Compositions and methods for treating wounds to significantly reduce the healing time, reduce the incidence of scar formation, improve the success of skin grafts, reduce the inflammatory response and providing anti-bacterial treatments to a patient in need thereof, that include small non-interlinked particles of bioactive glass or highly porous bioactive glass, are disclosed. Anti-bacterial solutions derived from bioactive glass, and methods of preparation and use thereof, are also disclosed. The compositions include non-interlinked particles of bioactive glass, alone or in combination with anti-bacterial agents and/or anti-inflammatory agents. The compositions can include an appropriate carrier for topical administration. Anti-bacterial properties can be imparted to implanted materials, such as prosthetic implants, sutures, stents, screws, plates, tubes, and the like, by incorporating small bioactive glass particles or porous bioactive glass into or onto the implanted materials. Anti-bacterial properties can also be imparted to devices used for in vitro and ex vivo cell culture by incorporating non-interlinked particles of bioactive glass into the devices. Anti-bacterial compositions derived from aqueous extracts of bioactive glass are also disclosed. These compositions can be used, for example, in food preparation, solutions used for cell culture, and buffer solutions, such as i.v. solutions.

The present invention relates to bioactive glass-containing compositions, aqueous extracts derived from such compositions, cosmetics including these compositions, implants including the compositions, and methods of using the compositions to accelerate healing, reduce inflammation and reduce bacterial infection. More specifically, the present invention relates to compositions including particles of bioactive glass, optionally including one or more agents which aid in the delivery and distribution of the particles and which may also have other therapeutic effects, and methods of use thereof.
When an injury occurs, cell damage initially comes from the precipitating event, such as a cut, resulting in ruptured cells and severed or crushed capillaries and other blood vessels. However, later damage can occur due to bacterial growth or to an inflammatory response.
The healing process involves several steps, including coagulation, inflammation, repair (or fibroplasia) of the damaged tissue, angiogenesis (or revascularization), re-epithelialization and remodeling. Several of these steps, while necessary to promote normal healing, can cause excessive scarring and other health related problems if unchecked.
For example, unchecked inflammation can have harmful consequences. For example, many chronic and even life-threatening disorders, such as asthma, rheumatoid arthritis, lung fibrosis, peritoneal adhesions, hypersensitivity and autoimmune diseases are a result of an uncontrolled inflammatory response. An unresolved inflammation in the lung resulting from bacterial infection (i.e., pneumonia) may eventually lead to extensive tissue damage and a chronic lung abscess. Inflammation of the peritoneal cavity and the resulting adhesions following abdominal surgery is a major cause of infertility in women. Asthma is an often life-threatening disorder which results from an inadvertently stimulated inflammatory response in the lungs.
An excessive inflammatory response can cause extensive swelling, which can lead to additional injury as a result of anoxia. Pain results from a combination of kinins and the effect of lysozymes and pressure from the swelling on nerve endings. Unchecked, the inflammatory response can set off a neural feedback loop and cause hyperalgesia, a phenomenon in which the surrounding area of injury remains painful. Accordingly, there is a great interest in the medical community to develop anti-inflammatory agents.
The amount of bacterial burden in a wound bed is an important factor in the healing of wounds, especially dermal ulcers. Some bacterial colonization is inevitable, and may even be beneficial in stimulating the body""s natural immune response. However, excessive bacterial colonization is clearly detrimental and can lead to high levels of bacterial waste products, chronic inflammation, heavy exudate, increased tissue necrosis and eventually, full infection. Wounds typically will not heal when the bacterial burden is above about 105 microorganisms per gram of tissue.
Topical anti-microbial agents, including organism specific antibiotics such as bacitracin and silver sulfadiazine are typically used in wound care. However, these agents are generally regarded as relatively weak in action. More importantly, the recent rise of strains of microorganisms resistant to these agents has led to many intractable cases of infection. Other typically used antimicrobial agents, such as iodine and alcohol, damage native tissue and repair cells, and retard the healing process of dermal wounds.
Many treatments have been proposed for treating wounds and accelerating wound healing. Often, such treatments involve the use of growth factors, such as platelet derived growth factor (PDGF) or the use of cultured cells derived from the wounded patient""s own skin. These methods are limited by the difficulty of preparing the growth factors, the time spent in preparing the cell cultures, and the high costs of such treatments. Further, potential side effects associated with such therapies are unknown at this time. For example, the prolonged use of corticosteroids is associated with untoward secondary effects.
It would be advantageous to provide compositions and methods for treating wounds, and, in particular, for treating bacterial infection and inflammatory response in patients. The present invention provides such compositions and methods.
Compositions and methods for treating wounds to significantly reduce the healing time and prevent the body""s natural defenses from proceeding unchecked are disclosed. The compositions and methods allow wounds to heal in significantly less time than would otherwise occur. Inflammation is greatly reduced around the wound site. The incidence of scar formation following a wound or burn is reduced. The presence of bacteria is also reduced. The success of skin grafts is increased.
The compositions include non-interlinked particles of bioactive glass, alone or in combination with an additional anti-bacterial and/or anti-inflammatory agent, and optionally include other therapeutic agents. Formulations including the compositions, alone or in combination with a suitable carrier, preferably for topical administration, are also disclosed. Also disclosed are anti-bacterial solutions derived from bioactive glass, and methods of preparation and use thereof.
The compositions can be incorporated into implanted materials, such as prosthetic implants, sutures, stents, screws, plates, tubes, and the like, to impart anti-bacterial and anti-inflammatory properties to the materials. Anti-bacterial properties can also be imparted to devices used for in vitro and ex vivo cell culture by incorporating the composition into the devices.
Anti-bacterial and anti-inflammatory compositions derived from aqueous extracts of bioactive glass can be formed by placing bioactive glass in an aqueous solution, allowing the glass to dissolve over a suitable period of time, for example, a week or more, and filtering out the undissolved glass particles. The solvent can also be evaporated to provide a solid material with anti-bacterial properties. These compositions can be used in situations where prevention or reduction of bacterial infections would be advantageous, for example, food preparation, cosmetics, media used for cell culture, and buffer solutions.
When used topically to treat a wound or burn, the wound or burn is contacted with an effective amount of the composition for the intended application. When used for skin grafting, the bioactive glass-containing composition is applied to either the graft site prior to placing the donor tissue, or to the donor tissue itself.
The compositions can be administered to the pulmonary system, for example, via an inhaler, as an adjunct therapy for treating pneumonia or chronic sinus infections. The compositions can also be co-administered to the pulmonary system with therapeutic agents which are themselves inflammatory, to minimize the inflammatory response to these agents. The compositions can be applied directly to a surgical site to minimize post-surgical adhesions, minimize inflammation around the site, and prevent or minimize infection at the site. In one embodiment, the compositions are included in a polymeric material, preferably a biodegradable polymeric material, which is then applied to a surgical site to minimize post-surgical adhesions.
Compositions and methods for treating wounds to significantly reduce the healing time and prevent the body""s natural defenses from proceeding unchecked are disclosed. The compositions and methods allow wounds to heal in significantly less time than would otherwise occur. Inflammation is greatly reduced around the wound site. The incidence of scar formation following a wound or burn is reduced. The presence of bacteria is also reduced. The success of skin grafts is increased.
The compositions include non-interlinked particles of bioactive glass, alone or in combination with an additional anti-bacterial and/or anti-inflammatory agent, and optionally include other therapeutic agents. Formulations including the composition and a suitable carrier, preferably for topical administration, are also disclosed. Also disclosed are anti-bacterial solutions derived from bioactive glass, and methods of preparation and use thereof.
Not being bound to any particular theory or mechanism, it is believed that the surface area and reactivity of particulate bioactive glass provides an adsorption of hydronium ions from a solution and a release of sodium that increases the pH of the environment. Through the pH-dependent binding of hemoglobin, the amount of oxygen in the wound or burn is thereby increased.
These reactions also cause a higher negative surface charge on the glass surface and the development of a high specific surface area (e.g. from 0.5 m2/g initially to over 50 m2/g by 12 hours) which attracts collagen fibrin, fibronectin and cells. Moreover, the bioactive glass provides for the precipitation of calcium and phosphorous naturally present in the wound exudate and blood which cause the rapid formation of a calcium phosphate layer that may incorporate collagen, fibrin and fibronectin to stabilize the wound quickly and effectively. In addition, the bioactive glass is believed to strongly inhibit the overactive inflammatory response present in chronic wounds. In some cases, wounds or burns healed with the compositions and methods disclosed herein heal without the necessity of eschar formation. That is, new epithelial tissue can be directly formed. The bioactive glass-containing compositions described herein have been shown to increase the IL-6 concentration when injected into the peritoneal cavity of mice, without a concomitant increase in other cytokines, such as TNF-xcex1, IL-1 and IL-10. The absence of the other cytokines indicates that the overall response is anti-inflammatory rather than pro-inflammatory.
The terms xe2x80x9cwoundxe2x80x9d and xe2x80x9cburn,xe2x80x9d collective referred to herein as xe2x80x9cinjuryxe2x80x9d have their usual meanings. xe2x80x9cNormalxe2x80x9d is used in the sense it is usually used in the medical arts. The terms xe2x80x9canti-bacterial agentsxe2x80x9d and xe2x80x9cantibioticsxe2x80x9d as used herein mean pharmacologically acceptable synthetic or natural agents which destroy or inhibit microorganisms and includes both antibacterial and antiviral agents. xe2x80x9cMedical practitionerxe2x80x9d means one of ordinary skill in the art wound and burn treatment. Typically this person is a physician, nurse, dentist, or paramedic.
Compositions including non-interlinked particles of bioactive glass, alone or in combination with anti-bacterial agents and/or anti-inflammatory agents, can be used for a variety of purposes.
As used herein the terms xe2x80x9cbioactive glassxe2x80x9d or xe2x80x9cbiologically active glassxe2x80x9d mean an inorganic glass material having an oxide of silicon as its major component and which is capable of bonding with growing tissue when reacted with physiological fluids.
Bioactive glasses are well known to those skilled in the art, and are disclosed, for example, in An Introduction to Bioceramics, L. Hench and J. Wilson, eds. World Scientific, New Jersey (1993), the contents of which are hereby incorporated by reference.
The glass preferably includes between 40 and 86% by weight of silicon dioxide oxide (SiO2), between about 0 and 35% by weight of sodium oxide (Na2O), between about 4 and 46% by weight calcium oxide (CaO), and between about 1 and 15% by weight phosphorus oxide (P2O5). More preferably, the glass includes between 40 and 60% by weight of silicon dioxide oxide (SiO2), between about 5-30% by weight of sodium oxide (Na2O), between about 10 and 35% by weight calcium oxide (CaO), and between about 1 and 12% by weight phosphorus oxide (P2O5). The oxides can be present as solid solutions or mixed oxides, or as mixtures of oxides.
CaF2, B2O3, Al2O3, MgO and K2O may be included in the composition in addition to silicon, sodium, phosphorus and calcium oxides. The preferred range for B2O3 is between 0 and 10% by weight. The preferred range for K2O is between 0 and 8% by weight. The preferred range for MgO is between 0 and 5% by weight.
Anti-microbial salts such as AgNO3, CuO, and ZnO, or other antimicrobial salts of the silver, copper and zinc ions, such as nitrates, acetates, etc., can be added. The preferred range for these salts is between 0 and 5% by weight.
The most preferred glass is Bioglass(copyright)(trademark) (a trademark of University of Florida), which has a composition including about 45% by weight silicon dioxide, about 24.5% by weight sodium oxide, about 6% by weight phosphorus oxide, and about 24.5% by weight calcium oxide. Another preferred material is hydroxyapatite.
Particulate, non-interlinked bioactive glass is preferred in the present invention. That is, the glass is in the form of small, discrete particles, rather than a fused matrix of particles or a mesh or fabric (woven or non-woven) of glass fibers. Note that under some conditions the discrete particles of the present invention may tend to cling together because of electrostatic or other forces but are still considered to be non-interlinked. Preferably the particle size is less than about 90 microns; more preferably, less than about 20 microns; even more preferably, less than about 5 microns, and ideally, less than about 2 microns, as measured by SEM or laser light scattering techniques.
Highly porous bioactive glass has similar anti-bacterial and anti-inflammatory properties to small particles of bioactive glass, due to its relatively fast degradation rate and high surface area, in comparison to non-porous bioactive glass compositions. When highly porous bioactive glass is used in place or in addition to small particles of bioactive glass, the pore size is between about 0 and 500 xcexcm, preferably between about 10 and 150 xcexcm, and more preferably, between about 50 and 100 xcexcm. The degree of porosity of the glass is between about 0 and 85%, preferably between about 30 and 80%, and more preferably, between about 40 and 60%. Porous bioactive glass can be prepared, for example, by incorporating a leachable substance into the bioactive glass composition, and leaching the substance out of the glass. Suitable leachable substances are well known to those of skill in the art, and include, for example, sodium chloride and other water-soluble salts. The particle size of the leachable substance is roughly the size of the resulting pore. The relative amount and size of the leachable substance gives rise to the degree of porosity. Also, as described herein, porosity can be achieved using sintering and/or by controlling the treatment cycle of glass gels to control the pores and interpores of the material.
The glass composition can be prepared in several ways, to provide melt-derived glass, sol-gel derived glass, and sintered glass particles. The sintered particles may be in sol-gel derived, or pre-reacted melt derived form. Sol-gel derived glass is generally prepared by synthesizing an inorganic network by mixing metal alkoxides in solution, followed by hydrolysis, gelation, and low temperature (around 200-900xc2x0 C.) firing to produce a glass. Sol-gel derived glasses produced this way are known to have an initial high specific surface area compared with either melt-derived glass or porous melt-derived glass. The surface area of the sol-gel derived glasses is at least about 50 m2/g. Melt derived glass is generally prepared by mixing grains of oxides or carbonates, melting and homogenizing the mixtures at high temperatures, typically between about 1250 and 1400xc2x0 C. The molten glass can be fritted and milled to produce a small particulate material.
The glass composition is preferably melt-derived. In each preparation, it is preferred to use reagent grade glass, especially since the glass is used to prepare materials which ultimately may be administered to a patient.
A. Melt Derived Glass
A melt-derived glass composition can be prepared, for example, by preparing an admixture of the individual metal oxides and other components used to prepare the glass composition, blending the admixture, melting the admixture, and cooling the mixture. The melting temperature is determined in large part by the glass composition, and ranges, for example, from about 900-1500xc2x0 C., preferably between about 1250 and 1450xc2x0 C. The melt is preferably mixed, for example, by oxygen bubbling, to ensure a thorough homogenation of the individual components.
The mixture can be cooled, for example, by adding the molten admixture to a suitable liquid, such as deionized water, to produce a glass frit. Porosity can be introduced by grinding the glass into a powder, admixing the powder with a foaming agent, and hot pressing the mixture under vacuum and elevated temperature. The particle size of the glass powder is between about 2 and 70 xcexcm, the vacuum is preferably less than 50 MPa, and the hot pressing is preferably performed at a temperature above 400xc2x0 C., preferably between about 400 and 500xc2x0 C. Suitable foaming agents include compounds which evolve carbon dioxide and/or water at elevated temperatures, for example, metal hydroxides, metal carbonates, and peroxides, such as hydrogen peroxide. Preferred metal carbonates are sodium bicarbonate, sodium carbonate and calcium carbonate. The foaming agents are preferably added in a range of between about 1-5, more preferably 2-3 percent by weight of the glass powder. The preparation of melt-derived porous glass is described, for example, in U.S. Pat. No. 5,648,301 to Ducheyne and El Ghannam, the contents of which are hereby incorporated by reference.
B. Sintered Glass Particles
Glass can be sintered using known methodology. In one embodiment, an aqueous slurry of the glass powder and a foaming agent with a suitable binder, such as polyvinyl alcohol, is formed. The slurry is then poured into a mold, allowed to dry, and sintered at high temperatures. These temperature may range, depending on the glass composition and foaming agent used, between about 500 and 1000xc2x0 C., more preferably between about 600 and 800xc2x0 C.
C. Spun Fibers of Sol-gel Derived Glass
It is known in the art to control the heat treatment cycle of glass gels to control the pores and interpores of the material to create a porous glass material. However, since a pore diameter larger than 0.1 microns is difficult to achieve using this method, the sintering and foaming processes described herein are generally more preferred.
D. Leaching of the Porous Material
To aid in preparing glass compositions with high porosity, the glass composition can include a material which can be preferably leached out of the glass composition, and, in doing so, provide the composition with high porosity. For example, minute particles of a material capable of being dissolved in a suitable solvent, acid, or base can be mixed with or melted into the glass, and subsequently leached out. The resulting voids have roughly the same size as the particle that was leached out. In the case of a material which is part of a melt-derived glass composition, the size of the pores and degree of porosity depends on the amount of added material relative to the amount of glass. For example, if the leached material constituted about 80% of the glass, then the glass would be approximately 80% porous when the material was leached out. When leaching the glass composition, care should be taken not to leach out those components which add to the bioactivity of the glass, i.e., the calcium and phosphorus oxides.
The bioactive glass may be administered to the wound in a topical, pharmaceutical formulation, such as in the form of a suspension, lotion, cream, ointment, or gel. Those skilled in the art will appreciate that there are other appropriate topical carriers such as those listed in U.S.P.D.
Other Therapeutic Agents
In addition to bioactive glass, the formulations can include other therapeutic agents such as antibiotics, antivirals, healing promotion agents, anti-inflammatory agents, immunosuppressants, growth factors, anti-metabolites, cell adhesion molecules (CAMs), bone morphogenic proteins (BMPs), vascularizing agents, anti-coagulants, and topical anesthetics/analgesics.
The antibiotics can be topical antibiotics suitable for skin treatment. Examples of such antibiotics include but are not limited to: chloramphenicol, chlortetracycline, clyndamycin, clioquinol, erythromycin, framycetin, gramicidin, fusidic acid, gentamicin, mafenide, mupiroicin, neomycin, polymyxin B, bacitracin, silver sulfadiazine, tetracycline and chlortetracycline.
Suitable antivirals include topical antivirals, such as acyclovir, and gancyclovir. Suitable anti-inflammatory agents include corticosteroids, hydrocortisone and nonsteroidal antinflammatory drugs. Suitable growth factors include basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), transforming growth factors xcex1 and xcex2 (TGF xcex1 and xcex2), platelet-derived growth factor (PDGF), and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF)). Suitable topical anesthetics include benzocaine and lidocaine.
In one embodiment, the therapeutic agent is one which would otherwise cause an inflammation at the site at which it is delivered, and the bioactive glass particles reduce the associated inflammation. For example, a number of compounds, for example, amine compounds, result in inflammation when administered topically, i.e., in a transdermal patch. A number of other compounds result in inflammation when administered via pulmonary administration, i.e., via an inhaler.
It is acceptable to place particulate bioactive glass directly into a wounded area or on a burn with no carrier or excipient. However, preferably bioactive glass alone or in combination with one or more other therapeutic agents is combined in any pharmaceutically acceptable carrier for topical use, such as a suspension, ointment, cream, or gel to facilitate application to the wound. For example, the composition of the present invention can be blended with white petrolatum to form an ointment, with mineral oil to form a suspension, with a commercially available, cream cosmetic base to form a non-greasy cream, or with a commercially available water soluble, lubricating gel, e.g., K Y Gel (trademark), to form a high moisture gel.
The bioactive glass and other therapeutic agents can be combined with other wound and burn treatments or dressings such as, but not limited to, collagen, fibrin, fibronectin, various growth factors, such as PDGF, TGF-xcex2, vitamin E, gauze, cotton, cellulose, synthetic wound or burn dressings and other wound or burn dressings/treatments known to those of ordinary skill in the art. Dressings of fiberglass, including fiberglass made from fibers of bioactive glass, can also be used. In addition, the bioactive glass may be combined with any biocompatible material, such as biodegradable polymer like polylactic/glycolic acid to form a composite material for accelerating would healing.
While the ratio of bioactive glass to carrier is not critical, preferably the blend of bioactive glass, other therapeutic agents, and carrier contains about 20% to about 80% bioactive glass. The preferred particle size range for the bioactive glass not greater than about 90 microns is recommended. Particle sizes specifically less than about 10 microns as well as less than about 2 microns can also be used, where the particle sizes are measured by SEM or laser light scattering techniques. Particles of such a small size range generally provide for the advantages of the present invention but do not illicit any undesirable immune response. This phenomenon is an unanticipated result, given the general history found in the literature on the biological response to small synthetic particles. The proportion other therapeutic agents varies according to the agent and the nature of the application. However, the preferred proportions are such that the amount of the agent administered to the wound or burn is in the dosage range accepted within standard medical care.
If the bioactive glass is to mixed with a topical carrier such as an ointment, then it is preferable that the glass not be significantly pre-reacted prior to application. This can be achieved, for example, by applying the composition immediately after mixing. Alternately, the topical carrier may be of such a nature as to not pre-react the glass, such as, for example glycerin. The bioactive particulate glass and topical carrier can be separate components in a two part system wherein the bioactive glass and topical carrier are mixed and simultaneously applied. For example, a two part mixing syringe with two separate storage chambers and a mixing chamber can be used. Other two part systems could also be used. For example, the particulate bioactive glass can be incorporated into a bandage and the topical carrier can be applied to the wound or burn which is followed by application of the bandage. Other two part delivery systems are known to those of ordinary skill in the art.
The compositions can be incorporated into implanted materials, such as prosthetic implants, sheets, pins, valves, sutures, stents, screws, plates, tubes, and the like, by incorporating bioactive glass particles into the implanted materials. The compositions can be moldable or machinable.
In another embodiment, anti-bacterial properties are imparted to devices used for in vitro and ex vivo cell culture by incorporating non-interlinked particles of bioactive glass into the devices.
The articles of manufacture are imparted with anti-bacterial properties via the incorporation of the bioactive glass, which will allow the articles to be implanted, or used to culture cells, with a reduced likelihood of bacteriological contamination.
The anti-bacterial (and anti-fungal) compositions derived from aqueous extracts of bioactive glass are formed by placing bioactive glass in an aqueous solution, allowing the glass to dissolve over a suitable period of time, and filtering out the undissolved glass particles. The solvent can be evaporated to provide a solid material with anti-bacterial properties. The compositions can be used in situations where bacteria are present, for example, food preparation, solutions used for cell culture, and buffer solutions.
Without being bound to a particular theory, it is believed that there is a complex relationship between the type of ion being released from the glass, the amount of that ion, the rate at which release occurs, the pH of the solution, and the resulting anti-microbial or anti-inflammatory response. This effect is observed with respect to the particles of bioactive glass themselves and also in the ionic solutions derived from the glass particles. Accordingly, in the uses described below, particles of bioactive glass can be used in place of or in addition to the solutions derived from the particles.
Food Preparation
Numerous foods are potentially infected with bacteria, such as E. coli. Ground beef and chicken are particularly susceptible to bacterial infection. Aqueous solutions including an aqueous extract from bioactive glass have anti-bacterial properties. As discussed below in Example 3, the anti-bacterial effect is due, in part, to the basic nature of the solution (pH greater than about 7, preferably greater than about 9, more preferably greater than about 10.5). However, sodium hydroxide solutions of relatively high pH are not as effective at killing bacteria. Accordingly, the solutions have additional antibacterial elements present than merely a relatively high pH.
The composition can be sprayed on contaminated surfaces, or incorporated into food products such as ground beef. Since bioactive glass has been approved for various uses by the FDA, the extract of bioactive glass should be harmless to humans.
Cosmetic Applications
Liquid-based cosmetics, such as skin lotions, shampoos and rinses, are directly applied to human skin. While current manufacturing processes generally control bacterial contamination when the products are in sealed containers, after unsealing the package, bacteria, fungi and/or mold may contaminate the cosmetics. Often, various antibacterial agents are added to the cosmetics to minimize this process.
The compositions can be included in cosmetic applications to minimize contamination by bacteria, fungi and/or mold. The compositions can be added, for example, to cosmetic bases such as liquid foundation, shampoo, rinse, lipstick, skin lotion, milky lotion, creams and the like. The cosmetics can include the ionic solutions described herein and/or particles of bioactive glass described herein.
Solid Compositions
The aqueous solutions can be dried, for example, by spray drying or by drying in vacuo to provide an antibacterial composition. The compositions can be incorporated into other bacterial solutions, such as Betadine(copyright) solution, to provide an additional anti-bacterial component to the solutions.
Cell Growth and Culture
There are many solutions used for culturing cells. These include Dulbecco""s minimal essential media, Hank""s balanced salt solution, and others. These solutions are essentially isotonic with the cells to be cultured. A problem associated with cell culture is often the growth of bacteria in culture along with the desired cells. Bacterial growth can be minimized by incorporating the extract of bioactive glass into the cell culture media.
Buffer Solutions
Buffer solutions, such as HEPES and TRIS, are often at the perfect pH to support bacterial growth. Addition of the extract of bioactive glass to the compositions will impart anti-bacterial properties to the solutions. While the anti-bacterial effect of the extract solution is due in part to the relatively high pH, lower pH""s are also somewhat effective. As shown in Example 3, even a pH of 7.6 was moderately effective as an anti-bacterial solution. Accordingly, although the buffer solutions will lower the pH somewhat, the solutions will still exhibit anti-bacterial properties. In one embodiment, the buffered solution is an i.v. solution, for example, phosphate buffered saline.
Particulate bioactive glass is capable of dramatically reducing the amount of time necessary for wound healing to occur. Further, a composition including non-interlinked particles of bioactive glass (or an implant including highly porous bioactive glass) and other anti-bacterial agents augments the natural healing process. The effectiveness of the composition is most dramatically illustrated in immune compromised patients whose ability to heal wounds is somewhat suppressed.
The compositions can be administered to a wound or burn in a similar manner as topical formulations currently in clinical use. The exact amount of application is at the discretion of the medical practitioner but is typically applied by generously spreading the composition into the desired area and placing a thin film on the surrounding area at least once a day. After application of the composition, the injured area is treated according to accepted medical practice. For example, after applying the composition, the injured area is typically covered with a sterile bandage, and the patient may be given antibiotics, analgesics and/or other medications systemically. Treatment of the injured area is continued until, in the judgement of the attending medical practitioner, the injury has healed and further treatment is not needed.
The methods for causing effective wound healing or providing an anti-bacterial treatment to wounds, involve contacting a wound with an effective wound healing or anti-bacterial amount of non-linked particles of bioactive glass, optionally in combination with an addition anti-bacterial or anti-inflammatory agent.
In one embodiment, the compounds are used to fill voids, including voids created during medical procedures. For example, during a root canal operation, the hollowed-out tooth can be filled with a composition including bioactive glass. This will help prevent bacterial infection until the tooth is ultimately filled. Also, bioactive glass-containing compositions can be used to fill the pockets that can develop between the teeth and gums. Compositions including bioactive glass can be used to fill voids present in aneurysms, and prevent bacterial growth inside the filled void. Other voids which can be filled include those formed surgically, such as removal of a spleen, ovary, gall bladder, or tumor.
The methods for grafting skin involve applying non-linked particles of bioactive glass to either the graft site prior to placing the donor tissue, or to the donor tissue itself.
The methods for grafting skin involve applying particulate bioactive glass to either the graft site or donor tissue before it is placed in its intended location. Those interested in a detailed description of skin grafting are referred to xe2x80x9cSkin Grafts,xe2x80x9d in Selected Readings in Plastic Surgery, vol. 7, No. 2, P. L. Kelton, MD, Baylor University Medical Center (1992). The graft may also be further treated with a topical carrier prior to placement. The application of bioactive glass to grafts is intended to increase the likelihood that the graft will xe2x80x9ctakexe2x80x9d and incorporate in the host bed. It is intended that the bioactive glass particulates will act as an intermediary bond between the host and graft tissue, suppress the overall inflammatory response which could lead to rejection, as well accelerate the overall healing process which will lead to a faster and more successful acceptance.
The methods for improving the appearance and structure of scar tissue, especially keloid scar tissue, formed as a wound heals, involve contacting a wound as it heals with an effective scar appearance-improving amount of non-linked particles of bioactive glass. In this method, the particles are preferably present in a sterile, pharmaceutically acceptable carrier such as an ointment or gel.
The presence of a bioactive glass particulate within the healing wound bed may alter the formation of scar tissue by at least two mechanisms. First, bioactive glasses will act to reduce the overall inflammatory response in the wound through the adsorption of inflammatory mediators such as prostaglandins, TNF-xcex1, IL-1 and a variety of cytokines and the release of ions that leads to an increase in extracellular osmotic pressure. A reduced inflammatory response will decrease the number and activity of macrophages and other inflammatory cells, thereby reducing the concentration of chemotactic molecules released to recruit fibroblasts. The end result of decreased fibroblast activity from otherwise overactive levels is a reduction in the density of scar tissue.
Secondly, bioactive glasses attract and bind collagen fibers to their surface. As fibroblasts infiltrate the wound they migrate among the glass particulate and lay down collagen among and on the surface of the particles. The random distribution of bioactive glass particles to which collagen fibers are attracted and attached will determine that the fibers themselves are randomly oriented. As the glass particles resorb, they leave behind a bed of randomly oriented collagen fibers whose mechanical properties more closely match those of unwounded tissue.
An added benefit of using the above methods for treating wound and grafting skin is that the scar tissue formed upon healing is more uniform and more closely matches the surrounding skin. Thus, the scar tissue, the formation of which is generally unavoidable, has a better appearance. This benefit is particularly important for treating wound and burns on the face. The compositions can also be used to improve the appearance and structure of scar formed as the wound or burn heals.
The compositions can be used to reduce inflammation in a patient. Overly acute or chronic inflammation can result in various disease states in a patient, for example, arthritis and tendinitis, pulmonary disorders such as asthma and emphysema, and post-surgical (peritoneal) adhesions.
Very small particulate bioactive glass has the property of exerting an anti-inflammatory effect when in contact with body tissue. It appears that the bioactive glass suppresses the production of tissue necrosis factor alpha (TNF-xcex1) and interleukin-1 (IL-1) at the earliest stages of administration of the bioactive glass. This effect is transient and does not induce any secondary immunologic response. This is very different than the administration of growth factors, antibiotics or other cytokines that all show secondary effects on the immune system, even though they may be small.
TNF-xcex1 is a powerful pro-inflammatory cytokine that not only participates in the normal inflammatory response, but is also implicated in myocardial dysfunction and cardiomyocyte death in ischemia-reperfusion injury, sepsis, chronic heart failure, viral myocarditis and cardiac allograft rejection, as well as a host of other inflammatory disorders. Accordingly, by suppressing the production of TNF-xcex1, the compositions reduce the likelihood of these disorders occurring.
The preferred size range for the bioactive glass, for this embodiment, is such that the particles do not physically obstruct vascular, lymph or pulmonary pathways as the particles pass through the body. Particles less than 20 microns in size, as measured by SEM or laser light scattering techniques, are particularly preferred, as immunochemistry results indicate that the body does not respond to these particles as it would to other particles, for example, silica particles. Experiments have shown that the body does not show abnormal or elevated recruitment of macrophages to the area where Bioglass(copyright) particles have been injected. This is in stark contrast to small particles of other materials, such as talcum, asbestos, silicone and metal debris, which are known to be strongly pro-inflammatory.
While not intending to be bound to any particular theory or mechanism, it is believed that the high surface area and reactivity of the particulate bioactive glass provides for the release of soluble sodium, calcium, phosphate, silica and other ionic species. The ionic environment, alone with the increased pH, is believed to act in such a way as to affect the expression of important cellular mediators of inflammation. In addition, direct contact of neutrophils, macrophages and other immune cells with the particle surface may elicit an unexpected an anti-inflammatory effect on cell function.
Incorporation of the anti-inflammatory bioactive glass particles into compositions intended for pulmonary delivery of therapeutic agents can be beneficial when those agents cause inflammation in the lung after delivery.
Topical inflammatory effects, such as those observed in some patients using transdermal patches, can be alleviated by incorporating bioactive glass particles into a topical formulation, such as a gel, creme, foam, lotion, or transdermal patch.
Numerous efforts have been made to deliver drugs via the pulmonary tract. Several therapeutic agents cause local inflammatory effects when delivered. These effects can be minimized by incorporating bioactive glass particles into the compositions for pulmonary administration. In one embodiment, an aqueous extract of bioactive glass can be used in place of or in addition to the bioactive glass particles to cause the same anti-inflammatory effect. The aqueous solution can be used as a pharmaceutical carrier in an intra-nasal drug delivery device.
Particles of bioactive glass, and/or solutions including the extract from bioactive glass, can be delivered by local injection to sites of inflammation in a patient, for example, at an inflamed joint or tendon.
Particles of bioactive glass, and/or solutions including the extract from bioactive glass, can be delivered by intravenous, intramuscular, or intra peritoneal injection to provide systemic anti-inflammatory effects. These effects can be therapeutic and/or prophylactic. For example, systemic delivery of bioactive glass, and/or solutions including the extract from bioactive glass, can be effective in reducing the onset of inflammation brought on by external challenge.
Particles of bioactive glass can be administered locally to a surgical site to minimize post-surgical adhesions. The glass particles can optionally be incorporated into a polymeric material which is applied to the surgical site. Preferably, the polymeric material is biodegradable, and the particles are released as the polymer degrades. Suitable polymeric materials for this purpose are disclosed, for example, in U.S. Pat. No. 5,410,016 to Hubbell et al., the contents of which are hereby incorporated by reference. Other materials suitable for this purpose, such as Interceed(copyright), agarose and crosslinked alginate, are well known to those of skill in the art.
Highly porous bioactive glass can have the same anti-inflammatory effects as the small glass particles, due to its relatively high surface area.
Biomedical implants are often associated with inflammation at the site of implantation. Incorporation of small particles of bioactive glass and/or highly porous bioactive glass into the implants, especially on the surface of the implants, can greatly reduce the inflammation associated with the implants. This can be especially useful in suture materials to minimize the inflammation associated with these materials. As discussed below, the anti-bacterial properties of the compositions also allow the sutures to minimize the infection surrounding the suture site.
An xe2x80x9ceffective, anti-inflammatory amount of bioactive glassxe2x80x9d refers to an amount of bioactive glass, with an appropriate particle size, which is effective at reducing the inflammation. Those of skill in the art can readily estimate the actual or anticipated inflammation associated with a wound site, for example, caused by an injury, a surgical procedure, arthritis or other autoimmune disorders, by administration of a therapeutic agent to the pulmonary system or to the skin, for example, via a transdermal delivery system, and the like. Those of skill in the art can also use this estimate to determine an appropriate anti-inflammatory amount of bioactive glass to administer to the inflamed site, or site of anticipated inflammation.
Large particles of bioactive glass and non-porous bioactive glass do not have appreciable bactericidal properties. However, small particles of bioactive glass and highly porous bioactive glass, when present in an aqueous environment, do have appreciable bactericidal properties. Bactericidal properties have been shown against Staph. aureus, Staph. epidermidis, and various streptococci, commonly found in and on the skin. While not being bound by a specific mechanism of action, it is believed that this action is a result of the greatly increased bioactivity of the small particulates, which leads to a sharply increased pH of the surrounding aqueous environment. The combined properties of being both broadly bactericidal while at the same time maintaining tissue biocompatibility make small particles of bioactive glass a suitable antibacterial treatment, in particular, for skin disorders such as dermal ulcers.
The bactericidal action increases with decreasing particle size. The preferred particle size depends, in part, on the initial bacterial burden and the desired bacterial kill. For normal bacterial loads and uninfected wounds, for example, a composition in the less than 20 micron size range is sufficient. However, for higher bacterial loads where the danger of infection appears pressing, the composition should include particles with a size less than five microns as measured by SEM or laser light scattering techniques.
An xe2x80x9ceffective, antibacterial amount of bioactive glassxe2x80x9d refers to an amount of bioactive glass, with an appropriate particle size, which is effective at reducing the bacterial infection. Those of skill in the art can readily estimate the bacterial load in a wound, and use this estimate to determine an appropriate particle size and amount of bioactive glass to administer to the wound. As used herein, the term xe2x80x9cantibacterialxe2x80x9d is also used to refer to the ability of the compositions to reduce infections due to fungi and mold.

Anti-inflammatory and antimicrobial uses for bioactive glass compositions


The invention relates to a method for cleaning a metallic or an enameled surface comprising flooding a metallic surface contaminated with deposits with a mixture comprising (i) water, (ii) chippings of woods selected from the group consisting of merantis, bongossis, mahoganies, sipos, khayas, lauans, and sapellis, and (iii) a member selected from the group consisting of polyaspartic acid, salts of polyaspartic acid, and polysuccinimide, and thereby cleaning the surface.

The invention relates to a method of cleaning surfaces with a mixture containing water and wood chippings, to a specific mixture, and to its use as a cleaner.
In the cleaning of equipment, in particular chemical reactors, pipes, dryers, storage containers and packaging plants, where deposits have formed during use, attempts are generally made to remove these deposits using solvents. However, the consumption of solvents is often very high and does not lead to the desired result. As a result, other cleaning methods, in particular those carried out manually, such as, for example, using high-pressure cleaners, are required in order to clean the equipment thoroughly. As well as being very labor-intensive, the results are often also unsatisfactory. This is the case particularly for equipment which [lacuna] in connection with the production, storage, conveyance and packaging of chemical products which have high purity requirements (GMP) such as, for example, photochemicals, pharmaceutical products or intermediates thereof.
We have now found a method of cleaning equipment, in which the soiled surfaces, in particular surfaces contaminated with deposits, are flooded with a mixture containing water and wood chippings.
Preferred wood chippings are rosin-free. Particular preference is given to wood chippings of meranti wood, and to the wood types bongossi, mahogany, sipo, khaya, lauan and sapelli and also subspecies of their families. The particle size of the wood chippings is preferably from 0.1 to 20 mm, in particular from 0.1 to 7 mm.
The ratio of water and wood chippings is in principle unimportant, provided that the mixture is flowable. Water is generally used in a considerable excess. The mixture preferably comprises from 70 to 99.9% by weight of water and from 30 to 0.1% by weight of chippings, the sum of these two components preferably being  greater than 90, in particular  greater than 95% by weight, based on the total mixture. The wood chippings mixture used for cleaning can optionally comprise other additives such as, for example, organic solvents, salts, surfactants, surface-active substances, additives customary for cleaners, such as, for example, polyaspartic acid. Suitable surfactants are, for example, nonionogenic, surface-active substances such as polyglycol ethers, which are obtained by adding ethylene oxide to alcohols, alkyl phenols, fatty amines or carboxamides. It is also possible to use anionic surfactants, such as alkali metal salts or amine salts of fatty acids, alkylsulfonic acid or alkylbenzenesulfonic acids.
Dispersants which may further be added are, for example, phosphonates, polymer phosphates, polycarboxylic acids, citric acid, nitriloacetic acid, iminodisuccinic acid, polyacrylates and glyconates.
In particular, but not exclusively, the addition of polyaspartic acid known from EP-B 256 366 has proven successful.
The cleaning is preferably carried out in a neutral to slightly acidic medium. The wood chippings mixture preferably has a pH of from 3 to 7.
The cleaning method according to the invention is preferably carried out at a temperature from 0xc2x0 C. to 120xc2x0 C., in particular from 20 to 60xc2x0 C., optionally under pressure.
Examples of equipment to be cleaned are chemical reactors, in particular stirred vessels, their inlet and outlet pipes, storage containers, dryers and packaging plants.
The equipment surfaces to be cleaned can, for example, be metallic or enameled. Preferred surface materials are metallic surfaces made from V2A or V4A steel, hastelloy, nickel or copper or enamels, and plastic surfaces such as, for example, rubberized surfaces.
The nature of the deposits is not subject to any limitation. They are preferably deposits which, when a product in the reactor, in the storage container, in the dryer or, for example, in the inlet and outlet pipes is changed, for example, from an intensely colored compound with high purity requirements such as photochemicals or else also pharmaceutical products or their precursors, contaminate the next product. The process according to the invention is preferably used to effectively remove activated carbon deposits, which have been obtained, for example, as a result of clarification stages of liquid products, and also oil- or fat-containing deposits.
Where the deposits are strongly adherent, it is possible to carry out high-pressure cleaning prior to treatment with wood chippings. Flooding of the equipment surfaces to be cleaned is, for example, carried out by stirring a mixture of water and wood chippings and optionally other additives, for example in a stirred vessel, or by passing over or passing through a suitable mixture through pipes which are provided with suitable deposits.
To clean a stirred vessel (SV), the latter is, for example, half-filled with water and, depending on the size, wood chippings (meranti) [lacuna] added. For a 6 m3 SV, from 5 to 20 kg (corresponds to about 50 to 200 l) of wood chippings, preferably of meranti wood, are, for example, used. The SV is then filled with water and the contents are heated to a temperature of about 60xc2x0 C. The wood chippings mixture is stirred for several hours depending on the degree of soiling. The contents of the SV are then cooled to about 40xc2x0 C. and emptied via a filtration apparatus.
Pipes which are covered, for example with activated carbon can, for example, be flushed through with an aqueous wood chippings mixture.
It is particularly advantageous to use a mixture of wood chippings, water and polyaspartic acid.
The invention thus further relates to a mixture comprising water, wood chippings and polyaspartic acid and/or derivatives thereof.
Suitable wood chippings are therefore preferably those given above.
The polyaspartic acid is preferably used as a salt, in particular as the sodium or potassium salt. It is, however, also possible to use a derivative of polyaspartic acid, for example the anhydride of polyaspartic acid, namely polysuccinimide. For the purposes of the present invention, polyaspartic acid is also taken to mean salts of these acids. Preferred polyaspartic acids are, for example, known from EP-A 672 625.
In a preferred embodiment, the polyaspartic acid is prepared by subjecting maleic acid monoammonium salts to thermal, optionally continuous, polymerization preferably at from 150 to 180xc2x0 C. in a reactor for a residence time of from 5 to 300 minutes, and converting the polysuccinimide obtained to polyaspartic acid or a salt thereof by hydrolysis. In a preferred embodiment, the polyaspartic acid contains essentially repeating units of the following structure:
The proportion of the B-form is generally more than 50%, in particular more than 70%.
In addition to the repeating polyaspartic acid units a) and b), it is also possible for other repeating units to be present, e.g.:
c) malic acid units of the formula
d) maleic acid units of the formula
e) fumaric acid units of the formula
Preference is given to polymers with a molecular weight, according to gel permeation chromatographic analysis, of from 500 to 10,000, preferably from 1000 to 5000, particularly preferably from 2000 to 4000 g/mol.
The invention also relates to the use of the mixture according to the invention as a cleaner.
The equipment surfaces cleaned by the process according to the invention have excellent cleanliness, with which subsequent rearrangement i.e. change of the product is very readily possible, without impurities of the preceding product being detectable.


According to the present invention there is provided a method for preparing a lithographic printing plate, comprising the step of dispensing in a predetermined pattern a hydrophobic or hydrophobizing composition onto a receiving element comprising on a support a layer comprising hydrophobic thermoplastic polymer particles dispersed in a hardened hydrophilic binder.

The present invention relates to a solution for the use of the same receiving element in combination with different writing heads.
More specifically the invention is related to a receiving element that can be imaged with heat and with ink jet.
In computer to plate lithography, there exist different recording techniques for imaging a printing plate such as a laser, a thermal head, an ink jet printing head, etc. . . .
The imaged printing plates can then be used as printing elements without any processing step or alternatively after some kind of processing. Such printing elements can allow recording on press.
It is a very desirable property of the printing press that it can be used with an imaging element that can be imaged with different writing heads; those different heads can all be present on the press and can be used for recording separately or in any combination.
EP-A-770 497 discloses a method for making a lithographic printing plate comprising the steps of: (1) image-wise exposing to light an imaging element comprising (i) on a hydrophilic surface of a lithographic base an image forming layer comprising hydrophobic thermoplastic polymer particles dispersed in a hydrophilic binder and (ii) a compound capable of converting light to heat, said compound being comprised in said image forming layer or a layer adjacent thereto; (2) and developing a thus obtained image-wise exposed imaging element by rinsing it with plain water or an aqueous liquid.
A method wherein an image or non-image portion is directly formed on a substrate by ink-jet printing is known to the art. The ink-jet printing system is a relatively rapid image output system and has a simple construction because it does not require any complex optical system. Therefore, the printing system makes an apparatus for making printing plates simple and the cost for making printing plates can be reduced since the maintenance labor is largely reduced.
As examples of the methods for preparing printing plates by using the ink-jet printing system, Japanese Kokai Publication 113456/1981 proposes the methods for preparing printing plates wherein ink-repelling materials (e.g. curable silicone) are printed on a printing plate by ink-jet printing. The printing plate obtained by this method is an intaglio printing plate in which the ink-repelling material formed on the surface of the substrate serves as a non-image part. As a result, the resolution of the printed images at shadow area or reversed lines is not so good. Moreover, a large amount of ink is needed in this method because the ink-repelling material must be deposited on the whole non-image part which occupies most of the surface of the printing plate, thereby delaying the printing process.
U.S. Pat. No. 5,511,477 discloses a method for the production of photopolymeric relief-type printing plates comprising: forming a positive or a negative image on a substrate by ink-jet printing with a photopolymeric composition, optionally preheated to a temperature of about 30xc2x0-260xc2x0 C., and subjecting the resulting printed substrate to UV radiation, thereby curing said composition forming said image.
The receiving layer is not specified.
U.S. Pat. No. 5,312,654 discloses a method for making lithographic printing plates comprising: forming an image on a substrate having an ink absorbing layer and a hydrophilized layer between the substrate and absorbing layer by ink-jet printing using a photopolymerizable ink composition, and exposing it to an active light in the wavelength region for which said ink composition is sensitized to cure the image. The printing endurance of said printing plates is low.
Japanese Kokai Publication 69244/1992 discloses a method for making printing plates comprising the steps of forming a printed image on a recording material subjected to a hydrophilic treatment by ink-jet printing using a hydrophobic composition containing photocurable components; and exposing the whole surface to an active light. However, the surface of the substrate to be used for the lithographic plate is usually subjected to various treatments such as a mechanical graining, an anodizing or a hydrophilic treatment to obtain good hydrophilic property and water retention property. Therefore, even the use of an ink composition having a very high surface tension results in a poor image on the surface of the substrate because of ink spreading and low printing endurance.
EP-A-533 168 discloses a method for avoiding said ink spreading by coating the lithographic base with an ink absorbing layer which is removed after ink printing. This is an uneconomical and cumbersome method.
Research Disclosure 289118 of May 1988 discloses a method for making printing plates with the use of an ink jet wherein the ink is a hydrophobic polymer latex. However said printing plates have a bad ink acceptance and a low printing endurance.
EP-A-003 789 discloses a process for the preparation of offset printing plates by means of an ink jet method with oleophilic compositions. There is not indicated how said compositions are made but from the examples it is clear that it concerns artificial lattices, which are difficult to prepare. The receiving layer is not specified.
JN-57/038142 discloses a method of preparing a printing plate by forming an ink image on a blank printing plate, and also by fixing this image thermally by making toner adhere to this image-formed area. The composition of the ink is not mentioned, only the composition of the toners is disclosed.
JN-07/108667 discloses a plate-making method forming an ink image containing a hydrophilic substance on a conductive support whose surface layer is made hydrophilic according to an electrostatic attraction type ink set system to dry or cure the same, by applying bias voltage to the conductive support at the time of ink jet writing. This is a cumbersome process.
U.S. Pat. No. 5,213,041 discloses a method for preparing a re-usable printing plate for printing, projecting an imaging deposit on the plate surface by jet printing using an ejectable substance containing a heat fusible component. The image forms an imaging deposit, which is fused to the surface of the printing plate using a variable frequency and variable power induction heater. This is a cumbersome method.
It is an object of the present invention to provide a method for preparing a printing plate by ink jet, using a receiving element that is also usable as imaging element in direct thermal or heat mode writing.
It is also an object of the present invention to provide a method for preparing a printing plate with a good ink acceptance and a good printing endurance.
According to the present invention there is provided a method for preparing a lithographic printing plate, comprising the step of dispensing in a predetermined pattern a hydrophobic or hydrophobizing composition onto a receiving element comprising on a support a layer comprising hydrophobic thermoplastic polymer particles dispersed in a hardened hydrophilic binder.
The advantage of using a receiving element according to the invention for ink jet printing lies in the fact that a part of the image can be made by contact with a thermal head or by irradiation with a laser (heat-mode).
The imaging element according to the present application comprises (i) on a support an image forming layer comprising hydrophobic thermoplastic polymer particles dispersed in a hardened hydrophilic binder and preferably (ii) a compound capable of converting light to heat, said compound being comprised in said image forming layer or a layer adjacent thereto.
Specific examples of hydrophobic polymer particles for use in connection with the present application have a Tg above 80xc2x0 C.
Preferably the polymer particles are selected from the group consisting of polyvinyl chloride, polyvinylidene chloride, polyacrylonitrile, polyvinyl carbazole etc., copolymers or mixtures thereof. Most preferably used are polystyrene, polymethylmethacrylate or copolymers thereof.
Suitable hydrophilic binders for use in an image-forming layer in connection with this application are water soluble (co)polymers for example synthetic homo- or copolymers such as polyvinylalcohol, a poly(meth)acrylic acid, a poly(meth)acrylamide, a polyhydroxy-ethyl(meth)acrylate, a polyvinylmethylether or natural binders such as gelatin, a polysaccharide such as e.g. dextran, pullulan, cellulose, arabic gum, alginic acid, inuline or chemically modified inuline.
The image-forming layer also comprises crosslinking agents such as formaldehyde, glyoxal, polyisocyanate or a hydrolyzed tetra-alkylorthosilicate. The latter is particularly preferred.
The imaging element further preferably includes a compound capable of converting light to heat. Suitable compounds capable of converting light into heat are preferably infrared absorbing components although the wavelength of absorption is not of particular importance as long as the absorption of the compound used is in the wavelength range of the light source used for image-wise exposure. Particularly useful compounds are for example dyes and in particular infrared dyes and pigments and in particular infrared pigments such as carbon black, metal carbides, borides, nitrides, carbonitrides, bronze-structured oxides and oxides structurally related to the bronze family but lacking the A component e.g. WO 2.9.
The support according to the present application can be a hydrophilic support such as aluminum e.g. electrochemically and/or mechanically grained and anodized aluminum.
As hydrophobic support in connection with the present embodiment it is particularly preferred to use a plastic film e.g. substrated polyethylene terephthalate film, substrated polyethylene naphthalate film, cellulose acetate film, polystyrene film, polycarbonate film etc. . . The plastic film support may be opaque or transparent. Also suitable as flexible support is glass with a thickness less than 1.2 mm and a failure stress (under tensile stress) equal or higher than 5xc3x97107.
It is particularly preferred to use a polyester film support to which an adhesion-improving layer has been provided. Particularly suitable adhesion improving layers for use in accordance with the present invention comprise a hydrophilic binder and colloidal silica as disclosed in EP-A-619 524, EP-A-620 502 and EP-A-619 525. Preferably, the amount of silica in the adhesion-improving layer is between 200 mg per m2 and 750 mg per m2. Further, the ratio of silica to hydrophilic binder is preferably more than 1 and the surface area of the colloidal silica is preferably at least 300 m2 per gram, more preferably at least 500 m2 per gram.
The hydrophobic composition can be a hot melt composition. The hot melt composition used in the present invention is a solid hydrophobic composition that is melted in the ink jet printhead. A hot melt composition, also called a phase change composition consists of a hot melt ink carrier composition, and a dye. The phase change ink carrier may be a composition containing optionally a natural wax or a mixture of natural waxes or a mixture of (a) natural and (a) synthetic wax(es). The main requirement for the composition according to the invention is to be a meltable, jettable hydrophobic substance having appropriate physical characteristics, e.g. a phase change ink carrier. Thus, dyes and coloring agents are not required , but can help the operator to see the image on the plate.
A phase change ink carrier composition typically comprises a fatty amide-containing material. The fatty amide-containing material of the phase change ink carrier composition preferably comprises a tetra-amide compound. The preferred tetra-amide compounds for producing the phase change ink carrier composition are diner acid-based tetra-amides which preferably include the reaction product of a fatty acid, a diamine (ethylene diamine) and a dimer acid. Fatty acids having from 10 to 22 carbon atoms are preferably employed in the formation of the dimer acid-based tetra-amide.
The fatty amide-containing material can also comprise a mono-amide. In fact, in the preferred case, the phase change ink carrier composition comprises both a tetra-amide compound and a mono-amide compound. The mono-amide compound typically comprises either a primary or secondary mono-amide, but is preferably a secondary mono-amide.
The preferred fatty amide-containing compounds of this invention comprise a plurality of fatty amide materials that are physically compatible with each other. Typically, even when a plurality of fatty amide-containing compounds are employed to produce the phase change ink carrier composition, the carrier composition has a substantially single melting point transition. The melting point of the phase change ink carrier composition is preferably at least about 70xc2x0 C., more preferably at least about 80xc2x0 C., and most preferably at least about 85xc2x0 C.
In a preferred case, the phase change ink carrier composition comprises a tetra-amide and a mono-amide compound, a tackifier, a plasticizer, and a viscosity-modifying agent. The preferred compositional ranges of this phase change ink carrier composition are as follows : from about 10 to 50 weight percent of a tetra-amide compound, from about 30 to 80 weight percent of a mono-amide compound, from about 0 to 25 weight percent of a tackifier, from about 0 to 25 weight percent of a plasticizer, and from about 0 to 10 weight percent of a viscosity modifying agent.
As previously indicated, the subject phase change ink formed from the phase change ink carrier composition exhibits excellent physical properties. More details are given in EP-A 353 979.
Other preferred phase change ink carriers and phase change inks are disclosed in EP-A-519 138, EP-A-604 023, EP-A-739 958, U.S. Pat. No. 5,592,204, WO-96/015201, U.S. Pat. No. 5,531,819, U.S. Pat. No. 5,560,765, WO 90/005893, WO-91/010711, WO-91/010710 and EP-A-723 999.
In still another embodiment of the present invention the composition can comprise a curable hydrophobic organic compound.
In a preferred embodiment of the present invention a curable fluid composition, more preferably an actinic light curable fluid composition, most preferably an UV-curable fluid composition is used as solidifiable organic compound. In one embodiment the curable composition to be used in the present invention usually contains as essential components a polymerizable compound having at least one ethylenically unsaturated double bond in the molecule and a polymerization initiator. In the polymerizable composition according to the present invention, linear organic polymers, volatilization preventing agents, surfactants, heat polymerization inhibitors, coupling agents, dyes, viscosity adjusting agents and other additives (e.g. plasticizers) are further added, if necessary.
The polymerizable compounds are the compounds characterized by having at least one ethylenically unsaturated double bound that is cured by radical addition polymerization initialized by a polymerization initiator activated by addition of energy such as actinic light or heat. These compounds include mono- and poly-unsaturated carboxylic acids esters such as acrylate esters of polyhydroxy compounds such as ethylene glycol, tetraethylene glycol, neopentylglycol, propylene glycol, 1,2-butanediol, trimethylolpropane, pentaerythritol and di-pentaerythritol and the like with the above-described unsaturated carboxylic acids, diglycidylester of phthalic acid and the like with the above-described unsaturated carboxylic acids. These photopolymerizable compounds are present in the photopolymerizable compositions according to the present invention in an amount of 20 to 99.9% by weight, preferably 25 to 99% by weight, more preferably 30 to 98% by weight.
The polymerization initiators are the compounds which generate radicals under the influence of added energy, preferably actinic light.
The photopolymerization initiators used in actinic light curable compositions are the compounds which generate radical species by absorbing the light from ultraviolet and visible wavelengths. These photopolymerization initiators are used in an amount of from 0.1 to 50% by weight, preferably 1 to 30% by weight, more preferably 2 to 20% by weight in the photopolymerizable compositions according to the present invention. When the content of the photopolymerization initiator is less than 0.1% by weight, the printing durability of the printing member decreases since curing of the image parts is insufficient or the curing time should be unpracticably long. Storage stability of the photopolymerizable ink compositions will be reduced when the content is above 50% by weight.
In still another embodiment of the present invention the composition can comprise latex of a hydrophobic organic particle in an aqueous medium. A latex is defined as a stable colloidal dispersion of a polymeric substance in an aqueous medium. The polymer particles are usually approximately spherical and of typical colloidal dimensions: particle diameters range from about 20 to 1000 nm. The dispersion medium is usually a dilute aqueous solution containing substances such as electrolytes, surfactants, hydrophilic polymers and initiator residues. The polymer lattices are classified in various ways. By origin, they are classified as natural lattices, produced by metabolic processes occurring in the cells of certain plant species; synthetic lattices, produced by emulsion polymerization of monomers; and artificial lattices, produced by dispersing a polymer in a dispersing medium.
A hydrophobic polymer for use in the present lattices has preferably a Tg below 150xc2x0 C., more preferably a Tg below 120xc2x0 C.
A hydrophobic polymer for use in the present invention has preferably a Tg of at least 30xc2x0 C., more preferably a Tg of at least 35xc2x0 C.
The hydrophobic polymer synthetic latex for use in the present lattices may contain conventional emulsifiers.
Hydrophobic polymers for use in synthetic lattices according to the present invention are, for example, polystyrene, polyacrylates such as polymethyl methacrylate and polybutyl acrylate, copolymers of butyl acrylate and methyl methacrylate, copolymers of butyl acrylate and styrene, homopolymers of butadiene, copolymers of butadiene and methyl methacrylate.
The hydrophobic polymer synthetic latex particles have preferably a particle size between 0.01 and 1 xcexcm, more preferably between 0.01 xcexcm and 0.25 xcexcm.
The latex can contain from 1 to 60% by weight of hydrophobic polymer, more preferably from 2 to 40% by weight of hydrophobic polymer, most preferably from 5 to 20% by weight of hydrophobic polymer.
In still another embodiment of the present invention the hydrophobizing composition can comprise a transition metal complex reactive component, preferably chromium complexes of organic acids. This transition metal complex reactive component reacts with polyvinyl alcohol. Even if hardened polyvinyl alcohol is used, sufficient reactive groups are present to interact with the reactive component.
The image forming requires the following steps. On demand, microdots of the hydrophobic composition are sprayed onto the receiving element according to the invention in a predetermined pattern as the plate passes through the printer or by a printhead shuttling over the plate. According to one embodiment of the invention, the microdots have a diameter of about 30 xcexcm.
The image forming can also be carried out with the lithographic base already on the printing cylinder.
The printing plate of the present invention can also be used in the printing process as a seamless sleeve printing plate. This cylindrical printing plate has such a diameter that it can be slided on the print cylinder. More details on sleeves are given in xe2x80x9cGrafisch Nieuwsxe2x80x9d ed. Keesing, 15, 1995, page 4 to 6.

Imaging element for different imaging systems