FIELD OF INVENTION

The present invention relates to glove with surface area coated with long acting broad spectrum antimicrobial formulation. In more specific, the disclosed invention is capable of exerting rapid killing of contacted hazardous microbes and sustaining the antimicrobial property in an exposed environment for an extended duration. BACKGROUND OF THE INVENTION

Disposable gloves are manufactured to be readily discarded upon utilization. Disposability of these gloves not only aims to reduces the likelihood of the user being exposed to such microbes contaminated-gloves after repeated use. Some of the gloves, such as protective gloves or facial mask, are particularly used in a condition which avoid transfer of microbial agent from an object to the user or vice versa. For example, protective gloves are widely used in hospitals, pharmaceutical plants, food plants, kitchens or even public place to isolate microorganisms from being transferred to or out of the user's hand so as to reduce the risk of microbial cross contamination. Nevertheless, once microbes attached to the surface of the glove are not halted or killed, the attached microbes may proliferate on the glove surface rendering the contaminated gloves a potential cross contaminating source. Likewise, facial masks are used to minimize inhalation or transmitting of airborne pathogens at household, schools healthcare, industrial etc. However, the typical pore size is usually too big to effectively block the pathogens. For a purpose of achieving continuous microbial protection, effort has been put in to have an effective antimicrobial coating made onto the surfaces, which are actively exposed to potential microbe contamination, of these glove to rapidly kill microorganisms upon contact the coated surface.

For example, United Kingdom patent application no. 1337617 details surgical gloves with antimicrobial substances coated at the finger portion of the gloves to minimize cross- contamination. Another United Kingdom patent application no. 2218617 describes another glove incorporated with non-ionic sparingly water soluble antimicrobial agent to form additional barrier to prevent infection caused by breach of microbes. Chlorhexidine and its derivatives are another anti-infective agent used for coating in United States patent application no. 5133090. Both Fuchs and Dresdner disclose another type of protective gloves in United States patent application no. 5459879 and 5335373 respectively. The disclosed gloves basically include an outer and inner layers sandwiching an antimicrobial solution in between that the antimicrobial ooze out from any torn parts inflicted to the layers to protect the user. Gloves equipped with rapid release anti-infective agent are described in United States application 5487896 that chlorhexidine is distributed in the matrix of latex and starch layers respectively, while gloves with sustained antimicrobial effect are offered in US6913758.

Considering that gloves like mask and gloves are often used for a short period of time before being discarded. Thus, it is vital that the coated antimicrobial agent has fast and effective kill- rate to attain the targeted purpose in such short duration. Failing of such will not benefit the users at all. The initial minutes which the gloves contact with the microorganisms are critical in determining if the coated antimicrobial agent was effective enough to kill the contacted microbes and successfully maintained the numbers of available microbes at a satisfying level. However, kill efficiency is the aspect where most prior arts fail. Further, boxes packaged with multiple copies of gloves may remain opened for weeks before the gloves are completely used up, while the antimicrobial property of suggested formulation in the prior art declines over such period. It is important that the antimicrobial property available on these products remains intact during this exposure time despite being constantly challenged by air impurities, moisture, humidity, organic matter or microorganisms. Failure in sustaining the antimicrobial property mainly attribute to the antimicrobial agents used in these prior arts do not exert sustained activity and the formulation is not stable over the surface for extended period of time. For example, earlier attempts of using antimicrobial agent such as chlorhexidine in mask failed to provide sustained activity or rapid kill-rate necessary to protect a user to minimize the risk of cross contamination when exhaling.

SUMMARY OF THE INVENTION The present invention aims to disclose gloves equipped with antimicrobial property to avoid proliferation of harmful microbes on the gloves which is likely to serve as a source of cross- contamination or infectious agent. With sustained long-acting broad-spectrum antimicrobial property, users of the gloves are shielded from acquiring any pathogens inherited thereto, minimizing cross contamination and reducing the risks of health hazard to the users.

Another object of the present invention is to offer gloves possessing long lasting antimicrobial property which can last for an extended period without much decline in an opened box condition exposed to the external environment. More specifically, the disclosed invention is coated with an antimicrobial formulation showing good chemical stability over time as long the disclosed invention is stored at normal room temperature and condition.

Still another object of the disclosed invention is to provide gloves coated with antimicrobial formulation that the formulation is designed to achieve broad -spectrum and rapid kill. The gloves may address microbial challenge in a specific use setting, especially in a working environment with high risk for pathogen transmission, (e.g. long term care facilities for the chronically ill, food service/processing common areas, food handling, industrial, healthcare) that limiting the growth of pathogens can significantly reduce the risk of infection. This contribute to an overall hygiene and lesser product spoilage as well as greater product acceptance by achieving rapid and broad-spectrum kill of spoilage microorganisms.

Object of the present invention also involves providing glove having a stable antimicrobial coating even subjected to environmental challenge. Earlier antimicrobial compounds has less tolerance to organic matter challenge on surfaces well. In fact, mere 10% organic matter challenge reduces chlorine efficacy by 50%. The antimicrobial formulation in this current invention tolerates up to 30% organic matter challenge and as such ideal to exert its sustained long antimicrobial activity.

Further object of the present invention is to provide a gloves which is substantially environmental friendly compared to some prior similar inventions. Some of the earlier so- called antimicrobial glove inventions mainly utilize silver technology. This led to major issue with regards to disposability of the treated gloves since silver is toxic and requires further treatment prior to disposal.

At least one of the preceding objects is met, in whole or in part, by the present invention, in which one of the embodiment of the present invention is a glove with treated surface area having a coating of antimicrobial formulation comprising a 5 ^th generation quaternary ammonium chloride derived compound; stabilized urea and optionally bacteriocin. More preferably, the formulation may further comprise dodecyl dimethyl ammonium chloride. Owing to the excellent chemical stability of the antimicrobial formulation, the treated surface area of the gloves has antimicrobial activity which can preferably last for a duration not less than 5 weeks in an open environment with kill rate range between 90 to 99.99%, more preferably 99.99%. To achieve effective killing, the 5 ^th generation quaternary ammonium chloride derived compound of the present invention is any one or combination of benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium, cetrimide, dofanium chloride, tetraethylammonium bromide, didecyldimethylammonium chloride and domiphen bromide, while the bacteriocin is any one or combination of agrocin, alveicin, carnocin, colicin, curvaticin, divercin, enterocin, enterolysin, epidermin, erwiniocin, glycinecin, halocin, lactococin, lacticin, leucoccin, mesentericin, nisin, pediocin, plantaricin, sakacin, subtilin, sulfolobicin, thuricin 17, vibriocin, and warnerin. Preferably, 5 ^th generation quaternary ammonium chloride derived compound has a concentration of 300 to 6000 ppm on the treated surface area.

In another aspect, the treated surface area of the gloves is fabricated from any one or combination of nitrile, polyurethane, vinyl, poly-isoprene, polyethylene, neoprene, cotton, polyester, nylon and derivatives derived thereof. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows the process flow of performing JIS Z 2801 :2000 test. DETAILED DESCRIPTION OF THE INVENITON

One skilled in the art will readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The embodiment describes herein is not intended as limitations on the scope of the invention.

The present invention is a glove with treated surface area having a coating of antimicrobial formulation comprising a 5 ^th generation quaternary ammonium chloride derived compound; stabilized urea and optionally bacteriocin. It was found by the inventors of the present invention that the antimicrobial formulation is chemically stable over a long period of time without much decline in killing efficiency. In more specific, through appropriate proportion of different antimicrobial agents in the formulation, the disclosed invention is able to achieve extended antimicrobial property albeit facing various challenges in an open environment, particularly in an open or broken box condition which the packaged gloves are subjected to environmental challenge. With the use of preferred antimicrobial formulation, the treated surface area of the manufactured gloves shows antimicrobial activity for a an extended duration not less than 5 weeks in an open environment, more preferably the duration can last not less than 10 weeks.

To boast the coating for broad-spectrum and rapid kill, the antimicrobial formulation may further comprising dodecyl dimethyl ammonium chloride in one embodiment of the present invention. Dodecyl dimethyl ammonium chloride renders the produced gloves with better resistance against growth of fungi and bacteria through disrupting cell membrane of the fungi and bacteria. Nevertheless, the antimicrobial formulation can also be formulated to include DDAC or silicon-bonded QAC biocide, replacing the 5 ^th generation QAC for greater and extended surface attachment for sustained antimicrobial activity.

Pursuant to the preferred embodiment, the 5 ^th generation quaternary ammonium chloride derived compounds used in the present invention can be any one or combination of benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium, cetrimide, dofanium chloride, tetraethylammonium bromide, didecyldimethylammonium chloride and domiphen bromide. These 5 ^th generation quaternary ammonium chloride derived compounds shows great chemical stability over a long period of time thus facilitating extended antimicrobial property in the present invention. In addition, bacteriocin is another major component to be included in the antimicrobial formulation to enhance the kill efficiency. The bacteriocin preferably used, but not limited to, is any one or combination of agrocin, alveicin, camocin, colicin, curvaticin, divercin, enterocin, enterolysin, epidermin, erwiniocin, glycinecin, halocin, lactococin, lacticin, leucoccin, mesentericin, nisin, pediocin, plantaricin, sakacin, subtilin, sulfolobicin, thuricin 17, vibriocin, and warnerin.

As setting forth, another major component in the antimicrobial formulation is GRAS (generally recognized as safe) urea that it enhances the kill efficiency and stabilizes the coating on the gloves. It is known that pores and crevices are naturally occurred on the surface of the gloves such as gloves and conventional antimicrobial compounds, restrained by surface tension, are incapable of penetrating into these pores or crevices to achieve effective kill. This provides opportunity for microbes to quickly multiply in numbers on the surfaces when condition is ideal for growing (typical in hot and humid storage and using conditions). The incorporation of GRAS urea on the surface coating lower the surface tension of water or moisture presented on the treated surface. Thus, the disrupted water or moisture with other dissolved antimicrobial agent can penetrate into pores and crevices on the irregular surfaces of the gloves. Greater penetration allow complete and fast eradication of the microbes hidden in these pores and crevices. The GRAS urea further potentiates the quaternary ammonium chloride (QAC) molecules in the antimicrobial activity synergistically. QAC molecules alone have limited efficacy to destroy non-enveloped viruses, endospores and Gram negative bacteria such as Pseudomonas spp.. Yet, in the presence of GRAS urea, the QAC can effectively act on these microbes disrupted by the GRAS urea. Moreover, QAC shows low tolerance to hardwater (only up to 200ppm) and organic matter as well while a far more stable formulation of QAC suitable for wider pH, temperature and organic matter tolerance is achieved in the present invention with the addition of GRAS urea. Most antimicrobial compound is effective only within a narrow range. For example, hypochlorites (chlorine) remain effective at pH6.5-7.5 only. In contrast, the antimicrobial formulation of the present invention incorporated with GRAS urea remains effective between pH3-l l ; typically in coagulant mixture of pH 10 used in online production of glove. The extreme pH constraint is a major cause for earlier inventions not being able to be mixed in coagulant to achieve ^" external surface coating in an online processing method.

The chemical and heat stability of the disclosed formulation also allow the present invention to be manufactured through an online process. For example, in typical online processing flow of glow manufacturing, the coagulant mix contains a multitude of chemicals and soluble solids that causes wide soluble solids variability and hardness. The wide range renders earlier antimicrobial formulations ineffective. Most antimicrobial compounds tend to lose their antimicrobial property when soluble solids and hardness exceeds 300ppm in the coagulant, while the typical coagulant mix in nitrile and latex glove manufacturing ranges between 3,000 - 220,000ppm. Nevertheless, the antimicrobial formulation used in the present invention remains effective even after the gloves are produced from such drastic processes..

In order to achieve rapid and effective kill, the active agents of the coated antimicrobial formulation, particularly the 5 ^th generation quaternary ammonium chloride derived compound, needs to attain a preferable concentration of 300 to 6000 ppm on the treated surface area. Effective eradication may not be able to complete for any concentration lower than 400ppm, while concentration above 6000 ppm is made redundant. Through the effective concentration, the disclosed invention exerts rapid killing efficacy when challenged by common organisms typically found in healthcare and processing environment such as Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Staphylococcus epidermidis. Enterobacter aerogenes, Candida albicans and Aspergillus niger. The treated antimicrobial gloves showed 95-99.99% kill-rate, preferably 99.99% kill rate, for bacteria and yeasts within the first minute of contact. The gloves achieved also able to have a 75-85% kill-rate based on 30 minutes contact for mould. The stabilized formulation and subsequent surface coating resists natural ultra-violet or oxidative degradation on glove surface exerting desired antimicrobial effect long after coating; up to not less than 5 weeks after opening and exposing the treated gloves to environment. It is important to be noted that the treated surface area are fabricated of material which is chemically inert to the antimicrobial formulation. Coating of the antimicrobial formulation shall pose no detrimental effect to the glove itself. Preferably, the gloves or the treated surface area of the gloves are fabricated from any one or combination of nitrile, polyurethane, vinyl, poly-isoprene, polyethylene, neoprene, cotton, polyester, nylon, natural latex and derivatives derived thereof. For example, disposable gloves typically used in healthcare, food processing industries and household applications are commonly manufactured from highly elastomeric materials, such as natural rubber latex or synthetic latex like vinyl, nitrile, polyurethane, polyethylene, poly-isoprene, neoprene and combinations thereof. The disposable glove may be further incorporated with hypo-allergenic property to minimize risk of potential inflammatory reaction to users. Additional substance like lubricating or emollient material may be included in the inner surface of the glove as well to moisturize the hands. Generally, the coating in the present invention can be acquired via mist-spraying the antimicrobial formulation in liquid form onto the surface area followed by drying the antimicrobial formulation sprayed on the surface area, or by dipping the glove into a tank containing the antimicrobial formulation in liquid form followed by drying the antimicrobial formulation coated on the surface area of the dipped glove. More specifically, for producing glove having coating of antimicrobial formulation over the external surface, mist-spraying or coagulant dipping may be employed in the glove manufacturing process. More specifically, in the mist-spraying approach, an enclosed rectangular misting chamber complete with 2-6 fine-nozzle mist-sprayer is designed and developed along the processing conveyor right after finger-stripping from the hand mould, while antimicrobial formulation mixed in a 20-35% alcohol (such as isopropyl alcohol) is sprayed to form a fine mist within the chamber to uniformly coat the gloves. Preferably, the antimicrobial misting is conducted continuously at glove size of 10-30 microns and dehydration temperature of 120- 170°C. Optionally, in the dipping approach, the anti- microbial gloves are manufactured by dipping the mould into the antimicrobial formulation mixed coagulant followed by high dehydration temperature ranging between 120°C - 170°C for 30-50 minutes. More specifically, the antimicrobial formulation is mixed into Ca(N0 ₃ )2 coagulant and polymer cocktail at 3-30% by weight of total mixture at pH8.0- 10 with total solid content of 2-25% where the hand mould/formers is dipped in an online processing prior to dipping into the nitrile material to ensure uniform external surface coating throughout the matrix. The glove is then oven dried at temperature ranging between 120°C - 170°C for 30-50 minutes and stripped before packed. Another way to coat the external surface of the gloves with the antimicrobial formulation involves adding the antimicrobial formulation capable of achieving a target concentration of 2,000 - 6,000 ppm at pH 6.5-7.0 and temperature of 25-75°C in a tank. Dipping the former/hand mould into the tank followed by the latex material permit a coating formed at the external surface of the gloves upon leaching and drying. Tumbler drier or cyclones may be used at drying temperature between 45-85°C for about 30-70 minutes in an "off-line" processing. The formed antimicrobial coating preferably is a thin layer of less than 0.01mm thickness over the external surface of the glove. The present invention also relates to incorporation of the said antimicrobial formulation at levels ranging between 300 - 2,000 ppm to ensure complete microbial kill during production, packaging to minimize proliferation of microbes during storage in boxes. This ensures bacterial, mould and yeast count on glove surfaces remains well within acceptable level. In order to obtain suitable physical properties like thickness, mechanical strength, integrity, colour, elasticity, deformation, etc. during and after application of the said antimicrobial agent, the drying temperature, dosage level, drying period and mist glove size is tightly controlled. In addition, according to the manufacturing process, the amount of the antimicrobial formulation is preferably limited below the optimum level (e.g. ranging between 300 - 6,000ppm) to avoid any impairment in the physical properties of the gloves.

Moreover, high processing temperature between 130-170°C in an online processing of gloves renders many earlier antimicrobial compounds ineffective and earlier attempts to incorporate the antimicrobial compounds into the coagulant mix proven futile. The antimicrobial formulation in current invention remains effective even at these extreme temperatures allowing such online processing possible saving time, effort and cost and ensuring high throughput in production line. The antimicrobial coating available on the treated surface of the gloves creates an environment not suitable or inhibiting proliferation of microbes on the treated surface. More preferably, the manufactured gloves are also capable of immediately within first 1 to 5 minute to kill 95-99.99% of the bacteria and yeasts upon contact; thus minimizing risks of cross contamination. For instance, inherent with gloves is the problem of microbes proliferation promoted by trapped high ambient heat and moisture from the user's hands and other sources. The present invention significantly minimizes microbial load on internal and external surfaces over an extended period of time for up to 5 weeks, or even 10 weeks, after being exposed to environment in an opened box condition.

Upon coating the antimicrobial compound onto the external surface of the gloves, the dehydration process will cause the antimicrobial to form a fine coating on the surface. In a typical storage condition within package boxes, the low humidity will ensure the active formulation to remain sustained for extended period of time. When in use, coupled with exposure to sweat or humidity, increase in water activity on the surface coating ensure release and make available of the antimicrobial formulation on the surface to kill any microorganism upon contact.

The present invention also has an added advantage of neutralizing the malodor on surfaces of the gloves, mainly fabricated from natural and synthetic rubber materials. It is known that gloves typically have strong offending rubber or chemical odor. The odor will remain long on hand surface even after hand washing. The said antimicrobial formulation coating onto the article surfaces tends to neutralize the odor by killing odor producing organisms on the surfaces of the gloves. In the past, deodorant activity is achieved by blocking the pores using predominantly aluminum salts such as aluminum hydroxychloride. Apart from denaturization of microbial protein, the salt tends to also block pores essential for heat regulation on user skin upon contact and these salts are potential carcinogen. In contrast, the antimicrobial formulation used in the present invention is safe and non-toxic, has no distinct intrinsic odor, wide safety margin and pose no danger to the user even over-dosage, and the formulation does not concentrate on skin surface or absorbed to sub-dermal after repeated use. The following example is intended to further illustrate the invention, without any intent for the invention to be limited to the specific embodiments described therein.

Example 1

As seen in Table 1 below, it has been found that the homogeneous addition of the target antimicrobial agent on to the glove or other article, results in article that is effective at significantly reducing, or all together inhibiting bacteria, yeasts and mold growth on the surfaces by up to 99.99% of bacteria and yeasts in the first 1 minute of contact and demonstrated 85% kill-rate for mold in 30 minutes. This provides extended sustained microbial killing efficacy upon surface contact for up to 10 weeks; as well as allows for longer and safer use of the articles. The following data was compiled using JIS Z 2801 :2000 and British Pharmacopoeia Test Method.

In the given method, an aliquot (typically 400 μΐ) of a cell suspension of organisms typical to the proposed use of the article, usually either Escherichia coli (1.5 - 5 x 105 cells ml- l ;ATCC 8739) or Staphylococcus aureus (1 .5 - 5 x 105 cells ml- 1 ; ATCC 6538p) in a 1 : 499 dilution of a nutrient broth are held in intimate contact with each of 3 replicates of a test surfaces supplied using a 40 x 40 mm polyethylene film (cut from a sterile Stomacher bag) for 24 hours at 35°C (the size of film used should be adjusted in proportion is a different volume of inoculum is employed). The size of the surviving population is determined by immersing the test specimens in individual aliquots (typically 10 ml) of a neutralizer validated for the antimicrobial agent employed (e.g. SCDLP for Ag+). The colony forming units in the resulting suspension are enumerated by a suitable dilution plate count method. An additional 3 replicates of the unfortified surfaces are also inoculated in the manner described above but then analyzed immediately to determine the size of microbial population present prior to incubation. The method is described schematically in Figure 1.

Table 1: Surface Activity and Efficacy Tests (Chemsil (Air & Water), 2010

Initial dose applied onto glove was 1ml of cell suspension at 10 ⁶ - 10 ⁷ /ml. Incubate 72 hours at 35°C with 2 replicates each. Four most common challenge organisms were used in this study.

Table 2: Glove Surface Rapid Kill Rate Tests for Staphylococcus aureus, E. coli,

Pseudomonas aeruginosa and Candida albicans (Chemsil (Air & Water), 2010

Initial dose applied onto glove was l ml of cell suspension at 10 ⁶ - 10 ⁷ /ml. Incubate 72 hours

Nitrite Glove Surface Killing Efficiency at 35°Cfor 24 hours in an Online Processing Flow using Coagulant + Anti-Microbial Mix

It is to be understood that the present invention may be embodied in other specific forms and is not limited to the sole embodiment described above. However modification and equivalents of the disclosed concepts such as those which readily occur to one skilled in the art are intended to be included within the scope of the.claims which are appended thereto. ^' ..