Patent Publication Number: US-2013244523-A1

Title: Method for the production of oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens, and use thereof

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a U.S. National Phase application under 35 U.S.C. §371 of International Application No. PCT/EP2011/003805, filed on Jul. 29, 2011, and claims benefit to German Patent Application No. DE 10 2010 034 782.5, filed on Aug. 18, 2010. The International Application was published in German on Feb. 23, 2012 as WO 2012/022421 under PCT Article 21(2). 
    
    
     FIELD 
     The present invention relates to a method for the production of oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens as well as to the use thereof. 
     BACKGROUND 
     The term fiber sheet material refers especially to an ordered or unordered single-layer or multi-layer combination of many fibers. 
     U.S. Pat. No. 3,364,200 A describes the oxidation of cellulose with nitrogen dioxide/dinitrogen tetroxide for use in the medical sector. According to U.S. Pat. No. 3,364,200 A, the cellulose is oxidized with liquid nitrogen dioxide, nitrogen tetroxide or mixtures thereof and the oxidized cellulose is treated by means of special washing methods that particularly also provide for the use of halogenated hydrocarbons. 
     The above-mentioned method is disadvantageous from an environmental standpoint and calls for additional cleaning steps. 
     German patent application DE 44 26 443 Al describes the oxidation of polysaccharide powder, especially starch, with nitrogen dioxide/dinitrogen tetroxide gases. In order to achieve a thorough mixing of the starch powder with the gas, preferably additional components are used such as, for example, zeolites or silica gel, which have to be separated out again after the process. The produced polycarboxylate powders are used as builders or co-builders in detergents and cleaning agents. 
     SUMMARY 
     In an embodiment the present invention provides a method for the production of at least one of oxidized cellulose fibers, oxidized cellulose fiber sheet materials and oxidized cellulose nonwovens. At least one of cellulose fibers, cellulose fiber sheet materials and cellulose nonwovens is introduced into a reactor. A temperature of the reactor is set in a range from 25° C. to 80° C. Gaseous nitrogen dioxide is introduced into the reactor so as to oxidize the at least one of cellulose fibers, cellulose fiber sheet materials and cellulose nonwovens. A temperature of the reactor is set in a range from 20° C. to less than 160° C. The at least one of oxidized cellulose fibers, oxidized cellulose fiber sheet materials and oxidized cellulose nonwovens are neutralized with at least one base. 
    
    
     DETAILED DESCRIPTION 
     The present invention provides, in an embodiment, an improved method for the production of oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens, especially for the production of oxidized cellulose wound dressings, said method being particularly simple and efficient as well as environmentally friendly, since it especially can make do without the use of additional mixing additives, and whereby especially no waste products are formed and/or no demanding cleaning steps are necessary. 
     In an embodiment, the oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens produced according to the method should exhibit an especially high absorption of an aqueous 0.9% sodium chloride solution (physiological saline solution), they should be water-insoluble, and they should be suitable for many uses, especially in medical applications, particularly for wound care. 
     The absorption of an aqueous 0.9% sodium chloride solution is determined on the basis of German standard DIN 53923. Instead of the absorption of water, the absorption of an aqueous 0.9% sodium chloride solution is determined. 
     According to an embodiment of the invention, the method for the production of oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens, especially with a degree of oxidation between 1% and 50%, preferably between 5% and 35%, comprises the following steps:
     a) using cellulose fibers, cellulose fiber sheet materials or cellulose nonwovens,   b) setting the temperature within the range from 25° C. to 80° C. [77° F. to 176° F.], preferably from 30° C. to 60° C. [86° F. to 140° F.],   c) introducing gaseous nitrogen dioxide,   d) setting the temperature within the range from 20° C. [68° F.] to less than 160° C. [320° F.], preferably up to 100° C. [212° F.], and   e) neutralizing the oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens with bases, particularly with gaseous ammonia.   

     The terms fibers, fiber sheet materials or nonwovens made of cellulose refer to those made of pure cellulose and also to those made of cellulose derivatives or of cellulose in combination with other polysaccharides. 
     Examples of these are preferably cellulose ethers, such as methyl cellulose, ethyl cellulose or butyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, cellulose esters, such as cellulose acetate, bacterial celluloses, viscoses as well as their copolymers, such as block copolymers, graft copolymers, random or alternating systems. 
     Cellulose fibers, cellulose fiber sheet materials or cellulose nonwovens as the starting material are preferably used at a fiber fineness of 0.5 dtex to 30 dtex, preferably between 1 dtex and 10 dtex, especially preferably between 1.5 dtex and 5 dtex, as well as especially with a fiber length between 3 mm and 120 mm, whereby fibers that are preferably between 5 mm and 80 mm are of interest for the production of nonwovens. Since the fibers, fiber sheet materials or nonwovens are porous and have capillary forces—in contrast, for instance, to the use of powders—this has a positive influence on the conveying of the gaseous oxidant, for instance, through the reactor. The gas is fed along the fibers, thereby permitting a homogeneous distribution of the oxidation gas. 
     In contrast, the process control becomes more difficult when powders are used since a special reactor design is needed and additives have to be used in order to ensure an intensive and thorough mixing, so as to avoid the agglomeration of a polysaccharide that is to be oxidized and so as to ensure the formation of a fluidized bed. 
     Consequently, the method according to an embodiment of the invention allows for a particularly simple and flexible reactor design. 
     In order to reduce the humidity to a moisture content of 7% by weight at the maximum and to bring the employed cellulose fibers, cellulose fiber sheet materials or cellulose nonwovens to the desired temperature, the reactor is preferably dried with inert gas that has been preheated to the reaction temperature such as, for instance, helium, argon or carbon dioxide or else air, preferably with nitrogen. The reaction temperature here is between 25° C. and 80° C. [77° F. and 176° F.], preferably between 30° C. and 60° C. [86° F. and 140° F.]. 
     In a preferred embodiment of the method, the gaseous nitrogen dioxide is introduced at gas throughput rates ranging from 0.1 to 10 molar equivalents of nitrogen dioxide per hour, relative to the hydroxy group that is to be oxidized. This is likewise carried out in the preheated state. 
     Through the use of gaseous instead of liquid nitrogen dioxide, it is possible to attain a high reactivity, especially a shorter retention time or reaction time. 
     The reaction process can be carried out at particularly low gas throughput rates since the use of cellulose fibers, cellulose fiber sheet materials or cellulose nonwovens does not call for intensive and thorough mixing. This is also advantageous in terms of safety since, for example, in case of an accident or leak in the reactor, the personnel is exposed to lower concentrations of nitrogen dioxide. At the same time, the homogeneous distribution of the gas can be easily achieved so that the result is a particularly uniformly oxidized product with a uniform degree of oxidation. 
     The desired degree of oxidation is advantageously 1% to 50%, preferably between 5% and 35%, relative to the number of OH groups in cellulose that are to be oxidized, and it is determined, for instance, by means of infrared spectroscopy (IR) or titration of the oxidized groups. 
     Higher degrees of oxidation are not of interest with an eye towards particularly desired products, especially towards their use as wound dressings, nor are they feasible, since, for example, the wound dressing is supposed to gel as it absorbs large quantities of water and, in particular, it should not dissolve as is the case, for instance, when used as a detergent or cleaning agent. 
     When the desired quantity of oxidant has been introduced, or the desired degree of oxidation has been reached in order to shift the equilibrium towards the product side, the entire system is set to a temperature within a range that is preferably between 20° C. and 100° C. [68° F. and 212° F.], whereby care is taken to ensure that the upper limit of 160° C. [320° F.] is not exceeded, since ever-greater degradation is observed at higher temperatures. 
     This step also ensures that the content of groups containing nitrogen is minimized in the final product, especially when nitrogen dioxide is used as the oxidant. 
     In order to remove the residues of oxidant, especially of nitrogen dioxide, flushing is carried out preferably with inert gas, especially with nitrogen. 
     The method according to an embodiment of the invention is particularly environmentally friendly, simple and efficient, since the gaseous oxidant, especially the gaseous nitrogen dioxide, can be circulated during the process control, and no additional chemicals have to be used such as, for instance, fluorocarbons or chlorofluorocarbons. 
     Nitrogen oxide that is formed during the reaction with nitrogen dioxide can be converted back into nitrogen dioxide by means of oxidation with oxygen and can be used for the further oxidation in order to improve the environmental balance of the process in that no waste product is formed. 
     Subsequently, the acid groups of the oxidized cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens are neutralized with bases, particularly with gaseous ammonia. 
     As an alternative, of course, the use of other basic reagents for the neutralization is also possible such as, for example, the use of alkaline alcoholic solutions such as, for instance, potassium hydroxide solution. 
     Thanks to the use of gaseous ammonia, however, there is no longer a need to clean and dry the product. Since this type of process control can thus make do without the use of solvents and since no waste products are generated, this reaction control is particularly efficient and environmental friendly. 
     Subsequent to the neutralization, flushing is preferably carried out again with inert gas, especially with nitrogen. 
     The method according to an embodiment of the invention takes place particularly quickly, especially in just a few hours. However, in other methods for manufacturing wound dressings such as, for instance, the method of Johnson &amp; Johnson according to U.S. Pat. No. 3,364,200 A, the process takes several days. 
     In an advantageous embodiment of the method, at least one additive can be added to the oxidized cellulose fibers, the oxidized cellulose fiber sheet materials or the oxidized cellulose nonwovens, and said additive can be selected from among the following synthetic polymers, biopolymers, active ingredients and/or special additives. 
     Examples of synthetic polymers that can be used are polyoxymethylenes, polyamides, such as polyamide-66, polyurethanes, polyvinylpyrrolidones, polyvinylamines, polyethylene imines, polyesters, such as polyethylene terephthalate, polycarbonates, polysiloxanes, such as polydimethylsiloxane, polyvinylalcohols, polyolefins, such as polyethylene or polypropylene, polycarboxylic acids, such as polyacrylic acid, polyacrylates, polymethacrylates, such as polymethyl methacrylate or poly-(2-hydroxyethyl methacrylate), polyalkylene oxides, such as polyethylene glycol or polyethylene oxides, polystyrenes, polyvinylacetates, polyvinylchloride, polycaprolactones, polylactides, polyglycolides or polyhydroxybutteric acids. 
     Examples of biopolymers that can be used are proteins, such as collagen, silks, keratins, albumins, polysaccharides, such as starches, modified starches, celluloses, cellulose derivates, such as cellulose ethers, cellulose esters, bacterial celluloses, viscoses, chitins, chitosanes, caseins, pectins, agar, guar gums, hyaluronic acid or alginates. 
     Examples of active ingredients or special additives that can be used are medications, such as antibiotics, analgesics, agents that promote wound healing, antibacterial, antiviral or antimicrobial preparations, organic acids, enzymes, vitamins, nicotine, proteins that have a positive effect on wound healing, growth factors, such as purines or pyrimidines, stabilizers, carbon compounds, such as activated charcoals, graphenes, carbon nanotubes, metals, such as gold or silver, cyclodextrines, inorganic particles, silicon particles, ceramics, such as silica gels or silicates. 
     The above-mentioned polymers can be used as homopolymers, as copolymers, for example, as block copolymers, graft copolymers, random or alternating systems, or in any mixture of these. 
     The above-mentioned active ingredients or additives can be added or adsorbed in pure form, in any desired mixture with each other and/or in encapsulated form. 
     As additives, special preference is given to polyvinyl alcohols, polyolefins, polyethylene glycols, polyesters, medications as well as agents that promote wound healing. 
     Another advantage of the method is that the reaction can be carried out practically pressure-free, that is to say, at normal pressure, preferably at a pressure in the range from 0.1 bar to 7 bar, especially preferably from 0.8 bar to 3 bar. 
     The oxidized cellulose fibers can be processed and bonded to form nonwovens. 
     The fibers, fiber sheet materials or nonwovens made of oxidized cellulose can be further processed in any desired form. Thus, they can be made into any three-dimensional shape, and can also be used in combination with supports, especially through application onto a support or through incorporation into a support such as, for example, so-called sandwich structures. 
     Subsequent chemical modification is also conceivable. 
     The cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens produced according to an embodiment of the invention have particularly low nitrate and nitrite contents, less than 10% by weight. 
     Moreover, they have an especially good capacity to absorb an aqueous 0.9% sodium chloride solution (physiological saline solution). 
     The cellulose fibers, oxidized cellulose fiber sheet materials or oxidized cellulose nonwovens according to an embodiment of the invention preferably exhibit an absorption of an aqueous 0.9% sodium chloride solution in a range from 400% to 10,000% by weight, especially preferably in a range from 400% to 5000% by weight, particularly preferably in a range from 400% to 3500% by weight. 
     Therefore, they are preferably used in the medical sector, especially preferably as or for wound dressings, tissue constructions or tissue growing (tissue engineering) or for implants, but also for packaging, cosmetic, hygiene or household products, especially cleaning supplies and/or for filters, insulating substances and/or support materials, especially for catalysts, furniture, clothing, especially as interlinings or interfacing, and for noise and/or heat protection. 
     EXAMPLE 
     Cellulose fibers (100 grams, made by means of the NMMO (N-methylmorpholine N-oxide) method in a titer of 1.7 dtex) are placed into a flask at about 50° C. [122° F.] and preferably at a pressure of 1 bar, whereby they are pre-dried if the moisture content is not in the range from 0% to 7% by weight. 
     In order to allow the defined conditions, the flask interior is flushed with preheated inert gas, preferably with nitrogen. Subsequently, 6 molar equivalents of nitrogen dioxide per hour, relative to the alcohol group that is to be oxidized, are used for the conversion into carboxyl groups amounting to 9% to 11% after 30 minutes and 30% to 35% after one hour in cellulose. The degree of oxidation of the primary alcohol groups of the glucose molecule, as a function of the fiber diameter, can be determined by means of infrared spectroscopy (IR) or titration of the oxidized groups. 
     After the reaction, the gas feed is shut off and the flask is heated to a temperature between 50° C. and 100° C. [122° F. and 212° F.], preferably to about 80° C. [176° F.], for about half an hour. This step ensures that the content of groups containing nitrogen in the final product is minimal. 
     In order to remove residues of nitrogen dioxide, the cellulose fibers are once again flushed with inert gas, preferably with nitrogen. 
     The nitrogen oxide that is formed during the reaction can be converted into nitrogen dioxide by means of oxidation with oxygen and, in order to avoid waste products, can be returned to the circulation system of the above-mentioned oxidation process of the cellulose. This improves the environmental balance of the process 
     The subsequent neutralization of the acid groups of the oxidized cellulose can be achieved with all kinds of bases. Preferably, the oxidized fibers are neutralized here with gaseous ammonia and checked for a gelling effect. The use of gaseous ammonia avoids the need for cleaning and drying the product. 
     After the neutralization, the flask is preferably flushed once again with nitrogen. 
     The oxidized cellulose fibers absorb 400% to 3500% by weight of an aqueous 0.9% sodium chloride solution as a function of the degree of oxidation. 
     The values for the absorption of an aqueous 0.9% sodium chloride are determined on the basis of DIN 53923. Instead of the absorption of water described in the DIN standard, the absorption of an aqueous 0.9% sodium chloride solution is determined. 
     While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. It will be understood that changes and modifications may be made by those of ordinary skill within the scope of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below. 
     The terms used in the claims should be construed to have the broadest reasonable interpretation consistent with the foregoing description. For example, the use of the article “a” or “the” in introducing an element should not be interpreted as being exclusive of a plurality of elements. Likewise, the recitation of “or” should be interpreted as being inclusive, such that the recitation of “A or B” is not exclusive of “A and B.” Further, the recitation of “at least one of A, B and C” should be interpreted as one or more of a group of elements consisting of A, B and C, and should not be interpreted as requiring at least one of each of the listed elements A, B and C, regardless of whether A, B and C are related as categories or otherwise.