Kausik Muk opadhyay, College Park, MD (US); Krishnaswamy Kast uri Rangan, Fairfax, VA (US); Tirarnalai Srinivas Sudarshan, Vienna, VA (US)

CLAY COMPOSITES AMD THEIR APPLICATIONS

RELATED APPLICATIONS

( I ] This Application claims benefit of co-pending US AppL Ser. No.

14/210.082 filed March 13, 2014, which is a nonprovisional of co-pending

US Application Serial No. 61/794420 filed March 15, 2013, all of which are incorporated in entirety by reference.

FIELD

[2] This disclosure relates to clay composites sheets and films prepared without adding polymer additives,

[3] This disclosure provides methods of preparing cla composite sheets and their applications such as for antimicrobial wound dressing, flame reiardants, solvent separation membrane, and drug delivery.

BACKGROUND

[4] In. this section, we discuss several aspects of related work, including background and conventional technologies. [6] Clay Is an aluminosilicate, which has a layered sheet-like structure with, silica ietrahedral bonded to alumina octahedral in. different ratios through Van. der Waal's forces. Types of clay with a 2:1 ratio of ietrahedral to octahedral are known as smectite clays. A common type of smectite clay is Montmorillonite (MMT).

[7] Clays are common ingredients in pharmaceutical products. Clay minerals are naturally occurring inorganic cationic exchangers and so they can undergo ion exchange with basic drugs in solution. In addition to ion- exchange, organic molecules can bond to clays via physical adsorption and ion-dipoie interactions of acidic and non-ionized molecules. For example, Wai and Banker demonstrated the loading of alkaloids in monteorillonite clay.

[8] Medicinal antl therapeutic applications of various clays and their products have long been. used, for the treatment of skin ailments. Montmorillonite (MMT) is one of the most widely used medicinal clays. Studies have shown thai MMT is non-toxic and thus has no side effects, Montmorinonite and. its products have a broad, spectrum of applications in medicine for cleansing and protection of skin, antibacterial activity and blood clotting capabilities. Clay can also accelerate healing in simple wounds. [9] MMT has also been used in the delivery of vitamins such as thiamine hydrochloride (VUamm Bl ; VBI) and pyridoxine hydrochloride (Vitamm B6; VB6) to the intestinal environment. The controlled release of VB1/VB6 was observed.

[10] Another major advantage of using clays to deliver drugs is the very low risk of 'dose dumping ^* . Dose dumping is an unexpected sudden release of the entire dose, which may cause severe or even, lethal side effects because of the narrow therapeutic, window of high potency drugs. Common topical medical dressings such as gauze, membranes and textiles can be subjected to dose dumping _, easily due- to external forces such as temperature change, pH change, and enzyme afivity. Thus, a material of high chemical and mechanical resistance is required to develop a safe, high potency opioid transdermal drug delivery vehicle. Clays are the most optimum materials for storage and delivery systems for drags such as analgesics because of the mechanical and chemical stability of clay. For example, FentanyJ has been loaded into a metakaotm clay, which provided a mechanically strong sustained drag release medium.

[1 1] Typically, clay particles are dispersed in aqueous drug solutions, dispersions are allowed to equilibrate for a suitable time, and finally solid particulates are recovered and dried. Clay in the particulate form (powders) are not suitable l r use in preparing topical wound dressing or for transdermal application of drugs because these methods require a continuous f lm so that drags can diffuse without interruption from the dressing. In the case of clay particles there does not exist a continuous path for drugs to diffuse from the clay particles to wound or skin surface. Clays in the form of thin sheets are preferable for topical wound dressing and transdermal drug delivery applications.

f 121 Clay sheets made using polymer binders which are commonly known as 'polymer-clay composites' are available in the market In these polymer- clay composites, the polymers act as a medium to disperse clay particles and to provide mechanical stability to the polymer-clay composite sheets. The clay nanoeoroposite of various polymeric materials such as polystyrene, tiylon-6, polyaniline, polymethyl meihacryiate (PMMA), polyurethane, polyethylene, poly (styrene-c»-acryloi?.itrile), polyaniline, poh'pyrrole, poiysulfone, polyacrylates, polyimide and epoxy have been investigated .for a variety of applications.

[13] The initial question that arose was how to create a clay film that does not fail apart and does not make use o significantly large polymers. It is preferable to have clay sheets without any polymer additives in certain applications where polymer additives can hinder or reduce the permeation of moisture, or chemicals or drugs though the clay sheets. It is also preferable to have a continuous sheet clay uninterrupted by the polymer .matrix. In this way special properties of day particles such as adsorption, permeability; high temperature stability, ion-exchange property, hemostasia property, and wound, healing property can. be fully utilized without, being disturbed by the properties of polymer additives.

[1.4] Antimicrobial Burn Wound Dressing

[ 15] Aiitimicrobiai silver-nylon dressing product known in the prior art prevents infection at a surgical site, enhances negative pressure therapy and help treat burns and wounds. These dressings have a permanently plated metallic surface. They continuously deliver a flow of silver ions into the wound, can be used for up to 7 days, do not increase the number of contaminating microbes before sterilization and. do not stain.

[16] Another prior art product contains two layers of silver-coated polyethylene mesh, enclosing a layer of rayon and polyester. The silver is put on the polyethylene mesh in a vapor deposition process. This process leads t the formation of nanoerystais of the .metallic silver which help fight against the various gram positive and negative bacteria. This product is mainly used as a barrier layer for bums and donor sites. The difference between these products and this disclosure is that these products release silver into the wounded area to fight the microbes. The silver ions in. this disclosure are contained within the clay film, j 1 7] Transdermal drug delivery

[ 18] Burns are among the most painlM and debilitating battlefield wounds iaced by the US arfighter. Burn wounds turn deadly when infection sets in. Since military operations began in Iraq in March 2003, hundreds of US military personnel have sustained burn injuries from explosions and other implements of war such as JED's. Not only is acute burn injury pain a source of immense suffering, but it has been linked to debilitating chronic pain and stress-related disorders. Severe pain is felt during acute treatment and rehabili.tati.ort, especially during dressing changes, debridement 's, and skin grafting, and continues through long- term follow up, The backbone of bum analgesia, is opioid therapy, typically administered via oral or parenteral routes. The use of opioid medications in bum patients is complicated by the side effects such as tolerance, hyperalgesia, hemodynamic instability, respiratory depression, and dependence. Therefore, beside the systemic administration of analgesics, attempts have been made to control the pain locally using topical analgesics which has shown encouraging results. Such topical dressings can be used to protect the bum wound from infection and thereby aid in wound healing f an antimicrobial property can be imparted onto them. ] Treatment for reducing the pain involves the usage of common and opioid analgesics, nonsteroidal anti-inflammatory drags (NSAIDs) and adjuvant analgesics. Pharmacologically, it is known that the main mechanism of action of analgesics is to act at specific sites located in the CMS and periphery. This observation led topical administration of pain reliever drugs such as NSAlD's, local anesthetics, capsaicin, tricyclic antidepressants, ketamine, elonidine, opioids, and eannabinoids. For example, fentanyl transdermal patches are used in chronic pain such as cancer pain or in the post-operat ve setting. The topical application of these drugs allows high concentrations, in peripheral effector sites. Thus, undesirable side effects are less likely to occur compared, to delivering these drugs systemic-ally. Even though opioid drugs are applied locally on the skin, the main analgesic action of opioids occurs only in the spinal cord. This will require the drug to be absorbed into the blood and travel from the skin surface to the spinal cord.

] Local anesthetic creams have been used in burn wound dressings.

For example, Lidocame prtlocame cream has been, used as a topical anesthetic by physicians performing plastic surgery and in patients with face bum injury. Topical application of loperamide also reduced the pain in full-thickness bum wounds by acting on the peripheral nociceptors. Therefore, a combination of local anesthetics such as lidocame and opioid drugs such as fenianyi may be incorporated in to the clay sheets and can be used in transdermal pain medication.

[21] Separation Membrane

[22] The United States must develop and deploy clean, affordable, domestic energy sources as quickly as possible to achieve energy security and independence. Batteries power everything from tools to cars to remote controls and have a major role in our daily lives. There is an increasing interest in the energy efficient production of Dimethyl Carbonate (DMC) that will support a growing market for hybrids and electric vehicles, and significantly reduce our dependence on foreign oil as well as correspondingly reduce greenhouse gas emissions.

[23] Dimethyl, carbonate is used as a substitute for toxic products such, as phosgene as well as traditional methylation agents. Other applications include as a solvent tor coatings, an octane booster in petrol, and as a component of diesel. In the last decade DMC has shown immense promise as an electrolyte solvent for lithium battery applications due to its inherent ^" safety and robustness. Despite the enormous promise of its industrial use, this chemical is currently entirely imported from China and Japan. Recently, South Korea has entered into the global DMC productio foray. Other global chemical industries include EniChem (Italy), Bayer (Germany) and Catalytic Distillation Technologies (Netherlands), and to a certain extent, BASF (Germany).

[24] Carbon dioxide conversion to DMC is a very challenging and sensitive reaction, because of the high Carbon dioxide activation energy required to convert Carbon dioxide and methanol. Most reports concentrate on gas phase reaction and conversion of carbon dioxide to DMC with 3.5% yield.

[25] One of the critical problems of catalytic direct synthesis of DMC is the co-generation of water, which causes hydrolysis of the DMC ^' formed during the reaction. It is thus important to remove the water generated during the reaction.

OBJECTS AND SUMMARY OF INVENTION

[26] The disclosure provides a polymer- free organo-modified clay product. The e!ay product has a clay and an organic compound. The organo-modiiled clay product is a film, a sheet, a mat or a membrane. The disclosed organo-modiiied clay product is referred to as polymer-free because polymer is not added for preparation of the clay product. The clay is moiiimortllonite, kaolinite, smectite, and beittonite. The organic compound is betake, betake hydrochloride, choline chloride, .l-Benzyl-S- (2-hydroxymeihyi)-4-methyltiriazoliom chloride, 3-βεηζ>Ί-5~(2- hy hoxymethyl)-4-methylthia¾olium bromide, 3-Bt .yl-5-(2- hydroxyme&y ^-memyitiuazolium fluoride or 3-Benzyl-5~(2- hydmxyniethy!)-4-methylthiaaiolium iodide.

] In some embodiments, a thickness of the polymer- free organo- modified clay product ranges from about 1 micrometer io about 500 micrometer, in some embodiments, a thickness of the polymer-free organo-raoditled clay product ranges from about 1 micrometer to about 100 micrometer. In some embodiments, a thickness of the polymer-free organa-modified clay product ranges .from about 20 micrometer io about 60 micrometer, m some embodiments, a thickness of the polymer-free organo-modified clay product is about 50 micrometer.

] In some embodiments, the polymer-free organo-modified clay product achieves a bending radius of curvature ranging from about 0.4 millimeter to about 10 centimeter. The bending radius of curvature is achieved without breaking the polymer-free organo-modiiied clay product. In some embodiments, the poiymer-free organo-modified clay product achieves a bending radius of curvature ranging from, about 0.3 millimeter to about 1 millimeter, in some embodiments, the polvmer-free oraano- modified clay product achieves a bending radius of curvature of about 0.5 millimeter. In some embodiments, the poiymer-free organo-modiSed clay product achieves a bending radius of curvature of about.0.4 millimeter. [29] In some embodiments, the polymer-free organo-modified clay produci has greater than 50 % absorption of visible light. In some embodiments, the polymer-free organo-modified clay product is non- transparent, in som embodiments of the polymer-free organo-modified clay product;, when the thickness of the product was about 50 micrometer, the film had greater than 50% absorption of visible light, in some embodiments, when the organo-modified clay produci was further modified by addition of sliver, the film absorbed greater than 82% of the visible light,

[30] in some embodiments, the polymer-free organo-niodified clay product does not incorporate a polymer. In some embodiments, the organo-modified clay product i a polymer fee composite.

[31 ] In some embodiments, the polymer-free organo-modified clay product includes an antimicrobial agent. ^' The antimicrobial agent can be silver ion, copper, iodine, proilavine, silver-containing compounds, copper containing compounds, quarternary ammonium compounds, or quarternary phosphonium compounds. Silver-containing compounds include but not limited to silver sulfadiazine, silver nitrate, silver oxide, and silver carbonate; copper containing compounds include but not limited to copper oxide, copper sulfate, copper acetate, and copper nitrate; quarternary ammonium compounds include but not limited to benzalkoniura aikyl chloride, cethyl tri lkyl ammonium chloride, and a!ky! diemthyl benzyl ammonium chloride and quarternary phosphonium compounds include but not limited to aikyl triraeihyl phosphonium chloride and ialkyl dimethyl phosphonium. bromide.

] In some embodiments, the polymer-free organo-modi tied clay product includes an analgesic. The analgesic can be opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and. adjuvant analgesics, capsaicin, elomdme. ketamlne. Morphine, feniatiyi. Biiprenorphine or cannabinoids.

] Some embodiments provide an antimicrobial dressing having the polymer-free organo-modified clay product, Some embodiments provide a bum wound dressing having the polymer-free organo-modified clay product.

] Some embodiments provide a lithium battery having the polymer- free organo-modified clay product. The organo-modified clay product is the electrolyte membrane i the lithium battery.

] Some embodiments provide a flame retardant. product having the polymer-free organo-modified clay product. In some embodiments, the flame retardant product resists breakdown following ethylene flame for 2 minutes. [36] Some embodiments provide a method of antimicrobial treatment by administering the polymer-itee organo-modified clay product.

[37] Some embodiments provide a method of treating burns by administering the polymer-free organo-modified clay product,

[38] Some embodiments provide a method of removing water from organic chemical mixtures using the polymer-tree organo-modified clay product

[39] Some embodiments provide a method of preparing a polymer-tree organo-modified clay product. The method includes mixing a clay particle and an organo-containing solution to form a slurry. Organo- containing solution' can be defined as 'an organic chemical dissolved in a solvent including but not limited to water and ethartoi'. Then the slurry is cast on a substrate to obtain a slurry cast. Then the slurry cast is dried to obtain a dried product of the slurry on the substrate. Then the dried slurry product is separated from the substrate. The separated dried slurry product is the polymer-free organo-modified clay product. The polymer-tree organo-modified clay product can be a film, a sheet, a mat or a membrane, to some embodiments, if the substrate is glass, then the dried slurry product has to be removed from glass substrate. In some embodiments, if the substrate is fabric or nylon, the dried, slurry product need not be removed from the fabric or nylon. The resulting dried slurry product on the fabdc or .nylon substrate can together form part of a wound dressing product. Thus, dried slurry need not be removed from a nylon or fabric substrate. In this disclosed methods, no polymer has been added to the clay for preparing the product. In some embodiments of the method, the substrate can be a silicone sheet a fabric, or a glass surface. In some embodiments, the fabric is nylon, In some embodiments of the method when the product i$ prepared at a temperature of about 25V _t the viscosity of the slurry prepared for spreading on the substrate ranges from about 2 centipoise to about 20 centipoise. In some embodiments of the method when the product is prepared at a temperature of about 25 V-, the viscosity of the slurry prepared for spreading on the substrate ranges from about 5 centipoise to about 10 centipoise. In some embodiments drying the slurry casted on the substrate is performed under conditions of slow, air. In some embodiments drying the slurry casted on the substrate is performed at 20-25 degrees Centigrade under ambient, room temperature conditions, [40] Some embodiments provide a method of preparing a polymer-tree orsa vmodified elav -product. The method includes mixing- a ctav particle and an orgaao-containing solution to form a slurry. Then the slurry is casted on a substrate to form a slurry casted on a substrate product. Then the slurry casted on the substrate is dried, to obtain the polymer- free organo-modified clay product. The organo-modified clay product can be a fihn, a sheet, a mat or a membrane,

[41 ] Some embodiments provide a method of preparing a polymer-free organo-modified clay product having an antimicrobial agent. The method includes mixing a clay particle and an organo-containing solution. Then an antimicrobial agent containing solution is added to obtain a slurry. The slurry is casted onto a substrate. The casted slurry and substrate are subjected to drying and a dried slurry is obtained on the substrate. The dried slurry is separated from the substrate to obtain the organo-modified clay product containing the antimicrobial agent,

[42] Some embodiments provide a method of preparing a polymer-free organo-modified clay product having an analgesic. The method includes mixing a clay particle and an organo-conta mg solution. Then an analgesic containing solution is added and a slurry is obtained. The slurry is casted on a substrate and dried to obtain a dried slurry on the substrate. The dried slurry is separated from the substrate to obtain, the polymer-tree organo-modified clay product having the analgesic compound.

[43] Some embodiments provide an antimicrobial wound dressing. The wound dressing has a polymer-tree organo-modified cla product having an antimicrobial agent. The wound dressing has successive layers of the following; a hyclrogel adhesive with a hydrophobic backing; polymer- free organo-modified clay product having an antimicrobial agent; and, a n y ion mem br n e .

Some embodiments provide a method of preparing an antimicrobial wound dressing. The method includes successively layering the following: a hydrogel adhesive with a hydrophobic backing; polymer-free organo-raodified cla product having an antimicrobial agent; and, a nylon membrane. In some embodiments, the method includes successively layering the following: a nylon membrane, the a polymer- free organo-modified clay product having an. antimicrobial agent; and, then a hydrogel adhesive with a hydrophobic backing,

] Some embodiments provide an analgesic wound, dressing. The analgesic wound dressing includes a polymer-tree organo-modified clay product having an analgesic. The wound dressing has successive layers of the following: a hydrogel adhesive with a hydrophobic backing; a polymer-free organo-modified clay product having an analgesic and, a nylon membrane. Some embodiments provide a transdermal wound dressing. Some embodiments provide a method of preparing a transdermal wound dressing.

Some embodiments provide a. method of preparing an analgesic wound dressing. The method includes successivel layering the following; a hydrogel adhesive with a hydrophobic backing; then a polymer-free organo-modified clay product having an analgesic and, then, a nylon .membrane. Alternatively, the successive layering can be as follows: nylon membrane, then then a polymer-free organo-modifted clay product having an analgesic followed by a. hydrogel adhesive with a hydrophobic backing.

BRI DESCRIPTION OF THE DRAWINGS

[47] The above objectives and advantages of the disclosed teachings will become more apparent by describing in detail preferred embodiments thereof with reference to the attached drawings in which:

[ 48] Figure L (A) Photograph of the 12 cm width x 8 cm height and 50 micrometer thick organomodified clay thin sheet prodoct (B) Photograph of the 5 cm width 6 cm height and 30 micrometer thick sil er exchanged organomodified clay thin sheet product (C) Photograph of the roHed-up clay sheet to demonstrate its flexibility and bend strength.

[49] Figure 2. Antimicrobial efficacy of organo-modified Ag-Clay films after 36 ^' hours. Bacteria specimens (a) Escherichia cob (b) Staphylococcus epiderrnldis (c) Bacillus subtifis and (d) Staphylococcus aureus and cultured in. petri dishes and tested at MML Distinct zones of inhibition from films (Ag~Beiaine~Clay) compared to pristine Betame- Clay films are to be noted. Betaine-elay film specimens are labeled as 1, 2 and 3 and silver-betain-clay film specimens are labeled as 4, 5 and 6. [50] Figure 3. Antimicrobial efficacy of organo-roodiiied silver-Clay •films after 24 hours. A. Nylon fabric prepared using 0.5wt% silver containing sslver-betaine- iay slurry B. Nylon fabric prepared using 0.4wt% silver containing silver-beiaine-elay slurry C Untreated Nylon fabric

[51] Figure 4. Schematic Iayered structure of antimicrobial bum wound dressing.

[52] figure 5. Photographs showing progress in barn wound, healing with gauze (negative control), Silvadine cream (positive control) and silver exchanged clay burn wound bandage.

[53] Figure 6, Photograph of heat resistant test conducted on clay

samples (A!) Fire side and (B) Sample is intact after 2 rnin of exposure to acetylene gas ilanie.

[54] The disclosure relates to preparation, properties and applications of thin clay sheets,

[55] Montmorilkmiie clay has excellent adsorbent as well as particle clumping properties. Cations such as sodium, lithium, and potassium reside in the gap between these layers known as the gallery or the mteriayer. The gallery allows for 3 processes to occur, hydrophobic modification, intercalation and exfoliation.

[56] intercalation is when an organic component is inserted in between the gallery, causing expansion, yet still maintaining a well-defined spatial, relationship between the layers. Intercalation causes the gallery to expand up to I to 2 angstrom. Exfoliation is a de!aminating process where the gallery expands to the point, where the Savers completely separate from each other. This is accomplished through the adsorption of desired molecules. During exfoliation, packets of clay platelets separate from one another. Platelets at the outermost region of each packet cleave off, exposing more platelets for separation. The galler expands up to 20 to 30 angstrom in the case of exfoliation, almost 20 tiroes more than intercalation.

[57] The initial question that arose was how to create a clay film that does not fall apart and does not make use of significantly large polymers, omniorilionite clay naturally forms stacks of plate-like structures called platelets, with each platelet being less than. 10 angstrom thick. The galler spaces between the platelets can be filled with monomers, oligomers, or polymers to increase the distance between the platelets. The clay must expand but not enough to lose its stack organization because if it becomes exfoliated, it will fail to form an intact film. [58] hi some embodiments orgaiKvmodi.fi ed clay sheet made by using zwitter ions (ionic compounds containing both positive and negative ions in the same molecule) such as Betake, Betaioe hydrochloride. Choline chloride, 3- Benzyl-5-(2-hydrox\mieihyl)-4-m£thyMhiazoliiim chloride and bromide, chloride, fluoride and iodide salts of tetraheptylammonium and

cetyltri.methylamnwmiura cations; ail of them having a very high charge density to intercalate the clay layer intergallery.

[5 J Solvents that can be used for making the clay and organo-modified clay may include water, alcohols, organic solvents such as toluene, dimethyl formamide, dimethyl carbonate, chloroform, and acetoniiri!e. The drying times required for formation of clay and organo-modified films ranges from aboiii 0 to about 24 days. In some embodiments, the drying time ranges from about 1 minute to about 24 hours, in some embodiments, the drying time ranges from about 5 to about 12 hours. The curing can be accelerated by heating using a microwave, or Ultra Violet radiation or Infrared radiation or conventional heat source. Low humidity can also accelerate the curing.

[60] The disclosed teachings provide preparation of clay in the form of thin film, cm into desirable sixes.

[61] The disclosure provides fabrication of a clay film covered with mesh and put onto the adhesive material that serves as the base of the bandage. [62] Some embodiments use clay film in a wound dressing. Some embodiments use clay film in a burn wound dressing. Some embodiments use clay film in an. antimicrobial dressing for gram negative and grain positive bacteria. Some embodiments use clay film in a hemostatic dressing.

1 ^" 63] Some embodiments us clay film as a packaging material.

[64] Some embodiments use clay film as a. permeable, semi-permeable and non-permeable membrane.

[65] Some embodiments use clay film self-extinguishing membrane and film .

[66] The disclosure relates to synthesis of organo-modified clay film that can be incorporated with metal and non-metallic cations and able to make small to large dimension free standing clay films and membranes upon drying.

[67] Some embodiments use clay film as a. fire retardant barrier film.

[68] Some embodiments prepare clay sheets without using binders and polymers.

[69] Some embodiments use clay sheets as a separation membranes for oil-water, organic molecules-water, organic molecules-organic molecules, polar-polar, nonpolar-nonpoiar, polar-nonpolar, metals-solutions, minerals -s lutions, pollutants and non-pollutants [70] Some embodiments use clay fii.ro as a UV-resistattt, I -resistant, hydrophobic and hydropkilic coating materials

[7 J ] Some embodiments use metal exchanged organo modified clay films tor energy storage devices such as batteries, capacitors,

supereapaeitors etc.

72] Organomodified clay can be exchanged with any group I

(monocaiionic). group Π (dicationk), group lit (tricationic), alkali metal, alkaline earth metal or combination of groups L ϋ and. HI metal, species and ions, and nano and micro sized particles form.

[73] Organo-modified clay can ^' be exchanged with any transition metal, late transition metal, lanthanide metal, heavy elements in ionic and nano and micro sized particles form.

[74] Organo-modified. clay ca be exchanged with organic molecules including but not limited to pharmacological dmgs, vitamins, and nutrients [75] Some embodiments use clay sheets to provide controlled delivery of analgesic drugs to burn wounds while assisting in wound healing with its antimicrobial and moisture control properties.

[76] Some embodiments use clay sheets to provide transdermal delivery of -nutrients and pharmacological agents.

[77] The disclosure provides a polymer- free organo-raodified clay

product. The organo-modified day product has a clay and an organic compound. The organo-modified clay product is alternatively referred to in the disclosure as a film, a sheet, a mat or a membrane. The disclosed organo-modified clay product is referred to as polymer- free because polymer is not added for preparation of the clay product. The clay is montmori lloiute, kao finite, smectite, and. bentomte. The organic compound is betaine, betaine hydrochloride, choline chloride, 3-BenzyS-5- (2-hydroxymethyl)-4-methylthiazolium chloride, 3-Ben2yl-5-(2- hydroxymethyl)~4~methylthiaxol ^' ium. bromide, 3~BeRzyl-5-(2~

bydroxyinediyl)-4-meth)1tluaxol.ium fluoride or 3~Benzyl-5~(2~ hydroxyniettiyl)^methyit iazoliura iodide,

] In some embodiments, a thickness of the polymer-free organo- modified clay product ranges from about 1 micrometer to -about 500 micrometer. I some embodiments, a thickness of the polymer- free organo-modified clay product ranges from about 1 micrometer to about 1 0 micrometer, in some embodiments, a thickness of the polymer-free organo-modified clay product ranges from about 20 micrometer to about. 60 micrometer, in some embodiments, a thickness of the polymer- free organo-modified clay product is about 50 micrometer.

] In some embodiments, the polymer-free organo-modified clay product achieves a bending radius of curvature ranging from, about 0.4 millimeter to about 10 centimeter. The bending radius of curvature is achieved without breaking he polymer-free organo-modified clay product, in some embodiments, the polymer-free organo-modified clay product achieves a bending radius of curvature ranging from about 0.3 millimeter to about 10 millimeter. In some embodiments, the polymer-free organo- modified clay product achieves a bending radi us of curvature of about 0.5 millimeter. I» some embodiments, the polymer-free organo-modified clay product achieves a bending radius of curvature of about 0.4 millimeter, [80] In some embodiments, the polymer-t ee organo-modified clay product has greater than 50 % absorption of visible light. In some embodiments, the polymer- free organo-modified clay product is non- transparent. In some embodiments of the polymer- iree organo-modified clay product, when the thickness of the product was about 50 micrometer _* the film had greater than 50% absorption of visible light. In some embodiments, when the organo-modified clay product was further modified by addition of silver, the film absorbed greater than 82% of the visible light.

81] In some embodiments, the polymer-free organo-modified clay product does not incorporate a polymer. In some embodiments, the organo-modified clay product is a. polymer tree composite.

Antimicrobial Wound Dressing Application of Clay Sheets [83] The disclosed organo-niodified clay materials stand out from the rest, as till date there is no available literatures on synthesis of free-standing organo- modified or unmodified clay films that are prepared without using polymers or binders. Clay tends to swell when water is drawn into the interla er space, allowing the cations to become easily exchangeable. In some embodiments, an AyV^V-trimemyiglycine, also known as Betaine is intercalated into the day. The hydroxy! groups of clay attach to the Betaine, expanding the clay. The sil ver ions in sil ver nitrate exchange with the sodium cations and take their place within the interstitial, space as well. The silver ions in silver nitrate, the component added within the Montmorillonite gallery, is the main driving force for eliminating the microbes. Silver ions tend io have antiseptic properties used for controlling burn and eye infections. Silver ions have the ability to disrupt the bacterial cell wall, penetrate the cell and disrupt the physiological function of cell respiration and metabolites. In addition, silver is a bactericidal against more than 150 species of bacteria, viruses, yeast and fungi, including MRSA, MD , Klebsiella and Pseudomonas species.

[84] Water acts as an essential component in the antimicrobial bandage as well.

Although most of it evaporates after the clay film is cast, some of it may remain within the clay film to provide moisture to the wound.

[85] Organo-modiiied Silver-clay film can he used as an antimicrobial wound dressing. The bare clay and organo-modiiled clay films thai can be used as burn and or wound bandages with membranes and adhesiv patches can also be used to stop bleeding hence can be used as a hemostatic agent or bandage against wound bleeding and healing in 0- 100 minutes time interval. The purpose of thi product is to fulfill the function of a bandage as well as kill microbes, when applied to the wound. I he product achieves its purpose of eliminating bacteria in less than 5 min-32 hour depending on the bacterial colony size.

[86 j The bandages can be made available in three different .film sizes ranging from 0.1 cm by 0.1 cm to 100 m by 1 0 in sizes (Figure 1 ). These sizes are produced to eater to small, medium or large wounds. In some embodiments, the larger film products are also referred to as sheets, in some embodiments, if the size of the wound is small., a smaller size of the film proditct is cut and is referred to as a mat.

[87] The silver clay sheet may also work effectively in eliminating other different types of microbes such a fungi or algae as well.

[88] Silver-clay sheets serve multiple purposes in the bum and sear healing process. Clay has well-known property to retain moisture and has been used as a promoter for hemostasis. C!a with optimal silver concentrations can reduce the cost without compromising the efficacy of the silver,

[89] There is large amount of clinical evidence to support the use of hydrogel. dressings in the treatment of hypertrophic scars. It may be due to the hydrogel dressing's ability to hydrate the damaged tissue, and allow oxygen to permeate to the surface of the skin. This will help in a localized increase in oxygen coacentraiioo leading to a down-regulation of signals thai stimulate growth near the skin surface, t us preventing or reducing scar formation.

[90] The final product was easily contoured as a bandage (strip or roll) with a silicone-based hydroge! adhesive. The bandage served as bum and wound care product, which has huge commercial market for military and civilian casualties. The wound dressing can be applied, to numerous applications, such as burn, wound and surgical care, and also in water filtration systems and for food packaging.

[ 1] In some embodiments, the polymer-free organo-modified clay product includes an antimicrobial agent.. The antimicrobial agent can be silver ion, copper, iodine, proflavine, silver-containing compounds, copper containing compounds, quarternary ammonium compounds, or quarternary phosphonium compounds. Silver-containing compounds include but not limited to silver sulfadiazine, silver nitrate, silver oxide, and silver carbonate; copper containing compounds include but not limited to copper oxide, copper sulfate, copper acetate, and copper nitrate; quarternary ammonium compounds include but not limited to henzalkoniuui alkyl chloride, cethyl trialkyl ammonium chloride, and alky! diemthyl benzyl ammonium chloride and quarternary phosphonium compounds include but not limited to alkyi. trimethyl. phosphonium chloride and dialkyl dimethyl, phosphonium bromide.

[92] In some embodiments, the polymer-free organo-modified clay product includes an analgesic. The analgesic can be opioid analgesics, nonsteroidal anti-inflammatory drugs (MSA lDs) and adjuvant analgesics, capsaicin, clonidine, ketamine, Morphine, fentanyl, Buprenorphlne or cannabinoids.

[93] Some embodiments provide an antimicrobial dressing having the polymer-free organo-modified clay product. Some embodiments provide a burn wound dressin having the polymer- free organo-modified clay product.

[94] Some embodiments provide a lithium battery having the polymer- free organo-modified clay product. The organo-modified clay product is the electrolyte membrane in the lithium ^' battery.

[95] Some embodiments provide a flame retardant product having the polymer-free organo-modified. clay product. In some embodiments, the flame retardant product resists breakdown following acetylene flame for .2 minutes.

[96] Some embodiments provide a method of antimicrobial treatment by administering the polymer-free organo-modified clay product. [97] Some embodiments provide a method, of treating hums by administering the polymer-free organo-modified clay product.

[98] A novel and successful approach to separate DMC from water and reaction products can be achieved by the clay sheets. The clay sheet can remove water from the organic chemical mixtures, efficiently. Nearly 100% of water can be removed from the mixture. This is an easier and energy conservative approach for separation of water from organic chemical mixture. Clay sheets are inert and will not react with organic compounds such as dimethyl carbonate and methanol, but clay absorbs water. Clay sheet will not get destroyed upon continuous application. Once saturated with water, the membrane can be heated to 50 degree C to get rid of the water, and reused again for separation. Energy consumption is almost, zero using this clay sheet compared to evaporation technique. Fast (< 2-3 h) and Cost-effective technology compared to pervaporation approach and polymer based .membranes used in the industry to separate water from organic chemicals.

[99] Some embodiments provide a method of removing water from organic chemical mixtures using the polymer-free organo-modi.fied clay product.

[ 1.00] to flame retardant applications, by employing clay sheets in the outer shells, the thickness of Fire fighter's gloves can be reduced by up to 40 percent, permitting the improvement of hand function leading to better dexterity in difficult situations. Some embodiments provide a method of preparing a polymer-free organo- odified clay product. The method includes mixing a clay particle and an organo-containing solution to form a slurry. Then the slurry is casied on a substrate to obtain a slurry easted. on a substrate. Then the slurry easted o the substrate is dried to obtain a dried product of the slurry on the substrate. Then the dried slurry produc is separated from the substrate. The separated dried slurry product is the polymer-free organo- modified clay product. The polymer-free organo-modified clay product can be a film, a sheet, a .mat or a membrane. In some embodiments, if the substrate is glass, then the dried slurry product has to be removed from glass substrate. In some embodiments, if the substrate is fabric or nylon, the dried slurry product need not be removed from the fabric or nylon. The resulting dried slurry product on the fabric or nylon substrate can together form part of a wound dressing product. Thus, dried slurry need not be removed from a nylon or fabric substrate. In this disclosed methods, no polymer has been added to the clay for preparing the product. In some embodiments of the method, the substrate can be silicone sheet, a fabric, or a glass surface. In some embodiments, the fabric is nylon. In some embodiments of the method when the product is prepared at a temperature of about 25 degrees C, the viscosity of the slurry prepared for spreading on the substrate ranges from about 2 centipoise to about 20 centipoise. In. some embodiments of the method when the product is prepared at a temperature of about 25 ?C the viscosity of the slurry prepared for spreading on the substrate ranges from about 5 centipoise to about 10 centipoise. hi some embodiments drying the slurry casted on the substrate is performed under conditions of slow air, in some embodiments drying the slurry casted on the substrate is performed at 20-25 degrees Centigrade under ambient, room temperature conditions.

1 ^" 101 j Some embodiments provide a method of preparing a polymer- free organo-modifled clay product, The method includes mixing a clay particle and an organo-containing solution to for a slurry. Then the slurr is casted on a substrate to form a slurry casted on a substrate product Then the slurry casted on the substrate is. dried to obtain the polymer-free organo-modified clay product The organo-modified clay product can. be a film, a sheet, a mat or a membrane.

[.102 J Some embodiments provide a method of preparing a polymer-free organo-modified clay product having an antimicrobial agent. The method includes mixing a clay particle and an organo-containing solution. The an antimicrobial agent containing solution is added to obtain a slurry. The slurry is casted onto a substrate- The casted slurry and substrate are subjected to drying and a dried slurry is obtained on the substrate. The dried slurry is separated from the substrate to obtain the organo-modified clay product containing the antimicrobial agent. [ 103] Some embodiments provide a method of preparing a polymer-free organo-modified clay product having an analgesic. The method includes mixing a clay particle and an organo-eontaming soitiiicm. Then an analgesic containing solution is added and a slurry is obtained. The slurry is casted. on a substrate and dried to obtain a dried slurry on the substrate. The dried slurry is separated from the substrate to obtain the polymer-free organo-modified clay product having the analgesic compound..

[104] Some embodiments provide an. antimicrobial wound dressing. The wound dressing has a polymer-free organo-modified clay product having an antimicrobial agent. The wound dressing has successive layer of the following; a hydrogel adhesive with a hydrophobic backing; a polymer- free organo-modified clay product having an antimicrobial agent; and, a nylon mem bran e .

[105] Some embodiments provide a method of preparing an antimicrobial wound, dressing. The method includes successively layering the following; a hydrogel adhesive with a hydrophobic backing; a polymer-free organo-modified clay product having an antimicrobial agent: and, a nylon membrane, in some embodiments, the method includes successively layering the following: a nylon membrane, then a polymer- free organo-modified clay product having an. antimicrobial agent; and, then a hydrogel adhesive with a hydrophobic backing. [ 106] Some embodiments provide an analgesic wound dressing. The analgesic wound dressing includes a polymer-free orga >modified clay product having an analgesic. The wound dressing has successive layers of the following: a hydrogel adhesive wit a hydrophobic backing; a polymer-free organo-modified clay product having an analgesic and, a nylon membrane. Some embodiments provide a transdermal wound dressing. Some embodiments provide a method of preparing a transdermal wound dressing,

[107] Some embodiments provide a method, of preparing an analgesic wound dressing. The method includes successively layering the following: a hydrogel adhesive with a hydrophobic backing; then a polymer-free organo-modified clay product having an analgesic and, then a nylon .membrane. Alternatively, the successive layering can be as follows; nylon membrane, then then a polymer-free organo-modified clay product having an analgesic followed by a hydrogel adhesive with a hydrophobic backing.

] It will be readily understood by the skilled artisan that numerous alterations may be made to the examples and instructions given herein. These and other objects and features of present invention will be made apparent from the following examples. The following examples as described are not intended to be construed as limiting the scope of the present invention. EXAMPLES

Exampl Ϊ

[109] 10 g sodium-exchanged montraorilloniie clay (PGW) clay (Nanocor, Inc., Arlington Heights, IL), 1 0 g deionized water and 1.7 g anhydrous Betaine

(TrimethylgS ycine) {.Alia Aesar, Ward Hi!!, MA) were added, in a bottle and left to stir for 24 k Tire resultant slurr was poured and spread on a glass plate with a large surface coverage. This aiiowed for formation of clay sheets with homogeneous thickness. Slurry was left to dry in air for 48 h on the glass plate at 20 to 25 degree C. After the slurry dried to form a clay sheet, the clay sheet was removed from the glass plate using a razor blade. The film thickness was varied from 1 um to 500 μπι by modifying the concentration and viscosity of the clay mixture and the spreading level of the slurry ont a surface.

Photograph of some clay films are provided in Figure I A,

[1 10] Example 2

[1 1 1 j Viscosity measurement of the cla siurry was performed to determine the viscosity required to optimize the flow ability of the clay slurry for the fabrication of clay sheets. Viscosity is the quantity that describes a fluid's resistance to flow and is heavily dependent on temperature. The viscosity of the slurry prepared in the example I was measured using a Brookfield DV-H 4- Pro Viscometer (Brookfieid instrument Laboratories inc.. Middleboro, MA) using a #42 spindle at 23- 2(H) RPM speed. The measurement is carried out at temperatures of 23-25 degree C. In Table 1 viscosity of betaine-clay slurry as a function of spindle speed is provided.

[1 12] Table 1

[ 1 3 ] The viscosity measurements showed that the consistency of the clay

mixture before it was east was similar to that of milk (about S cP at 25 degree C). The viscosity of the slurry ranging from about 2 centipotse to 20 eentipoise depending on the concentration of the clay in the mixture, yielded highly flowable slurry to form uniformly thick and mechanically durable clay sheets.

[ 1 1 j Example 3

[1 15] 10 g sodium-exchanged montmorillonite clay ί PGW) day, 1 0 g

deio zed water and 1.7 g anhydrous Betaine were added in a bottle and left to stir for 24 h. The resulting slurry was easted onto a silicone sheet After drying the clay sheet was easily peeled off from the silicone tray surface. [1 16] Example 4

j l 17] Preparation of Clay Film on Nylon Fabric

[118 J 10 g sodium-exchanged montrnorilloniie clay (PGW) clay, 190 g

deioiiized water and 1.7 g anhydrous Betaine were added in a bottle and left to stir for 24 Si. The slurry was casted onto a 12 inch x 12 inch nylon fabric. Nylon fabric was cut into a smaller segment that was large enough to tightly wrap around a glass-casting sheet. Tape was used on the back to securely fasten the fabric onto the glass sheet The clay slurry was then slowly poured out directly onto the fabric a doctor blade knife was then used to thin out and spread an even layer of clay on the fabric. The casted slurry was left to dry and was taken off as one piece with the nylon fabric.

[1 9] Casting of clay on nylon fabric provided additional benefits compared to dry-casting of the clay alone. The added benefit was to shape and cat, or to even stitch pieces together gave us the option to create new shapes that might be needed with odd-shaped injuries located on areas such as the hands or feet.

[ 120] Example 5

121] Preparation of silver ion-exchanged Clay sheets

[ 122] 10 g PGW clay, 1 0 g Deionized water and 1.734 g Betaine was combined in capped plastic bottle and gently shook to initially combine all ingredients together into a slurry. A homogenize was used to create a uniform viscosity mixture. The horaogenkation was continued until lumps of clay particles were no longer v isibl settled at the bottom . Then the mixture was allowed to sit for 24 hours in a closed plastic bottle. 0.816 g silver nitrate (Alfa Aesar, Ward Hill, MA) was added to the clay slurry and homogenized again, the bottle was then wrapped in aluminum fo l to prevent silver from being exposed to light and was left to sit for an additional 24 hours, Mixture was then washed and centrifuged to remove excess silver nitrate. Then the slurry was poured and easted on to glass plates, silicone trays and nylon fabrics.

[123] It was critical to treat clay with betaine before ion-exchanging with silver nitrate. Reversing the order of preparation by first treating with silver ions and then treating with betaine resulted in poor quality si lver clay sheets. Further, a silver clay fi lm with higher betaine loading yielded a thicker and more flexible, film that was both easier to remove from, the glass sheet and was less susceptible to tearing for use. For example, 148 percent betaine exchanged clay yielded better silver clay sheets compared to 100 percent, betaine exchanged clay. Photograph of the typical silver exchanged clay films are provided in Figure IB.

[124] The first batch of the organo-ciay film turned out to be very thick and did not flow smoothly onto the glass after it was cast. The film, after drying, felt very thick as well and since it didn't homogenize well, clumps could be observed. The film had a light shade of gray, unlike the dark gray

"¾7 or black lhat was expected. The film had. many uneven areas, with some parts being very thin and some parts being very thick. It was easy to peel off the parts that were considerably thick. The reason for the clay film mixture being so thick was thought to be due k> the feet that silver nitrate was added before the Betaine. The first batch was discarded because of all the problems mentioned above and a new batch was made with a modification in the procedure, which was the addition of Betaine before the silver. The purpose for this is so that the Betaine can intercalate within the interlaycr first and then the silver can exchange with the cations, primarily sodium,

[ 125] Additional water was also added to make the mixture easier to flow. The additional water had no effect on. the concentration of the silver and most of it evaporated as the clay was drying,

[126] Alter the change in procedure, the second batch turned out to be ranch smoother and flowed easily (similar to milk) onto the glass. There were no areas that were thinner or thicker than the rest. The color of the mixture as it was being cast was a peachy brown and the mixture spread on the glass by itself, as if was being poured. After 3 days of drying, the film was observed, io be black, in color towards the outside and lighter gray towards the inside. Since the film was appropriately thin, it was a bit difficult to initially start peeling it off from the glass but then it slid off easily. Circular rings of black and gray were also found on the film. These rings were observed on the other batches as well.

[ 127] The occurrence of these rings was predicted, to be because of how the mixture was being poured onto the glass plate, it was not being evenly spread, therefore some spots ended up with more material and some spots with less, causing the color variation. Although the rings had no effect on the antimicrobial testing (it still kills the bacteria), efforts were made to reduce the number of rings and produce a completely black f lm. The new batches of clay were poured very carefull and slowly in the center of the glass plate and allowed, to spread by them. This technique seems to have worked and produced a considerably black film without many grayish areas or significant amount of rings.

[ Ϊ 28} The gray area is restricted in the middle unlike, where a lot more gray is observed. Also there is no brownish area in the middle either. Although a couple of rings can be observed, they arc less in number compared to previous films.

[129] Example 6

[ 130] Clay product thicknesses

f 13 ] Thickness of the clay sheet prepared according to the Example 1 was measured using a micrometer. The average thickness obtained from, the clay product, samples was about 50 micrometer. [ 132] Example 7

[ 133] Opacity of Clay films and silver-clay film

[ 134] The op tical absorption spectra of clay films was measured on a Beekmaii DU 530 U V-V!S Spectrophotometer using fixed wavelength (600nm) mode. The percentage absorption of 600 nm wavelength light by the day film having a thickness of about 50 micrometer was 56%. The percentage absorption by silver-clay film having a thickness of about 50 micrometer w s 82%.

[135] Example 8

[ 136] The flexibility of the clay films was determined, by measuring the maximum bending angle and the corresponding radios of curvature before breaking of the product The bending angle was measured by mounting a rectangular clay specimen of size 2 inch by 2 Inch and 50 micrometer thickness on a Mitutoyo No. 1 80-301 B protractor head mounted to a Mitutoyo No. 180-703 steel rule. The measured angle of bending at the break of the clay sample was 36 degree. The radius of curvature derived from the bend angle at the break of the sample was about 0,5 mm. Figure 1 C provides a photograph of the cla film rolled up to show its flexibility.

[ 137] Example 9

[ 138] The bending angle at the break of a rectangular sii ver-ciay

specimen of size ^' 2 inch by 2 inch and 30 micrometer thickness of the clay sample was 30 degree. The radius of curvature derived from the bend angle at break of the sample was about 0.4 mm.

[ 139] Example .10

[140] Antimicrobial Testing Clay Sheets and Silver ion-exchanged Clay sheets

[ 141] The efficacy of silver ion -exchanged clay sheet was tested using the antibacterial susceptibility test, (agar diffusion test) which utilizes the size and presence of the zone of inhibition, to measure antimicrobial effectiveness. The testin process was carried out by spreading a thin layer of bacieria, grown in a growth medium, over the agar and then placing the circular cutouts of the clay film on top. The purpose was to determine the zone of bacterial growth inhibition around the pieces of film.

[142] Typical, gram negative and gram positive bacteria for a single test were Escherichia eoli. Staphylococcus epidermidis. Staphylococcus aureus and Bacillus subtilis. Unmodified Clay sheets were used as control samples along with silver ion-exchanged clay sheet in the antimicrobial tests,

[143] Photographs showing the zone of inhibition for all 4 types of

bacteria, by Silver organo-modtfied clay film disks (labeled as 4, 5 and 6 m Figure 2) along with control pristine clay film discs (labeled as 1 , 2 and 3 in the Figure 2) are provided in Figure 2. The smallest zone was for B, subtilis and the largest was for S. epidermidis. In general, gram-positive bacteria are easier to kill and since S. epidermidis is a gram-positive bacterium, it could explain why the zone of inhibition for it is larger within the incubated time period (48 hours). The ^' unmodified betaine-clay sheet control specimens did not exhibit a zone of bacterial growth inhibition.

[ 144] The presence of the zone of inhibition showed thai the silver successfully inhibited the growth of bacteria ami that the clay film was suitable for use as an antiseptic.

[145] Example 1 1

[ i 46] Methods and Materials:

[ 1 7} A., 0.4wt% of si i ver containing betaine-clay slurry

[ 148} I Og PGW clay, 19Gg !Deionized water and I -734g Betaine was combined in a capped bottle and gently shook to initiall combine all elements together into a slurry,

[149] The homogenizer was then used t -create a uniform viscosity throughout the mixture. It was used until lumps of clay were no longer visibly settled at the bottom,

f i 50] The mixture was allowed to sit for 24 hours. [151] 0.81 g AgN03 was added in and homogenized again, the bottle was then wrapped in aluminum foil (to prevent the Ag from being exposed to light) and was left to sit for an additional 24 hours,

152] Mixture was then washed and eentrifuged 3 times (should be 4 times but cla would not settle to be decanted properly )

[ 153 ] Mixture is ready to be poured and casted on to ^' Nylon fabric.

[ 154] B. 0.4 t% of silver containing betaine-clay slurry

[155] lOg PGW clay, 190g Deionized water and I .?34g Beiaiiie ^■ was combined in a capped bottle and gently shook to initially combine a!! elements together i to a slurry,

[ i 56] The homogenizer was then used to create a uniform viscosity

throughout the .mixtiire. It was used until lamps of clay were no longer visibly settled at the bottom.

[157] The mixture, was allowed to sit for 24 hours.

[ 1 8] 1 ,020g. AgN03 was added in and homogenized, again, the bottle was then wrapped in aluminum foil (to prevent the Ag .from being exposed to light) and was left to sit tor an additional 24 hours.

[ 159] Mixture was washed, decanted and eentrifuged times, f 1 0] Mixture is ready to be poured and casted on. to Nylon fabric.

[ 161] Casting on to Nylon. Fabric: [Ί 62] Nylon fabric was cut into a smaller segment that was large enough to tightly wrap around a glass-casting sheet. Tape was used on the back to securely fasten the fabric onto the glass sheet.

[163] Ag clay was then slowly poured out directly onto the fabric

(mixture was very thick and sat upon, the fabric rather than soaking in) a raicroscope slide was then used in an attempt to thin out and spread an even layer of clay upon the fabric.

[164] Cast was left to dry and was taken off as one piece with the Nylon fabric.

[ 165] Nylon clay film was then rolled on to a dowel,

[ 1 6] Anti-Bacterial Efficacy of Silver-Clay Nylon Fabric

[ 167] This experiment was to test the efficacy of ariti- bacterial Nylon, fabric samples from 0.4wt% silver slurry, nylo fabric samples from 0.5wt% silver slurry and untreated nylon fabric was. used as a control [ 1 8] Bacii!is siibiilis was the bacteria type used for testing; pre-made .ImL of growth media was dropped onto hardened agar using a micro pipette. The bacterium wa then spread evenly in the Petri -dish upon the agar using a UV-sterilized rubber policeman.

[ 169] Two punch outs were made with each type of test material All instruments and both sides of each material were sterilized using UV light and placed on to the agar containing B, suhtiiis. Two Petri -dishes containing 2 types of each material were made for comparison. All two •finished Petri -dishes were then placed in the incubator at 37 degree C.

[ 170] Zones of Inhibition can be clearly noted, by the distinctive halo-like effect around, the Silver Clay Nylon punch outs, both on the 0.4 wt% silver (labeled as A in the Figure 3} and 0.5wt¾ silver (labeled as B in the Figure 3) t concentrations. There was no zone of inhibition observed for control uncoated-nylon fabric sample (labeled as C in the Figure 3),

[ 171] Example 12

[ 172] Water Vapor Transmission Rate (WVTR) Testing for Silver Clay sheets on Nylon Cloth

[ i 73] Historically it was believed that wet wound environments would introduce a wound to increased risk factors related, to bacteria and infection. However, there is increasing amounts of evidence that wound healing takes place most rapidly In clean, moist environments.

Researchers have stated that a low WVTR is a dependable indication of the dressing's ability to retain moisture and thus create a moist, ideal environment that promotes rapid healing.

[ 174] WVTR values were measured to determine the moisture retention ability of the Nylon-Cast stiver clay sheet. The moisture permeability of the silver clay sheet was determined by measuring the water vapor transmission, rate (WVTR) across the material as stipulated by a modified AS TM standard method E96. The test involved .mounting a disc of the test, material in a specially designed vial containing water. The material was posi tioned across the opening of the cup, in a desiccator at 35 degree C and. with relative humidity maintained at 15 to 20 percent. The weight of the water filled vial with the test material was measured, at hourly intervals to calculate the amount of water loss per hour.

[ 175] Dressings with WVT values less than 35 g per square meter per hour can be defined as moisture retentive. Typical WVTR values observed, for silver organo-modified clay sheets were 16 to 36 g per square meter per hour depending on the thickness and amount of silver present in the clay sheet,

[ 176] Example 13

[ ί 77] Burn Wound Dressing Fabrication incorporating silver clay sheet [ 178] A prototype burn bandage was developed by successive layering of (a) Nylon membrane (b) silver clay sheets and (c) hydrogel adhesive. Typical Dimensions were as follows. Silver clay sheet: 1.5 inch by 2.4 inch; Delnet Membrane: 2 inch by 3 inch; Hydrogel sheet; 3 inch by 4 inch; Cover slip: either cut to the size of the hydrogel or cut to 3 inch by 5.5 inch. Schematic diagram of the antimicrobial bum wound dressing is provided in ^' Figure 3. 179] The nylon membrane serves as a porous membrane to control moisture flow to the organo-modified silver clay film, while at the same keeping the film and place and preventing particles irom the film breaking off into the wound,

[ 180] Clay sheet acted as a moderator layer between the wound surface and hydrogei

[181 j The hydrogei bandage provided both adhesive to bold the bandage i place and a soothing cooling sensation beneficial for born care. The hydrogei was also a water reservoir to keep the wound surface moist.

[ 182] The multilayer wound dressing was packaged in heat-sealable foil pouches,

[ 183] The final product was easil contoured as a bandage (strip or roll) with a silkone-based hydrogei adhesive.

[1.84] Example 14

[ 185] In-vivo Testing of Silver clay sheet, wound dressing

[ ί 86] Silver clay sheet antimicrobial wound dressing was evaluated using animal burn, wound models. Wound dressing was prepared as in Example 13. Two Yorkshire cross pigs were randomized to three treatment protocols alter full thickness burns were created. Contact bums were created paravertebral under aseptic conditions. A h.tnhari Electric Dehomer was heated to a maximum temperature of 1 ,000 degree F and was placed on the dorsum of the animal until the proper depth of 1 cm was reached (typically 10 seconds). A total of six bum sites, each 11 square centimeter was created on the dorsum of the animal with 4-5 cm between each site.

[ 187] The wound received three treatment protocols, namely Gauze, silvadine cream and silver clay sheet dressing. Silver clay wound dressing was prepared as described in the Example 13. Dressings were changed 3 times a week for the first .14 days for the ganze and silvadine cream treatments. The silver clay sheet dressing was changed only every 7 days. Photographs showing the wound heating progress is provided in Figure 5.

[ i 88] Sites treated with silver clay sheet (or mat) dressing required less daily care and dressing changes as compared to the other two treatments unmedieated eauze and silvadine cream for the first 10 da vs. Time to lull granulation for each group was 14 days, in summary, silver clay sheet dressing demonstrated similar healing activity with that of Si!vadene¾> cream, albeit with significantly less wound care and number of dressing changes.

[189] Example 15

f 190] The application of clay sheets as transdermal delivery patches were evaluated by measuring the uptake and release of organic dyes by the clay sheets. A clay sheet similar to the one described in the Example I as dipped in methylene blue dye solution in water. 10 g sodium-exchanged montmorilloiiite clay (PGW) clay, .190 g deionized water nd 1.7 g anhydrous Betake were added in a bottle and left io stir for 24 h. The slurry was casted onto a silicone sheet. After drying the clay sheet was easily peeled off from the tray surface. Then a 2 inch by 2 inch sheet was cut from the dried clay sheet and dipped in methylene blue dye solution in water. After 5 minutes the clay sheet was taken out of the methylene blue solution _* The color of the clay sheet, turned from yellowish brown to dark blue due to the uptake of the organic dye. This demonstrates that organic chemicals such as drugs could be loaded onto a clay sheet and used as transdermal patches for drug delivery. After 5 minutes the clay sheet was taken out of the methylene blue solution. The color of the clay sheet turned from yellowish brown to dark blue due to the uptake of the organic dye. This change in color was similar to loading of drugs to a patch.

[ 1 1 j The dye loaded-clay sheet was then placed in a phosphate buffer solution. The dye was slowly released into the solution with the clay sheet intact. This experiment showed that the clay sheets could be used in preparing a drug delivery patch,

[ 192] Example 16

[1 3] Clay sheets as prepared in the Example 1 were used as fire- resistant sheet. Clay sheet are a safe -al ernative to asbestos because clay sheet are inorganic materials similar to asbestos but without the hamiful side effects.

[ 1 4] 5 g sodium-exchanged montmoril!onite day (PGW) clay, 190 g dek ized water and 0.9 g anhydrous Betake were added in a bottl and left to stir for 24 h. The slurry was easied onto a silicone sheet. After drying the clay sheet was easily peeled off from the tray surface. The thickness of the dried clay sheet was 0.2 mm. This sheet was used in flame penetration tests.

[1 5] Flame penetration tests were conducted on thin clay fabrics (0.2 mm thick). Horizontal and verticai flame bum tests were conducted on several candidate sheets. Clay sheets were found to be. immediately self- exiingiushing, Burn damage on the clay sheet was confined locally to the heated zone beneath and around the lit torch tip's flame. All flames were immediately self-extinguishing beyond those regions, with zero after flame times recorded. The clay fabric exhibited a rise in back-side temperature less than 10 degree F after 20 second flame exposure.

Pho tographs of the fire reiardant tested samples are provided in Figure 6.

[196] Example .17

f i 97] Application of clay sheets as a membrane for separating organic molecule from a mixture [1 8] Clay sheet produced as in the example .1 were tested for use as a membrane for separation technologies, such as Dimethyl carb nate- Meihanoi-waier under ambient conditions.

[ 199] Betaine-Clay membrane submerged in DMC per Methanol per Water Solution:

1200] 30 mL Dimethyl Carbonate, 60 mL Methanol and 5 mL of distilled water were mixed together in a 500 mL beaker. 3 such mixtures- were in separate beakers

[201] Two clay sheets were cut into rectangle sheets of size 4.5 inch x 2.25 inch and were placed in the dimethyl, carbonaie/methanol/water mixture solution for 2 h. Then the beakers were left undisturbed for 2 h and resulting clay sheets arid solutions were weighed.

[202] Clay sheet 1

[203] Thickness of the clay sheet 30.48 micron

[204] Weight of the clay sheet before dipping in test solution 0,5574 g

[205] Weight of the clay sheet after dipping in test solution 0,8854 g

[206] Increase in weight due to water absorption 0.3280 g

[207] Clay sheet 2

[208] Thickness of the clay sheet 99,60 micron

[209] Weight of the clay sheet before dipping in test solution 1 2.17 g

[210] Weight of the clay sheet after dipping in test solution 1 ,7080 g [21 i] increase in weight due to water absorption 0.3863 g

[212] The increase in weight clearly demonstrate the efficiency of water removal from organic mixtures by the clay sheets.

[213] Other modifications and variations to the invention will be

apparent to those skilled in the art from the foregoing disclosure and teachings. Thus, while only certain embodiments of the inven tion have been specifically described herein, it will be apparent that numerous modifications may be made thereto without departing irom the spiri t and scope of the invention.