Materials comprising water-soluble polymer particles and methods of making and using them
Abstract
A material comprising a substrate, one or two layers of foam, and a plurality of water-soluble polymer particles; wherein each of the plurality of water soluble polymer particles comprise an active ingredient, and wherein either the material comprises a foam layer, the foam permeates the substrate, and the water soluble polymer particles are trapped within the substrate by the foam, or the material comprises two layers of foam, The substrate is sandwiched between the two layers of foam and the water soluble polymer particles are trapped inside the substrate by the two layers of foam.

Term
1.7 yearsto projected expiry
Projected expiry 19 June 2028, counted from filing; an application has no term until it is granted.
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16 claims: 11 independent, 5 dependent
- 1ES 2 395 877 T3 REIVINDICACIONES 1. Un material que comprende un sustrato, una o dos capas de espuma, y una pluralidad de partículas poliméricas solubles en agua;en donde cada una de la pluralidad de partículas poliméricas solubles en agua comprenden un ingrediente activo, y en donde o bien el material comprende una capa de espuma, la espuma permea en el sustrato, y las partículas poliméricas solubles en agua están atrapadas dentro del sustrato por la espuma, o bien el material comprende dos capas de espuma, el sustrato está intercalado entre las dos capas de espuma y las partículas poliméricas solubles en agua están atrapadas dentro del sustrato por las dos capas de espuma.
- 2El material de la reivindicación 1, en donde el sustrato es un material no tejido, preferiblemente en donde el sustrato es un material no tejido con aberturas, o en donde el sustrato es un material no tejido que comprende una superficie de malla, o en donde el sustrato es una tela no tejida o un género no tejido.
- 3El material de una cualquiera de las reivindicaciones 1 o 2, en donde la espuma es una espuma de poliuretano preparada a partir de agua, un tensioactivo y una mezcla prepolimérica.
- 4El material de la reivindicación 3, en donde el tensioactivo se selecciona del grupo que consiste en tensioactivos basados en silicona, copolímeros de bloques de polisiloxano-polioxialquileno, cianoalquilpolisiloxanos, alquilpolisiloxanos, polidimetilsiloxano, dimetilpolisiloxanos modificados con polioxialquileno, sales de ácidos grasos, sales de ésteres de ácido sulfúrico, sales de ésteres de ácido fosfórico y sulfonatos, materiales de Triton™, Cocamida MEA (monoetanolamida de cocamida), Brij 72® (éter estearílico de polioxietileno (2)) y alfa-olefin sulfonato de sodio, preferiblemente en donde el tensioactivo es dimetilpolisiloxanos modificados con polioxialquileno.
- 5El material de una cualquiera de las reivindicaciones 3 o 4, en donde la mezcla prepolimérica se selecciona del grupo que consiste en poli(éter) de alquilo ramificado taponado con isocianato, poli(éter) de alquilo no ramificado taponado con isocianato, poli(éter) de aromático ramificado taponado con isocianato, poli(éter) de aromático no ramificado taponado con isocianato, copolímero de poli(éter) de alquilo ramificado taponado con isocianatopoli(éster), copolímero de poli(éter) de alquilo no ramificado taponado con isocianato-poli(éster), copolímero de poli(éter) de aromático ramificado taponado con isocianato-poli(éster), y copolímero de poli(éter) de aromático no ramificado taponado con isocianato-poli(éster), preferiblemente en donde la mezcla prepolimérica es polietilenglicol terminado o taponado con diisocianato de tolueno con menos que 6% de grupos nCo sin reaccionar disponibles y con una funcionalidad de isocianato menor que 2.
- 6El material de una cualquiera de las reivindicaciones 1 a 5, en donde las partículas poliméricas solubles en agua se preparan a partir de uno o más monómeros seleccionados del grupo que consiste en estireno, acetato de vinilo, óxido de etileno, acrilonitrilo, ácido acrílico, anhídrido maleico, compuestos monovinílicos de silicio, éter etilvinílico, cloroestireno-vinilpiridina, cloruro de vinilideno, éter butilvinílico, metacrilato de metilo y acrilato de 2-etilhexilo, o en donde las partículas poliméricas solubles en agua son partículas poliméricas de poli(óxido de etileno) o partículas poliméricas de polietilenglicol.
- 7El material de una cualquiera de las reivindicaciones 1 a 6, en donde el ingrediente activo se selecciona del grupo que consiste en sales de plata, nitrato de plata, sulfato de plata, nafcilina, nistatina, ácido undecilénico, ácido salicílico, ácido salicilsulfónico, ácido nicotínico, difosfato de adenosina, clorhexidina, bacitracina, clortetraciclina, gentamicina, kanamicina, neomicina B, polimixina B, estreptomicina, tetraciclina, anfotericina B, clotrimazol, miconazol, cisteína, glicina, treonina, lidocaína, tripsina, estreptoquinasa, plasmina, estreptodornasa, desoxirribonucleasa, epinefrina, serotonina y digluconato de clorhexidina.
- 8El material de una cualquiera de las reivindicaciones 1 a 7, en donde las partículas solubles en agua que contienen el agente activo forman al menos el 10% en peso del material, preferiblemente en donde las partículas solubles en agua que contienen el agente activo forman al menos el 20% en peso del material, y lo más preferiblemente en donde las partículas solubles en agua que contienen el agente activo forman al menos el 50% en peso del material.
- 9Un método para preparar un material impregnado con partículas poliméricas solubles en agua que comprende una o dos capas de espuma, comprendiendo el método para preparar un material con una capa de espuma las etapas de:revestir un sustrato con una pluralidad de partículas poliméricas solubles en agua;agitar una mezcla que comprende agua, tensioactivo y una mezcla prepolimérica;verter la mezcla sobre el sustrato revestido con partículas poliméricas solubles en agua, permeando de este modo en el sustrato, y dejar que la mezcla se cure hasta una espuma, formando de este modo un material impregnado con partículas poliméricas solubles en agua;y comprendiendo el método para preparar un material con dos capas de espuma ES 2 395 877 T3 las etapas de: agitar una primera mezcla que comprende agua, tensioactivo y una mezcla prepolimérica;verter la primera mezcla sobre una superficie;poner un sustrato en la parte superior de la primera mezcla y dejar que la primera mezcla se cure hasta una primera capa de espuma, uniendo de este modo el sustrato y la primera capa de espuma;revestir el lado del sustrato que no está unido a la primera capa de espuma con una pluralidad de partículas poliméricas solubles en agua;agitar una segunda mezcla que comprende agua, tensioactivo y una mezcla prepolimérica;verter la segunda mezcla sobre una superficie que contiene las partículas poliméricas solubles en agua y dejar que la segunda mezcla se cure, atrapando de este modo la pluralidad de partículas poliméricas solubles en agua dentro del material y formando un material impregnado con partículas poliméricas solubles en agua.
- 10El método de la reivindicación 9, en donde el sustrato es un material no tejido, preferiblemente en donde el sustrato es un material no tejido con aberturas, o en donde el sustrato es un material no tejido que comprende una superficie de malla, o en donde el sustrato es una tela no tejida o un género no tejido.
- 11El método de la reivindicación 9 o 10, en donde la espuma es una espuma de poliuretano preparada a partir de agua, un tensioactivo y una mezcla prepolimérica.
- 12El método de la reivindicación 9 o 10, en donde el tensioactivo se selecciona del grupo que consiste en tensioactivos basados en silicona, copolímeros de bloques de polisiloxano-polioxialquileno, cianoalquilpolisiloxanos, alquilpolisiloxanos, polidimetilsiloxano, dimetilpolisiloxanos modificados con polioxialquileno, sales de ácidos grasos, sales de ésteres de ácido sulfúrico, sales de ésteres de ácido fosfórico y sulfonatos, materiales de Triton TM , Cocamida MEA (monoetanolamida de cocamida), Brij 72® (éter estearílico de polioxietileno (2)) y alfa-olefin sulfonato de sodio, preferiblemente en donde el tensioactivo es dimetilpolisiloxanos modificados con polioxialquileno.
- 13El método de una cualquiera de las reivindicaciones 9 a 12, en donde la mezcla prepolimérica se selecciona del grupo que consiste en poli(éter) de alquilo ramificado taponado con isocianato, poli(éter) de alquilo no ramificado taponado con isocianato, poli(éter) de aromático ramificado taponado con isocianato, poli(éter) de aromático no ramificado taponado con isocianato, copolímero de poli(éter) de alquilo ramificado taponado con isocianatopoli(éster), copolímero de poli(éter) de alquilo no ramificado taponado con isocianato-poli(éster), copolímero de poli(éter) de aromático ramificado taponado con isocianato-poli(éster), y copolímero de poli(éter) de aromático no ramificado taponado con isocianato-poli(éster), preferiblemente en donde la mezcla prepolimérica es polietilenglicol terminado o taponado con diisocianato de tolueno con menos que 6% de grupos nCo sin reaccionar disponibles y con una funcionalidad de isocianato menor que 2.
- 14El método de una cualquiera de las reivindicaciones 9 a 13, en donde las partículas poliméricas solubles en agua se preparan a partir de uno o más monómeros seleccionados del grupo que consiste en estireno, acetato de vinilo, óxido de etileno, acrilonitrilo, ácido acrílico, anhídrido maleico, compuestos monovinílicos de silicio, éter etilvinílico, cloroestireno-vinilpiridina, cloruro de vinilideno, éter butilvinílico, metacrilato de metilo y acrilato de 2-etilhexilo, o en donde las partículas poliméricas solubles en agua son partículas poliméricas de poli(óxido de etileno) o partículas poliméricas de polietilenglicol.
- 15El método de una cualquiera de las reivindicaciones 9 a 14, en donde el ingrediente activo se selecciona del grupo que consiste en sales de plata, nitrato de plata, sulfato de plata, nafcilina, nistatina, ácido undecilénico, ácido salicílico, ácido salicilsulfónico, ácido nicotínico, difosfato de adenosina, clorhexidina, bacitracina, clortetraciclina, gentamicina, kanamicina, neomicina B, polimixina B, estreptomicina, tetraciclina, anfotericina B, clotrimazol, miconazol, cisteína, glicina, treonina, lidocaína, tripsina, estreptoquinasa, plasmina, estreptodornasa, desoxirribonucleasa, epinefrina, serotonina y digluconato de clorhexidina.
- 16El método de una cualquiera de las reivindicaciones 9 a 15, en donde las partículas solubles en agua que contienen el agente activo forman al menos el 10% en peso del material, preferiblemente en donde las partículas solubles en agua que contienen el agente activo forman al menos el 20% en peso del material, y lo más preferiblemente en donde las partículas solubles en agua que contienen el agente activo forman al menos el 50% en peso del material.
Independent claims16
101 paragraphs in 9 sections, as filed
ES 2 395 877 T3
DESCRIPTION
Materials comprising water-soluble polymeric particles and methods for preparing and using them.
RELATED REQUESTS
This application claims priority benefit to United States Provisional Patent Application Serial Number 60 / 944,860, filed June 19, 2007.
BACKGROUND
When drugs are administered systemically to treat wounds (including cuts, abrasions, incisions, ulcers, and infected wounds or burns), a large part of the drugs is either degraded or adsorbed by non-target tissues, and only a small part of the initial dose reaches the target site. The efficacy of systemic dosing is further decreased in the trauma patient (such as accidents, earthquakes, fires, and wars) who often suffer from decreased vascular flow and thus have reduced drug circulation. In addition, the trauma patient is often unable to provide information regarding drug sensitivity, or is unable to take drugs orally. Topical drug administration, in theory, would provide immediate, direct, and sustained effects at the target site, and reduce side effects and drug degradation found at systemic dosing. Topical application also allows rapid withdrawal and replacement of drugs when adverse effects are noted. When cleaning cannot easily be done, topical application is more effective in destroying microbial spores because a higher concentration of drugs can be applied. Thus, the treatment of wounds or burns will benefit from improved topical administration, whether used alone or in conjunction with systemic dosing.
Currently, antibiotics, eg, fusidic acid, chlorhexidine, neomycin, polymyxin, and bacitracin, are applied topically in gel, cream, or ointment (occasionally spray and powder). Because a high concentration of the drugs are in direct contact with the target tissue, some of the drugs cause allergic reaction by contact with the target tissue, some of the drugs cause allergic dermatitis, particularly in patients with stasis ulcers or eczema, or exhibit toxicity.
Absorption of drugs on supports is known in the art. For example, Canadian Patent No. 486,203 to Johnson & Johnson showed the use of gauze as a support, Canadian Patent No. 503,389 to Casumano showed the use of gauze pads as a support, and Canadian Patent No. 823,628 , from Wyant, used paper towel fabrics as backing.
Canadian Patent No. 547,091 to Lerner used materials, eg, aluminum foil, regenerated cellulose sheets, or waterproof, grease-resistant glassine paper having non-capillary faces, as vehicles.
Canadian Patent No. 588,169 to Chicopee used nonwoven fabrics, optionally bonded with internally plasticized polyvinyl acetates.
Canadian Patent No. 839,229 to Astra used sheets of water soluble film-forming compounds.
Canadian Patent No. 1,049,407 to Pharmacia used hydrophilic, water-insoluble macromolecular materials.
US Patent No. 2,381,621, patented on August 7, 1945 by Wallace & Teiman Products, Inc., showed a therapeutic article that included a base material comprising a thin, flexible, hydrophilic, non-porous material. but penetrable by water in the form of a film and a plurality of distributed water-soluble medicinal substances being absorbed but not ionically bound to the base material.
US Patent No. 2,804,425, patented August 27, 1957, by the American Cyanamid Company, showed a sterile, anhydrous, storage-stable chlortetracycline-containing wound filler comprising a lint-free gauze, free of heavy metals, impregnated with, but not ionically bound to, chlortetracycline.
US Patent No. 3,817,702, patented June 18, 1974 by Bayer Aktiengessellschaft, showed an antimicrobial fabric comprising a fabric containing reactive hydrogen sites, e.g., cotton treated with a reagent for introducing active sites to anions, which was then chemically reacted with a biocide to form a salt of the biocide with the textile material. The fabric was thus made anion-active, and finished by treatment with a cation-active microbiocide, the ionic bond being strong enough to provide a durable, partially anion-active fabric.
US Patent No. 3,987,793, patented October 26, 1976 by Ethicon Inc., provided a surgical suture that was coated with an ionically bonded elastomeric block copolymer such that it was receptive to treatment. with antimicrobial compounds, the bond between the copolymer and the antimicrobial compound being so strong as to produce a substance having long-lasting antimicrobial properties.
US Patent No. 4,549,011, patented October 22, 1985 by Orgenics Ltd., provided a sheet
ES 2 395 877 T3 of cellulose or plastic material that was activated with a compound that can covalently bind a liquid thereto, and then a ligand is coated on the sheet. The ligand is one that has an affinity for a substance to be separated from a mixture of substances.
US Patent No. 4,585,652, patented April 29, 1986 by the presidents of the University of Minnesota, provided a controlled drug release system that comprised a polymer that, in its ionic state, was charged with bioactive counterions. When the polymer was neutralized the counter ions were released into the surrounding medium. The patent holder used an electrode comprising a polymer that changed its ionic state for charging and discharging purposes. This was an unnecessarily complicated system and had no general use feasibility.
UK Patent Application GB 2007096 A, published May 16, 1979, provided an indicator to show when an antimicrobial composition, which was impregnated in, but not ionically bound to, a fabric was no longer present in the fabric. The antimicrobial composition was ionically bound to a colorant, such that when the antimicrobial composition was exhausted on the fabric, the colorant was also exhausted, and therefore no more color remained.
To provide controlled drug release, a US Army medical team had developed microcapsules (<10μ diameters) containing ampicillin for topical application to wound sites. However, these delivery systems (gel, cream, ointment, powder and microcapsule) suffer from a practical problem: their uniform application or removal to and from the target site requires gentle handling and is too time consuming to treat large numbers of patients with trauma in emergencies.
To overcome this problem, gauze bandages impregnated with a suspension of antibiotics (eg, fusidic acid and Neomycin) in appropriate media (eg, petroleum jelly and lanolin) had also been developed. However, such a delivery system did not control drug release, and therefore did not solve allergy or toxicity problems. Furthermore, the gel or liquid impregnated bandages did not adsorb the exudate, and may not have provided the sufficient breathability that would be desired for the treatment.
Enzymes, eg, fibrinolytic proteases and deoxyribonucleases, have occasionally been used to dissolve fibrous or purulent clumps in infected wounds or burns. These enzymes are currently applied in the form of gels (eg, carboxymethyl cellulose gel) or ointments. Such systems would suffer from the same time consuming and allergy problems described above. Furthermore, they did not provide mechanisms for the removal of enzyme hydrolysates that are potential irritants.
Apparatus for treating fabrics with aqueous solutions of treating agents are also known in the art. For example, the US patent. No. 3,910,230, patented October 7, 1975 by HL Mercer, provided an apparatus for applying a desired weight percent of liquid to a fast moving textile fabric.
US Patent No. 2,426,668, patented on January 27, 1981 by W. Spillman et al., Provided apparatus and methods for treating a canvas or several canvases of material guided side by side in space. of pressing between treatment rollers, the canvas or canvases of material being impregnated with or containing treatment agents.
US Patent No. 3,817,702, patented on June 18, 1974 by Bayer Aktiengessellschaft, provides a laboratory-scale procedure for preparing textiles that are durably protected against moisture and mold stains and against rot. by a cation-active microbial. The procedure shown involved impregnating the fabric, squeezing to remove excess, and then drying the fabric. The cation-active microbial was then absorbed into the tissue from an aqueous solution. The excess was squeezed out and the unfixed portions of the active compound were washed away.
However, even given the materials discussed above, there is still a need for new materials that control drug release and / or address problems related to allergy or toxicity.
COMPENDIUM
One aspect of the invention relates to new materials for storing, protecting, selectively releasing, and applying active ingredients (eg, pharmaceuticals and other chemicals). In certain embodiments, the invention provides foam coated substrates comprising water soluble polymeric particles containing active ingredients; Such materials can be used to selectively release and dispense the active ingredients in response to contact with water or other liquid. In certain embodiments, the foam is a hydrophilic foam, a hydrophobic foam, or a hydrogel. In certain embodiments, the foam is a hydrophobic polyurethane foam. In certain embodiments, the water soluble polymeric particles are ethylene oxide particles. In certain embodiments, the impregnated foam is a polyurethane foam impregnated with polyethylene oxide particles.
One aspect of the invention relates to a material comprising a substrate, a foam and a plurality of
ES 2 395 877 T3 water soluble polymeric particles; wherein each of the plurality of water soluble polymer particles comprises an active ingredient, the foam permeates the substrate, and the water soluble polymer particles are entrapped within the substrate by the foam.
Another aspect of the invention relates to a material comprising a substrate, two layers of foam, and a plurality of water-soluble polymeric particles; wherein each of the plurality of water-soluble polymer particles comprises an active ingredient, the substrate is sandwiched between the two layers of foam, and the water-soluble polymer particles are trapped within the substrate by the two layers of foam.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the substrate is a non-woven material. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the substrate is an apertured nonwoven material. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the substrate is a non-woven material comprising a mesh surface. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the substrate is a non-woven fabric or a non-woven fabric.
In certain embodiments, the present invention relates to any of the aforementioned materials, wherein the foam is a polyurethane foam prepared from water, a surfactant, and a prepolymer blend.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the surfactant is selected from the group consisting of silicone-based surfactants, polysiloxane-polyoxyalkylene block copolymers, cyanoalkylpolysiloxanes, alkylpolysiloxanes, polydimethylsiloxane, modified dimethylpolysiloxanes polyoxyalkylene, fatty acid salts, sulfuric acid ester salts, salts of phosphoric acid esters and sulfonates, Triton materials, Tergitol materials, Emerest materials, Emulgade materials, Cocamide MEA, Pluronic materials, Brij 72 and sodium alpha-olefin sulfonate. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the surfactant is polyoxyalkylene modified dimethylpolysiloxanes.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the prepolymer mixture is selected from the group consisting of isocyanate-capped branched alkyl poly (ether), non-branched alkyl poly (ether) capped with isocyanate, isocyanate capped branched aromatic poly (ether), isocyanate capped unbranched aromatic poly (ether), isocyanate-capped branched alkyl poly (ether) copolymer, isocyanate-capped unbranched alkyl poly (ether) copolymer, isocyanate-capped branched aromatic poly (ether) copolymer poly (ester), and isocyanate-plugged unbranched aromatic poly (ether) copolymer-poly (ester). In certain embodiments, the present invention relates to any of the aforementioned materials, wherein the prepolymer mixture is toluene diisocyanate capped or capped polyethylene glycol with less than 6% unreacted NCO groups available and with isocyanate functionality less than 2.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the water-soluble polymeric particles are prepared from one or more monomers selected from the group consisting of styrene, vinyl acetate, ethylene, oxide ethylene, acrylonitrile, acrylic acid, acrylamide, maleic anhydride, monovinyl silicon compounds, ethyl vinyl ether, chlorostyrene-vinyl pyridine, vinylidene chloride, butyl vinyl ether, methyl methacrylate and 2-ethylhexyl acrylate. In certain embodiments, the present invention relates to any of the aforementioned materials, wherein the water-soluble polymeric particles are polyethylene oxide polymeric particles or polyethylene glycol polymeric particles.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the active ingredient is selected from the group consisting of silver salts, silver nitrate, silver sulfate, nafcillin, nystatin, undecylenic acid, salicylic acid. , salicylsulfonic acid, nicotinic acid, adenosine diphosphate, chlorhexidine, bacitracin, chlortetracycline, gentamicin, kanamycin, neomycin B, polymyxin B, streptomycin, tetracycline, Amphotericin B, Clotrimazole, Miconazole, Cysteine, Glycine, Threonine, Lidocaine, Trypsin, Streptokinase, Plasmin, Streptodornase, Deoxyribonuclease, Epinephrine, Serotonin, Amphotericin B, Clotrimazole, Miconazole, and Chlorhexidine Digluconate.
In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the water soluble particles containing the active agent form at least 10% by weight of the material. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the water soluble particles containing the active agent form at least 20% by weight of the material. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the water soluble particles containing the active agent form at least 30% by weight of the material. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the water soluble particles containing the active agent form at least 40% by weight of the material. In certain embodiments, the present invention relates to any of the aforementioned materials, wherein the water-soluble particles containing the agent
Active ES 2 395 877 T3 form at least 50% by weight of the material.
Another aspect of the invention relates to a method for preparing a material impregnated with water-soluble polymeric particles comprising the steps of: coating a substrate with a plurality of water-soluble polymeric particles; stirring a mixture comprising water, surfactant and a prepolymer mixture; pouring the mixture into the substrate coated with water soluble polymeric particles, thereby permeating the substrate, and allowing the mixture to cure to a foam, thereby forming a material impregnated with water soluble polymeric particles.
Another aspect of the invention relates to a method for preparing a material impregnated with water-soluble polymeric particles comprising the steps of: stirring a first mixture comprising water, surfactant and a prepolymeric mixture; pour the first mixture onto a surface; putting a substrate on top of the first mix and allowing the first mix to cure to a first foam layer, thereby bonding the substrate and the first foam layer; coating the side of the substrate that is not bonded to the first foam layer with a plurality of water-soluble polymer particles; stirring a second mixture comprising water, surfactant, and a prepolymer mixture; pouring the second mixture onto a surface containing the water-soluble polymeric particles and allowing the second mixture to cure, thereby trapping the plurality of water-soluble polymeric particles within the material and forming a material impregnated with water-soluble polymeric particles .
In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the substrate is a non-woven material. In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the substrate is an apertured nonwoven material. In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the substrate is a non-woven material comprising a mesh surface. In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the substrate is a non-woven fabric or a non-woven fabric.
In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the foam is a polyurethane foam prepared from water, a surfactant, and a prepolymer blend.
In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the surfactant is selected from the group consisting of silicone-based surfactants, polysiloxane-polyoxyalkylene block copolymers, cyanoalkylpolysiloxanes, alkylpolysiloxanes, polydimethylsiloxane, modified dimethylpolysiloxanes polyoxyalkylene, fatty acid salts, sulfuric acid ester salts, salts of phosphoric acid esters and sulfonates, Triton materials, Tergitol materials, Emerest materials, Emulgade materials, Cocamide MEA, Pluronic materials, Brij 72 and sodium alpha-olefin sulfonate. In certain embodiments, the present invention relates to any of the materials mentioned above, wherein the surfactant is polyoxyalkylene modified dimethylpolysiloxanes.
In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the prepolymer mixture is selected from the group consisting of isocyanate-capped branched alkyl poly (ether), non-branched alkyl poly (ether) capped with isocyanate, isocyanate capped branched aromatic poly (ether), isocyanate capped unbranched aromatic poly (ether), isocyanate-capped branched alkyl poly (ether) copolymer, isocyanate-capped unbranched alkyl poly (ether) copolymer, isocyanate-capped branched aromatic poly (ether) copolymer poly (ester), and isocyanate-plugged unbranched aromatic poly (ether) copolymer-poly (ester). In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the prepolymer mixture is toluene diisocyanate capped or capped polyethylene glycol with less than 6% unreacted NCO groups available and with lower isocyanate functionality. than 2.
In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the water-soluble polymer particles are prepared from one or more monomers selected from the group consisting of styrene, vinyl acetate, ethylene, oxide ethylene, acrylonitrile, acrylic acid, acrylamide, maleic anhydride, monovinyl silicon compounds, ethyl vinyl ether, chlorostyrene-vinyl pyridine, vinylidene chloride, butyl vinyl ether, methyl methacrylate and 2-ethylhexyl acrylate. In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the water-soluble polymeric particles are polyethylene oxide polymeric particles or polyethylene glycol polymeric particles.
In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the active ingredient is selected from the group consisting of silver salts, silver nitrate, silver sulfate, nafcillin, nystatin, undecylenic acid, salicylic acid. , salicylsulfonic acid, nicotinic acid, adenosine diphosphate, chlorhexidine, bacitracin, chlortetracycline, gentamicin, kanamycin, neomycin B, polymyxin B, streptomycin, tetracycline, Amphotericin B, Clotrimazole, Miconazole, Cysteine, Glycine, Threonine, Lidocaine, Trypsin, Streptokinase, Plasmin, Streptodornase, Deoxyribonuclease, Epinephrine, Serotonin, Amphotericin B, Clotrimazole, Miconazole, and Chlorhexidine Digluconate.
ES 2 395 877 T3
In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the water soluble particles containing the active agent form at least 10% by weight of the material. In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the water-soluble particles containing the active agent form at least 20% by weight of the material. In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the water-soluble particles containing the active agent form at least 30% by weight of the material. In certain embodiments, the present invention relates to any of the aforementioned methods, wherein the water soluble particles containing the active agent form at least 40% by weight of the material. In certain embodiments, the present invention relates to any of the above-mentioned methods, wherein the water-soluble particles containing the active agent form at least 50% by weight of the material.
BRIEF DESCRIPTION OF THE FIGURE
Figure 1 shows a pictorial representation of a nonwoven substrate having polyethylene oxide particles captured in the "pockets" of the substrate. This material can then be contacted with a foam, thereby forming a material comprising a foam-coated substrate, as described herein.
DETAILED DESCRIPTION
One aspect of the present invention relates to a method for trapping water-soluble polymeric particles between a substrate and a hydrophilic or hydrophobic polyurethane foam. In certain embodiments, the water-soluble polymeric particles can be spread across a surface of a substrate, including into any openings, voids, or pockets, and the foam can permeate the substrate and cure, thereby trapping the particles within the substrate. material.
However, if a substrate is too thick, any foam poured on top of it would not permeate through or bind to all the particles, exposing the risk of any unbonded particles falling off the non-foam side of the substrate. said substrate. This is not the case with a substrate with voids or pockets where the back of the substrate acts as a barrier to contain any unbound particles. One way to overcome the thickness problem is to cast a foam bottom layer, lay an apertured nonwoven fabric on top of it before it fully cures to achieve adhesion, fill the apertures with particles, and back foam on top of the composite material. The end result is two layers of foam both bonded to an inner layer of the nonwoven fabric with its openings filled with particles. The thickness of the assembly is not dependent on the foam that permeates the particles, and is now limited only by the thickness of the available nonwovens. Therefore, another aspect of the invention relates to such a process (and the materials prepared by it): trapping water-soluble polymeric particles within a substrate by first coating one side of the substrate with a hydrophilic or hydrophobic polyurethane foam, putting then water soluble polymeric particles on the uncoated side of the substrate, and finally sealing the particles within the material by another layer of foam.
Importantly, when the impregnated foams of the invention are brought into contact with a liquid, such as water, the water-soluble polymeric particles dissolve and release the active ingredients contained therein. In addition, by altering the molecular weight or chemical composition of the water-soluble polymer particles and / or the characteristics of the foam (such as composition and thickness), one skilled in the art will be able to tailor the physical properties of the product to better meet the requirements. needs of a specific application (that is, to be able to alter the rate at which the water-soluble polymer particles dissolve and thus release the active agent contained therein).
Foams
The term "foam", as used herein, refers to any lightweight cellular plastic material that contains gas-filled voids. In certain embodiments, the foam material of the invention has a matrix of substantially open cells (pores) formed therein. The foam can have, for example, 8 to 60 pores per centimeter. In certain embodiments the foam can have 20 to 30 pores per centimeter. In certain embodiments, the impregnated foam can be in the form of a block, strip, sheet, or extruded form.
Typical foams include polyurethanes, polyvinyl chlorides, and polyesters. In certain embodiments of the invention, the foam that is impregnated with water-soluble polymeric particles is a polyurethane foam.
Hydrophilic and hydrophobic polyurethanes can be prepared by what is commonly referred to as the "Prepolymer Process". A prepolymer, in this context, is an isocyanate-capped polyol or polyurethane. In the case of hydrophobic polyurethanes, a hydrophobic polyol is used. In the case of a hydrophilic polyurethane, a hydrophilic polyol is used, usually a polyethylene glycol. In a typical procedure, an aqueous phase and the prepolymer are emulsified. A chemical reaction takes place between the water in the aqueous phase and the isocyanates, which release carbon dioxide gas and polymerize the mass, simultaneously. Foam quality is governed in part
ES 2 395 877 T3 for the quality of the emulsion that is created. Although other factors, including temperature and mixing speed, also influence foam structure, it is common to use a surfactant to control foam quality. It is clear that adding another component to the formulation, particularly a surface active ingredient, will affect the quality of the foam. Once prepared, however, such hydrophilic and hydrophobic foams are known to be both chemically and physically stable.
A representative sample of suitable hydrophilic prepolymers would include polyether polyols capped with polyfunctional aromatic isocyanates, for example, toluene diisocyanate (TDI) or methylene diphenylisocyanate (MDI), or with aliphatic isocyanates, for example, isopherone diisocyanate (IPDI) or diphenyl isocyanate (IPDI). hydrogenated methylene (HMDI). Polyether polyols are hydrophilic polyoxyalkylenes with a minimum of 40 mole% ethylene oxide. Crosslinking sites are developed, when necessary, during prepolymer formation by adding water to the prepolymer polyols to form urea and subsequently biuret bonds in the prepolymer, formation of allophate bonds by prolonged heating at elevated temperatures, branching of prepolymers by the addition of triols or tetraols (for example, trimethylolpropane, glycerol or pentaerythritol), or branching through the use of selective catalysts.
Hydrophilic prepolymers are available from various companies for use in making foams. A representative list of prepolymers includes Trepol®, sold by Rynel (discussed below), HYPOL<sup>TM</sup>, sold by Dow, Prepol, sold by Lendell Manufacturing, Inc. (St. Charles, MI), Hydropol, sold by Mace Adhesives & Coatings Co., Inc., Aquapol, sold by Carpenter Co. (Richmond, VA), and Urepol , sold by EnviroChem Technologies. These prepolymers are activated by contact with water, and it is known that the amount of water can influence the properties of the foam. Typical prepolymer to water ratios range from 2: 1 to 0.5: 1, depending on the desired properties of the resulting polymer.
TREPOL® prepolymer is a toluene diisocyanate capped or capped polyethylene glycol polyether-urethane prepolymer, with less than 6% unreacted NCO groups available and with isocyanate functionality less than 2. A feature and advantage of the type prepolymer TREPOL<sup>TM</sup>, characterized by a low density of available NCO reactive sites and an isocyanate functionality less than 2, accompanied by only small amounts of monomeric or low molecular weight components, is that the resulting polymerization with the aqueous phase generates a more exothermic heat low, allowing the limitation of the reaction temperature to the range of, for example, 49 ° C and below. An additional advantage of the TREPOL ™ prepolymer is that the high water content produces a higher specific heat prepolymer for more efficient dissipation of exothermic heat during the reaction. The resulting open foam substrate generated by reaction with the prepolymer with lower density available NCO sites is also characterized by lower toxicity.
Various polymeric foams are suitable for the present invention. Representative examples of polymeric foams are poly (alkyloxyurethane) foams, polycarbonate foams, and poly (oxyether) polyol foams, such as polyethylene glycol, polypropylene glycol, or a copolymer of polyethylene glycol and polypropylene glycol.
It is known that hydrophilic polyurethane foams having improved moisture resistance properties can be prepared from a reaction mixture comprising a select blend of three polyols. As such, these foams are of particular utility in wet scrubbing and cleaning applications. In the preparation of these polyurethane foams, the so-called "one-step method" or the "prepolymer technique" can be used. These foams are prepared from a reaction mixture comprised of an organic polyisocyanate, a foaming agent, a reaction catalyst and, as the polyol reactant, a select mixture or combination of three polyether polyols. Any organic polyisocyanate that is useful in the preparation of polyurethane foams can be used in the practice of the process. This includes, for example, toluene diisocyanate, such as the 80:20 mixture or the 65:35 mixture of the 2,4- and 2,6- isomers, ethylene diisocyanate, propylene diisocyanate, methylene bis- 4-phenyl, 3,3'-bitoluene 4,4'-diisocyanate, hexamethylene diisocyanate, naphthalene 1,5-diisocyanate, polymethylene polyphenylisocyanate and mixtures thereof. A preferred organic polyisocyanate is an aromatic diisocyanate, such as TDI or MDI. The amount of polyisocyanate employed in a process should be sufficient to provide the range of about one isocyanate group per hydroxyl group present in the reaction system, which includes all polyol reactants as well as any additives or foaming agents employed. An excess of the isocyanate compound may conveniently be employed; however, this is generally undesirable, due to the high cost of isocyanate compounds. It is therefore preferable to employ sufficient isocyanate to provide no more than 1.25 isocyanate groups per hydroxyl group, and preferably between 0.9 and 1.2 isocyanate groups per hydroxyl group. The ratio of isocyanate groups to OH groups multiplied by 100 is called the "index." See the following U.S. Patents for additional examples: No. 3,194,773, No. 3,238,273, No. 3,336,242, No. 3,380,967, No. 3,461,086, No. 3,457,203, No. 3,546,145, and 3,457,203.
Surfactants
Various surfactants are known in the art and are suitable for the present invention. One type of surfactant is a silicone-based surfactant. Silicone surfactants known in the art include: "hydrolyzable" polysiloxane-polyoxyalkylene block copolymers, "non-hydrolyzable" polysiloxane-polyoxyalkylene block copolymers, cyanoalkylpolysiloxanes, alkylpolysiloxanes, modified polydimethylsiloxanes, and dimethylpolysiloxanes with polysiloxanes. The type of silicone surfactant used and the amount required depends on the type of foam
ES 2 395 877 T3 produced, as recognized by those skilled in the art. Silicone surfactants can be used as such or dissolved in solvents such as glycols. Other types of surfactants suitable for the present invention relate to anionic surfactants such as fatty acid salts, sulfuric acid ester salts, phosphoric acid ester salts and sulfonates, and the like. Certain preferred surfactants are Triton materials marketed by Union Carbide, Tergitol materials marketed by Union Carbide, Emerest materials marketed by Henkel Corp., Emulgade materials marketed by Henkel Corp., Cocamide MEA marketed by Chemron, Pluronic materials marketed by BASF , Brij 72 available from ICI, and sodium alpha-olefin sulfonate available from Witco.
Water soluble polymer particles
The term "water soluble polymeric particle", as used herein, refers to a polymeric particle that degrades over time when in contact with water or other liquid. The particle sizes can range from powder size, for example in the range of 1 to 5 microns, to granular and bead sizes of 2,000 to 5,000 microns.
In certain embodiments, the water-soluble polymeric particles are prepared from one or more monomers selected from the group consisting of styrene, vinyl acetate, ethylene, ethylene oxide, acrylonitrile, acrylic acid, acrylamide, maleic anhydride, monovinyl compounds of silicon, ethyl vinyl ether, chlorostyrene vinyl pyridine, vinylidene chloride, butyl vinyl ether, methyl methacrylate, and 2-ethylhexyl acrylate. In certain embodiments, the water-soluble polymeric particles are selected from the group consisting of starch, starch derivatives, modified starch derivatives, polyvinyl alcohol, cellulose derivatives, polysaccharide gums, and maltodextrin. In certain embodiments, the water soluble polymeric particles are selected from the group consisting of polyethylene oxide (PEO) and polyethylene glycol (PEG).
The term "impregnated", as used herein, means that it is contained within. For example, a poly (ethylene oxide) impregnated polyurethane foam is a polyurethane foam with poly (ethylene oxide) particles diffused throughout its interior.
Active ingredients
The invention contemplates the application of the dispensing composite to selectively store, protect, and release and dispense various liquids, solids, and other active or functional components, collectively referred to herein as "active ingredients." Water soluble polymeric particles containing active ingredients for use in impregnated foam materials include physiologically or biologically active agents, such as antibacterial agents, antifungal agents, analgesic agents, tissue healing agents, local anesthetic agents, anti-hemorrhagic agents, enzymes or vasoconstrictors. Active ingredients can also be selected from the group consisting of fragrances and antiperspirants. In certain embodiments, the physiologically or biologically active agent is selected from the group consisting of: antibacterials selected from the group consisting of Silver Nitrate, Chlorhexidine, Bacitracin, Chlortetracycline, Gentamicin, Kanamycin, Neomycin B, Polymyxin B, Streptomycin, Tetracycline, Acid fusidic, pseudomonic acid, and Ceftriaxone (Rocephin); antifungals selected from the group consisting of Amphotericin B, Clotrimazole, Miconazole, Nafcillin, Nystatin, and undecylenic acid; tissue healing agents selected from the group consisting of cysteine, glycine, and threonine; analgesics selected from the group consisting of lidocaine, salicylic acid, salicylsulfonic acid, and nicotinic acid; anti-hemorrhagic agents selected from the group including adenosine diphosphate (said anti-hemorrhagic agents being such that they make platelets sticky, an initial step required for stopping bleeding); enzymes selected from the group consisting of trypsin, streptokinase, plasmin (Fibrinolysin), and streptodornase; deoxyribonuclease; and cationic vasoconstrictors selected from the group consisting of epinephrine and serotonin. Such physiologically or biologically active agents can be used in the form of their salts.
Substrates
As mentioned above, another embodiment of the inventive materials incorporates a substrate (eg, a nonwoven material) that can be impregnated with particles and interpenetrated (and permeated) by foam. In certain embodiments, the substrate is a nonwoven material that can be of a desired contour. When the foam polymerizes in the presence of the substrate, the foam binds to the fibers and fills the interstices of the substrate, while the water-soluble polymeric particles of active ingredient are trapped between the surfaces of the substrate and the foam.
In general, the substrate can be any of a multitude of materials, including plastic, metallic fiber, wood fiber, glass, fiberglass, and fabrics. Representative examples include: cotton, wool, silk, jute, linen, rayon, acetate, polyesters, poly (ethylene terephthalate), polyamides, nylon, acrylics, olefins, aramids, azlones, glass, fiberglass, modacrylics, novoloids, nitriles, scratches, saranos , spandex, vinal, vinyon, foams, films, foamed sheets, natural leathers, split leathers, synthetic leathers, vinyl, urethane, polyurethane, polyurethane films, polyethylene, polymeric silicon layers, filtration membranes, polysulfones, polyimides, nitrocellulose, cellulose acetate, cellulose and regenerated cellulose, alginates, hydrocolloids, metallized films,
ES 2 395 877 T3 sheets of paper, silicones, latex, polycarbonates and combinations thereof.
Preferred substrates have surfaces that contain apertures or pockets that can be filled with particles, or are structured so that the particles can be dispersed within the substrate. Examples of such preferred substrates are apertured nonwovens such as Ahlstrom Grade A0568 or 192B (Ahlstrom Head Office - PO Box 329, FIN-00101 Helsinki, Salmisaarenaukio 1, FIN-00180 Helsinki, Finland).
Methods for impregnating a foam with a water-soluble polymeric particle
One aspect of the invention relates to a method for producing materials impregnated with water-soluble polymeric particles in which the particles are trapped by a foam within the substrate. In certain embodiments, the water soluble polymeric particles comprise an active ingredient.
To produce such three-component materials, the invention provides the method of mixing the aqueous phase and the prepolymer phase and dispensing the flowable mixture onto a substrate that has been coated with water-soluble polymeric particles. After polymerization of the foam, the substrate binds to the open foam substrate and interpenetrates and permeates into the open foam substrate. In certain embodiments, the foam substrate fills the interstices of the fabric skeleton or matrix with defined density, bonding to the nonwoven fibers and trapping the particles. Such a skeleton or matrix gives added strength to the material and allows a greater number of particles to be present than if the particles were simply distributed in the foam.
In certain embodiments, the aqueous phase and the prepolymer phase are mixed together in a weight ratio of aqueous phase to prepolymer phase in the range of at least 0.02 / 1 or greater, but preferably in the range of 1/1 to 12/1, and within that range the preferred range is 1/1 to 3/1.
In certain embodiments, the foam can be cured by supporting the substrate on rigid glass or synthetic plastic plates, while resting on spaced trays, or stacked on top of one another, in a circulating oven. Importantly, the above curing methods are provided as examples only; other methods of curing foams are well known to those of skill in the art and are contemplated for use herein.
Method for associating an active ingredient with a water-soluble polymeric particle
One method of introducing an active ingredient (such as a drug) into the water-soluble polymer particles (such as polyethylene oxide) would be to dissolve (suspend) it in a liquid (such as polyethylene glycol) and then coat it on the particles. Another method would be to add the active ingredient directly to a molten water-soluble polymer and then spray-cool the resulting mixture back to a powder (which can then be incorporated into the foam or foam sheet as described herein). Importantly, the above methods for incorporating active ingredients into water soluble polymeric particles are provided as examples only; Other methods for incorporating active ingredients into polymeric particles are well known to those of skill in the art and are contemplated for use herein.
EXAMPLES
With the invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention.
Example 1 - Polyurethane foams impregnated with polyethylene oxide
Two hydrophobic foams (A and B) impregnated with polyethylene oxide (PEO) were prepared from the components listed in Table 1.
Table 1. Components of hydrophobic foams impregnated with polyethylene oxide
<td>TO</td><td>B</td><td>Component</td>
<td>16.3 g</td><td>16.3 g</td><td>Bayfit® 568B polyether polyol from Bayer</td>
<td>6.0 g</td><td>9.0 g</td><td>Poly (ethylene oxide) (powder)</td>
<td>0.1 g</td><td>0.1 g</td><td>NIAX L-5309 (Union Carbide L5309 silicone surfactant, a commercially available poly (oxyalkylene) (dimethylsiloxane) copolymer)</td>
<td>3.0 g</td><td>3.0 g</td><td>Diphenylmethane Diisocyanate 566A from Bayer</td>
NIAX L-5309 was first mixed with Bayfit® 568B polyether polyol from Bayer. The poly (oxide) was then added
ES 2 395 877 T3 ethylene) to the mixture. To that mixture, Bayer diphenylmethane diisocyanate 566A was added, and the resulting four component mixture was stirred with a conventional stirrer. After stirring, the pre-foam mixture was cast between release papers. The dimension between the release papers was 0.08 centimeters. The foam was initially cast to the 0.08 centimeter dimension and then rolled with a laboratory roll to the desired dimension before final cure. This procedure gave a polyurethane foam composite product (A) with 23.6% by weight of poly (ethylene oxide) particles fully dispersed; or (B) with 31.8% by weight of fully dispersed polyethylene oxide particles. Although it is believed that as much as about 33% by weight of polyethylene oxide particles could be achieved with the conventional agitator method, foams with more than this amount of particles are not accessible with this methodology.
Interestingly, the fact that the product felt slippery when wet indicated that some of the polyethylene oxide particles were exposed on the surface. It is also safe to assume that some of the particles were in contact with each other within the foam matrix, and that since this was an open cell foam, that most of the particles were exposed to the open cells as well. This would mean that if water or liquid were introduced into the foam, most of the particles would be moistened.
Example 2 - Polyurethane foam sheets impregnated with poly (ethylene oxide)
A method of dealing with the limitation in the amount of particles that can be incorporated into a material is provided below by the method provided in Example 1.
In this example, a nonwoven substrate was first coated with PEO powder. Coating was carried out by dipping the substrate in a PEO container and shaking. The result was that the substrate was coated on both sides and the PEO particles were captured in the "pockets" of the nonwoven substrate. See Figure 1.
The substrate was then placed on a release paper sheet. A mixture of polyurethane prepolymer (eg, Trepol®) and water in a ratio of about 1 to about 1.5 was applied to the top of the substrate, which was then covered with another sheet of release paper and the " resulting sandwich ”was allowed to cure. After curing, the resulting product was removed from the release paper.
Importantly, it was observed that the polymer / water foam inclusions had permeated the substrate such that it was coated on both sides, and such that all of the PEO was trapped within the material. Notably, when hardened, the product exhibited "slippery" characteristics, indicating that the now-captured PEO was accessible by water.
It was also evident that the characteristics could be easily modified by different means, such as using different substrates. These could include thicker or thinner substrates, or substrates with more or less "pockets". These substrates could be woven or non-woven, where the "pockets" could be formed or simply be spaces between the fibers. The substrate could be another foam material in which PEO particles could be loaded into the open cells on its surface. Another variation would be a substrate with foam and PEO only on one side, such that the uncoated side could be used to bond to another material. The composite material could also be made thicker or thinner, which would change the absorption of water or liquid.
One of the main advantages of the compositions is that by coating the substrate with the PEO, the difficulties of loading PEO in the polymeric or aqueous part are eliminated. The substrate also serves to keep the reluctant dispersions of the composite material stable, and can also serve as a bonding surface. Electrostatic deposition of PEO on the substrate is also a possibility.
Example 3 - Incorporation of active ingredients in foams and foam sheets
Based on the results presented in Example 2, it is proposed that a wound dressing or the like could be prepared in a similar manner, but active ingredients could be incorporated into the polyethylene oxide. In the case of an exuding wound, the exudate would dissolve the polyethylene oxide as it became wet, thereby releasing the active ingredient in the process. It is expected that varying the molecular weight of the polyethylene oxide would also vary the rate at which the polyethylene oxide would dissolve, and as such would control the rate at which the active ingredients are introduced. In addition, other water soluble polymers could be used as carriers for the active ingredients as well, such as, for example, polyethylene glycol.
Contents9
1 sheet
Sheet 1
9 members in 5 offices
Priority claims9
| Document | Office | Kind | Date |
|---|---|---|---|
| 944860P | United States of America | – | |
| 94486007 | United States of America | P | |
| 94486007 | United States of America | P | |
| 2008067528 | United States of America | W | |
| 2008067528 | United States of America | W | |
| 944860P | – | – | – |
| PCTUS2008067528 | – | – | – |
| US20070944860P | – | – | – |
| WO2008US67528 | – | – | – |
Members9
| Document | Office | Kind | |
|---|---|---|---|
| WO2008157711A2 | World Intellectual Property Organization (WIPO) | A2 | |
| WO2008157711A3 | World Intellectual Property Organization (WIPO) | A3 | |
| EP2167549A2 | European Patent Office (EPO) | A2 | |
| EP2167549A4 | European Patent Office (EPO) | A4 | |
| US2011171282A1 | United States of America | A1 | |
| EP2167549B1 | European Patent Office (EPO) | B1 | |
| ES2395877T3This record | Spain | T3 | |
| PL2167549T3 | Poland | T3 | |
| US8962027B2 | United States of America | B2 |
Numbers
- Publication
- 2395877
- Publication, DOCDB
- 2395877
- Publication, EPODOC
- ES2395877T
- Application
- 8771497
- Application, DOCDB
- 08771497
- Application, EPODOC
- ES20080771497T
Titles2
- Spanish
- Materiales que comprenden partículas poliméricas solubles en agua y métodos para prepararlos y usarlos
- English
- Materials comprising water soluble polymer particles and methods for preparing and using them
Classification
- IPC, 3
- C08F2 18
- A61K31 745
- C08J3 00