Indian Patents. 279323:NATURAL RUBBER LATEX HAVING REDUCED ALLERGENICITY AND METHOD OF MAKING

Title of Invention	NATURAL RUBBER LATEX HAVING REDUCED ALLERGENICITY AND METHOD OF MAKING
Abstract	A rubber latex composition is disclosed having reduced allergenicity. Methods for producing a rubber latex composition having reduced allergenicity are also disclosed.

Full Text	NATURAL RUBBER LATEX EAVING REDUCED ALLERGENICITY ND METHOD OF MAKING FIELD OF THE INVENTION The present invention relates to a natural rubber latex composition having reduced allergenicity and a method of making the same. BACKGROUND OF THE INVENTION The use of Hevea brasiliensis natural rubber latex (NRL) as a protective thaterial has a long history of usage dating back to the 1800s. The widespread use of barrier NRL articles like gloves and condoms increased tremendously in the 1980s primarily due to the "universal precautions" policy outlined by the Centers for Disease Control NRL's popularity and longevity can be attributed to several factors. The physical properties of NRL are superior to non-latex synthetic products. Field latex, the feedstock thaterial for NRL that continues to be readily available in Malaysia and Thailand, is now available in several new regions around the world including India, Vietnam, Indonesia, Liberia, Guatemala, and China. NRL is significantly less expensive than most petroleum-based synthetic thaterials whose cost continues to fluctuate with the cost of crude oil Additionally, the reduced environmental impact of natural rubber latex compared to petroleum-based synthetic thaterials continues to be the preferred thaterial of choice in an environmentally conscious society. The availability, ease of production and the performance of NRL products continue to make NRL the chosen thaterial by manufacturers and users among industry and medical professionals. Today, there are over 40,000 commercially available products made from NRL A concern with NRL continues to be its petential involvement with adverse health effects due to the antigenicity of NRL products. An intuitive means of controlling this parameter in the NRL source thaterial is by de- proteination / protein modification. Validation of tins process can be achieved by specific methods of protein quantification. Although the first description of an allergic reaction to latex gloves appeared in the American Literature in 1933 when usage was slight, the majority of latex allergic reactions were documented in the late 80s and throughout the 90s and 2000s. Published data indicate 17% of American healthcare workers and up to 73% or more of frequently exposed patients, such as those with spina bifida, were sensitized to latex proteins. Several attempts, including new source crops, synthetic lattices and various treatment methods, have been made to eliminate these problem proteins from Hevea NRL by biological, physical and/or chemical methods that affect the complex acid-base behavior of proteins. One approach has been to introduce the latex articles to multiple leaching steps and chlorination. This approach does reduce the protein levels in the finished product; however it weakens the latex film thus compromising the physical properties of the product Another attempt to reduce proteins in NRL is the use of proteolytic enzymes to degrade the proteins in the latex solution. The issue with this approach is the introduction of another protein (the enzyme) to the latex, which may itself be allergenic. The most logical solution is the use of low-protein latex, such as the treated NRL of the present invention as this approach will more than likely reduce the possibility for an allergic response in the end user of the finished product If high levels of protein are not present in the raw thaterial they cannot appear in the manufactured product. Two other non-Hevea NRL thaterials have been attempted to be commercialized in the US; guayule rubber latex and Taraxacum kok-saghyz, also known as the Russian dandelion. These thaterials are reported to be higher in cost compared to natural rubber and presently are available only in limited quantities. Hevea NRL has been around for more than a century and its antigenic proteins have been thoroughly researched. The allergenic properties and economic viability of latex from the guayule & Taraxacum kok-saghyz have yet to be scrutinized in the way that Hevea has been. Being natural products, both of these thaterials have their own unique set of proteins with potential allergenic behavior not yet understood. Recently, it has been shown that allergens are distributed into few protein families and possess a restricted number of biochemical functions. The allergen functions found most frequently were limited to hydrolysis of proteins, polysaccharides, and lipids; binding of metal ions and lipids; storage; and cytoskeleton association. The limited number of protein families that are allergenic and the narrow functional distribution of most allergens support the existence of yet unknown factors that render proteins allergenic. Many of these specific protein functions play into the chemistry used to manipulate them yielding a modified NRL source thaterial. The last decadrf and a half lias seen a great change in latex use as a result of publicity concerning these allergies. Today in the U.S. there is almost universal awareness of the risks associated with repeated latex exposure, particularly in the healthcare fields where exposure is more profound. Awareness of the risks, however, extends into the industrial glove market, and even to the general public, who have received risk warnings from various government and health-watch groups. As a result mere exists much interest in the market, fueling a strong trend to reduce exposure to latex-associated allergens. Manuiacturers nave responded in several ways: I) reduction or elimination of donning powder, 2) utilization of chlorinated glove washing and additional processing steps to reduce antigenic protein load, 3) use of coatings to reduce actual contact with latex, and 4) introduction of alternative thaterials that mimic, natural latex performance characteristics. Each of these industry reactions represents compromises either from ease of use, performance, or cost standpoint In short, nothing beats the tactile, comfort, and barrier protection that is provided by natural latex products. In the last ten years there has been an increasing awareness of the possible immunologic and other reaction risks associated with the use of latex gloves. This awareness is the result of the proliferation in glove usage among healthcare workers in order to avoid potential exposure to HIV/AIDS transmission sources. An increase in the reported incidence of latex allergic sensitivity and other skin reactions has been concomitant with increased glove usage. This has spurred an effort by industry leaders and manufacturers to reduce exposure to latex. Glove makers have initiated latex substitution in the manufacture of gloves, limited use of donning powder so as to prevent antigenic proteins leached into the cornstarch powder from becoming airborne (a source of respiratory exposure and subsequent sensitization), and the introduction of low 'protein methods for latexes to reduce the overall protein content of gloves. Latex rubber in its natural form consists of polymeric, long chain molecules consisting of repeating units of isoprene: When it is harvested from the rubbertree, Hevea brasilieasis, the liquid, sticky substance also contains proteins like heavarnine, hevein, and rubber elongation factor. Although the basic isoprene polymer is non-antigenic, the associated proteins are highly antigenic. It is important to note this difference in order to minimize the antigenic impact of natural latex without destroying its underlying structure. In its natural state, natural latex does not possess characteristics that are commercially useful. In order to achieve utilitarian value, including strength, elasticity, and memory, the chains of isoprene must be cross-linked to one another. Depending on the type of rubber end product desired, this is achieved with either application of heat and sulfur, or in the case of latex rubber used in the manufacture of gloves, various chemical accelerators that donate or bind sulfur, thus speeding the cross-linking process. The major accelerators are thiurams, mercaptobenzothaizoles (MBTs) and carbathates. In addition to accelerators, latex glove manufacturers utilize another class of additives, called sensitizers, which most frequently consist of substituted phenols. These substances are used to impede oxidation, and resultant degradation, of natural latex. Foreign thaterials, natural latex proteins, accelerators, and sensitizers can all provoke human reactions, but the allergenic reactions due to the proteins are considered to be the most problethatic in the healthcare field. The following briefly describes three major types of foreign thaterial reactions most commonly associated with latex use: Irritant derthatitis is skin irritation that does not involve the body's immune response, that is, it is not an allergic response. Frequent hand washing and inadequate drying, aggressive scrubbing technique or detergents, mechanical abrasive effect of powder, clithatic irritation, and emotional stress can all cause this condition. Even though this is not an allergic reaction, irritant hand derthatitis can cause breaks in the skin which can facilitate entry of the sensitizing latex protein or chemicals found in the commercial product, and in turn lead to latex allergy. Delayed cutaneous hypersensitivity (type PV allergy) is contact (hand) derthatitis generally due to the chemicals used in latex production. It is mediated via T-cells causing a skin reaction that is typically seen 6-48 hours after contact The reaction is local and limited to the skin that has contact with the glove. While not life threatening, those with type IV allergy are at increased risk to develop type I allergy. As in irritant derthatitis, the broken skin barrier can provide an entry site into the body for foreign thaterials. This can produce sensitization to latex proteins leading to a more serious type of reaction. The third and potentially most serious type of reaction associated with latex use is a true IgE/histamino-mediated allergy to protein (also called immediate, or type I hypersensitivity). This type of reaction can involve local or systemic symptoms. Local symptoms include contact urticaria (hives), which appear in the area where contact occurred, Le., the hands, but can spread beyond that area and become generalized. More generalized reactions include allergic rhinbconjunctrvitis and asthma. The presence of allergic manifestations to natural latex indicates an increased risk for anaphylaxis, a rare but serious reaction experienced by some individuals who have developed an allergy to certain proteins (e.g., insect stings, natural rubber, penicillin). This type I reaction can occur within seconds to minutes of exposure to the allergen. When such a reaction occurs, it can progress rapidly from swelling of the lips and airways, to shortness of breath, and may progress to shock and death, sometimes within minutes. While any of these signs and symptoms may be the first indication of allergy, in many workers with continued exposure to the allergen, mere is progression from skin to respiratory symptoms over a period of months to years. Some studies indicate that individuals with latex allergy are more likely than latex non- allergic persons to be atopic (have an increased immune response to some common allergens, with symptoms such as asthma or eczema). Once natural latex allergy occurs, allergic individuals continue to experience symptoms, which have included life-threatening reactions. There are several classes of people known to be at increased risk for latex allergy. Medical patients who have had multiple hospitalizations and have been exposed numerous . times to latex medical products, healthcare workers, and atopic individuals comprise this high-risk group. Current estithates are that 8-17% of healthcare workers become sensitized. Despite the recent emphasis on universal precautions, the marked increase in glove usage due to commutable disease prevention is largely blamed for the increase in latex allergies among these groups. Atopic individuals (those with other allergies or asthma) are at significantly greater risk to develop latex allergy than the general population. It is estithated that as many as 25-30% of atopic healthcare workers may become sensitized. The problems presented by allergic reactions to latex are exacerbated by the proliferation and widespread use of latex-based products. Latex presents great risk to persons in the health care industry where latex products are used extensively in the form of gloves, casts, dressings, tapes, catheters, tubes, drains, airway management devices, med delivery, tourniquets, monitoring devices, and others. One persistent threat lies in the cornstarch powder used to lubricate and ease donning of rubber gloves. The proteins absorb onto the powder and become aerosolized during use and when the gloves are donned and removed. Products containing latex are also found throughout the home in the form of balloons, art supplies, toys, swimming equipment, contraceptive devices, cosmetics, bottle nipples, pacifiers, clothing, chewing gum, rubber bands, and others. Groups at risk include particularly children with spina bifida, those who have been shown to have a very high risk of latex sensitivity, patients with congenital urologic abnormalities, healthcare providers and rubber industry workers. Since the severe allergic reactions to latex are due to their naturally occurring proteins, the prior art offers little in the way of solutions. For example, ammonia treatment of the NRL proteins can cause breakdown and precipitation of some latex proteins, but the allergeniciry appears to be preserved and other antigenic latex proteins are unextractable. In short, the literature recommends that the only treatment available for latex allergy is avoidance. The Food and Drug Adrninistration (FD A), as well as other state and federal agencies, has received requests to ban the use of glove powder. It has been suggested that experimental and clinical studies demonstrate that glove powder on medical gloves can enhance foreign body reactions, increase infections and act as a carrier of natural latex allergens. The National Institute of Occupational Safety and Health (NIOSH) recently issued a safety alert recommending the use of powder-free, reduced protein content latex gloves to reduce exposure to natural latex proteins (allergens). Experimental and clinical data demonstrate that some NRL proteins are allergenic. Further natural latex proteins bind to cornstarch while aerosolized powder on. NRL gloves is allergenic and can cause respiratory allergic reactions. Published studies support the conclusion that airborne glove powder represents a threat to individuals allergic to NRL and may represent an important agent for sensitizing non-allergic individuals. There are also published data (although limited) and clinical experience that cornstarch powder on NRL gloves may also be a contributing factor in the development of irritation and type IV allergy. In addition to dusting powder, other lubricants may also be used in the manufacturing process. Latex and some polymers, are tacky and dipped products such as condoms and gloves made of these thaterials stick to the mold or former. A mold-release lubricant such as calcium carbonate or a mixture of calcium carbonate and cornstarch is used to enable the removal of these dipped products like condoms and gloves from molds. The other aide of the dipped product may be coated with a donning lubricant, such as cornstarch or silicone oils, to make donning easier and to prevent dipped products from sticking during the manufacturing process. Over the past three years, the FDA has received requests to ban the use of all glove powders. These requests have been based on repeated clinical and experimental studies reporting that cornstarch on surgical gloves can damage tissue's resistance to infection, enhance the development of infection, serve as a potential source of occupational asthma, and provide a source of natural latex protein exposure to natural latex allergic individuals. The issues regarding the use of glove powder, except for the transport of natural latex protein allergens, apply to the use of glove powder on both NRL and synthetic gloves. Several states, acting on their own initiative have banned the sale and use of glove powders. Thus, mere is a need to develop a NRL composition and method of making the same that can provide reduced allergenicity. It is an object of the present invention is to teach a method of reducing the allergenicity of NRL prior to vulcanization to enable the creation of a commercial product relatively free of allergenicity with no apparent loss of physical properties. SUMMARY OF THE INVENTION The present invention provides a natural latex composition having reduced allergenicity and a method of making the inventive compositian.- In accordance with the purposes of this invention, as embodied and broadly described herein, the invention therefore provides, in one aspect a NRL composition having reduced allergenicity. In another aspect, the present invention provides a method of reducing allergenicity of NRL, the method comprising subjecting a NRL, prior to vulcanization, to aluminum hydroxide so as to reduce protein levels in the latex rubber. Additional advantages of the invention will be set forth in part in the description that follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. DETAILED DESCRIPTION OF THE INVENTION The present invention may be understood more readily by reference to the following detailed description of preferred embodiments of the invention and the Examples included therein and their previous and following description. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates . otherwise. Thus, for example, reference to "a natural latex composition" includes mixtures of natural latex compositions. Often, ranges are expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values arc expressed as approxithations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings: A weight percent of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not For example, the phrase "optionally present" means that the substance at reference may or may not be present, and that the description includes instance wherein the substance is and is not present. As used herein, "parts per hundred rubber" or "PHR" means the proportion of a component per 100 grams of elastomer. "Treated NRL" as used herein, is intended to refer to a NRL composition that has been treated in accordance with the various methods of the present invention. "Antigenic protein," as used herein, refers to a protein that can induce the generation of antibothes and can cause an immune response in a subject who comes in contact with the antigenic protein. As briefly described above, the present invention provides a NRL composition having reduced allergenicity. The present invention also provides a method of making such a reduced allergenicity NRL, the method comprising contacting a NRL composition with an aluminum hydroxide, optionally agitating the resulting mixture, and then vulcanizing the resulting mixture. While not wishing to be bound by theory, it is believed that under certain conditions and in accordance with the instant disclosure, NRL can be treated with aluminum hydroxide to produce protein complexes. Further, the formed protein complexes can then be removed from a treated NRL composition. In one aspect, the NRL of the present invention can be produced by exchanging and/or complexing at least a portion of the proteins from, for example, a field latex sap emulsion with aluminum hydroxide. Aluminum hydroxide can be stable under most conditions. Various ionic forms of aluminum hydroxide can bond with proteins of complementary charge which are driven toward ionic equilibria or an isoionic point. . Aluminum hydroxide is an amphoteric substance, meaning it can act as either an acid or a base and can readily share electrons with proteins. Amino acids, the blocks that build the proteins, are both very weak acids and very weak bases, thus creating the basis for both ionic and covalent bonding to aluminum hydroxide. Aluminum hydroxide is commonly used as an absorbent, emulsifier, ion exchanger or antacid. Aluminum hydroxide can also be used in the purification, of water because it can form a jelly-like structure, suspending unwanted thaterials in water, including bacteria. METHOD OF MAKING REDUCED ALLXRGENICITY NRL In one embodiment, the present invention involves a method of reducing allergenicity of NRL comprising contacting a NRL composition to an aluminum hydroxide and agitating the resulting mixture to produce an intithate admixture. The individual concentrations of latex and aluminum hydroxide can vary depending upon the process parameters and the desire properties of the resultant product The individual concentrations of latex and aluminum hydroxide can also vary depending on variations of, for example, protein levels in raw thaterials. In one aspect, the present invention comprises any amount of latex combined with any amount of aluminum hydroxide^and is not intended to be limited to any particular concentration range of one or more components. In various exemplary embodiments, latex comprises from about 27 phr (parts per hundred rubber) to about 30 phr and aluminum hydroxide comprises from about 0.01 phr to about 5 phr, for example, about 0.01,0.02,0.04, 0.06,0.08,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8, 0.9,1,12,1.4,1.6,1.8,2, 2.5,3,3.5,4,4.5, or 5 phr, or from about 0.1 phr to about 1 phr, for example, about 0.1,0.2, 0.3, 0.4, 0.5,0.6,0.7,0.8, 0.9, or 1 phr. In a specific embodiment, at least about 0.1 phr aluminum hydroxide is admixed with the NRL composition. In another specific embodiment, about 0.4 phr aluminum hydroxide is contacted with a NRL composition. In another specific embodiment, about 1 phr aluminum hydroxide is contacted with a NRL composition. Any duxoinum hydroxide suitable for contacting with a NRL composition can be utilized in the present invention. The average particle size and distribution, the chemical purity, and/or the density of a particular aluminum hydroxide can vary depending upon the specific process parameters and/or the requirements of the desired final latex article. In various embodiments, the aluminum hydroxide has an average particle size of from about 1 to-about 100 niicrometers, foe example, about 1,2,3,4,5,6,7, 8,9,10,12,14,15,16,20, 30,40,50,60,70,80,90, or 100 micrometers; from about 1 to about 20 micrometers, for example, about 1,2,3,4,5,6,7,8,9,10,12,13,14,15,16, or 20 micrometers; or from about 5 to about 15 micrometers, for example, about 5,6,7, 8, 9,10,12,14, or 15 micrometers. It should be noted that aluminum hydroxide particles having a smaller size and/or increased surface area can typically provide greater levels of protein reduction man larger sized particles. In one embodiment, the aluminum hydroxide has a molecular weight of about 78.00 and a density of about 2.42 g/cm3. The aluminum hydroxide of the present invention can be contacted with the NRL composition at any time prior to vulcanization. NRL compositions are frequently centrifuged to concentrate the composition with the added benefit of purifying the thaterial by removal of a portion of water soluble protein thaterial contained therein. In one embodiment of the present invention, the NRL composition is not centrifuged. In another embodiment, the NRL composition is centrifuged to remove at least a portion of the protein thaterial contained therein. If a NRL composition is centrifuged, aluminum hydroxide can be added to the composition prior to or subsequent to centrifugation. In a preferred embodiment, aluminum hydroxide is contacted with the NRL composition prior to centrifugmg, and the resulting mixture is then centrifuged. In another embodiment, the aluminum hydroxide can be admixed with a NRL composition for a period of time, such as, for example, from about less man an hour to about 72 hours, for example, about 0.5,1,2, 3,4, 5, 8,10,12,15,20,22,24,26, 28,30,36, 40,45,50,55,60,65,70 or 72 hours, and optionally agitated. la another embodiment, the admixture is contacted for a period of time from about 18 to about 36 hours, for example, about 18,20,22,24,26, 28,30,32,34, or 36 hours with agitation. In a specific embodiment, the aluminum hydroxide is contacted with the NRL composition for about 5 hours. In another embodiment, the aluminum hydroxide is contacted with the NRL composition for about 36 hours, m yet another embodiment, the aluminum hydroxide is contacted with the NRL composition for about 72 hours. While not wishing to be bound by theory, it is believed that contacting the NRL composition with aluminum hydroxide modifies at least a portion of the antigenic protein within the NRL composition. It should be noted that other components, such as, for example, fillers, additives, Theological and/or processing aids can be added to the NRL composition before, - simultaneous with, and/or after addition of the aluminum hydroxide. In various embodiments, one or more Burfactants can be mixed with the NRL composition. A surfactant, if used, can be contacted with and/or mixed with a NRL composition at any time prior to vulcanization. In a preferred embodiment, a surfactant is mixed with a NRL and aluminum hydroxide composition prior to the optional removal of aluminum hydroxide. Addition of a surfactant can, while not wishing to be bound by theory, facilitate the association and/or removal of both hydrophobic and hydrophilic proteins from the NRL composition. In addition, a surfactant, if used, can, in various embodiments, result in facile removal of proteins from the composition by a subsequent leaching and/or extraction step. A surfactant, if used, can be any surfactant suitable for use in a NRL composition. In various embodiments, a surfactant can comprise an anionic surfactant, a catiomc surfactant, a non-ionic surfactant, or a combination thereof Further, a surfactant, if used, can be added or contacted in any concentration suitable for use in a given process and/or for producing a desired latex article. The combination of an aluminum hydroxide/surfactant treatment can, in various embodiments, result in significantly improved removal of protein from the NRL , composition. The addition of an optional surfactant can facilitate liberation of proteins -, absorbed onto the latex particle layer. In such a treatment, the liberated (hydrolyzed) proteins can associate with and/or bind to the aluminum hydroxide present in the solution. At near neutral pH values, aluminum hydroxide is not substantially water soluble and can be removed via centrifugation, as described above. The use of a surfactant can provide additional benefits upon aging of a latex solution and/or article. In one embodiment, proteins in a latex composition that has not been treated with a surfactant can remain absorbed onto latex particles and can be subsequently released upon aging. In various embodiments, a NRL composition not treated with aluminum hydroxide can have an antigenic protein value of from about 32 to about 96 % higher than a composition treated with aluminum hydroxide and surfactant after 21 days storage. While the specific improvement of a composition can vary depending on, for example, the properties of the feedstock thaterial, it should be appreciated that the addition of a surfactant to a treatment process can result in reduced antigenic protein levels, even after storage, and thus, improved stability of the resulting latex solution or article. Once the admixture of NRL and aluminum hydroxide is contacted and optionally . agitated, thus complexhig and/or modifying at least a portion of the antigenic protein, the treated latex containing modified protein can be vulcanized to produce a latex article. In one embodiment, a vulcanizing step can be performed without substantially disrupting the physical and/or chemical properties of the NRL. After treatment with aluminum hydroxide, the aluminum hydroxide and any antigenic protein that has associated with and/or bound to the aluminum hydroxide can be optionally removed. In one embodiment, at least a portion of the aluminum hydroxide is removed from the NRL composition after contacting and agitation. In another embodiment, substantially all of the aluminum hydroxide is removed from the NRL composition after contacting and agitation. Removal of aluminum hydroxide from a treated NRL composition can be performed by any suitable technique. In various embodiments, removal of aluminum hydroxide can be performed by filtration techniques, centrifugation, or a combination thereof. Treated NRL compositions can also be subjected to a treatment step comprising exposure to hot water and/or chlorine or a chlorine containing solution, such as, for example, chlorine containing solutions commonly utilized in latex manufacturing processes. After the optional removal of aluminum hydroxide from a NRL composition, the resulting latex can exhibit improved optical properties, such as, for example, a cleaner color and/or appearance, reduced color, and/or increased translucency. Such improvements, while not wishing to be bound by theory, are believed to be due to the removal or proteins, lipids and/or lutoids, or a combination thereof from the NRL composition. While not wishing to be bound by theory, it is believed that untreated NRL containing these thaterials can hydrate quicker, thus compromising the resultant articles tensile strength and chemical barrier, especially for example, upon aging. In another aspect, a portion of, substantially all of, or all of the aluminum hydroxide can remain in a treated NRL composition. In yet another aspect, an excess of aluminum hydroxide can be used and/or additional aluminum hydroxide added to the composition such that a residual amount of aluminum hydroxide remains, for example, suspended in a liquid latex solution. Such an amount of aluminum hydroxide can be added prior to, simultaneous to, or subsequent to the addition of any other amounts of aluminum hydroxide, and optionally after removal of at least a portion of any earlier added aluminum hydroxide that can be complexed to protein. Residual aluminum hydroxide can be useful in various aspects due to the fact that some protein that is covalently bonded to a rubber particle can persist, but in the continued presence of an alkali pH, and in some aspects, especially when compounded, the backbone of such a protein can break and the protein/peptide subsequently go into the aqueous phase of the composition. Thus, the presence of aluminum hydroxide can, in various aspects, complex proteins, creating an insoluble precipitate known as an organic lake. Further, while not wishing to be bound by theory, it is hypothesized that as water is removed during production of a latex article, a salt of the protein and aluminum hydroxide can be formed that displaces water as a byproduct Once such a salt is formed, the protein will have no available reactive sites. Such a protein can remain present in the composition or produced article as part of a neutral and non-reactive molecule, without resulting in allergenictty. Digestion of any remaining protein can be thermodynamically driven and can be well suited to achieving low protein levels in, for example, dipping applications such as gloves and condoms. Further, such a digested precipitate can be easily washed and/or extracted using common industry techniques. Removal of proteins and unreacted compounds from a composition can be performed by a variety of suitable methods. In one aspect, a wet-gel leaching technique can be used to remove, for example, excess calcium nitrate and/or other water-soluble non- rubber thaterials, such as, for example, proteins and added compounding ingrethents. Literature references describe protein removal by wet-gel leaching to be ineffective due to the fact that a significant portion of such proteins have typically not migrated to a surface when, for example, a film was healed to attain the wet-gel state. In one aspect, since the techniques of the present invention can remove significant portions of protein during NRL creation, the typically expected increases in protein at various stages of article (e.g., glove) production do not occur, allowing manufacturers opportunities to reduce the complexity of and/or the number of steps in the manufacturing process. In one embodiment, the methods of the present invention provide an advantage over traditional latex processing methods can be easily integrated into the current processing scheme without the need to acquire and/or install additional capital equipment TREATED NRL HAVING REDUCED ALLERGENICTTY The NRL composition formed by the method described herein can provide reduced allergenicity over traditional latex rubber products and can be suitable for use in a variety of applications. While not intending to be limited, applications for products produced from treated NRL can include medical, health care, and personal care products, such as, for example, examination and surgical gloves, condoms, breather bags, latex tubing, probe covers, and catheters, along with other applications such as threads, foams, cold seal and pressure sensitive adhesives, and balloons. Products produced from the treated NRL composition of the present invention can demonstrate excellent resistance to aging compared to untreated NRL (e.g., Hevea) samples. In one embodiment, and while not wishing to be bound by theory, the use of aluminum hydroxide can bind and/or remove antigenic protein from a Latex composition and can also assist in the removal of species vulnerable to free radical breakdown. Removal of such species can prevent, reduce, and/or delay degradation of rubber articles produced form NRL. For example, the presence and/or contacting of aluminum hydroxide with a NRL composition can provide increased stability of freshly harvested latex. The aluminum hydroxide treatment can thus be used as a partial and/or complete replacement for surfactants. In one embodiment, a NRL composition is treated with aluminum hydroxide and is not treated and/or contacted with a surfactant In another embodiment, a NRL composition is treated with aluminum hydroxide and is treated and/or contacted with a surfactant The combination of aluminum hydroxide and surfactant treatment and/or contacting with a NRL composition can, in various embodiments, provide enhanced stability and protein removal Film samples and products made from a NRL treated in accordance with the methods of the present invention can provide a significant reduction in protein levels over products prepared using traditional methods. A treated NRL composition can have any level of antigenic protein present that is suitable for an intended application. As tolerances for antigenic proteins can vary depending upon the intended application, method of use, and human factors, the target level of antigenic protein in a treated NRL composition can also vary and the present invention is not intended to be limited to a treated NRL composition having antigenic protein level In one aspect, a treated NRL composition is free of or substantially free of - antigenic- protein. In other aspects, a treated NRL composition can-have less than .about 100 µg, less than about SO µg, less than about 30 µg, less than about 20 µg, less than about 10 µg, less' than about 5 µg, or less than about 2 µg of antigenic protein per gram of composition. In still other aspects, a treated NRL composition can have less man about 100 µg/dm2, less than about 50 µg/dm2, less than about 30 µg/dm2, less than about 20 µg/dm2 less than about 10 µg/dm2, less than about 5 µg/dm2, or less than about 2 µg/dm2 of antigenic protein. EXPERIMENTAL The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the reduced allergenic NRL compositions and associated processes and methods are constructed, used, and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, film thickness, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C (Celsius) or is at ambient temperature, and pressure is at or near atmospheric. EXAMPLE 1 A series of films were created, a first being a control sample of NRL not involving the teachings of the present invention. This thaterial was applied to a glass plate. A series of three additional films were created, in each instance, using the same NRL which was employed to make the above-reference film. 0.05% aluminum hydroxide by weight having a density of 2.42 g/cm3 and molecular weight of 78.00 was mixed and agitated with the NRL for 72 hours. Next, this sample was processed into a film on a glass plate and labeled "RA-8". A second film was created labeled "RAL-1,2". Sample RAL-1-2 differed from sample RA-8 in that 0.5% lignin by weight having a density of 0.6 g/ml was mixed with 0.06% by weight aluminum hydroxide having a density of 2.42 g/cm3 and NRL for 72 hours. Next, this sample was processed into a firm on a glass plate. A third firm was created labeled "RAFS-4" Sample RAFS-4 differed from the other samples in that 0.5% fumed silica by weight having a density of 22 g/cm3 and surface area 255 mVg was mixed with 0.06% by weight aluminum hydroxide having a density of 2.42 g/cm3 and NRL for 72 hours. Next, this sample was processed into a film on a glass plate. Films RA-8, RAL-I -2 and RAFS-4 were analyzed by conducting LEAP assays. The following results were measured noting that, in addition to the films, the control sample of latex film was also scrutinized. ELISA Inhibition Assay (ASTM D6499-03). The data is expressed as antigenic latex protein in micrograms/gram of sample. The untreated liquid latex contained 636.3 µg/g while the control film from untreated liquid latex contained 33.0 µg/g of antigenic protein. The RA-S liquid latex sample contained 12.1 µg/g of protein and latex film from the same sample contained 17.1 µg/g of antigenic protein. The RAL-1-2 liquid latex sample contained 12.3 µg/g of protein and the latex film from the same sample contained 0.4 µg/ml. The RAFS-4 liquid latex sample contained 12.3 µg/g of protein and latex film from the same sample contained 1.1 µg/g. Two additional samples, identified as RAP L-10 and RAPL-11 were prepared. RAPL-10 had a sample weight of 11.5g, an .extract volume of 58 ml, an inhibition assay concentration of less than 0.03 mg/ml and a surface area 2.9 dm2 when spread upon a planar surface. RAPL-10 consisted of NRL that was premixed with 0.15% (wt) Al(OH)3 in concentrated KOH and 0.50% (wt.) hgnin, for 72 hours. RAPL-11 had a sample weight of 10.5 g, an extract volume of 53 ml, an inhibition assay concentration of 0.2 mg/ml and a surface area of 2.9 dm2 when spread upon a planar surface. RAPL-11 consisted of NRL that was pre-mixed for 72 hours with 0.20% (wt) AI(OH) 3 in concentrated KOH and 0.50% (wt.) lignin prior to vulcanization. The antigenic protein levels of RAPL-10 and RAPL-11 were measured. RAPL-10 exhibited a level of less than 0.2 mg/g or 0.8 mg/ml and RAPL-11 exhibited a.level of approxithately 0.8 mg/g or 2.7 mg/ml. It is quite apparent from the test data which was developed and reported above that drathatic reduction in protein levels is achieved by the relatively simple processes of denaturing protein found in natural latex rubber with, ahnnmum hydroxide alone or with lignin and a fumed silica. All of these processes are employed prior to vulcanization of the NRL. In doing so, products can be produced while reducing risks imposed upon users of NRL products, including healthcare professionals, as a result of type I hypersensitivity. Most importantly, this is accomplished without diminishing the physical properties of NRL which makes commercial products made from this thaterial so desirable. EXAMPLE 2 - HEVEA VS TREATED NRL PROTEIN DETERMINATION In a second example, Hevea NRL proteins are measured by accredited test methods. The most frequently used test methods include the Modified Lowry ASTM D5712-05 (Lowry) and ELISA Inhibition ASTM D6499-03 (ELISA). These test methods have unique sensitivities and specificity. They measure total protein and antigenic protein, respectively. The Lowry test involves the reaction of latex proteins with an alkaline copper tartrate compound and the subsequent reaction of the protein-copper tartrate complex with Folin reagent, resulting in a blue color read using a spectrophotometer at 700 nm. The Lowry test is subject to interference by chemical accelerators, such as carbathates, thiurams, benzothiazoles and guanidines, used in the production of latex gloves and phenolic chemicals naturally found in latex. The Lowry test has been standardized as an ASTM test method D5712-05 for the analysis of protein in NRL and is recognized by the FDA for determination of protein levels in medical gloves. The ELISA inhibition test measures NRL antigens by using latex-specific antibothes collected from hyperimmunized rabbits. This immunochemical method is much more sensitive and reproducible than the Lowry test It also does not suffer from the limitations of interferences as does the Lowry test. The FDA does not allow protein level claims below 50 micrograms per dm2 of glove. This value has no established biological relevance but is used because of the reportable limit of detection of the Lowry method. The ELISA test is designed and performed to quantify native NRL proteins in an ammoniated state. NRL film extracts, prepared in accordance with the methods of the present invention, consistently yield low total protein and antigenic protein content using the ASTM methods, however reproducibility issues and divergent values were commonly observed due to protein modification. The Lowry does not have the required sensitivity and the ELISA is prone to variable protein hydrolysis occurring during treated latex formulation which causes anomalies in antigenic protein detection. It is worth noting that donning powder can create false positives and interfere with enzyme assays (ELISA) to some degree in research laboratories. In an on-going effort to further describe treated NRL throughout its formulary process, we subjected several treated NRL unleached film extracts to direct spectrophotometric testing at 280 nm. At this wavelength, absorbed proteins can be read directly from the extract This assessment of protein has the ability to measure all proteins including any morphed proteins no longer immuno-reactive (recognized by the ELISA antibothes). The utility of this method will rely on acceptable sensitivities and freedom from interferences. Preliminary 280 nm data are consistent in a downward trend in measured protein content demonstrating reasonable reproducibility. Table 1: Spectrophtometrk testing of 280nm and antigenic protein in treated NRL films versos untreated Hevea NRL films. (Results provided are an average of four test film samples) EXAMPLE 3 - thatERIALS AND METHODS One metric ton each of two treated NRL variants was prepared using a scale-up process ready for commercialization and distributed to selected industrial working partners. Both treated NRL variants used for production included the same amount of Al(OH)3 with the difference being fresh vs. aged and when Al(OH)3 was added to the latex. These samples are designated as "Treated NRL A" & 'Treated NRL B" respectively. It is important to note that the treated NRL was prepared on a commercial scale and was scrutinized against a double cenirifuged untreated Hevea NRL sample designated as "Control". The double centrifuge process is a popular approach taken by suppliers of latex rubber seeking to separate latex protein from latex rubber. This method is reported to reduce proteins levels by 50% compared to single centrifuged latex. The double centrifuge process yields a highly purified Hevea latex concentrate prepared by re-ceritrifuging the first centrifuged latex which has been suitably diluted. Films prepared from double centrifuged latex typically exhibit excellent clarity, low water absorption and high thelectric properties. The colloidal properties were tested on the freshly prepared treated NRL and the control Hevea NRL then again after the lattices had thatured for 21 days. The results of Treated NRL A, Treated NRL B and the control are listed in Table 2. Table 2: Colloidal properties on fresh and aged Treated NRL and Hevea NRL. The colloidal property results from the treated NRL pilot trial were deemed acceptable by industry standards, and therefore the lattices were compounded by standard additives, which are commonly used to produce surgical gloves. EXAMPLE 4 - SURGICAL GLOVES MADE FROM TREATED NRL Surgical gloves were coagulant dipped from all three compounds and were evaluated (Table 3) for physical property measurements according to ASTM standards. Table 3: Physical properties of surgical gloves made from Treated NRL and Hevea NRL. The physical properties of both Treated NRL A & B were within industry specifications. While not wishing to be bound by theory, again, it is believed that the surgical gloves made from Treated NRL demonstrate good stability upon aging due to the removal and deactivation by aluminum hydroxide of those molecular species that can be vulnerable to free radical breakdown. Protein results listed below in Table 4 appear to support this theory. Table 4: ELISA ud Lowry test results for surgical gloves made from Treated NRL versos Hevea NRL. EXAMPLE 5 - CONDOMS MADE FROM TREATED NRL Hevea NRL condoms are produced in very, large numbers on highly autothated production lines. This industry relies almost exclusively on Hevea NRL since its ability to form smooth, continuous films on drying and exhibits high strength.and elasticity when vulcanized and leached. A straight dipped production process is typically used for the production of condoms where a suitably shaped former is immersed in a latex mix and withdrawn, usually twice dipped, to produce a uniform layer of latex on the former. The latex deposit is dried and vulcanized before removal from the former. A suitable mixture of compounding ingrethents was used for all samples to ensure colloidal stability of the latex during processing. These properties are expressed in Table 5 below: Table 5: Influence of compounding ingrethents on Treated NRL and Hevea NRL. To prepare for dipping, the latex compounds were adjusted to 50% total solids. Using a clean straight wall condom former for two straight dips for each sample, the former was dipped into the respective latex compound and dried for 5 minutes @125° C. Next, the former was cooled at room temperature for 2 minutes then dipped again into the latex compound. This dip was followed by a drying time of 2 minutes @125° C then the bead was rolled. After drying, the new created condom was cured for 25 minutes @125° C. The leaching was performed in hot water (93° C) for 1 minute. After leaching, the condoms were dried for 3 minutes @125?-C, then cooled at room temperature for a brief period. Next, the condoms were stripped from the former using dry starch powder. Finally the condoms were tested for physical performance (Table 6) and for EUSA and Lowry protein testing with results expressed below in Table 7. Table 6: Physical properties of condoms made from Treated NRL and Bevea NRL. Table 6 illustrates that condoms made from Treated NRL were 30% stronger than condoms made from Hevea NRL when aged and demonstrated much better resistance to aging compared to Hevea NRL condoms. Table 7: ELISA and Lowry test results for condoms made from Treated NRL versas Hevea NKL. EXAMPLE 6 - ADHESTVES MADE FROM TREATED NRL NRL was the first polymer to be used to produce pressure sensitive adbesives (PSA). NRL has inherent advantages when used in pressure sensitive and contact adhesive formulations. NRL has a very low glass transition temperature (Tg) and also low surface energy which enables it to flow over surfaces very effectively, a key attribute of PSA. Furthermore, NRL's extremely high molecular weight gives it high internal strength preventing it from splitting during removal. The high molecular weight of NRL makes it the only thaterial that can function as a "cold seal" contact adhesive at room temperature. This is made possible because the low Tg and surface energy allow rubber films to flow cold very well while the mixing of the polymer chains is retarded by molecular weight. Some disadvantages of NRL are its ability to oxidize and become embrittled, loosing its tack and adhesion properties over time and its ability to "sensitize" skin as a result of allergic reactions. Oxidation is dealt with through use of anti-oxidants. Sensitization can be overcome with the use of a low protein starting NRL such as treated NRL, as it is understood that if high levels of protein are not present in the raw thaterial they cannot appear m the manufactured product The objective of mis phase of testing was to formulate cold seal (contact) and pressure sensitive adhesives using treated NRL and a Hevea NRL sample formulated for an adhesive compound and to conduct appropriate comparative testing for each sample. Test results are expressed in Table 8. During the formulary process, one particular observation regarding treated NRL and the/Hevea control NRL samples was the smoothness of the treated NRL sample, which is attributed to improved stability. This can eliminate the need for filtering during compounding and assist in the adhesive coating process downstream. Table 8: Physical properties of cold seal and pressure sensitive adhesives made from treated and Hevea NRL. It is concluded that low protein treated NRL can be substituted for versions of untreated Hevea NRL whether treated or not in the production of cold seal and pressure sensitive adhesives without compromising the physical performance of the resultant products. The use of the low protein NRL for adhesive applications is of particular importance because post leaching techniques commonly used for the removal of water soluble thaterials are not applicable for these product applications. EXAMPLE 7 - BREATHER BAGS, TUBING AND PROBE COVERS MADE FROM TREATED NRL Several additional medical products have been produced from treated NRL. The aim of this work was to coagulant dip breather bags and tubing and to straight dip probe covers using treated NRL under manufacturing conditions used to produce products made from Hevea NRL. The protein results are illustrated below in Table 9. Table 9: ELISA and Lowry test results for projects made from Treated NRL. Throughout this application, various publications are referenced: The disclosures of these publications in their entireties are hereby incorporated by reference into this, application. EXAMPLE 8 - FOAM MADE FROM TREATED NRL -Natural latex foam has been accepted by consumers and retailers as a premium bedding component For example, due to the impact on soundness of sleep and the increased education of consumers, one-sided thattresses that do not require flipping are becoming an industry standard. The performance and silky, luxurious feel of latex have separated latex from other foam source materials in the marketplace. limited inforthation exists regarding antigenic protein values in foam made with Hevea latex. Total latex proteins have been analyzed in Hevea latex foam that was prepared in a manner similar to that of the present invention for the production of NRL. Table 10, below, provides a comparison of protein data for foams made with the inventive NRL and with Hevea NRL. Table 10: ELISA and Lowry Protein Test Results for Foam made from Treated NRL and Hevea NRL In addition to having significantly fewer total proteins than foam produced with Hevea NRL, the inventive NRL foam was less odorous. This beneficial feature can be attributed to a lower level of biodegradable proteins in the inventive NRL. Other beneficial properties of the foam produced from the inventive NRL included noticeably higher opacity and whiteness. EXAMPLE 9 - PREPARATION OF TREATED NRL FILMS In another example, a series of films were prepared from field latex. The preparation of each film sample included the addition of 0.5 phr of Al(OH)3. Since Al(OH)3 is insoluble, it was added to a quantity of field latex (27 % TSC) in the form of a slurry. The Al(OH)3 slurry was a combination of 1 phr of 10% ammonium hydroxide (NH4OH) and 0.5 phr Al(OH)3. m addition, 0.1 phr of ammonium laurate was added to the field latex composition. The prepared mixture was added to the field latex and agitated for 24 hours under typical industry mixing conditions (for example, 30 rpm for 24 hours). A calculated amount of diarnmonium hydrogen phosphate (DAP), based on the amount of free magnesium present, was added to treat free Mg2+, followed by a period of 16 hours for desludging. The field latex composition was men centrifnged to obtain desirable TSC of from about 63 % to about 64 %. The composition was then diluted to about 30 % TSC with ammoniated water, followed by a centrifuge step to reach a TSC of from about 60 % to about 62 %. Films for antigenic protein testing were then prepared according to ASTM D6499-07. Protein levels of the treated and untreated control samples are detailed in Table 11, below. Table 11 - Proteia levels of Treated and Untreated Control Samples EXAMPLE 10 - PREPARATION OF TREATED NRL FILMS In a tenth example, a foam compound was prepared having reduced amounts of antigenic protein, relative to a non-treated foam compound. The ingrethents of the natural latex composition are listed in Table 12. Table 12 - Foam Compound Ingrethents The foam mixing process comprises first stirring Fart A to homogeneity. Next, the desired amount of Part A is weighed out into a mixing port. Part A is then added to Part B; Part B is shaken or stirred prior to the addition of Part A. The resulting mixture is kept under slow stirring for about 2 hours at ambient temperature. The mixture is then transferred into the foam mixer. The whipping speed is increased to moderate, and this speed is maintained for about 4 minutes. The whipping speed is increased above moderate, and then 50% ZnO is slowly added into the foam, ZnO, in various aspects, can be added to . destabilize the liquid NRL and assist in the foaming process. After the addition, whipping is continued until a very fine foam is obtained. 50% SSF is then added, followed by whipping for another 40-80 seconds. The foam is then immediately transferred into the mould. The foam is then gelled for about 5 to 10 minutes. Once the foam is gelled, the mould is transferred into a steam chamber, and steamed at 110 to about 120 °C for at least about IS minutes. The foam is then removed from the mould washed with water. The foam is then cured at about 50 °C for about 10 to 12 hours. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims. CLAIMS What is claimed is: 1. A natural latex composition comprising less than about 100 µg of antigenic protein per gram of composition. 2. The natural latex composition of claim 1, comprising less man about 50 µg of antigenic protein per gram of composition. 3. The natural latex composition of claim 1, comprising less than about 30 µg of antigenic protein per gram of composition. 4. The natural latex composition of claim 1, comprising less than about 20 µg of antigenic protein per gram of composition. 5. The natural latex composition of claim 1, comprising less than about 10 µg of antigenic protein per gram of composition. 6. The natural latex composition of claim 1, comprising less than about 5 µg/dm2 of antigenic protein. 7. The natural latex composition of claim 1, comprising less than about 2 µg/dm2 of antigenic protein. 8. The natural latex composition of any of the preceding claims, farther comprising aluminum hydroxide. 9. The natural latex composition of any of the preceding claims, further comprising up to about 5 parts per million aluminum hydroxide. 10. The natural latex composition of any of the preceding claims, wherein latex is present at a concentration of from about 27 parts per hundred rubber to about 30 parts per hundred rubber. 11. The natural latex composition of any of the preceding claims, wherein aluminum hydroxide is present at a concentration of from about 0.01 parts per hundred rubber to about 5 parts per hundred rubber. 12. The natural latex composition of any of the preceding claims, wherein aluminum hydroxide is present at a concentration of from about 0.1 parts per hundred rubber to about 1 parts per hundred rubber. 13. The natural latex composition of any of the preceding claims, wherein aluminum hydroxide is present at a concentration of at least about 0.01 parts per hundred rubber. 14. The natural latex composition of any of the preceding claims, wherein aluminum hydroxide is present at a concentration of about 0.4 parts per hundred rubber. 15. The natural latex composition of any of the preceding claims, wherein aluminum hydroxide is present at a concentration of about 1 part per hundred rubber. 16. The natural latex composition of any of the preceding claims, wherein the composition is present in one or more of an adhesive, a condom, glove, breather bag, tube, probe cover, catheter, thread, or foam. 17. A method of removing or denaturing at least a portion of antigenic protein to a natural latex composition, the method comprising contacting an un-vulcanized natural latex composition with aluminum hydroxide, thereby removing or denaturing at least a portion of antigenic protein from the natural latex composition. 18. The method of claim 17, further comprising centrifuging the natural latex composition after contacting with aluminum hydroxide. 19. The method of claim 17 or 18, further comprising removing the aluminum hydroxide from the natural latex composition after contacting. 20. The method of any of claims 17-19, further comprising adding at least one of lignin or fumed silica. 21. The method of any of claims 17-20, further comprising producing an article from the natural latex composition after contacting with aluminum hydroxide. 22. The method of claim 21, wherein the article is one or more of an adhesive, a condom, glove, breather bag, tube, probe cover, catheter, thread, or foam. 23. The product of the method of any of claims 17-22. A rubber latex composition is disclosed having reduced allergenicity. Methods for producing a rubber latex composition having reduced allergenicity are also disclosed.

Full Text

NATURAL RUBBER LATEX EAVING REDUCED ALLERGENICITY
ND METHOD OF MAKING
FIELD OF THE INVENTION
The present invention relates to a natural rubber latex composition having reduced
allergenicity and a method of making the same.
BACKGROUND OF THE INVENTION
The use of Hevea brasiliensis natural rubber latex (NRL) as a protective thaterial has
a long history of usage dating back to the 1800s. The widespread use of barrier NRL
articles like gloves and condoms increased tremendously in the 1980s primarily due to the
"universal precautions" policy outlined by the Centers for Disease Control NRL's
popularity and longevity can be attributed to several factors. The physical properties of
NRL are superior to non-latex synthetic products. Field latex, the feedstock thaterial for
NRL that continues to be readily available in Malaysia and Thailand, is now available in
several new regions around the world including India, Vietnam, Indonesia, Liberia,
Guatemala, and China. NRL is significantly less expensive than most petroleum-based
synthetic thaterials whose cost continues to fluctuate with the cost of crude oil
Additionally, the reduced environmental impact of natural rubber latex compared to
petroleum-based synthetic thaterials continues to be the preferred thaterial of choice in an
environmentally conscious society. The availability, ease of production and the
performance of NRL products continue to make NRL the chosen thaterial by manufacturers
and users among industry and medical professionals. Today, there are over 40,000
commercially available products made from NRL A concern with NRL continues to be its
petential involvement with adverse health effects due to the antigenicity of NRL products.
An intuitive means of controlling this parameter in the NRL source thaterial is by de-
proteination / protein modification. Validation of tins process can be achieved by specific
methods of protein quantification.
Although the first description of an allergic reaction to latex gloves appeared in the
American Literature in 1933 when usage was slight, the majority of latex allergic reactions
were documented in the late 80s and throughout the 90s and 2000s. Published data indicate

17% of American healthcare workers and up to 73% or more of frequently exposed patients,
such as those with spina bifida, were sensitized to latex proteins.
Several attempts, including new source crops, synthetic lattices and various
treatment methods, have been made to eliminate these problem proteins from Hevea NRL
by biological, physical and/or chemical methods that affect the complex acid-base behavior
of proteins. One approach has been to introduce the latex articles to multiple leaching steps
and chlorination. This approach does reduce the protein levels in the finished product;
however it weakens the latex film thus compromising the physical properties of the product
Another attempt to reduce proteins in NRL is the use of proteolytic enzymes to degrade the
proteins in the latex solution. The issue with this approach is the introduction of another
protein (the enzyme) to the latex, which may itself be allergenic. The most logical solution
is the use of low-protein latex, such as the treated NRL of the present invention as this
approach will more than likely reduce the possibility for an allergic response in the end user
of the finished product If high levels of protein are not present in the raw thaterial they
cannot appear in the manufactured product.
Two other non-Hevea NRL thaterials have been attempted to be commercialized in
the US; guayule rubber latex and Taraxacum kok-saghyz, also known as the Russian
dandelion. These thaterials are reported to be higher in cost compared to natural rubber and
presently are available only in limited quantities. Hevea NRL has been around for more
than a century and its antigenic proteins have been thoroughly researched. The allergenic
properties and economic viability of latex from the guayule & Taraxacum kok-saghyz have
yet to be scrutinized in the way that Hevea has been. Being natural products, both of these
thaterials have their own unique set of proteins with potential allergenic behavior not yet
understood.
Recently, it has been shown that allergens are distributed into few protein families
and possess a restricted number of biochemical functions. The allergen functions found
most frequently were limited to hydrolysis of proteins, polysaccharides, and lipids; binding
of metal ions and lipids; storage; and cytoskeleton association. The limited number of
protein families that are allergenic and the narrow functional distribution of most allergens
support the existence of yet unknown factors that render proteins allergenic. Many of these
specific protein functions play into the chemistry used to manipulate them yielding a
modified NRL source thaterial.

The last decadrf and a half lias seen a great change in latex use as a result of publicity
concerning these allergies. Today in the U.S. there is almost universal awareness of the risks
associated with repeated latex exposure, particularly in the healthcare fields where exposure
is more profound. Awareness of the risks, however, extends into the industrial glove
market, and even to the general public, who have received risk warnings from various
government and health-watch groups. As a result mere exists much interest in the market,
fueling a strong trend to reduce exposure to latex-associated allergens.
Manuiacturers nave responded in several ways: I) reduction or elimination of
donning powder, 2) utilization of chlorinated glove washing and additional processing steps
to reduce antigenic protein load, 3) use of coatings to reduce actual contact with latex, and
4) introduction of alternative thaterials that mimic, natural latex performance characteristics.
Each of these industry reactions represents compromises either from ease of use,
performance, or cost standpoint In short, nothing beats the tactile, comfort, and barrier
protection that is provided by natural latex products.
In the last ten years there has been an increasing awareness of the possible
immunologic and other reaction risks associated with the use of latex gloves. This
awareness is the result of the proliferation in glove usage among healthcare workers in order
to avoid potential exposure to HIV/AIDS transmission sources.
An increase in the reported incidence of latex allergic sensitivity and other skin
reactions has been concomitant with increased glove usage. This has spurred an effort by
industry leaders and manufacturers to reduce exposure to latex. Glove makers have initiated
latex substitution in the manufacture of gloves, limited use of donning powder so as to
prevent antigenic proteins leached into the cornstarch powder from becoming airborne (a
source of respiratory exposure and subsequent sensitization), and the introduction of low
'protein methods for latexes to reduce the overall protein content of gloves.
Latex rubber in its natural form consists of polymeric, long chain molecules
consisting of repeating units of isoprene:
When it is harvested from the rubbertree, Hevea brasilieasis, the liquid, sticky
substance also contains proteins like heavarnine, hevein, and rubber elongation factor.
Although the basic isoprene polymer is non-antigenic, the associated proteins are highly

antigenic. It is important to note this difference in order to minimize the antigenic impact of
natural latex without destroying its underlying structure.
In its natural state, natural latex does not possess characteristics that are
commercially useful. In order to achieve utilitarian value, including strength, elasticity, and
memory, the chains of isoprene must be cross-linked to one another. Depending on the type
of rubber end product desired, this is achieved with either application of heat and sulfur, or
in the case of latex rubber used in the manufacture of gloves, various chemical accelerators
that donate or bind sulfur, thus speeding the cross-linking process. The major accelerators
are thiurams, mercaptobenzothaizoles (MBTs) and carbathates.
In addition to accelerators, latex glove manufacturers utilize another class of
additives, called sensitizers, which most frequently consist of substituted phenols. These
substances are used to impede oxidation, and resultant degradation, of natural latex.
Foreign thaterials, natural latex proteins, accelerators, and sensitizers can all provoke
human reactions, but the allergenic reactions due to the proteins are considered to be the
most problethatic in the healthcare field. The following briefly describes three major types
of foreign thaterial reactions most commonly associated with latex use:
Irritant derthatitis is skin irritation that does not involve the body's immune
response, that is, it is not an allergic response. Frequent hand washing and inadequate
drying, aggressive scrubbing technique or detergents, mechanical abrasive effect of powder,
clithatic irritation, and emotional stress can all cause this condition. Even though this is not
an allergic reaction, irritant hand derthatitis can cause breaks in the skin which can facilitate
entry of the sensitizing latex protein or chemicals found in the commercial product, and in
turn lead to latex allergy.
Delayed cutaneous hypersensitivity (type PV allergy) is contact (hand) derthatitis
generally due to the chemicals used in latex production. It is mediated via T-cells causing a
skin reaction that is typically seen 6-48 hours after contact The reaction is local and limited
to the skin that has contact with the glove. While not life threatening, those with type IV
allergy are at increased risk to develop type I allergy. As in irritant derthatitis, the broken
skin barrier can provide an entry site into the body for foreign thaterials. This can produce
sensitization to latex proteins leading to a more serious type of reaction.

The third and potentially most serious type of reaction associated with latex use is a
true IgE/histamino-mediated allergy to protein (also called immediate, or type I
hypersensitivity). This type of reaction can involve local or systemic symptoms. Local
symptoms include contact urticaria (hives), which appear in the area where contact
occurred, Le., the hands, but can spread beyond that area and become generalized. More
generalized reactions include allergic rhinbconjunctrvitis and asthma. The presence of
allergic manifestations to natural latex indicates an increased risk for anaphylaxis, a rare but
serious reaction experienced by some individuals who have developed an allergy to certain
proteins (e.g., insect stings, natural rubber, penicillin). This type I reaction can occur within
seconds to minutes of exposure to the allergen. When such a reaction occurs, it can progress
rapidly from swelling of the lips and airways, to shortness of breath, and may progress to
shock and death, sometimes within minutes. While any of these signs and symptoms may be
the first indication of allergy, in many workers with continued exposure to the allergen,
mere is progression from skin to respiratory symptoms over a period of months to years.
Some studies indicate that individuals with latex allergy are more likely than latex non-
allergic persons to be atopic (have an increased immune response to some common
allergens, with symptoms such as asthma or eczema). Once natural latex allergy occurs,
allergic individuals continue to experience symptoms, which have included life-threatening
reactions.
There are several classes of people known to be at increased risk for latex allergy.
Medical patients who have had multiple hospitalizations and have been exposed numerous
. times to latex medical products, healthcare workers, and atopic individuals comprise this
high-risk group. Current estithates are that 8-17% of healthcare workers become sensitized.
Despite the recent emphasis on universal precautions, the marked increase in glove usage
due to commutable disease prevention is largely blamed for the increase in latex allergies
among these groups. Atopic individuals (those with other allergies or asthma) are at
significantly greater risk to develop latex allergy than the general population. It is estithated
that as many as 25-30% of atopic healthcare workers may become sensitized.
The problems presented by allergic reactions to latex are exacerbated by the
proliferation and widespread use of latex-based products. Latex presents great risk to
persons in the health care industry where latex products are used extensively in the form of
gloves, casts, dressings, tapes, catheters, tubes, drains, airway management devices, med
delivery, tourniquets, monitoring devices, and others. One persistent threat lies in the

cornstarch powder used to lubricate and ease donning of rubber gloves. The proteins absorb
onto the powder and become aerosolized during use and when the gloves are donned and
removed.
Products containing latex are also found throughout the home in the form of
balloons, art supplies, toys, swimming equipment, contraceptive devices, cosmetics, bottle
nipples, pacifiers, clothing, chewing gum, rubber bands, and others. Groups at risk include
particularly children with spina bifida, those who have been shown to have a very high risk
of latex sensitivity, patients with congenital urologic abnormalities, healthcare providers
and rubber industry workers.
Since the severe allergic reactions to latex are due to their naturally occurring
proteins, the prior art offers little in the way of solutions. For example, ammonia treatment
of the NRL proteins can cause breakdown and precipitation of some latex proteins, but the
allergeniciry appears to be preserved and other antigenic latex proteins are unextractable. In
short, the literature recommends that the only treatment available for latex allergy is
avoidance.
The Food and Drug Adrninistration (FD A), as well as other state and federal
agencies, has received requests to ban the use of glove powder. It has been suggested that
experimental and clinical studies demonstrate that glove powder on medical gloves can
enhance foreign body reactions, increase infections and act as a carrier of natural latex
allergens. The National Institute of Occupational Safety and Health (NIOSH) recently
issued a safety alert recommending the use of powder-free, reduced protein content latex
gloves to reduce exposure to natural latex proteins (allergens).
Experimental and clinical data demonstrate that some NRL proteins are allergenic.
Further natural latex proteins bind to cornstarch while aerosolized powder on. NRL gloves
is allergenic and can cause respiratory allergic reactions. Published studies support the
conclusion that airborne glove powder represents a threat to individuals allergic to NRL and
may represent an important agent for sensitizing non-allergic individuals. There are also
published data (although limited) and clinical experience that cornstarch powder on NRL
gloves may also be a contributing factor in the development of irritation and type IV
allergy.

In addition to dusting powder, other lubricants may also be used in the
manufacturing process. Latex and some polymers, are tacky and dipped products such as
condoms and gloves made of these thaterials stick to the mold or former. A mold-release
lubricant such as calcium carbonate or a mixture of calcium carbonate and cornstarch is
used to enable the removal of these dipped products like condoms and gloves from molds.
The other aide of the dipped product may be coated with a donning lubricant, such as
cornstarch or silicone oils, to make donning easier and to prevent dipped products from
sticking during the manufacturing process.
Over the past three years, the FDA has received requests to ban the use of all glove
powders. These requests have been based on repeated clinical and experimental studies
reporting that cornstarch on surgical gloves can damage tissue's resistance to infection,
enhance the development of infection, serve as a potential source of occupational asthma,
and provide a source of natural latex protein exposure to natural latex allergic individuals.
The issues regarding the use of glove powder, except for the transport of natural latex
protein allergens, apply to the use of glove powder on both NRL and synthetic gloves.
Several states, acting on their own initiative have banned the sale and use of glove powders.
Thus, mere is a need to develop a NRL composition and method of making the same
that can provide reduced allergenicity. It is an object of the present invention is to teach a
method of reducing the allergenicity of NRL prior to vulcanization to enable the creation of
a commercial product relatively free of allergenicity with no apparent loss of physical
properties.
SUMMARY OF THE INVENTION
The present invention provides a natural latex composition having reduced
allergenicity and a method of making the inventive compositian.- In accordance with the
purposes of this invention, as embodied and broadly described herein, the invention
therefore provides, in one aspect a NRL composition having reduced allergenicity.
In another aspect, the present invention provides a method of reducing allergenicity of
NRL, the method comprising subjecting a NRL, prior to vulcanization, to aluminum
hydroxide so as to reduce protein levels in the latex rubber.
Additional advantages of the invention will be set forth in part in the description that
follows, and in part will be obvious from the description, or may be learned by practice of

the invention. The advantages of the invention will be realized and attained by means of the
elements and combinations particularly pointed out in the appended claims. It is to be
understood that both the foregoing general description and the following detailed
description are exemplary and explanatory only and are not restrictive of the invention, as
claimed.
DETAILED DESCRIPTION OF THE INVENTION
The present invention may be understood more readily by reference to the following
detailed description of preferred embodiments of the invention and the Examples included
therein and their previous and following description. It is also to be understood that the
terminology used herein is for the purpose of describing particular embodiments only and is
not intended to be limiting.
It must be noted that, as used in the specification and the appended claims, the
singular forms "a," "an" and "the" include plural referents unless the context clearly dictates
. otherwise. Thus, for example, reference to "a natural latex composition" includes mixtures
of natural latex compositions.
Often, ranges are expressed herein as from "about" one particular value, and/or to
"about" another particular value. When such a range is expressed, another embodiment
includes from the one particular value and/or to the other particular value. Similarly, when
values arc expressed as approxithations, by use of the antecedent "about," it will be
understood that the particular value forms another embodiment. It will be further
understood that the endpoints of each of the ranges are significant both in relation to the
other endpoint, and independently of the other endpoint
In this specification and in the claims that follow, reference will be made to a number
of terms that shall be defined to have the following meanings:
A weight percent of a component, unless specifically stated to the contrary, is based
on the total weight of the formulation or composition in which the component is included.
"Optional" or "optionally" means that the subsequently described event or
circumstance may or may not occur, and that the description includes instances where said
event or circumstance occurs and instances where it does not For example, the phrase

"optionally present" means that the substance at reference may or may not be present, and
that the description includes instance wherein the substance is and is not present.
As used herein, "parts per hundred rubber" or "PHR" means the proportion of a
component per 100 grams of elastomer.
"Treated NRL" as used herein, is intended to refer to a NRL composition that has
been treated in accordance with the various methods of the present invention.
"Antigenic protein," as used herein, refers to a protein that can induce the generation
of antibothes and can cause an immune response in a subject who comes in contact with the
antigenic protein.
As briefly described above, the present invention provides a NRL composition
having reduced allergenicity. The present invention also provides a method of making such
a reduced allergenicity NRL, the method comprising contacting a NRL composition with an
aluminum hydroxide, optionally agitating the resulting mixture, and then vulcanizing the
resulting mixture. While not wishing to be bound by theory, it is believed that under certain
conditions and in accordance with the instant disclosure, NRL can be treated with aluminum
hydroxide to produce protein complexes. Further, the formed protein complexes can then
be removed from a treated NRL composition.
In one aspect, the NRL of the present invention can be produced by exchanging
and/or complexing at least a portion of the proteins from, for example, a field latex sap
emulsion with aluminum hydroxide. Aluminum hydroxide can be stable under most
conditions. Various ionic forms of aluminum hydroxide can bond with proteins of
complementary charge which are driven toward ionic equilibria or an isoionic point.
. Aluminum hydroxide is an amphoteric substance, meaning it can act as either an acid or a
base and can readily share electrons with proteins. Amino acids, the blocks that build the
proteins, are both very weak acids and very weak bases, thus creating the basis for both
ionic and covalent bonding to aluminum hydroxide. Aluminum hydroxide is commonly
used as an absorbent, emulsifier, ion exchanger or antacid. Aluminum hydroxide can also
be used in the purification, of water because it can form a jelly-like structure, suspending
unwanted thaterials in water, including bacteria.

METHOD OF MAKING REDUCED ALLXRGENICITY NRL
In one embodiment, the present invention involves a method of reducing allergenicity
of NRL comprising contacting a NRL composition to an aluminum hydroxide and agitating
the resulting mixture to produce an intithate admixture. The individual concentrations of
latex and aluminum hydroxide can vary depending upon the process parameters and the
desire properties of the resultant product The individual concentrations of latex and
aluminum hydroxide can also vary depending on variations of, for example, protein levels
in raw thaterials. In one aspect, the present invention comprises any amount of latex
combined with any amount of aluminum hydroxide^and is not intended to be limited to any
particular concentration range of one or more components. In various exemplary
embodiments, latex comprises from about 27 phr (parts per hundred rubber) to about 30 phr
and aluminum hydroxide comprises from about 0.01 phr to about 5 phr, for example, about
0.01,0.02,0.04, 0.06,0.08,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8, 0.9,1,12,1.4,1.6,1.8,2,
2.5,3,3.5,4,4.5, or 5 phr, or from about 0.1 phr to about 1 phr, for example, about 0.1,0.2,
0.3, 0.4, 0.5,0.6,0.7,0.8, 0.9, or 1 phr. In a specific embodiment, at least about 0.1 phr
aluminum hydroxide is admixed with the NRL composition. In another specific
embodiment, about 0.4 phr aluminum hydroxide is contacted with a NRL composition. In
another specific embodiment, about 1 phr aluminum hydroxide is contacted with a NRL
composition.
Any duxoinum hydroxide suitable for contacting with a NRL composition can be
utilized in the present invention. The average particle size and distribution, the chemical
purity, and/or the density of a particular aluminum hydroxide can vary depending upon the
specific process parameters and/or the requirements of the desired final latex article. In
various embodiments, the aluminum hydroxide has an average particle size of from about 1
to-about 100 niicrometers, foe example, about 1,2,3,4,5,6,7, 8,9,10,12,14,15,16,20,
30,40,50,60,70,80,90, or 100 micrometers; from about 1 to about 20 micrometers, for
example, about 1,2,3,4,5,6,7,8,9,10,12,13,14,15,16, or 20 micrometers; or from
about 5 to about 15 micrometers, for example, about 5,6,7, 8, 9,10,12,14, or 15
micrometers. It should be noted that aluminum hydroxide particles having a smaller size
and/or increased surface area can typically provide greater levels of protein reduction man
larger sized particles. In one embodiment, the aluminum hydroxide has a molecular weight
of about 78.00 and a density of about 2.42 g/cm3.

The aluminum hydroxide of the present invention can be contacted with the NRL
composition at any time prior to vulcanization. NRL compositions are frequently
centrifuged to concentrate the composition with the added benefit of purifying the thaterial
by removal of a portion of water soluble protein thaterial contained therein. In one
embodiment of the present invention, the NRL composition is not centrifuged. In another
embodiment, the NRL composition is centrifuged to remove at least a portion of the protein
thaterial contained therein. If a NRL composition is centrifuged, aluminum hydroxide can
be added to the composition prior to or subsequent to centrifugation. In a preferred
embodiment, aluminum hydroxide is contacted with the NRL composition prior to
centrifugmg, and the resulting mixture is then centrifuged.
In another embodiment, the aluminum hydroxide can be admixed with a NRL
composition for a period of time, such as, for example, from about less man an hour to
about 72 hours, for example, about 0.5,1,2, 3,4, 5, 8,10,12,15,20,22,24,26, 28,30,36,
40,45,50,55,60,65,70 or 72 hours, and optionally agitated. la another embodiment, the
admixture is contacted for a period of time from about 18 to about 36 hours, for example,
about 18,20,22,24,26, 28,30,32,34, or 36 hours with agitation. In a specific
embodiment, the aluminum hydroxide is contacted with the NRL composition for about 5
hours. In another embodiment, the aluminum hydroxide is contacted with the NRL
composition for about 36 hours, m yet another embodiment, the aluminum hydroxide is
contacted with the NRL composition for about 72 hours. While not wishing to be bound by
theory, it is believed that contacting the NRL composition with aluminum hydroxide
modifies at least a portion of the antigenic protein within the NRL composition.
It should be noted that other components, such as, for example, fillers, additives,
Theological and/or processing aids can be added to the NRL composition before,
- simultaneous with, and/or after addition of the aluminum hydroxide.
In various embodiments, one or more Burfactants can be mixed with the NRL
composition. A surfactant, if used, can be contacted with and/or mixed with a NRL
composition at any time prior to vulcanization. In a preferred embodiment, a surfactant is
mixed with a NRL and aluminum hydroxide composition prior to the optional removal of
aluminum hydroxide. Addition of a surfactant can, while not wishing to be bound by
theory, facilitate the association and/or removal of both hydrophobic and hydrophilic
proteins from the NRL composition. In addition, a surfactant, if used, can, in various

embodiments, result in facile removal of proteins from the composition by a subsequent
leaching and/or extraction step. A surfactant, if used, can be any surfactant suitable for use
in a NRL composition. In various embodiments, a surfactant can comprise an anionic
surfactant, a catiomc surfactant, a non-ionic surfactant, or a combination thereof Further, a
surfactant, if used, can be added or contacted in any concentration suitable for use in a given
process and/or for producing a desired latex article.
The combination of an aluminum hydroxide/surfactant treatment can, in various
embodiments, result in significantly improved removal of protein from the NRL
, composition. The addition of an optional surfactant can facilitate liberation of proteins
-, absorbed onto the latex particle layer. In such a treatment, the liberated (hydrolyzed)
proteins can associate with and/or bind to the aluminum hydroxide present in the solution.
At near neutral pH values, aluminum hydroxide is not substantially water soluble and can be
removed via centrifugation, as described above. The use of a surfactant can provide
additional benefits upon aging of a latex solution and/or article. In one embodiment,
proteins in a latex composition that has not been treated with a surfactant can remain
absorbed onto latex particles and can be subsequently released upon aging. In various
embodiments, a NRL composition not treated with aluminum hydroxide can have an
antigenic protein value of from about 32 to about 96 % higher than a composition treated
with aluminum hydroxide and surfactant after 21 days storage. While the specific
improvement of a composition can vary depending on, for example, the properties of the
feedstock thaterial, it should be appreciated that the addition of a surfactant to a treatment
process can result in reduced antigenic protein levels, even after storage, and thus, improved
stability of the resulting latex solution or article.
Once the admixture of NRL and aluminum hydroxide is contacted and optionally
. agitated, thus complexhig and/or modifying at least a portion of the antigenic protein, the
treated latex containing modified protein can be vulcanized to produce a latex article. In
one embodiment, a vulcanizing step can be performed without substantially disrupting the
physical and/or chemical properties of the NRL.
After treatment with aluminum hydroxide, the aluminum hydroxide and any
antigenic protein that has associated with and/or bound to the aluminum hydroxide can be
optionally removed. In one embodiment, at least a portion of the aluminum hydroxide is
removed from the NRL composition after contacting and agitation. In another embodiment,

substantially all of the aluminum hydroxide is removed from the NRL composition after
contacting and agitation. Removal of aluminum hydroxide from a treated NRL composition
can be performed by any suitable technique. In various embodiments, removal of
aluminum hydroxide can be performed by filtration techniques, centrifugation, or a
combination thereof. Treated NRL compositions can also be subjected to a treatment step
comprising exposure to hot water and/or chlorine or a chlorine containing solution, such as,
for example, chlorine containing solutions commonly utilized in latex manufacturing
processes.
After the optional removal of aluminum hydroxide from a NRL composition, the
resulting latex can exhibit improved optical properties, such as, for example, a cleaner color
and/or appearance, reduced color, and/or increased translucency. Such improvements,
while not wishing to be bound by theory, are believed to be due to the removal or proteins,
lipids and/or lutoids, or a combination thereof from the NRL composition. While not
wishing to be bound by theory, it is believed that untreated NRL containing these thaterials
can hydrate quicker, thus compromising the resultant articles tensile strength and chemical
barrier, especially for example, upon aging.
In another aspect, a portion of, substantially all of, or all of the aluminum hydroxide
can remain in a treated NRL composition. In yet another aspect, an excess of aluminum
hydroxide can be used and/or additional aluminum hydroxide added to the composition
such that a residual amount of aluminum hydroxide remains, for example, suspended in a
liquid latex solution. Such an amount of aluminum hydroxide can be added prior to,
simultaneous to, or subsequent to the addition of any other amounts of aluminum
hydroxide, and optionally after removal of at least a portion of any earlier added aluminum
hydroxide that can be complexed to protein. Residual aluminum hydroxide can be useful in
various aspects due to the fact that some protein that is covalently bonded to a rubber
particle can persist, but in the continued presence of an alkali pH, and in some aspects,
especially when compounded, the backbone of such a protein can break and the
protein/peptide subsequently go into the aqueous phase of the composition. Thus, the
presence of aluminum hydroxide can, in various aspects, complex proteins, creating an
insoluble precipitate known as an organic lake.
Further, while not wishing to be bound by theory, it is hypothesized that as water is
removed during production of a latex article, a salt of the protein and aluminum hydroxide

can be formed that displaces water as a byproduct Once such a salt is formed, the protein
will have no available reactive sites. Such a protein can remain present in the composition
or produced article as part of a neutral and non-reactive molecule, without resulting in
allergenictty.
Digestion of any remaining protein can be thermodynamically driven and can be
well suited to achieving low protein levels in, for example, dipping applications such as
gloves and condoms. Further, such a digested precipitate can be easily washed and/or
extracted using common industry techniques.
Removal of proteins and unreacted compounds from a composition can be
performed by a variety of suitable methods. In one aspect, a wet-gel leaching technique can
be used to remove, for example, excess calcium nitrate and/or other water-soluble non-
rubber thaterials, such as, for example, proteins and added compounding ingrethents.
Literature references describe protein removal by wet-gel leaching to be ineffective due to
the fact that a significant portion of such proteins have typically not migrated to a surface
when, for example, a film was healed to attain the wet-gel state. In one aspect, since the
techniques of the present invention can remove significant portions of protein during NRL
creation, the typically expected increases in protein at various stages of article (e.g., glove)
production do not occur, allowing manufacturers opportunities to reduce the complexity of
and/or the number of steps in the manufacturing process.
In one embodiment, the methods of the present invention provide an advantage over
traditional latex processing methods can be easily integrated into the current processing
scheme without the need to acquire and/or install additional capital equipment
TREATED NRL HAVING REDUCED ALLERGENICTTY
The NRL composition formed by the method described herein can provide reduced
allergenicity over traditional latex rubber products and can be suitable for use in a variety of
applications. While not intending to be limited, applications for products produced from
treated NRL can include medical, health care, and personal care products, such as, for
example, examination and surgical gloves, condoms, breather bags, latex tubing, probe
covers, and catheters, along with other applications such as threads, foams, cold seal and
pressure sensitive adhesives, and balloons.

Products produced from the treated NRL composition of the present invention can
demonstrate excellent resistance to aging compared to untreated NRL (e.g., Hevea) samples.
In one embodiment, and while not wishing to be bound by theory, the use of aluminum
hydroxide can bind and/or remove antigenic protein from a Latex composition and can also
assist in the removal of species vulnerable to free radical breakdown. Removal of such
species can prevent, reduce, and/or delay degradation of rubber articles produced form
NRL. For example, the presence and/or contacting of aluminum hydroxide with a NRL
composition can provide increased stability of freshly harvested latex. The aluminum
hydroxide treatment can thus be used as a partial and/or complete replacement for
surfactants. In one embodiment, a NRL composition is treated with aluminum hydroxide
and is not treated and/or contacted with a surfactant In another embodiment, a NRL
composition is treated with aluminum hydroxide and is treated and/or contacted with a
surfactant The combination of aluminum hydroxide and surfactant treatment and/or
contacting with a NRL composition can, in various embodiments, provide enhanced
stability and protein removal
Film samples and products made from a NRL treated in accordance with the
methods of the present invention can provide a significant reduction in protein levels over
products prepared using traditional methods.
A treated NRL composition can have any level of antigenic protein present that is
suitable for an intended application. As tolerances for antigenic proteins can vary
depending upon the intended application, method of use, and human factors, the target level
of antigenic protein in a treated NRL composition can also vary and the present invention is
not intended to be limited to a treated NRL composition having antigenic
protein level In one aspect, a treated NRL composition is free of or substantially free of
- antigenic- protein. In other aspects, a treated NRL composition can-have less than .about 100
µg, less than about SO µg, less than about 30 µg, less than about 20 µg, less than about 10
µg, less' than about 5 µg, or less than about 2 µg of antigenic protein per gram of
composition. In still other aspects, a treated NRL composition can have less man about 100
µg/dm2, less than about 50 µg/dm2, less than about 30 µg/dm2, less than about 20 µg/dm2
less than about 10 µg/dm2, less than about 5 µg/dm2, or less than about 2 µg/dm2 of
antigenic protein.

EXPERIMENTAL
The following examples are put forth so as to provide those of ordinary skill in the art
with a complete disclosure and description of how the reduced allergenic NRL
compositions and associated processes and methods are constructed, used, and evaluated,
and are intended to be purely exemplary of the invention and are not intended to limit the
scope of what the inventors regard as their invention. Efforts have been made to ensure
accuracy with respect to numbers (e.g., amounts, temperature, film thickness, etc.) but some
errors and deviations should be accounted for. Unless indicated otherwise, parts are parts
by weight, temperature is in °C (Celsius) or is at ambient temperature, and pressure is at or
near atmospheric.
EXAMPLE 1
A series of films were created, a first being a control sample of NRL not involving
the teachings of the present invention. This thaterial was applied to a glass plate.
A series of three additional films were created, in each instance, using the same
NRL which was employed to make the above-reference film. 0.05% aluminum hydroxide
by weight having a density of 2.42 g/cm3 and molecular weight of 78.00 was mixed and
agitated with the NRL for 72 hours. Next, this sample was processed into a film on a glass
plate and labeled "RA-8". A second film was created labeled "RAL-1,2". Sample RAL-1-2
differed from sample RA-8 in that 0.5% lignin by weight having a density of 0.6 g/ml was
mixed with 0.06% by weight aluminum hydroxide having a density of 2.42 g/cm3 and NRL
for 72 hours. Next, this sample was processed into a firm on a glass plate. A third firm was
created labeled "RAFS-4" Sample RAFS-4 differed from the other samples in that 0.5%
fumed silica by weight having a density of 22 g/cm3 and surface area 255 mVg was mixed
with 0.06% by weight aluminum hydroxide having a density of 2.42 g/cm3 and NRL for 72
hours. Next, this sample was processed into a film on a glass plate. Films RA-8, RAL-I -2
and RAFS-4 were analyzed by conducting LEAP assays. The following results were
measured noting that, in addition to the films, the control sample of latex film was also
scrutinized.
ELISA Inhibition Assay (ASTM D6499-03). The data is expressed as antigenic latex
protein in micrograms/gram of sample. The untreated liquid latex contained 636.3 µg/g
while the control film from untreated liquid latex contained 33.0 µg/g of antigenic protein.

The RA-S liquid latex sample contained 12.1 µg/g of protein and latex film from the same
sample contained 17.1 µg/g of antigenic protein. The RAL-1-2 liquid latex sample
contained 12.3 µg/g of protein and the latex film from the same sample contained 0.4 µg/ml.
The RAFS-4 liquid latex sample contained 12.3 µg/g of protein and latex film from the
same sample contained 1.1 µg/g. Two additional samples, identified as RAP L-10 and
RAPL-11 were prepared.
RAPL-10 had a sample weight of 11.5g, an .extract volume of 58 ml, an inhibition
assay concentration of less than 0.03 mg/ml and a surface area 2.9 dm2 when spread upon a
planar surface. RAPL-10 consisted of NRL that was premixed with 0.15% (wt) Al(OH)3 in
concentrated KOH and 0.50% (wt.) hgnin, for 72 hours.
RAPL-11 had a sample weight of 10.5 g, an extract volume of 53 ml, an inhibition
assay concentration of 0.2 mg/ml and a surface area of 2.9 dm2 when spread upon a planar
surface. RAPL-11 consisted of NRL that was pre-mixed for 72 hours with 0.20% (wt)
AI(OH) 3 in concentrated KOH and 0.50% (wt.) lignin prior to vulcanization.
The antigenic protein levels of RAPL-10 and RAPL-11 were measured. RAPL-10
exhibited a level of less than 0.2 mg/g or 0.8 mg/ml and RAPL-11 exhibited a.level of
approxithately 0.8 mg/g or 2.7 mg/ml.
It is quite apparent from the test data which was developed and reported above that
drathatic reduction in protein levels is achieved by the relatively simple processes of
denaturing protein found in natural latex rubber with, ahnnmum hydroxide alone or with
lignin and a fumed silica. All of these processes are employed prior to vulcanization of the
NRL. In doing so, products can be produced while reducing risks imposed upon users of
NRL products, including healthcare professionals, as a result of type I hypersensitivity.
Most importantly, this is accomplished without diminishing the physical properties of NRL
which makes commercial products made from this thaterial so desirable.
EXAMPLE 2 - HEVEA VS TREATED NRL PROTEIN DETERMINATION
In a second example, Hevea NRL proteins are measured by accredited test methods.
The most frequently used test methods include the Modified Lowry ASTM D5712-05
(Lowry) and ELISA Inhibition ASTM D6499-03 (ELISA). These test methods have unique
sensitivities and specificity. They measure total protein and antigenic protein, respectively.

The Lowry test involves the reaction of latex proteins with an alkaline copper
tartrate compound and the subsequent reaction of the protein-copper tartrate complex with
Folin reagent, resulting in a blue color read using a spectrophotometer at 700 nm. The
Lowry test is subject to interference by chemical accelerators, such as carbathates, thiurams,
benzothiazoles and guanidines, used in the production of latex gloves and phenolic
chemicals naturally found in latex. The Lowry test has been standardized as an ASTM test
method D5712-05 for the analysis of protein in NRL and is recognized by the FDA for
determination of protein levels in medical gloves.
The ELISA inhibition test measures NRL antigens by using latex-specific antibothes
collected from hyperimmunized rabbits. This immunochemical method is much more
sensitive and reproducible than the Lowry test It also does not suffer from the limitations of
interferences as does the Lowry test. The FDA does not allow protein level claims below 50
micrograms per dm2 of glove. This value has no established biological relevance but is used
because of the reportable limit of detection of the Lowry method.
The ELISA test is designed and performed to quantify native NRL proteins in an
ammoniated state. NRL film extracts, prepared in accordance with the methods of the
present invention, consistently yield low total protein and antigenic protein content using
the ASTM methods, however reproducibility issues and divergent values were commonly
observed due to protein modification. The Lowry does not have the required sensitivity and
the ELISA is prone to variable protein hydrolysis occurring during treated latex formulation
which causes anomalies in antigenic protein detection. It is worth noting that donning
powder can create false positives and interfere with enzyme assays (ELISA) to some degree
in research laboratories.
In an on-going effort to further describe treated NRL throughout its formulary
process, we subjected several treated NRL unleached film extracts to direct
spectrophotometric testing at 280 nm. At this wavelength, absorbed proteins can be read
directly from the extract This assessment of protein has the ability to measure all proteins
including any morphed proteins no longer immuno-reactive (recognized by the ELISA
antibothes). The utility of this method will rely on acceptable sensitivities and freedom
from interferences. Preliminary 280 nm data are consistent in a downward trend in
measured protein content demonstrating reasonable reproducibility.

Table 1: Spectrophtometrk testing of 280nm and antigenic protein in treated NRL
films versos untreated Hevea NRL films.

(Results provided are an average of four test film samples)
EXAMPLE 3 - thatERIALS AND METHODS
One metric ton each of two treated NRL variants was prepared using a scale-up
process ready for commercialization and distributed to selected industrial working partners.
Both treated NRL variants used for production included the same amount of Al(OH)3 with
the difference being fresh vs. aged and when Al(OH)3 was added to the latex. These
samples are designated as "Treated NRL A" & 'Treated NRL B" respectively. It is
important to note that the treated NRL was prepared on a commercial scale and was
scrutinized against a double cenirifuged untreated Hevea NRL sample designated as
"Control". The double centrifuge process is a popular approach taken by suppliers of latex
rubber seeking to separate latex protein from latex rubber. This method is reported to
reduce proteins levels by 50% compared to single centrifuged latex. The double centrifuge
process yields a highly purified Hevea latex concentrate prepared by re-ceritrifuging the first
centrifuged latex which has been suitably diluted. Films prepared from double centrifuged
latex typically exhibit excellent clarity, low water absorption and high thelectric properties.
The colloidal properties were tested on the freshly prepared treated NRL and the
control Hevea NRL then again after the lattices had thatured for 21 days. The results of
Treated NRL A, Treated NRL B and the control are listed in Table 2.

Table 2: Colloidal properties on fresh and aged Treated NRL and Hevea NRL.

The colloidal property results from the treated NRL pilot trial were deemed acceptable by
industry standards, and therefore the lattices were compounded by standard additives, which
are commonly used to produce surgical gloves.
EXAMPLE 4 - SURGICAL GLOVES MADE FROM TREATED NRL
Surgical gloves were coagulant dipped from all three compounds and were evaluated (Table
3) for physical property measurements according to ASTM standards.
Table 3: Physical properties of surgical gloves made from Treated NRL and Hevea
NRL.

The physical properties of both Treated NRL A & B were within industry specifications.
While not wishing to be bound by theory, again, it is believed that the surgical gloves made
from Treated NRL demonstrate good stability upon aging due to the removal and
deactivation by aluminum hydroxide of those molecular species that can be vulnerable to
free radical breakdown. Protein results listed below in Table 4 appear to support this
theory.

Table 4: ELISA ud Lowry test results for surgical gloves made from Treated NRL
versos Hevea NRL.

EXAMPLE 5 - CONDOMS MADE FROM TREATED NRL
Hevea NRL condoms are produced in very, large numbers on highly autothated
production lines. This industry relies almost exclusively on Hevea NRL since its ability to
form smooth, continuous films on drying and exhibits high strength.and elasticity when
vulcanized and leached. A straight dipped production process is typically used for the
production of condoms where a suitably shaped former is immersed in a latex mix and
withdrawn, usually twice dipped, to produce a uniform layer of latex on the former. The
latex deposit is dried and vulcanized before removal from the former.
A suitable mixture of compounding ingrethents was used for all samples to ensure
colloidal stability of the latex during processing. These properties are expressed in Table 5
below:

Table 5: Influence of compounding ingrethents on Treated NRL and Hevea NRL.

To prepare for dipping, the latex compounds were adjusted to 50% total solids.
Using a clean straight wall condom former for two straight dips for each sample, the former
was dipped into the respective latex compound and dried for 5 minutes @125° C. Next, the
former was cooled at room temperature for 2 minutes then dipped again into the latex
compound. This dip was followed by a drying time of 2 minutes @125° C then the bead
was rolled. After drying, the new created condom was cured for 25 minutes @125° C. The
leaching was performed in hot water (93° C) for 1 minute. After leaching, the condoms
were dried for 3 minutes @125?-C, then cooled at room temperature for a brief period.
Next, the condoms were stripped from the former using dry starch powder. Finally the
condoms were tested for physical performance (Table 6) and for EUSA and Lowry protein
testing with results expressed below in Table 7.
Table 6: Physical properties of condoms made from Treated NRL and Bevea NRL.

Table 6 illustrates that condoms made from Treated NRL were 30% stronger than
condoms made from Hevea NRL when aged and demonstrated much better resistance to
aging compared to Hevea NRL condoms.

Table 7: ELISA and Lowry test results for condoms made from Treated NRL versas
Hevea NKL.

EXAMPLE 6 - ADHESTVES MADE FROM TREATED NRL
NRL was the first polymer to be used to produce pressure sensitive adbesives (PSA).
NRL has inherent advantages when used in pressure sensitive and contact adhesive
formulations. NRL has a very low glass transition temperature (Tg) and also low surface
energy which enables it to flow over surfaces very effectively, a key attribute of PSA.
Furthermore, NRL's extremely high molecular weight gives it high internal strength
preventing it from splitting during removal. The high molecular weight of NRL makes it
the only thaterial that can function as a "cold seal" contact adhesive at room temperature.
This is made possible because the low Tg and surface energy allow rubber films to flow
cold very well while the mixing of the polymer chains is retarded by molecular weight.
Some disadvantages of NRL are its ability to oxidize and become embrittled, loosing
its tack and adhesion properties over time and its ability to "sensitize" skin as a result of
allergic reactions. Oxidation is dealt with through use of anti-oxidants. Sensitization can be
overcome with the use of a low protein starting NRL such as treated NRL, as it is
understood that if high levels of protein are not present in the raw thaterial they cannot
appear m the manufactured product
The objective of mis phase of testing was to formulate cold seal (contact) and
pressure sensitive adhesives using treated NRL and a Hevea NRL sample formulated for an
adhesive compound and to conduct appropriate comparative testing for each sample. Test
results are expressed in Table 8.
During the formulary process, one particular observation regarding treated NRL and
the/Hevea control NRL samples was the smoothness of the treated NRL sample, which is

attributed to improved stability. This can eliminate the need for filtering during
compounding and assist in the adhesive coating process downstream.
Table 8: Physical properties of cold seal and pressure sensitive adhesives made from
treated and Hevea NRL.

It is concluded that low protein treated NRL can be substituted for versions of
untreated Hevea NRL whether treated or not in the production of cold seal and pressure
sensitive adhesives without compromising the physical performance of the resultant
products. The use of the low protein NRL for adhesive applications is of particular
importance because post leaching techniques commonly used for the removal of water
soluble thaterials are not applicable for these product applications.
EXAMPLE 7 - BREATHER BAGS, TUBING AND PROBE COVERS MADE FROM
TREATED NRL
Several additional medical products have been produced from treated NRL. The aim
of this work was to coagulant dip breather bags and tubing and to straight dip probe covers
using treated NRL under manufacturing conditions used to produce products made from
Hevea NRL. The protein results are illustrated below in Table 9.
Table 9: ELISA and Lowry test results for projects made from Treated NRL.

Throughout this application, various publications are referenced: The disclosures of
these publications in their entireties are hereby incorporated by reference into this,
application.
EXAMPLE 8 - FOAM MADE FROM TREATED NRL
-Natural latex foam has been accepted by consumers and retailers as a premium
bedding component For example, due to the impact on soundness of sleep and the
increased education of consumers, one-sided thattresses that do not require flipping are

becoming an industry standard. The performance and silky, luxurious feel of latex have
separated latex from other foam source materials in the marketplace.
limited inforthation exists regarding antigenic protein values in foam made with
Hevea latex. Total latex proteins have been analyzed in Hevea latex foam that was prepared
in a manner similar to that of the present invention for the production of NRL. Table 10,
below, provides a comparison of protein data for foams made with the inventive NRL and
with Hevea NRL.
Table 10: ELISA and Lowry Protein Test Results for Foam made from Treated NRL
and Hevea NRL

In addition to having significantly fewer total proteins than foam produced with
Hevea NRL, the inventive NRL foam was less odorous. This beneficial feature can be
attributed to a lower level of biodegradable proteins in the inventive NRL. Other beneficial
properties of the foam produced from the inventive NRL included noticeably higher opacity
and whiteness.
EXAMPLE 9 - PREPARATION OF TREATED NRL FILMS
In another example, a series of films were prepared from field latex. The
preparation of each film sample included the addition of 0.5 phr of Al(OH)3. Since Al(OH)3
is insoluble, it was added to a quantity of field latex (27 % TSC) in the form of a slurry.
The Al(OH)3 slurry was a combination of 1 phr of 10% ammonium hydroxide (NH4OH) and
0.5 phr Al(OH)3. m addition, 0.1 phr of ammonium laurate was added to the field latex
composition.
The prepared mixture was added to the field latex and agitated for 24 hours under
typical industry mixing conditions (for example, 30 rpm for 24 hours). A calculated amount
of diarnmonium hydrogen phosphate (DAP), based on the amount of free magnesium
present, was added to treat free Mg2+, followed by a period of 16 hours for desludging. The
field latex composition was men centrifnged to obtain desirable TSC of from about 63 % to
about 64 %. The composition was then diluted to about 30 % TSC with ammoniated water,

followed by a centrifuge step to reach a TSC of from about 60 % to about 62 %. Films for
antigenic protein testing were then prepared according to ASTM D6499-07. Protein levels
of the treated and untreated control samples are detailed in Table 11, below.
Table 11 - Proteia levels of Treated and Untreated Control Samples

EXAMPLE 10 - PREPARATION OF TREATED NRL FILMS
In a tenth example, a foam compound was prepared having reduced amounts of
antigenic protein, relative to a non-treated foam compound. The ingrethents of the natural
latex composition are listed in Table 12.
Table 12 - Foam Compound Ingrethents

The foam mixing process comprises first stirring Fart A to homogeneity. Next, the
desired amount of Part A is weighed out into a mixing port. Part A is then added to Part B;
Part B is shaken or stirred prior to the addition of Part A. The resulting mixture is kept
under slow stirring for about 2 hours at ambient temperature. The mixture is then transferred
into the foam mixer. The whipping speed is increased to moderate, and this speed is
maintained for about 4 minutes. The whipping speed is increased above moderate, and then
50% ZnO is slowly added into the foam, ZnO, in various aspects, can be added to .
destabilize the liquid NRL and assist in the foaming process. After the addition, whipping
is continued until a very fine foam is obtained. 50% SSF is then added, followed by
whipping for another 40-80 seconds. The foam is then immediately transferred into the
mould. The foam is then gelled for about 5 to 10 minutes. Once the foam is gelled, the

mould is transferred into a steam chamber, and steamed at 110 to about 120 °C for at least
about IS minutes. The foam is then removed from the mould washed with water. The foam
is then cured at about 50 °C for about 10 to 12 hours.
It will be apparent to those skilled in the art that various modifications and variations
can be made in the present invention without departing from the scope or spirit of the
invention. Other embodiments of the invention will be apparent to those skilled in the art
from consideration of the specification and practice of the invention disclosed herein. It is
intended that the specification and examples be considered as exemplary only, with a true
scope and spirit of the invention being indicated by the following claims.

CLAIMS
What is claimed is:
1. A natural latex composition comprising less than about 100 µg of antigenic protein
per gram of composition.
2. The natural latex composition of claim 1, comprising less man about 50 µg of
antigenic protein per gram of composition.
3. The natural latex composition of claim 1, comprising less than about 30 µg of
antigenic protein per gram of composition.
4. The natural latex composition of claim 1, comprising less than about 20 µg of
antigenic protein per gram of composition.
5. The natural latex composition of claim 1, comprising less than about 10 µg of
antigenic protein per gram of composition.
6. The natural latex composition of claim 1, comprising less than about 5 µg/dm2 of
antigenic protein.
7. The natural latex composition of claim 1, comprising less than about 2 µg/dm2 of
antigenic protein.
8. The natural latex composition of any of the preceding claims, farther comprising
aluminum hydroxide.
9. The natural latex composition of any of the preceding claims, further comprising up
to about 5 parts per million aluminum hydroxide.
10. The natural latex composition of any of the preceding claims, wherein latex is
present at a concentration of from about 27 parts per hundred rubber to about 30
parts per hundred rubber.
11. The natural latex composition of any of the preceding claims, wherein aluminum
hydroxide is present at a concentration of from about 0.01 parts per hundred rubber
to about 5 parts per hundred rubber.

12. The natural latex composition of any of the preceding claims, wherein aluminum
hydroxide is present at a concentration of from about 0.1 parts per hundred rubber to
about 1 parts per hundred rubber.
13. The natural latex composition of any of the preceding claims, wherein aluminum
hydroxide is present at a concentration of at least about 0.01 parts per hundred
rubber.
14. The natural latex composition of any of the preceding claims, wherein aluminum
hydroxide is present at a concentration of about 0.4 parts per hundred rubber.
15. The natural latex composition of any of the preceding claims, wherein aluminum
hydroxide is present at a concentration of about 1 part per hundred rubber.
16. The natural latex composition of any of the preceding claims, wherein the
composition is present in one or more of an adhesive, a condom, glove, breather bag,
tube, probe cover, catheter, thread, or foam.
17. A method of removing or denaturing at least a portion of antigenic protein to a
natural latex composition, the method comprising contacting an un-vulcanized
natural latex composition with aluminum hydroxide, thereby removing or denaturing
at least a portion of antigenic protein from the natural latex composition.
18. The method of claim 17, further comprising centrifuging the natural latex
composition after contacting with aluminum hydroxide.
19. The method of claim 17 or 18, further comprising removing the aluminum
hydroxide from the natural latex composition after contacting.
20. The method of any of claims 17-19, further comprising adding at least one of lignin
or fumed silica.
21. The method of any of claims 17-20, further comprising producing an article from the
natural latex composition after contacting with aluminum hydroxide.
22. The method of claim 21, wherein the article is one or more of an adhesive, a
condom, glove, breather bag, tube, probe cover, catheter, thread, or foam.

23. The product of the method of any of claims 17-22.

A rubber latex composition is disclosed having reduced allergenicity. Methods for producing a rubber latex
composition having reduced allergenicity are also disclosed.

Documents:

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Patent Number

279323

Indian Patent Application Number

2487/KOLNP/2010

PG Journal Number

03/2017

Publication Date

20-Jan-2017

Grant Date

18-Jan-2017

Date of Filing

08-Jul-2010

Name of Patentee

VYSTAR CORPORATION

Applicant Address

2480 BRIARCLIFF RD NE,#6, SUITE 159, ATLANTA, GA 30329, UNITED STATE OF AMERICA

Inventors:

#	Inventor's Name	Inventor's Address
1	HONEYCUTT, TRAVIS	3544 MILL ROAD, GAINESVILLE, GA 30504 UNITED STATES OF AMERICA
2	DOYLE, WILLIAM	3235 SATELLITE BOULEVARD, BUILDING 400, SUITE 290, DULUTH, GA 30096, UNITED STATES OF AMERICA
3	CLARK, MATTHEW	2695 DANIEL PARK RUN, DACULA, GA 30019 UNITED STATES OF AMERICA

PCT International Classification Number

C08F 283/00

PCT International Application Number

PCT/US2009/031445

PCT International Filing date

2009-01-20

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	61/081,927	2008-07-18	U.S.A.
2	61/022,250	2008-01-18	U.S.A.