-octyl cyanoacrylate, 2-octyl cyanoacrylate, nonyl cyanoacrylate, and decyl cyanoacrylate. The shorter alkyl chain cyanoacrylates are those containing 4 or less carbon atoms in the alkyl group, which include but are not limited to methyl cyanoacrylate, ethyl cyanoacrylate, n-pro- pyl cyanoacrylate, isopropyl cyanoacrylate, n-butyl cyanoacrylate, isobutyl cyanoacrylate, 3-acetoxypropyl cyanoacrylate, 2-methoxypropyl cyanoacrylate, and 3-chlo- ropropyl cyanoacrylate. [0056] Varying the composition ratio of cyanoacrylate with different alkyl chains allows modification of the properties of cyanoacrylate compositions so that bonding strength, flex- ibility, cure time, degradability and biocompatibility can be controlled. Cyanoacrylates with long alkyl chains lacking oxygen-containing functional groups tend to form polymers that degrade slowly. Compared to longer chain cyanoacry- lates, the shorter cyanoacrylate monomers have a higher degree of tissue toxicity due to their rapid degradation into formaldehyde and the corresponding cyanoacetate. Polymer films comprising longer alkyl chain cyanoacrylate tend to be more flexible than those made of shorter alkyl chain cyanoacrylates. Shorter alkyl chain cyanoacrylates have advantageous properties as tissue adhesives. For example, shorter alkyl chain cyanoacrylates provide faster curing speed and stronger bond strength as compared to longer alkyl chain cyanoacrylates. [0057] In a preferred embodiment of compositions of the present invention, liquid microbial sealant drape composi- tions comprise 2-octylcyanoacrylate (OCA) in combination with n-butyl cyanoacrylate (BCA). In order to investigate the stability of the mixture of 2-octyl cyanoacrylate and n-butyl cyanoacrylate, a series of mixed cyanoacrylate compositions with different ratio of OCA/BCA were prepared and sub- jected to sterilization. Sterilization of the compositions is a requirement for their use as microbial sealants. Therefore it is important that the compositions can be sterilized without significant viscosity change. The compositions tested were composed of cyanoacrylates having the following ratios of n-butyl cyanoacrylate to 2-octyl cyanoacrylate: 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20 and 90:10. Table 1 shows the viscosity of the 2-octyl cyanoacrylate and n-butyl cyanoacrylate mixtures before and after the E-beam steriliza- tion. The compositions were sterilized in HDPE bottles (1 ounce). Viscosity change correlates with the stability of cyanoacrylate monomers, stability being an important crite- rion for selecting the appropriate cyanoacrylate mixture com- positions for use as microbial sealants. As shown in Table 1, E-beam sterilization has different effects on different mix- tures of 2-octyl cyanoacrylate and n-butyl cyanoacrylate depending on the ratio of the two cyanoacrylates. The viscos- May 6, 2010 ity of the different compositions before the sterilization ranges from 3.68 to 3.88 cps and the difference is within the measurement accuracy of the viscometer. Mixed cyanoacry- late compositions having approximately 60% to about 90% 2-octyl cyanoacrylate demonstrate slight viscosity increases after E-beam sterilization. The preferred range of viscosity change is approximately 0% to 200%. The viscosity of the mixed cyanoacrylate compositions having about 50% or less of 2-octyl cyanoacrylate increases dramatically after the E-beam sterilization. This is indicative of instability of those compositions after undergoing E-beam sterilization. Mixed cyanoacrylate compositions having about 20% or less of 2-octyl cyanoacrylate cured after the E-beam sterilization and are unsuitable for microbial sealant compositions. In a more preferred embodiment of compositions of the present inven- tion, compositions with about 60% to about 90% of 2-octyl cyanoacrylate are used as the liquid microbial sealant to pre- vent the surgical site infections. More preferably, composi- tions with about 70% to about 90% of 2-octyl cyanoacrylate are used. Even more preferably, compositions with about 80% of 2-octyl cyanoacrylate and about 20% of n-butyl cyanoacrylate is used as the liquid microbial sealant to pre- vent the surgical site infections. TABLE 1 Viscosity ofmixed OCNBCA compositions before and after E-beam sterilization. Average viscosity cps Formulation Composition Before Sterilization After Sterilization la 1:9 BCNOCA 3.68 5.11 1b 2:8 BCNOCA 3.68 5.71 1c 3:7 BCNOCA 3.68 5.11 1d 4:6 BCNOCA 3.88 6.95 le 5:5 BCNOCA 3.88 15.77 1f 6:4 BCNOCA 3.88 68.03 lg 7:3 BCNOCA 3.68 505.63 1h 8:2 BCNOCA 3.68 Cured 11 9:1 BCNOCA 3.68 Cured [0058] In preferred embodiments of the present invention the liquid microbial sealant drape compositions provide at least two-year shelf life. The stability of the sterile cyanoacry- late adhesive compositions has evaluated by the accelerated aging. The accelerated aging test of the mixed cyanoacrylate microbial sealant composition was performed in an oven at 80° C. for a period of 12 days. The investigated compositions were tested for viscosity at intervals of 3, 6, 9 and 12 days. Based onASTM F1980-2, 12 days accelerated aging at 80° C. correlates to 2 years of shelf life at ambient temperatures. Table 2 shows the viscosity of a sterile microbial sealant composition in an applicator containing 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanaocrylate at day 0, 3, 6, 9 and 12 of the accelerated aging at 80° C. The viscosity of the cyanoacrylate-based microbial sealant compositions increases as the accelerated aging proceeds but the increased viscosity of the aged samples at day 12 does not affect the performance of liquid drape compositions nor the dispensing of the compositions from the applicator. US 2010/0112036 A1 TABLE 2 Viscosity of the sterile microbial sealant drape composition before and after the accelerated aging at 80° C. for 12 days. Viscosi c s Test 1 Test 2 Test 3 Average Day 0 4.29 3.68 3.06 3.68 Day 3 4.29 3.68 4.90 4.29 Day 6 4.90 4.90 5.52 5.11 Day 9 6.13 6.13 6.74 6.33 Day 12 27.0 25.7 30.6 27.8 [0059] In preferred embodiments of the present invention the microbial sealant drape composition is packaged in a user-friendly, single use applicator. As shown in FIG. 1, the applicator comprises a compartment containing the mixed cyanoacrylate compositions and a sponge applicator tip through which the liquid drape compositions may be applied to the surgical site. The applicator compartment is preferably air and water tight with a sealing mechanism to prevent con- tamination to the mixed cyanoacrylate monomers inside. When the compartment is opened, the mixed cyanoacrylate liquid sealant is evenly distributed onto the sponge applicator tip. Cyanoacrylate liquid drape compositions can be easily dispensed onto the sponge from an applicator once the sponge connection is folded. A uniform sealing film is formed by applying the cyanoacrylate-saturated sponge tip onto surgical sites. [0060] According to the present invention, the microbial sealant drape compositions of the present invention can effec- tively reduce the amount of microorganisms in the surgical site. In preferred embodiments the microbial sealant compo- sitions are at least 99.9% effective in preventing the spread of the clinically relevant bacteria on the surgical sites under a variety of usage conditions. The in vitro immobilization of microorganisms by the microbial sealant compositions was evaluated using sterile pig skin incised with a sterile surgical scalpel. Microorganisms used to challenge the surgical site may include without limitation pathogenic gram negative bacteria, gram positive bacteria, yeast and Corynebaczerium sp. The immobilization of microorganisms by the microbial sealant compositions of the present invention was evaluated under different conditions which included without limitation using the microbial sealant composition without incision, using the microbial sealant composition with incision, using the microbial sealant composition with incision and skin sur- gical preps, and using the microbial sealant composition with incision and surgical incise drapes. [0061] The microbial sealant drape compositions of the present invention were effective in preventing the mitigation in the test organism on the surgical site. Complete effective- ness was manifest as greater than 3 .9 log 10 mitigation in the case of S. epidermidis, MRSA, Corynebaczerium species, Pseudomonas aeruginosa and greater than 4 log 10 mitiga- tion for Candida albicans. The microbial sealant composi- tions do not have an adverse effect on the effectiveness of surgical preps. The microbial sealant compositions do not need to be used in combination with an antimicrobial surgical incise drape. Instead the microbial sealant compositions of the present invention may be used as a substitute for an antimicrobial surgical incise drape. May 6, 2010 [0062] According to the present invention, the preferred microbial sealant drape compositions can reduce microbial colonization by at least 99.9% within 15 minutes of applica- tion and maintain at least a 99. 9% reduction throughout the 24 hours post treatment [0063] According to the present invention, the microbial sealant drape compositions are resistant to the passage of blood-borne pathogens. Testing based on ASTM F1671 “Test Method for Resistance of Materials Used in Protective Cloth- ing to Penetration by Blood-Bome Pathogens Using Phi- X174 Bacteriophage Penetration as a Test System” was con- ducted to demonstrate the pathogen resistance. The test results indicated that the disclosed microbial sealant film is resistant to the passage of blood-borne pathogens using a viral penetration as a test system. [0064] Preferred microbial sealant drape compositions of the present invention generate less heat during the application compared to commercially available drape products. Poly- merization of cyanoacrylate is an exothermic process. The amount of heat released during polymerization is related to the length of the alkyl chain of the cyanoacrylate. Cyanoacry- lates with shorter length chains release more heat. Too much heat generated from the application of cyanoacrylates onto human skin makes the patient uncomfortable. The exother- mic effect of microbial sealant product of the present inven- tion and a commercially available product was evaluated using an Infrared Thermometer to measure the temperature change on human skin. The skin temperature of patients was measured before and after the application of the drape prod- ucts onto human skin. The average temperature increase after applying microbial sealant composition disclosed in the present invention and a commercially available product were 0.25 and 0.41 ° C., respectively. The test results indicate that less heat is released from the application of the preferred composition disclosed in the present invention than that of a commercially available product. [0065] According to the present invention, the microbial sealant drape compositions of the present invention have a high flashpoint for safe use in the operating room or clinical surgery suite. The test was performed in accordance with ASTM D56-05, ISO 3679:2004 determination of flashpoint- rapid equilibrium closed cup method. The flashpoint for the microbial sealant compositions of the present invention is greater than 240° F. The flashpoint of the 100% butyl cyanoacrylate microbial sealant compositions is about 227° F [0066] According to the present invention, no cyanoacry- late residue was detected on a surgical blade through which an incision was made on a substrate covered with a microbial sealant drape compositions disclosed herein. The detection limit of the test was 5 ppm. The residue analysis on a surgical blade confirmed that no detectable cyanoacrylate sealants were transferred into the incision wound site. [0067] According to the present invention, the preferred microbial sealant drape compositions of the present invention provide a desirable degradation profile. The integrity (degra- dation over time) of the disclosed microbial sealant film was evaluated following topical application to the skin of three pigs and comparisons were made to commercially available drapes. The microbial sealant films applied at each applica- tion site were evaluated for degradation at approximately 8 hours after application, and 1, 2, 3, 4, 6, 8, 10, 12, 14, and 16 days after application. Degradation of both the disclosed microbial sealant film and the commercial product was evi- US 2010/0112036 A1 dent by the first observation interval (8 hours after applica- tion). At this time, 2 out of 12 test sites with the disclosed microbial sealant film remained intact and 5 out of 12 sites with the predicate device were intact. When the study ended on day 16, the microbial sealant film of the present invention was partially present in 2 of the 12 sites, while the commercial product was absent from all 12 sites. [0068] According to the present invention, the liquid microbial sealant compositions are compatible with currently available skin preparation products, surgical incise drape products and wound closure products. Compatibility with current products means that the application of the disclosed microbial sealant drape composition does not adversely affect the performance of wound closure products and surgi- cal incise drapes. Skin preparation products that may be used in concert with the compositions of the present invention include without limitation Chloraprep, Duroprep, 10% Povi- done iodine and Betadine. Duraprep is preoperative skin preparation product comprising iodine povacrylex and iso- propyl alcohol. ChloraPrep is a rapid-acting, persistent, and broad- spectrum preoperative skin preparation product, which consists of 2% Chlorhexidine Gluconate in 70% isopropyl alcohol. Betadine is a consumer-available topical antiseptics containing 10% of povidone-iodine. Surgical incise drapes may also be used with the cyanoacrylate compositions of the present invention including without limitation 3M Steri-strip and loban 2. Steri-Strip is an antimicrobial skin closure prod- uct that is made of a porous, non-woven backing coated with a pressure-sensitive adhesive which contains iodophor and is reinforced with polyester filaments for improved strength. loban 2 is an antimicrobial surgical incise drape with an iodophor impregnated adhesive providing a sterile surface and antimicrobial activity throughout the procedure. The compatibility of the preferred liquid microbial sealant com- positions with current commercial products used for prevent- ing surgical site infections was investigated by observing the effect of the disclosed liquid drape product on the adhesion property of surgical incise drape in the absence and presence of different skin preparation products. [0069] The liquid cyanoacrylate sealant compositions of the present invention are also compatible with currently avail- able wound closure products. The wound closure products may include SurgiSeal, Dermabond and Steri-Strip. Derrna- bond is a liquid bonding adhesive that holds cuts, incisions and wounds together. SurgiSeal is cyanoacrylate-based topi- cal skin adhesive for the closure of wound and incisions to provide a flexible, water-resistant, antimicrobial protective coating, which provides the optimal balance between bond strength and flexibility. [0070] According to the present invention, the preferred liquid cyanoacrylate sealant drape composition is compatible with lasers. The lasers that may be used in concert with the compositions of the present invention include without limi- tation CO2, Nd:YAG, and Diode. The disclosed microbial sealant is intended to be used after typical operative skin preparation prior to a surgical incision. Lasers may be required to be used for skin incision, ablation, or coagulation for a surgical procedure. The in vitro study was conducted to evaluate the effect of both free beam and contact use of the lasers on the disclosed microbial sealant film formed on pig skin. The combined use of a skin prep such as Betadine with the disclosed microbial sealant composition was also inves- tigated using a Diode laser. The integrity of the disclosed microbial sealant film was evaluated by macroscopic obser- May 6, 2010 vations for cracking, blistering and peeling. The intense ther- mal energy of the lasers was used to determine if the disclosed microbial sealant film would ignite. The results showed that the disclosed microbial sealant film did not ignite, crack, blister or peel for all three laser types when used with either free beam or contact thermal energy applications so that the microbial sealant maintains its integrity and effectiveness as a sealant for the surgical procedure. These same results were obtained when combined with the surgical skin preparation product when the Diode laser was used with either free beam or contact laser. [0071] According to the present invention, the cyanoacry- late-based microbial sealant compositions are compatible with defibrillators and an electrocautery. The in vitro study was conducted on porcine skin to evaluate the effect of the microbial sealant compositions of the present invention on the performance of the defibrillator and electrocautery. The microbial sealant composition was applied onto porcine skin. A metal plate or probe was attached on the underneath side of the porcine skin to measure the voltage of the defibrillator. In order to evaluate the compatibility with Electrocautery, a commercially available Electrocautery device was used to make incisions and coagulations on the porcine skins covered with the disclosed microbial sealant film. The Electrocautery settings were made at 70 watts for both incision and coagu- lation. The single coat application of the microbial sealant compositions of the present invention did not significantly decrease the conductance of the energy being discharged from the defibrillator. There was no observation of ignition, blistering, cracking or peeling. When used with the electro- cautery, the microbial sealant compositions demonstrated desirable performance with regard to charring, plume discol- oration and cleaning of the blade upon completion of the incision and coagulation. [0072] According to the present invention, the cyanoacry- late liquid drape compositions provide a thin and uniform film on the surgical sites. In preferred embodiments of the present invention the drape film has a thickness of from about 5 to about 400 pm. More preferably, the drape film provides a thickness of about 10 to 200 pm, more preferably from about 30 to 80 um and still more preferably from about 50 to 60 pm. The film thickness study indicates the formation of thin and uniform films of the disclosed liquid drape compositions. [0073] According to the present invention, the liquid microbial sealant drape compositions provide greater resis- tance to penetration of water by impact than the commercially available liquid drapes. The resistance of the microbial seal- ant compositions of the present invention to the penetration of water by impact was investigated according to the American Association of Textile Chemists and Colorists (AATCC) test method. A volume of water is allowed to spray against the taut surface of the disclosed microbial sealant film backed by a weighted blotter. The blotter was then reweighed to determine water penetration. The microbial sealant compositions of the present invention have an average value of 0.03 grams from penetration of water by impact compared to an average value of 0.07 grams for a commercial drape composition. The test results indicate that the disclosed microbial sealant composi- tion provides twice more resistance to water penetration by impact than the commercial product. [0074] According to the present invention, the cyanoacry- late liquid sealant drape compositions are safe and effective as a surgical sealant product useful for inhibiting surgical site infections. The safety and biocompatibility of the disclosed US 2010/0112036 A1 liquid drape composition has been evaluated based on the International Organization for Standardization (ISO) 10993, Biological Evaluation of Medical Devices. Cytotoxicity was measured on the preferred liquid microbial sealant composi- tion using an in vitro biocompatibility study. The liquid microbial sealant compositions of the present invention are not cytotoxic. For comparison, the in vitro cytotoxicity of prior art device was also evaluated, which showed no evi- dence of causing cell lysis or toxicity. [0075] According to the present invention, the preferred liquid cyanoacrylate-based microbial sealant drape composi- tion is less irritating than the prior art device, which was confirmed by the primary skin irritation study and ISO intra- cutaneous study. [0076] According to the present invention, the preferred liquid microbial sealant drape composition is not genotoxic. Bacterial reverse mutation test, mouse peripheral blood micronucleus study and in vitro chromosomal aberration study in mammalian cells confirmed that the compositions are not genotoxic. [0077] The mixed cyanoacrylate compositions may be sta- bilized with a combination of free radical stabilizer and anionic stabilizer. In embodiments of the present invention, the preferred primary free radical stabilizer is butylated hydroxyl anisole (BHA). BHA is used in an amount of about 200 to about 15000 ppm, preferably about 1000 to about 10000 ppm, more preferably about 2000 to about 8000 ppm. Other free radical stabilizers that may be used include without limitation, hydroquinone; catechol; hydroquinone monom- ethyl ether and hindered phenols such as butylated hydroxya- nisol; 4-ethoxyphenol; butylated hydroxytoluene (BHT, 2,6- di-tert-butyl butylphenol), 4-methoxyphenol (MP); 3-methoxyphenol; 2-tert-butyl-4methoxyphenol; 2,2-meth- ylene-bis-(4-methyl-6-tert-butylphenol). [0078] In embodiments of the present invention, the pre- ferred primary anionic stabilizer is sulfur dioxide in an amount of about 2 to about 500 ppm, preferably from about 10 ppm to about 200 ppm. The anionic stabilizer may be a very strong acid including without limitation perchloric acid, hydrochloric acid, hydrobromic acid, toluenesulfonic acid, fluorosulfonic acid, phosphoric acid, ortho, meta, or para- phosphoric acid, trichloroacetic acid, and sulfuric acid. The very strong acid may be used in an amount of 0 to about 250 ppm, preferably from about 5ppm to 50 ppm. Preferably, the very strong acid stabilizer is sulfuric acid, phosphoric acid or perchloric acid. [0079] According to the present invention, the cyanoacry- late-based microbial sealant drape compositions are sterilized for medical use. The sterilization can be accomplished by common techniques, and is preferably accomplished by methods including, but not limited to, chemical, physical, and irradiation methods. An example of a chemical method includes, but is not limited to, exposure to ethylene oxide. Examples of irradiation methods include, but are not limited to, gamma irradiation, electron beam irradiation (E-beam), and microwave irradiation. [0080] In preferred embodiments of the present invention, E-beam is used to sterilize the cyanoacrylate-based microbial sealant compositions. The dose of E-beam irradiation applied should be sufficient enough to sterilize both the package and the adhesive inside. The E-beam irradiation may be in a dosage of from about 5 to 50 kGy, and more preferably from about 12 to about 25 kGy. E-beam irradiation is preferably conducted at ambient atmosphere conditions and the expo- May 6, 2010 sure time to the irradiation is preferably from about 1 to about 60 seconds, more preferably from about 10 seconds to 60 seconds. [0081] In preferred embodiments of the present invention, the viscosity of the preferred cyanoacrylate-based microbial sealant composition changes upon the E-beam sterilization. The average viscosity of the preferred microbial sealant drape composition comprising 20% butyl cyanoacrylate and 80% octyl cyanoacrylate before sterilization is 3.68 cps. After the sealant composition is subjected to E-beam sterilization the viscosity was measured to be 5.71 cps. The prior art refer- ences indicate that E-beam sterilization can induce serious partial polymerization of cyanoacrylate, which would lead to a large increase in viscosity. [0082] In order to reduce the bioburden, the cyanoacrylate- based microbial sealant drape compositions may be filtered through a 0.2 pm filter. The applicators with the overpack may also be sterilized with heat, ethylene oxide prior to the final E-beam irradiation. [0083] The sterility of the cyanoacrylate-based microbial sealant drape compositions may be analyzed by Bacteriosta- sis and Fungistasis tests. In embodiments of the present invention, a Sterility Assurance Level (SAL) should be obtained at a minimum of 10‘3 , which means that the prob- ability of a single unit being non-sterile after sterilization is 1 in 1000. In more preferred embodiments, the Sterility Assur- ance Level may be at least 10‘6. [0084] The following non-limiting examples are intended to further illustrate the present invention. EXAMPLE 1 Setting Time Measurement [0085] Pig skin (4>< MEM) with 5% serum and 2% antibi- otics. The test extract was placed onto three separate mono- US 2010/0112036 A1 layers of L-929 mouse fibroblast cells propagated in 5% CO2. High density polyethylene was used as the negative control and tin stabilized polyvinylchloride was used as the positive control. All monolayers were incubated at 37° C. in the pres- ence of 5% CO2 for 48 hours, which was then examined microscopically to determine any change in cell morphology. The liquid microbial sealant compositions of the present invention did not cause cell lysis or toxicity. EXAMPLE 8 Genotoxicity Study 1 [0092] A glass rod was cleaned with 70% isopropyl alcohol and allowed to air dry. The rod was then coated with a micro- bial sealant drape composition comprising 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanoacrylate up to 4 cm and allowed to dry for at least 1 minute prior to extraction with dimethyl sulfoxide (DMSO) and 0.9% sodium chloride at 37° C. for 72 hours. Another glass rod without cyanoacrylate liquid drape was similarly subjected to the extraction condi- tions for use as a negative control. Known mutagens, benzo [a]pyrene and 2-nitrofluorene, were used as positive control to demonstrate that tester strain TA 98 was sensitive to muta- tion reversion to wild type. For tester strains TA100 and TA 1535, sodium azide and 2-aminoanthracene were used as positive controls. For tester 1537, 2-aminoanthracene and ICR-191 were used as positive controls. For tester strain WP2uvrA, 2-aminoanthracene and methylmethane-sul- fonate were used as positive controls. [0093] Tubes containing molten top agar supplemented with tryptophan for the Escherichia coli or with histidine- biotin solution for the Salmonella zyphimurium were inocu- lated with culture for each of the five tester strains and with the DMSO and saline extracts of the disclosed cyanoacrylate liquid drape film. Sterile water for injection (SW1) or S9 homogenate simulating metabolic activation was added as necessary. Trytophan-free media plates (for E. coli) and his- tidine-free media plates (for S. zyphimurium) were prepared in triplicate as follows: 1) DMSO and saline extracts of the cyanoacrylate liquid drape film with and without S9 activa- tion; 2) negative controls with and without S9 activation; and 3) positive controls with different tester strains in the absence and presence of S9 activation. [0094] The plates were incubated at 37° C. for 2 to 3 days. Following the incubation period, the revertant colonies on each plate were recorded. The mean number of revertants and standard deviation was determined. The mean number of revertants of the test plates was compared to the mean number of revertants of the negative control for each of the five tester strains. It was concluded that, under the study conditions, the disclosed liquid microbial sealant compositions in both DMSO and saline extracts were not mutagenic to Salmonella Zjzphimurium strains (TA98, TA100, TA1535, and TA1537), and were not mutagenic to tryptophan-dependent Escheri- chia coli strain WP2uvrA. EXAMPLE 9 Genotoxicity Study 11 [0095] A glass rod was cleaned with 70% isopropyl alcohol and allowed to air dry, and then coated with the microbial sealant drape compositions comprising 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanoacrylate up to 4 cm. The drape was allowed to dry for at least 1 minute prior to May 6, 2010 extraction with dimethyl sulfoxide (DMSO) and 0.9% sodium chloride at 37° C. for 72 hours. Additional test rods without cyanoacrylate microbial sealant were subjected to the same extraction conditions as the test article and were used as negative controls. Methyl methanesulfonate (MMS) in saline, an antineoplastic drug known to have mutagenic properties, was used as a positive control. [0096] Five groups of mice, each of which consisted of 6 male and 6 female, were injected with cyanoacrylate liquid drape in SC extract, cyanoacrylate liquid drape in SO extract, negative control in SC, negative control in SO, and positive control with methyl methanesulfonate, respectively. Each mouse received an intraperitoneal injection at a dose of 20 ml/kg of the appropriate extract accordingly for consecutive three days.All animals were observed immediately following injection and on a daily basis to access general health. On day 4, blood was collected from the tail veins of each mouse and solutions were prepared. The normochromatic erythrocytes were evaluated for the presence of micronuclei. The fre- quency of micronucleated reticulocytes (MN-RETs) was determined and used as an index of genotoxicity. The fre- quency of reticulocytes relative to total erythrocytes was cal- culated as an indication of stem cell toxicity. Both SC and SO extracts of the cyanoacrylate liquid drapes of the present invention did not show statistically significant increases in the frequency of MN-RETs. Cyanoacrylate liquid microbial sealant compositions of the present invention are not geno- toxic under the study conditions. Also, there was no evidence of cellular toxicity from extracts of the disclosed cyanoacry- late liquid drape composition. EXAMPLE 10 Local Irritation and Toxicity Study [0097] Local irritation or toxicity effect after implantation of the microbial sealant drape compositions comprising 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanoacrylate was conducted to evaluate the potential for a local irritant or toxic response to the drape implanted in direct contact with muscle tissue. High density polyethylene was used as the negative control. Three Albino New Zealand rabbits were used for the test. One incision was made on each side of the rabbit back. The fascia was cut to expose the paravertebral muscle. A pocket was formed with a hemostat between the muscle fibers into which the implant material was introduced. After four weeks, the rabbits were weighed and then eutha- nized by an intravenous injection of a sodium pentobarbital based drug. The paravertebral muscles were dissected free and fixed in 10% neutral buffered formalin to facilitate cut- ting. The tissue was macroscopically examined using low magnification to look for capsule formation or other signs of irritation. The excised sections were also histologically pro- cessed for microscopic evaluations. The disclosed microbial sealant drapes of the present invention caused no macro- scopic reaction under the study conditions, while micro- scopic examination indicated the disclosed composition was moderately irritating to the tissue. EXAMPLE 11 ISO lntracutaneous Study [0098] lntracutaneous study of microbial sealant drape compositions comprising 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanoacrylate was conducted to determine US 2010/0112036 A1 whether leachables extracted from the disclosed microbial sealant composition wound cause local dermal irritant effects following injection into rabbit skin. The glass rods were wiped clean with 70% isopropyl alcohol and allowed to air dry. The glass rod was coated with the disclosed microbial sealant compositions up to 4 cm and allowed to air dry for at least one minute prior to placing in the extraction container. The test article was extracted in 0.9% sodium chloride USP solution (SC) and sesame oil, NF 9 (S0) at 37° C. for 72 hours. A 0.2 ml dose of the test article extract was injected by the intracutaneous route into five separate sites on the right side of the back of each rabbit. Injections were spaced approximately 2 cm apart. The appearance of each injection site was noted immediately after injection. Observations for erythema and edema were conducted at 24, 48, and 72 hours after injection. Under the conditions of this study, there was no erythema and no edema from the SC extract injected intracutaneously into rabbits. There was very slight erythema and very slight edema from the SO extracts injected intracu- taneously into rabbits. EXAMPLE 12 ISO Skin Irritation Study [0099] Skin irritation study of cyanoacrylate-based micro- bial sealant drape compositions comprising 80% of 2-octyl cyanoacrylate and 20% of n-butyl cyanoacrylate was con- ducted to evaluate the potential for a single topical application of the disclosed microbial sealant composition to irritate skin. New Zealand white male rabbits were used for this study. On the day of treatment, four sites, two on each side of the back cranially and caudally, were designated on each rabbit. A 0.5 ml portion of the disclosed microbial sealant composition was applied topically to each cranial site by introduction under a 4 ply gauze layer to an area of skin approximately 25 mm>99% effective in preventing the spread of the microorganisms into the wound site. EXAMPLE 19 In vivo Bacteria Immobilization [0109] A total of 60 healthy volunteers (29 females and 31 males) were recruited to evaluate the in vivo bacteria immo- bilization of a microbial sealant composition comprising 20% butyl cyanoacrylate and 80% octyl cyanoacrylate. The study included a 14-day pretreatment washout period for stabiliza- tion of skin bacteria flora. During the washout period, sub- jects refrained from using any topical antimicrobials, sys- temic antibiotics, medical soaps, lotions, shampoos, etc, for at least two weeks before the evaluation and throughout the study. The tested area consisted of the right inguinal region. May 6, 2010 Mean difference score (test — control) Very slight edema (barely perceptible) Well-defined edema (edges ofarea well-defined by definite raising) Severe edema (raised more than 1 mm, and extending beyond exposure area) Hair was removed using a sterile disposable clipper device. A sterile drape was used to isolate the inguinal area from the rest of the body and then a surgical marker was used to draw four different 1 inch squares separated by 1 inch of normal skin in which the microbial sealant composition was applied. Using sterile gloves the products were applied onto the skin in its designated areas and allowed to dry. Sterile gauze was placed over the test area to avoid sub sequent contamination. Swabbed samples from skin were collected at 15 minutes, 4 hours and 24 hours after the initial application of the micro- bial sealant composition. The sample collection procedure was performed using a sterile technique including sterile gloves, sterile microbial sealants, surgical masks and hats. After the sampling was completed the entire contents of the tube was poured carefully onto a 1 mL Petrifilm aerobic plate (plate count agar) and the plates were incubated for 48 hours at 30° C. 3MTM PetrifilmTM plate was used to quantify colony counts. At 15 minutes, the absolute log reduction was 5.568 for the disclosed microbial sealant composition. The absolute log reduction of bacteria for the disclosed microbial sealant composition is 4.299 and 3 .33 at 4 hours and 24 hours, respec- tively. EXAMPLE 20 In vitro Chromosomal Aberration Study in Mamma- lian Cells [0110] A chromosomal aberratioin study was conducted to determine whether an extract of the microbial sealant drape composition wound cause clastogenic changes in Chinese Hamster Ovary (CHO). A glass rod was sterilized with 70% isopropyl alcohol and allowed to air dry. The glass rod was then coated (4 cm) with a microbial sealant composition comprising 20% butyl cyanoacrylate and 80% octyl cyanoacrylate and allowed to air dry for at least 1 minute prior to placing the coated rod in the extraction container. A single preparation was extracted with DMSO with agitation at 37° C. for 72 hours. Following extraction, the DMSO extract was diluted with McCoy’s 5A medium to a final concentration of 25% prior to testing. Aveclor 1254:induced rat liver (S9 homogenate) was used as metabolic activation. The S9 homo- genate is prepared from male, Sprague Dawley rats. An US 2010/0112036 A1 uncoated glass rod was subjected to the same extraction con- ditions to serve as a negative control. A known direct acting genotoxic compound, Mitomycin C (MMC), was used as a positive control to demonstrate that CHO cells were sensitive to mutagens in the absence of metabolic activation. The microbial sealant composition extract, negative control, and positive control were tested in triplicate. For the assays con- ducted without metabolic activation, the growth medium in each of three test culture flasks was replaced with 10 ml of the prepared extracts. For the assay conducted with metabolic activation, the test samples were supplemented with isocitrate dehydrogenase (NADP+) at 60 111/ ml and S9 at 20 p.l/ml.After 18 hours of incubation at 37° C. in the presence of CO2, the medium was decanted and the cultures were rinsed twice with 4-6 ml of calcium magnesium free phosphate buffered saline (CMF-PBS). The flasks were incubated for an additional 2 hours at 37° C. After harvesting, slides of the cells were prepared, stained with Giemsa, and examined microscopi- cally for chromosomal aberrations at 100>< magnification. Under the conditions of this assay, the DMSO test extract of the disclosed microbial sealant composition was not consid- ered genotoxic to Chinese Hamster Ovary cells in the absence of S9 metabolic activation. The prepared McCoy’s extract was not considered genotoxic to Chinese Hamster Ovary cells in the presence or absence of S9 metabolic activation. The positive and negative controls performed as expected. EXAMPLE 21 Resistance to Impact Penetration [0111] The resistance of a microbial sealant drape compo- sition comprising 20% butyl cyanoacrylate and 80% octyl cyanoacrylate to the penetration of water by impact was evaluated by following the American Association of Textile Chemists and Colorists (AATCC) test method. Test sample films of the microbial sealant composition were made that measured 178x230 mm. The samples and the blotting paper were conditioned in an atmosphere of 65:2% relative humid- ity (RH) at 21:1° C. for 4 hours before testing. After clamping the film onto an inclined stand, a standard blotter 152x230 mm was weighed and inserted beneath the test sample. A 500110 ml volume of distilled water at 27:1° C. was poured into a funnel of the tester and allowed to spray onto the test sample of the microbial sealant composition. After the spray- ing, the test sample was carefully lifted, the blotter removed and reweighed to determine the amount of water that pen- etrated the film during the test. The mean value for the micro- bial sealant composition was 0.03 grams. Under the same conditions a commercial microbial sealant film comprised of 100% butyl cyanoacrylate displayed a mean value of 0.07 grams. EXAMPLE 22 Sealant Film Integrity Over Time [0112] The integrity (degradation over time) of a microbial sealant composition comprising 20% butyl cyanoacrylate and 80% octyl cyanoacrylate was evaluated following topical application to the skin of three pigs and compared to another microbial sealant product. The pigs were restrained in a sling for up to 30 minutes during the application procedures. To reduce possible stress at being restrained in the sling, the pigs were initially conditioned to the sling over the course of 3 days prior to commencement of the application procedures. May 6, 2010 The day prior to treatment, each pig was weighed and placed in a sling. The hair on the dorso-lateral area was removed. The depilated skin was washed with povidone iodine scrub, rinsed well with water, and dried. On the day of the application procedure, each pig was placed in a sling. The depilated area of the back was scrubbed with povidone iodine, wiped with 70% isopropyl alcohol andpainted with 10% povidone iodine antiseptic. The microbial sealant composition of the present invention and another commercial drape were applied to four sites approximately 1>X< * >X< *