 NANOFIBRILLARY CELLULOSE, METHOD FOR THE MANUFACTURE OF NANOFIBRILLARY CELLULOSE, MEMBRANE, USE OF N
专利摘要:
nanofibrillar cellulose, method for the manufacture of nanofibrillar cellulose, membrane, use of nanofibrillar cellulose, and, product. the present invention relates to nanofibrillar cellulose. moreover, the invention relates to a method for the manufacture of nanofibrillar cellulose, and to a nanofibrillar cellulose obtainable by said method. the invention also relates to uses of nanofibrillar cellulose. 公开号:BR112017023567B1 申请号:R112017023567-6 申请日:2015-05-04 公开日:2021-03-30 发明作者:Markus Nuopponen 申请人:Upm-Kymmene Corporation； IPC主号:
专利说明:
FIELD OF THE INVENTION [001] The invention concerns nanofibrillar cellulose. In addition, the invention relates to a method for the manufacture of nanofibrillar cellulose, and to a nanofibrillar cellulose obtainable through said method. The invention also concerns the uses of nanofibrillar cellulose. FUNDAMENTALS [002] Nanofibrillar cellulose (NFC) has recently found applications in several areas, including biomedical and pharmaceutical applications. In higher plants, cellulose is organized into a morphologically complex structure consisting of β-D-glycopyranose chains (1 ^ 4). These chains are laterally connected by hydrogen bonds to form nanoscale diameter microfibrils, which are again organized into microfibril bundles. In addition, cellulose molecules are associated with other polysaccharides (hemicelluloses) and lignin on the walls of the plant cell, resulting in even more complex morphologies. Nanoscale cellulose fibers can be released from the highly regular structure through the mechanical process, combined with other treatments such as enzymatic pretreatment. [003] Nanofibrillar cellulose is typically obtained through mechanical disintegration of the cellulose pulp, carried out with suitable disintegration equipment. Mechanical disintegration is an energy-consuming operation where production capacity is limited. In this way, several measurements have been proposed to improve the shredding or fibrillation process, such as pulp modification before disintegration. The modification may comprise the chemical modification of the pulp to produce the anionic or cationically charged grades of nanofibrillar cellulose (NFC). Said chemical modification can be based, for example, on carboxymethylation, oxidation, esterification, or etherification of cellulose molecules. However, said methods of chemical modification can result in degrees of NFC, which are not desirable for all applications and therefore, alternative methods have also been studied, such as an enzymatic treatment. [004] US patent 7,838,666 discloses a cellulose dispersible in fine fibrous water derived from a plant cell wall having a starting cellulosic substance, wherein the starting cellulosic substance has an α-cellulose content of 60 to 90% by weight and an average degree of polymerization from 400 to 1300, or the starting cellulosic substance has an α-cellulose content of 60 to 100% by weight and an average degree of polymerization greater than 1300, water-dispersible cellulose being crystalline having a crystallinity of 55% or more, and fine fibrous material without a tangle between the fibers, and the water dispersible cellulose substantially having no branched bundles of fibers, the water dispersible cellulose comprising 30% by weight or more than one a component that can be stably suspended in water, the component comprising a fibrous cellulose having a length of 0.5 to 30 μm and a width of 2 to 600 nm, and a length / width ratio of 20 to 400, and the cellulose dispersiv el in water having a loss tangent <1, when made in a 0.5% by weight aqueous dispersion. [005] Bhattacharya ET AL 2012 disclose nanofibrillar cellulose, which contains fiber bundles with a thickness of more than 50 nm. Although cellulose nanofibers are very thin, their organization in thick bundles results in light scattering. Light scattering causes limitations in the use of the NFC hydrogel in applications requiring optical detection, for example, with light microscopy. [006] Paakko et al. 2007 disclose a method of producing cellulose fribrils using a combination of enzymatic hydrolysis and mechanical shear. This indicates that previous attempts to prepare MFC only through extensive mechanical shear resulted in the homogenizer becoming blocked and the resulting material was inhomogeneous. However, enzymatic treatment leaves traces of enzymes in the final product and an enzymatic removal or inactivation step may be necessary before downstream applications. Additionally, enzymes have a significant effect on the morphology of cellulose nanofibrils: the enzymatic pretreatment leads to a decreased degree of polymerization, decreased length and decreased network of cellulose nanofibrils, and can lead to crystals or cellulose hair in the form of bat. [007] Therefore, there is a need to provide improved nanofibrillar cellulose and methods for making nanofibrillar cellulose. SUMMARY [008] The present invention is based on studies of different pretreatments of cellulose pulp before mechanical disintegration. It has been found that mechanical disintegration in individual cellulose nanofibrils can be improved through a specific combination of pretreatment steps and a microfibrillary cellulose with improved properties is achieved. [009] An objective of the invention is to provide a nanofibrillar cellulose, in which said nanofibrillar cellulose has an average degree of polymerization greater than 1000, and in which said nanofibrillar cellulose is of plant origin. [0010] Another objective of the invention is a method for the manufacture of a nanofibrillar cellulose. The method comprises the steps of providing an aqueous suspension of cellulose pulp of vegetable origin, preferably of wood origin, more preferably of birch; ion exchanging at least part of the carboxyl groups present in the cellulose pulp, preferably with Na +; pre-refining said exchanged ion cellulose pulp; subjecting said pre-refined cellulose pulp to a high-pressure mechanical disintegration to obtain the nanofibrillar cellulose; and optionally sterilizing said nanofibrillar cellulose; and / or optionally forming a nanofibrillar cellulose membrane. [0011] The present invention also relates to a nanofibrillar cellulose obtainable through said method. [0012] The present invention also relates to a membrane comprising the nanofibrillary cellulose as defined in the present invention or as obtained by the method of the present invention. [0013] The present invention also relates to nanofibrillar cellulose for use as a pharmaceutical product. [0014] The present invention also relates to nanofibrillar cellulose for use in or as a matrix for drug release, cell release, tissue engineering, wound care, or implants, or as a wound healing agent, a anti-inflammatory agent, or a hemostatic agent. [0015] The present invention also concerns the use of nanofibrillar cellulose in or as a cosmetic, a composition for personal care, a flocculant system or for water treatment, a composite, a bulking agent, a thickener, a modifier of rheology, a food additive, an ink additive, a paper, cardboard or pulp additive, or in or as a matrix for cell or tissue culture. [0016] The invention also relates to a pharmaceutical, cosmetic, food, agrochemical, paint, coating, paper, cardboard, pulp, filter, adhesive, canvas, personal care composition, toothpaste, or culture cell or tissue matrix, or cell or tissue release matrix comprising the nanofibrillary cellulose of the present invention or as obtained by the method of the present invention. BRIEF DESCRIPTION OF THE FIGURES [0017] Figure 1 shows an optical microscopy photo of the dispersion (0.8%). The width of the photo is 1200 μm. [0018] Figure 2 shows a FE-SEM image of the nanofibrillar cellulose hydrogel, 50,000 x magnification, 100 nm scale bar. [0019] Figure 3 shows the distribution of the width of the fibril measured with an automatic image analysis routine, based on the 5 FE-SEM images captured at 50,000 x magnification. [0020] Figure 4 shows the FE-SEM image of the nanofibrillar cellulose hydrogel, 5,000 x magnification, 1 μm scale bar. [0021] Figure 5 shows the FE-SEM image of the nanofibrillar cellulose hydrogel, 10,000 x magnification, 1 μm scale bar. [0022] Figure 6 shows the flow profiles of the NFC dispersions of Sample 1 and Sample 2 as a function of the applied shear stress. [0023] Figure 7 illustrates the viscoelastic properties of the 0.5% NFC dispersion of Sample 1 by measuring frequency sweeping (10% constant voltage). The voltage dependence of G '(storage module) and G ”(loss module) and a loss tangent are presented. [0024] Figure 8 illustrates the viscoelastic properties of the 0.5% NFC dispersion of Sample 1 by measuring frequency sweeping (10% constant voltage). The stress dependency of G ’(the storage module) and G” (the loss module) and a loss tangent are presented. [0025] Figure 9 illustrates the viscoelastic properties of the 0.5% NFC dispersions of Sample 1 and Sample 2 by measuring the voltage sweep. The stress dependency of G ’(the storage module) and G” (the loss module) and a loss tangent are presented. DEFINITIONS [0026] Unless otherwise specified, the terms, which are used in the specification and claims, have the meanings commonly used in the field of the pulp and paper industry, as well as in the field of cell culture. Specifically, the following terms have the following meanings indicated below. [0027] As used herein, the term "nanofibrillary cellulose" or nanofibrillated cellulose or NFC is understood to encompass the nanofibrillary structures released from the cellulose pulp. The nomenclature related to nanofibrillar celluloses is not uniform and there is an inconsistent use of terms in the literature. For example, the following terms have been used interchangeably for nanofibrillary cellulose: cellulose nanofiber, nanofibril cellulose (CNF), nanofibrillated cellulose (NFC), nanoscale fibrillated cellulose, microfibrillary cellulose, cellulose microfibrils, microfibrillated cellulose (MFC) , and fibril cellulose. The smallest cellulosic entities of cellulose pulp of plant origin, such as wood, include cellulose molecules, elementary fibrils, and microfibrils. Microfibril units are elementary fibril bundles formed by physically conditioned coalescence as a mechanism for reducing the free energy of surfaces. Their diameters vary depending on the source. The term "nanofibrillary cellulose" or NFC refers to a collection of cellulose nanofibrils released from cellulose pulp, particularly from microfibril units. Nanofibrils typically have a high aspect ratio: the length exceeds one micrometer while the diameter is typically below 100 nm. The smaller nanofibrils are similar to the so-called elementary fibrils. The dimensions of the released nanofibrils or nanofibril bundles are dependent on the raw material, any pretreatment and disintegration method. The intact, non-fibrillated microfibril units may be present in the nanofibrillary cellulose, but only in insignificant amounts. [0028] The term “cellulose pulp” refers to cellulose fibers, which are isolated from any plant-based cellulose or lignocellulose raw material, using chemical, mechanical, thermo-mechanical, or chemothermo-mechanical pulp processing , for example, kraft pulp formation, sulfate pulp formation, soda pulp formation and organosolv pulp formation. The cellulose pulp can be bleached using conventional bleaching processes. [0029] The term "native cellulose pulp" or "native cellulose" here refers to any cellulose pulp, which has not been chemically modified after the pulping process and the optional bleaching process. [0030] The term "suspension" here refers to a heterogeneous fluid containing solid particles and also covers slurries and dispersions, typically in aqueous liquid. [0031] The term "ion exchange" here refers to the replacement of different cations present in the cellulose pulp with a desired cation, preferably with Na +. The cellulose carboxyl and hemicellulose groups, if present, are transformed into their protonated form by acidifying an aqueous suspension of the cellulose pulp, followed by the removal of water and washing to remove the original cations and excess acid. Then, a water-soluble salt of the desired cation is added and the pH is adjusted to a value above 7 to replace the protons with the desired cation, followed by the removal of water and washing. [0032] The term "pre-refining" here refers to a delamination treatment of cellulose pulp. In the present invention, the ion-exchanged cellulose pulp is pre-refined until a freedom of at least 60 ° SR (Schopper-Riegler) is obtained. The pre-refining step can comprise delamination using a PFI mill or refining equipment with fibrillation blades. “Pre-refining” is not intended to cover fiber cutting or fiber shortening treatments such as pre-crushing with conventional crushers, for example, with a Masuko crusher. Such fiber cutting treatments deteriorate the fibers in a way that results, in combination with the subsequent homogenization treatment in products having a low degree of polymerization and still similar with cellulosic alignments. [0033] The term "high pressure mechanical disintegration" here refers to the disintegration of the pre-refined cellulose pulp using high pressure, typically 20 MPa (200 bar) or more, such as 100 MPa (1000 bar) or more, resulting in the release of cellulose nanofibrils. A high pressure mechanical disintegration can be carried out, for example, using a pressure type homogenizer, preferably a high pressure homogenizer or high pressure fluidizer, such as a microfluidizer, macrofluidizer or fluidizer type homogenizer. [0034] The term "matrix" in connection with cells, tissues or drugs refers to a material comprising, consisting essentially of or consisting of nanofibrillar cellulose and the material of which is used to grow, maintain, transport or release the cells or tissues, or for tissue engineering, or for the release of drugs, medications or other active agents. The nanofibrillar cellulose can be in the form of a hydrogel or membrane. Said matrix can also contain various additives such as extra special cell matrix components, serum, growth factors, and proteins. [0035] The term "hydrogel" in connection with the nanofibrillar cellulose refers to a form where an aqueous dispersion of the nanofibrillar cellulose has a loss tangent of less than 1. The term "membrane" in connection with the nanofibrillar cellulose refers to to a slide-like assembly of the nanofibrillary cellulose obtained through at least partial liquid removal of a dispersion of the nanofibrillary cellulose. DETAILED DESCRIPTION OF THE INVENTION [0036] It has surprisingly been discovered that nanofibrillar cellulose with improved properties can be obtained through cellulose pulp of plant origin using a method comprising specific combination steps for ion exchange, pre-refining and high-pressure mechanical disintegration. The present inventors were able to obtain nanofibrillar cellulose having a high degree of polymerization. [0037] The degree of polymerization (DP) of cellulose is the number of glucose units that form a polymeric molecule. The DP of the cellulose nanofibrils correlates with the aspect ratio of the nanofibrils, and thus can be used to assess their length. The length of the nanofibrillar cellulose is related to the degree of polymerization (DP) of the cellulosic chains. This can be calculated from an average intrinsic viscosity value using the ISO 5351 method and the parameters based on the Mark-Houwink equation: [n] = KMa the parameters, a and K, are system dependent and in this case, the K values of 2.28 and a = 0.76 are used. [0038] A higher DP is desirable for nanofibrillar cellulose, because this increases the inherent tensile strength of the cellulose. The intensely hydrolyzed fibers, for example, due to enzymatic treatment or certain chemical treatments have a substantially reduced fiber length and DP, and such material is close to microcrystalline cellulose, and the resulting microfibrils are expected to have a low aspect ratio. The mechanical properties of materials based on or reinforced with nanofibrillar cellulose are dependent on the length of the fibril. For example, the nanofibrillar cellulose DP provides information about the mechanical properties of membranes prepared or reinforced using nanofibrillar cellulose. [0039] The nanofibrillar cellulose obtained is especially suitable for use as a matrix for cell or tissue culture, maintenance, release or transport. The nanofibrillar cellulose obtained is also useful in other applications involving direct contact with cells or tissues. [0040] The tissues are viscoelastic and are made of cells and extracellular matrices (ECM). The hardness or resistance of the matrix is one of many forces that act on cells and is appreciated as an important mediator of cellular behavior. It regulates cell signaling and has an effect, for example, on growth, survival, cell alignment and motility. Optimal hardness varies widely for different cell types. For example, different types of liver cells have been shown to respond in different ways to matrix hardness. It was also indicated that human pluripotent stem cells (hPSC) form spheroids in 0.5% by weight of nanofibrillar cellulose hydrogel, but said spheroid formation was prevented by 1% by weight. [0041] It has also been shown that the hardness of individual collagen fibrils can be reproductively varied and has a significant impact on the cell phenotype. [0042] In addition, cells are known to mechanosense over relatively short distances, approximately the width of an adjacent cell. Therefore, in a tissue, it is unlikely that a cell will feel mechanical forces beyond its immediate vicinity. In addition, the cells that form tissues are adherent, linked to some combination of their adjacent cells surrounding the ECM. Most cells require adhesion for survival. [0043] Nanofibrillar cellulose has been shown to work well as a cell culture matrix. It is believed that the network of cellulose nanofibrils mimics the extracellular matrix (ECM) that supports cell survival and proliferation. The hardness of nanofibrillary cellulose hydrogels can be easily adjusted by dilution. However, at the same time, the consistency of the nanofibrillary cellulose hydrogels used for cell culture may have become less than optimal. This is due to the previous manufacturing methods of nanofibrillar cellulose based mainly on high-pressure mechanical disintegration having provided a lot of heterogeneous material and the presence of fibril bundles between the individual nanofibrils provided relatively hard hydrogels even at low consistency. On the other hand, manufacturing methods based, for example, on enzymatic pretreatment or fiber refining pretreatment, provided nanofibrillar celluloses having a very low DP to achieve sufficient gel properties. [0044] The present nanofibrillar cellulose has properties that allow an optimal matrix for the culture of cells and tissues. [0045] There were difficulties in maintaining and growing cells in all thicknesses of hydrogels. In the present invention, maintenance and growth conditions, or cells, are improved. The present nanofibrillar cellulose and hydrogel of this provide an excellent hardness or resistance and an excellent thickness. [0046] In the present invention, the amount of nanofibrillar cellulose required may be less than previously to obtain the desired hardness. [0047] In addition, high DP is beneficial to the resistance properties of a membrane when the nanofibrillar cellulose is in the form of a membrane, or when a membrane comprises the nanofibrillar cellulose of the invention as a reinforcement. [0048] A nanofibrillar cellulose of the present invention is of vegetable origin, preferably of wood origin, more preferably of birch. Suitably, the nanofibrillar cellulose is native cellulose pulp. [0049] A nanofibrillary cellulose of the present invention has an average degree of polymerization greater than 1000. Preferably, the average degree of polymerization (DP) of nanofibrillary cellulose is greater than 1150 or 1200, preferably greater than 1300 or 1400, more preferably greater than 1500, 1600, 1700, or 1800. [0050] A nanofibrilated cellulose of the present invention has a turbidity of 200 NTU or less, preferably 150 NTU or less, more preferably 130 NTU or less. The turbidity can be between 200 and 50 NTU, more preferably between 150 and 80 NTU, such as 80, 90, 100, 110, 120, 130, 140 or 150, even more preferably between 130 and 100 NTU in water at a concentration of 0.1% by weight. [0051] Turbidity can be measured quantitatively using optical turbidity measurement instruments. There are several commercial turbidometers available to measure turbidity quantitatively. In the present case, the nephelometry-based method is used. The turbidity units of a calibrated nephelometer are called Nephelometric Turbidity Units (NTU). The measuring devices (turbidometer) are calibrated and controlled with standard calibration samples, followed by the measurement of the turbidity of the diluted NFC sample. [0052] The final product has excellent gelling and transparency properties, as well as a homogeneous structure. Transparency is due to the lack of fibril bundles, which results in a homogeneous structure. The transparency of the final nanofibrillar cellulose hydrogel allows optical detection of the cells with light microscopy due to the lower light diffraction (Fig. 1). In addition, no autofluorescence originates from nanofibrillar cellulose. Therefore, the nanofibrillary cellulose of the present invention has improved visualization properties. The use of the present nanofibrillar cellulose and hydrogel allows 3D visualization, which was not previously possible. In addition, fluorescent visualization is performed. [0053] The crystallinity of the present nanofibrillar cellulose can vary from 60% to 80%, preferably from 65 to 75%. Crystallinity can be, for example, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73% , 74%, 75%, 76%, 77%, 78%, 78%, 79%, or 80%. [0054] A nanofibrillar cellulose preferably has a slightly anionic surface charge of -1 to -5 mV. It is observed that the dispersion and dilution of the nanofibrillar cellulose is notably made easier if a cellulose having a slightly anionic surface is used. Such a surface charge is obtained when the hemicellulose content of the cellulose is relatively high. Therefore, a nanofibrillary cellulose of the present invention can have a hemicellulose content greater than 10% by weight, preferably greater than 18% by weight, more preferably greater than 20% by weight. The hemicellulose content can vary between 10 and 30% by weight, preferably between 18 and 28% by weight; more preferably between 20 and 26% by weight. The hemicellulose content can be, for example, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight , 18% by weight, 19% by weight, 20% by weight, 21% by weight, 22% by weight, 23% by weight, 24% by weight, 25% by weight, 26% by weight, 27% by weight , 28% by weight, 29% by weight, or 30% by weight. [0055] It is essential that the fiber length to aspect ratio is high enough to obtain a satisfactory hydrogel resistance. Typically, DP decreases during the manufacture of nanofibrillar cellulose. [0056] In order to obtain sufficient strength of the nanocellulose hydrogel, the average numerical length of the nanofibrils should be long enough, such as from 2 to 20 μm. Preferably, the average numerical length of the nanofibrils is between 4 and 15 μm, more preferably between 5 and 10 μm. The length of the nanofibrils can be, for example, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 13 μm, 14 μm, 15 μm, 16 μm, 17 μm, 18 μm, 19 μm, or 20 μm. The average numerical diameter is between 2 and 15 nm, preferably between 4 and 12 nm, more preferably between 6 and 10 nm. The average numerical diameter can be, for example, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, or 15 nm. A numerical aspect ratio is greater than 500, preferably greater than 700, more preferably greater than 900 (Figs. 4, 5 and 6). An average aspect ratio can be, for example, greater than 500, 600, 700, 800 or 900. [0057] When dispersed at a concentration of 0.5% in water, a zero shear viscosity of the present nanofibrillar cellulose can be in a range of 100 to 8,000 Pa * s, such as 200, 300, 400, 500, 600, 700, 800 or 900. Preferably, the zero shear viscosity of the present nanofibrillar cellulose is in the range of 200 to 2,000 Pa ^ s, more preferably 300 to 1,000 Pa ^ s. A yield stress of the present nanofibrillar cellulose can be in the range of 0.5 to 8 Pa, preferably 1 to 4 Pa, when dispersed at a concentration of 0.5% by weight in water. A yield stress can, for example, be 0.5 Pa, 1 Pa, 2 Pa, 3 Pa, 4 Pa, 5 Pa, 6 Pa, 7 Pa, or 8 Pa, when dispersed at a concentration of 0.5 % by weight in water. [0058] The nanofibrillary cellulose can have a storage module between 0.3 and 20 Pa, preferably between 1 and 10, more preferably between 1 and 5, when dispersed at a concentration of 0.5% by weight in water. The storage module can be, for example, 0.3 Pa, 0.4 Pa, 0.5 Pa, 0.6 Pa, 0.7 Pa, 0.8 Pa, 0.9 Pa, 1 Pa, 2 Pa, 3 Pa, 4 Pa, 5 Pa, 6 Pa, 7 Pa, 8 Pa, 9 Pa, 10 Pa, 11 Pa, 12 Pa, 13 Pa, 14 Pa, 15 Pa, 16 Pa, 17 Pa, 18 Pa, 19 Pa, or 20 Pa. [0059] A loss tangent of the present nanofibrillar cellulose is less than 0.3, preferably less than 0.2, when dispersed at a concentration of 0.5% by weight in water. [0060] More than 90% by weight of the fibrils of the nanofibrillar cellulose, preferably more than 95% by weight, are in the fiber fraction from 0 to 0.2 mm. [0061] A nanofibrillary cellulose of the present invention can be in the form of a hydrogel or a membrane. [0062] Any cellulose pulp of any plant origin, obtained from any plant-based cellulose raw material can be used as a starting material. Preferably, the cellulose pulp comprises secondary cell wall cellulose. Preferably, the plant material is of wood origin. Said wood can be selected from softwood trees (SW), such as spruce, pine, spruce, larch, douglasia and hemlock, from hardwood trees (HW), such as birch, aspen, poplar, alder, eucalyptus and acacia, and mixtures of soft and hard woods. The wood can be any hardwood that belongs to the BETULACEAE family. Most preferably, the wood is birch. [0063] The term “cellulose pulp” refers to cellulose fibers, which are isolated from any plant-based cellulose raw material, using chemical, mechanical, thermo-mechanical, or chemo-thermo-mechanical pulping processes , for example, kraft pulping, sulphate pulping, soda pulping, organosolv pulping. The cellulose pulp can be bleached. In particular, cellulose pulp is of wood origin. Suitably, the cellulose pulp comprises holocellulose, namely, cellulose and hemicellulose. Preferably, the cellulose pulp does not contain substantial amounts of lignin, or contains only traces of lignin or undetectable amounts of lignin. Particularly preferred, the cellulose pulp is a bleached birch pulp. [0064] The cellulose pulp can be native cellulose pulp. In addition, cellulose pulp that has been chemically modified is not intended to facilitate pre-refining or mechanical disintegration, but to facilitate the end use of nanofibrillar cellulose can be used. Such modification can be, for example, hydrophobization or labeling, or incorporation of functional side groups suitable, for example, for cell culture or tissue or diagnostic applications. The desired chemistry for end use can also be added to the cellulose pulp without reacting, for example, through mixing. Preferably, the nanofibrillar cellulose is native cellulose pulp. [0065] The cellulose pulp comprises crystalline and amorphous regions. The crystallinity of the cellulose pulp used as a starting material can be at least 50%. Suitably, the crystallinity of the cellulose pulp is at least 55%. Preferably, the crystallinity of the cellulose pulp is at least 60%, more preferably at least 65%, even more preferably at least 70%. [0066] The enzymatic pretreatments decrease the DP because the enzymes break the structure of the cellulose fibers and especially the amorphous regions. Chemical modifications decrease DP depending on the chemicals used, and the severity of treatment conditions. The DP of the cellulose pulp used as a starting material in the present method for the manufacture of nanofibrillar cellulose does not decrease during the ion exchange pretreatment. [0067] The DP decreases during mechanical refining, especially when a type of fiber shredder or shortening is used. Here, a type of pre-refining delamination is used to prevent excessive PD from decreasing. DP decreases mainly when the ion exchange and the pre-refined cellulose pulp are subjected to a high-pressure mechanical disintegration. However, the overall decrease in PD remains modest. [0068] The cellulose pulp used as the starting material must be selected so that the predicted decrease in the DP is taken into account. Suitably, the cellulose pulp has a DP greater than 2000, or greater than 2200, or greater than 2500. [0069] The cellulose pulp of vegetable origin, particularly of wood origin, and where the cellulose pulp is obtained in one of the methods described above, can be disintegrated to obtain the nanofibrillar cellulose of the present invention using the procedure described below . [0070] The method for manufacturing the nanofibrillar cellulose of the present inventions comprises the following steps: 1. providing an aqueous suspension of the cellulose pulp of plant origin, and exchanging in ions at least part of the carboxyl groups present in the cellulose pulp, preferably with Na +; 2. pre-refine said ion exchange cellulose pulp; 3. subject the pre-refined cellulose pulp to a high-pressure mechanical disintegration to obtain the nanofibrillar cellulose; and optionally sterilizing said nanofibrillar cellulose; and / or optionally forming a nanofibrillar cellulose membrane. 1. Ion exchange [0071] The aqueous solution and cellulose pulp of vegetable origin are combined to obtain an aqueous suspension for the subsequent ion exchange step. The solid matter content of the cellulose pulp aqueous suspension can vary from 0.1 to 20% by weight, suitably from 0.5 to 3% by weight. [0072] The cellulose pulp of vegetable origin is pre-treated with an ion exchange with acid and base before pre-refining and high-pressure mechanical disintegration. The ion exchange is carried out by submitting the aqueous suspension of the cellulose pulp to mild acid treatment to positively remove the charged ions, followed by treatment with a base containing defined positively charged ions, to replace the previous ions. The pre-treated cellulose pulp is subsequently pre-refined and mechanically disintegrated using high pressure. [0073] The ion exchange of at least part of the carboxyl groups present in the cellulose pulp, preferably with Na +, comprises adjusting the pH of the aqueous suspension of the cellulose pulp to a value below 5.0, suitably below 4.0 , using an organic or inorganic acid; removing water to produce a solid matter, washing the solid matter with water, and forming an aqueous suspension of the solid matter; adding at least one water-soluble salt of NH4 +, alkali metal or alkaline earth metal or metal to the formed suspension; adjusting the pH of the suspension to a value above 7.0 using an inorganic base; removing water to produce solid matter, washing the solid matter with water, preferably distilled water or deionized water, to produce the cellulose pulp exchanged in ions; and forming an aqueous suspension of ion-exchanged cellulose pulp. [0074] In said ion exchange stage, the water-soluble salt of NH4 +, alkali metal, alkaline earth metal or metal is suitably used in an amount to obtain a concentration of 0.001 to 0.01 M (0.1 to 1 mol / kg of fiber or solid material), particularly from 0.002 to 0.008 M. In ion exchange, the content of solid matter in the suspension can vary from 0.1 to 20% by weight, suitably from 0.5 to 3% in weight. [0075] Organic or inorganic acid is suitably an acid that can be easily washed, does not leave unwanted residues in the product and has a pKa value between -7 and 7. Organic acid can be selected from short-chain carboxylic acids, such as such as acetic acid, formic acid, butyric acid, propionic acid, oxalic acid and lactic acid. The short chain carboxylic acid here refers to C1-C8 acids. Inorganic acid can be suitably selected from hydrochloric acid, nitric acid, hydrobromic acid and sulfuric acid. [0076] Suitably, the acid is used as a diluted aqueous solution of 0.001 to 5 M, which can be conveniently added to the suspension. Suitably, the acid addition time is between 0.2 to 24 hours. The pH is adjusted using the acid below 5.0, suitably below 4.0, even more appropriately below 3.0. [0077] The water used in the method can be tap water, distilled water, deionized water, purified water or sterile water. Suitably, distilled water or deionized water is used, particularly in the washing step after adjusting the pH to more than 7. [0078] The removal of water from the suspension or slurry can be carried out by any suitable means, for example, with web press, pressure filtration, suction filtration, centrifugation and spindle press. [0079] The solid matter can be washed 1 to 5 times, suitably 2 to 3 times with water after acid treatment to remove excess acid. The washing of the solid matter with water can be adequately carried out after the water removal steps using the same equipment. [0080] NH4 + water-soluble salt, alkali metal, alkaline earth metal or metal, can be selected from inorganic salts, complexes and salts formed with organic acid, NH4 +, alkali metal, alkaline earth metal or metals, suitably NH4 + , Na, K, Li, Ag and Cu. The inorganic salt is suitably a sulfate, nitrate, carbonate or bicarbonate salt, such as NaHCO3, KNO3 or AgNO3. M refers to alkali metal, alkaline earth metal or metal. According to a suitable embodiment, the water-soluble salt is the sodium salt. The inorganic base is selected from NaOH, KOH, LiOH and NH3. [0081] The pH of the suspension is adjusted with the inorganic base to more than 7, suitably from 7.5 to 12, particularly suitable from 8 to 9. After adjusting the pH with the inorganic base, the removal of water it is carried out and the solid matter is washed with distilled or deionized water. Suitably, the washing is repeated or carried out until the conductivity of the used washing liquid, such as the filtrate, is less than 200 μS / cm, suitably less than 100 μS / cm, particularly suitably less than 20 μS / cm. [0082] After adding the components (acid, salt, base) to the suspensions the mixtures formed can be stirred and left to stand before continuing the method. 2. Pre-refining [0083] A pre-refining step is necessary to prevent the deposit of dirt in the subsequent mechanical disintegration step, a high pressure homogenization. It is possible to fibrillate the cellulose pulp without the pre-refining step, but in this case, the disintegration is laborious and industrially not scalable. In addition, mechanical disintegration without pre-refining causes unnecessary shortening of the fibers. Adequate pre-refining is a prerequisite for obtaining the hydrogel having the desired characteristics. Pre-refining is directed to the fiber surface. The purpose of pre-refining is to fibrillate the fibers externally or internally, as opposed to shortening the fibers. If the cut type treatment is used, the final degree of polymerization (DP) of the nanofibrils decreases, which is unacceptable for the targeted end use. The type of shredding treatment (eg Masuko shredding) and the disc and conical refiners used in pulp refining are known to shorten the fibers. It is also known that the crushing causes greater damage globally to the crystalline structure of the cellulose, decreasing the crystallinity. Compared to such equipment, the PFI mill is a refining device of very low intensity and high energy. PFI produces a differentiated refining effect. The PFI mill mainly causes internal fibrillation which is a result of preferred pre-refining. In addition, refiners (eg Voith refiner) using fibrillation blades can be used to obtain an appropriate pre-refining result. During pre-refining, Schopper-Riegler (SR) freedom is followed by pre-refined samples. SR is widely used to track changes in the drainage rate of various chemical slurries during mixing and refining. The SR value must be greater than 60 SR, such as at least 75, preferably the SR is 80 to 85. The SR measurement is made according to the ISO 5267-1 standard. [0084] It is believed that by exchanging ions at least part of the carboxyl groups that are present in the cellulose part and in the hemicellulose part of the cellulose pulp, the interfibrillary repulsive forces are provided between the nanofibrils in the cellulose fibers swelling the structure of fiber, and facilitating the pre-refining of the type of delamination instead of the type of fiber cut of the cellulose pulp exchanged in ions. Through this combination of pretreatments, the degree of polymerization of the fibrils is not reduced as much as if high mechanical pressure disintegration is preceded by simple mechanical refining, combination of enzymatic treatment and mechanical refinement or chemical pretreatment using various chemical compounds and treatment conditions. 3. Mechanical disintegration [0085] The pre-refined cellulose pulp obtained is subjected to a high-pressure mechanical disintegration to obtain the nanofibrillar cellulose. The pre-refined cellulose is subjected to high-pressure mechanical disintegration until an NTU of 200 or less, preferably 150 or less, more preferably 130 NTU or less, is obtained. The turbidity can be between 200 and 50 NTU, more preferably between 150 and 80 NTU, such as 80, 90, 100, 110, 120, 130, 140 or 150, more preferably between 130 and 100 NTU in water at a concentration of 0 , 1% by weight. In this way, it can be guaranteed that the fibril bundles are substantially disintegrated and a uniform nanofibrillar cellulose is obtained. [0086] The mechanical disintegration of high pressure is adequately performed from 1 to 10 passages, in a particularly adequate way from 1 to 5 passages. High mechanical disintegration is performed, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 passes. The pressure can vary between 30 to 200 MPa (300 to 2000 bar), suitably, the pressure is at least 60 MPa (600 bar), particularly suitable for 150 MPa (1500 bar). The pressure can be, for example, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 MPa (300, 400 , 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, or 2000 bar). [0087] High pressure mechanical disintegration can be conducted using a pressure type homogenizer, preferably high pressure homogenizer or high pressure fluidizer. [0088] Optionally, the nanofibrillar cellulose obtained is sterilized by autoclaving or irradiation, for example, using UV irradiation. [0089] Optionally, the obtained nanofibrillar cellulose, sterilized or not, is formed on a membrane. The membrane can be formed through filtration, vacuum filtration, pressure filtration, casting, film coating, pan coating, electro-extrusion, wet spinning, dry spinning, wet jet spinning, melt spinning, gel spinning, electrospray, spray, spray drying, molding, pressing or extruding, or other suitable methods, optionally followed by drying. Preferably, the membrane is formed from nanofibrillar cellulose with a method comprising providing the fibril cellulose dispersion in a filter layer, draining the liquid from a fibril cellulose dispersion by the effect of reduced pressure through the filter layer which is impervious to fibrils of fibril cellulose, but permeable to the liquid to form a membrane sheet on the filter tissue, applying heat on the opposite side of the membrane sheet to the membrane sheet while continuing to drain the liquid through the filter layer through the difference in pressure on the filter layer, and removing the membrane sheet from the filter layer as a free fibril cellulose membrane, or alternatively maintaining the filter layer on the membrane as a constituent layer of a membrane product comprising the filter layer and a fibril cellulose membrane. [0090] The membrane can be formed into a standardized membrane comprising cavities and / or protuberances. [0091] It is possible to modify the cellulose pulp, cellulose pulp exchanged in ions, or pre-refined cellulose pulp through the physical or chemical incorporation of a desired chemical, excluding chemical modifications aimed at increasing disintegration. Examples of a chemistry that is desired for end use include the incorporation of functional side groups, hydrophobization, amination, labeling, addition of nutrients, etc. Examples of chemical modifications aimed at increasing disintegration include, for example, TEMPO-mediated oxidation, carboxymethylation, or cationization. [0092] It is possible to modify the nanofibrillar cellulose obtained through the incorporation of a desired chemical, preferably through the incorporation of functional side groups, hydrophobization, amination, and / or labeling. The secondary functional group can be, for example, an azide, or an amine. [0093] Nanofibrillar cellulose is characterized by very high water retention values, a high degree of chemical accessibility and the ability to form gels that are stable in water or other polar solvents. The nanofibrillary cellulose product is typically a dense network of highly fibrillated celluloses. NFC can also contain some hemicelluloses; the amount is dependent on the plant source and pulping conditions. [0094] Several different degrees of NFC have been developed using various production techniques. The grades have different properties depending on the method of manufacture, degree of fibrillation and chemical composition. The chemical compositions of the grades also vary. Depending on the source of raw material, for example HW VS. SW pulp, a different polysaccharide composition exists in the final NFC product. [0095] The NFC can be sterilized before use, properly in a gel form. In addition, if desired, prior to disintegration, the cellulose pulp can be aseptically collected from the pulp mill immediately after the bleaching stage when the pulp is still sterile. [0096] The obtained NFC has excellent gelation capacity, which means that it forms a hydrogel already in a low consistency in an aqueous medium. [0097] The nanofibrillary cellulose of the present invention is useful in cell culture applications, such as in the cell culture matrix or drug release composition. The plant-derived nanofibrillar cellulose of the present invention can be used without any modifications as a human biomimetic ECM for 3D cell culture. The nanofibrillar cellulose hydrogel is an excellent biomaterial for 3D cell frames for high-throughput screening tests based on advanced functional cell in drug development, drug toxicity testing and regenerative medicine and also for drug release and IN VIVO cell. Due to its properties of imitating ECM and non-toxicity, nanofibrillar cellulose can be used in any type of applications involving cell or tissue contact, such as drug release, cell release, tissue engineering, wound treatment, or implants, or as an agent for wound healing, an anti-inflammatory agent, or a hemostatic agent. The matrix for the cell culture or drug release composition of the present invention can also comprise suitable additives selected from the group consisting of extra special cell matrix components, serum, growth factors, and proteins. [0099] The present invention also relates to a cell culture or drug release matrix, in which the matrix comprises living cells and the cell culture or drug release composition forms a hydrogel and in which the cells are present in the matrix in a three-dimensional or two-dimensional arrangement. [00100] The cells can be any cells. Any eukaryotic cell, such as animal cells, plant cells and fungal cells, is within the scope of the present invention as well as prokaryotic cells. Prokaryotic cells comprise microorganisms such as aerobic or anaerobic bacteria, viruses, or fungi, such as yeast and molds. Even stem cells, such as non-human stem cells, can be developed using the matrix comprising nanofibrillar cellulose. Depending on the cell line, the experiments are carried out in 2D or 3D, that is, the cells are grown on CNF membranes or gels or the cells are homogeneously dispersed in CNF hydrogels or CNF membranes. The cells are grown in the matrix or on the 3D matrix. The matrix can be injectable hydrogel or sheet-like membrane optionally with an appropriate surface topology. The composition comprising the cellulose nanofibers or derivatives thereof can be used to immobilize the cells or enzymes. [00101] The properties of CNF are close to optimum for the maintenance of culture, transport and cell and tissue release: transparent, non-toxic, highly viscous, high suspending power, high water retention, good mechanical adhesion, not based on animals, dimensions similar to ECM, insensitive to salts, temperature or pH, non-degradable, without auto-fluorescence. CNF has a negligible fluorescence background due to the chemical structure of the material. In addition, the CNF gel is non-toxic to cells. It is known that strong interactions are formed between adjacent nanofibrils due to surface hydroxyl groups, and this in combination with high hardness results in a rigid network that also improves the hardness and strength of polymer-based nanocomposites. In addition to the improved mechanical properties, the advantages of nanofibrillar cellulose as reinforcement in composites are increased thermal stability, decreased thermal expansion, and increased thermal conductivity. If a transparent composite matrix is used, it is possible to maintain most of the transparency due to the thin size ratio of the nanofibrils. In addition, the high degree of crystallinity and DP are physical properties that are useful for the preparation of strong nanofibrillar cellulose composites. [00102] In addition, the rheological properties, transparency, absence of toxicity, and insensitivity to salts, temperature or pH make the nanofibrillar cellulose desired in cosmetics, compositions for personal care, flocculating systems or for water treatment, composites, as a bulking agent, a thickener, a rheology modifier, a food additive, an ink additive, a paper, cardboard or pulp additive. Compared to chemically modified grades, such as oxidized TEMPO grade, the native cellulose nanofibrillar cellulose is insensitive to salts, temperature or pH, which can be beneficial in many end uses. [00103] In this way, pharmaceuticals, cosmetics, food, agrochemicals, paint, coatings, paper, cardboard, pulp, filters, composite products, adhesives, canvas, compositions for personal care, toothpaste, or cell culture matrices or tissue, or improved cell or tissue release matrices can be obtained. [00104] In aspect 1, the invention provides a nanofibrillar cellulose, in which said nanofibrillar cellulose has an average degree of polymerization greater than 1000, and in which said nanofibrillar cellulose is of plant origin. [00105] Aspect 2 provides nanofibrillar cellulose according to aspect 1, wherein said nanofibrillar cellulose has an average degree of polymerization greater than 1150, preferably greater than 1300, more preferably greater than 1500. [00106] Aspect 3 provides the nanofibrillar cellulose according to any one of aspects 1 or 2, wherein said nanofibrillar cellulose is of wood origin, preferably birch. [00107] Aspect 4 provides nanofibrillar cellulose according to any of aspects 1 to 3, wherein said nanofibrillar cellulose is native cellulose. [00108] Aspect 5 provides the nanofibrillar cellulose according to any one of aspects 1 to 4, wherein said nanofibrillar cellulose has a turbidity of 200 NTU or less, preferably 150 NTU or less, more preferably 130 NTU or less, preferably, the turbidity is between 200 and 50 NTU, more preferably between 150 and 80 NTU, in water at a concentration of 0.1% by weight. [00109] Aspect 6 provides the nanofibrillar cellulose according to any one of aspects 1 to 5, wherein the crystallinity of the nanofibrillar cellulose is 60% to 80%, preferably 65% to 75%. [00110] Aspect 7 provides nanofibrillar cellulose according to any of aspects 1 to 6, wherein the nanofibrillar cellulose has a hemicellulose content greater than 10% by weight, preferably greater than 18% by weight, more preferably greater than 20% by weight. [00111] Aspect 8 provides the nanofibrillar cellulose according to any one of aspects 1 to 7, wherein the nanofibrillar cellulose has an average numerical diameter between 2 and 15 nm, preferably between 4 and 12 nm, more preferably between 6 and 10 nm. [00112] Aspect 9 provides the nanofibrillar cellulose according to any one of aspects 1 to 8, wherein the nanofibrillar cellulose has an average numerical length between 2 and 20 μm, preferably between 4 and 15 μm, more preferably between 5 and 10μm. [00113] Aspect 10 provides the nanofibrillar cellulose according to any one of aspects 1 to 9, wherein the nanofibrillar cellulose has an average aspect ratio greater than 500, preferably greater than 700, more preferably greater than 900 . [00114] Aspect 11 provides the nanofibrillar cellulose according to any of aspects 1 to 10, wherein the nanofibrillar cellulose has a zero shear viscosity in the range of 100 to 8 000 Pa ^ s, preferably from 200 to 2 000 Pa ^ s, more preferably from 300 to 1000 Pa ^ s, and a yield stress in the range of 0.5 to 8 Pa, preferably from 1 to 4 Pa, when dispersed in a concentration of 0.5% by weight in Water. [00115] Aspect 12 provides nanofibrillar cellulose according to any of aspects 1 to 11, wherein the nanofibrillar cellulose has a storage module between 0.3 and 20 Pa, preferably between 1 and 10, more preferably between 1 and 5, when dispersed at a concentration of 0.5% by weight in water. [00116] Aspect 13 provides nanofibrillar cellulose according to any of aspects 1 to 12, wherein the nanofibrillar cellulose has a loss tangent less than 0.3, preferably less than 0.2, when dispersed in water in a concentration of 0.5% by weight. [00117] Aspect 14 provides nanofibrillar cellulose according to any of aspects 1 to 13, in which more than 90%, preferably more than 95% by weight of the nanofibrillar cellulose is in the fiber fraction from 0 to 0 , 2 mm. [00118] Aspect 15 provides the nanofibrillar cellulose according to any of aspects 1 to 14, wherein the nanofibrillar cellulose is in the form of a hydrogel or a membrane. [00119] Aspect 16 provides a method for the manufacture of nanofibrillar cellulose, wherein the method comprises the steps of providing an aqueous suspension of cellulose pulp of vegetable origin, preferably of wood origin, more preferably of birch; ion exchange of at least part of the carboxyl groups present in the cellulose pulp, preferably with Na +; pre-refining said cellulose pulp exchanged in ions; subjecting said pre-refined cellulose pulp to a high-pressure mechanical disintegration to obtain the nanofibrillar cellulose; and optionally sterilizing said nanofibrillar cellulose, preferably by autoclaving or irradiation; and / or optionally forming a nanofibrillar cellulose membrane. [00120] Aspect 17 provides the method according to aspect 16, wherein the method also comprises modifying said cellulose pulp, said ion-exchanged cellulose pulp, or said pre-refined cellulose pulp through incorporation physical or chemical of a desired chemistry, excluding chemical modifications aiming at improved disintegration, and / or in which the method comprises modifying said nanofibrillar cellulose by incorporating a desired chemical, preferably functional side groups, hydrophobization, amination, and / or lettering. [00121] Aspect 18 provides the method according to either aspect 16 or 17, wherein the ion exchange comprises adjusting the pH of the aqueous suspension of the cellulose pulp to below 5.0 using an organic acid or inorganic; removing water to produce a solid matter, washing the solid matter with water, and forming an aqueous suspension of the solid matter; adding at least one water-soluble salt of NH4 +, alkali metal or alkaline earth metal or metal to the formed suspension; adjust the pH of the suspension to a value above 7.0 using an inorganic base; removing the water to produce the solid matter, washing the solid matter with water, preferably distilled or deionized water, to produce the ion-exchanged cellulose pulp; and forming an aqueous suspension of the ion-exchanged cellulose pulp. [00122] Aspect 19 provides the method according to any aspect 16 to 18, in which the cellulose pulp exchanged in ions is pre-refined until a freedom of at least 75 ° SR (Schopper-Riegler), preferably at least 80 ° SR, is obtained. [00123] Aspect 20 provides the method according to any of aspects 16 to 19, wherein the pre-refining comprises subjecting the ion-exchanged cellulose pulp to delamination using a PFI mill or refining equipment equipped with fibrillation slides. [00124] Aspect 21 provides the method according to any of aspects 16 to 20, in which the pre-refined cellulose is subjected to high-pressure mechanical disintegration until the NTU of 200 or less, preferably 150 or less, is obtained. [00125] Aspect 22 provides the method according to either aspect 16 or 21, wherein the high pressure mechanical disintegration is conducted using the pressure type homogenizer, preferably high pressure homogenizer or high pressure fluidizer. [00126] Aspect 23 provides the method according to any of aspects 16 to 22, in which the membrane is formed by filtration, vacuum filtration, pressure filtration, casting, film coating, covers, electrospinning, wet spinning, dry spinning, wet spinning with spinning, melt spinning, gel spinning, electrospray, spraying, spray drying, molding, pressing or extrusion, or other suitable methods, optionally followed by drying. [00127] Aspect 24 provides a nanofibrillar cellulose obtainable through the method of any of aspects 16 to 23. [00128] Aspect 25 provides a membrane comprising nanofibrillar cellulose as defined in any of aspects 1 to 15 or 24 or as obtained using the method of any of aspects 16 to 23. [00129] Aspect 26 provides nanofibrillar cellulose according to any one of aspects 1 to 15 or 24 or as obtained using the method of any one of aspects 16 to 23 for use as a pharmaceutical product. [00130] Aspect 27 provides nanofibrillar cellulose according to any of aspects 1 to 15 or 24, or as obtained using the method of any of aspects 16 to 23 for use in or as a matrix for release of drug, cell release, tissue engineering, wound care, or implants, or as a wound healing agent, an anti-inflammatory agent, or a hemostatic agent. [00131] Aspect 28 provides the use of nanofibrillar cellulose according to any of aspects 1 to 15 or 24 or as obtained using the method of any of aspects 16 to 23 in a cosmetic, a composition for personal care , a flocculating or water treatment system, a composite, a bulking agent, a thickener, a rheology modifier, a food additive, an ink additive, a paper, cardboard or pulp additive, or in or as a matrix for cell or tissue culture. [00132] Aspect 29 provides a pharmaceutical, cosmetic, food, agrochemical, paint, coating, paper, cardboard, pulp, filter, composite product, adhesive, canvas, personal care composition, toothpaste, or matrix cell or tissue culture, or cell or tissue release matrix comprising nanofibrillar cellulose as defined in any of aspects 1 to 15 or 24 or as obtained using the method of any of aspects 16 to 23. The following examples are illustrative embodiments of the present invention as described above, and are not intended to limit the invention in any way. EXAMPLES Materials [00134] Birch kraft pulp, which was used as a starting cellulose substance, has the following cellulose contents: α- cellulose 78%, β-cellulose 9%, Y — cellulose 11% (method : Alpha, beta, and gamma-cellulose in the pulp, reaffirmation of Tappi 203 cm-99). Methods [00135] The measurements mentioned in the examples were performed as follows. [00136] The Schopper-Riegler (SR) measurement was performed according to the ISO 5267-1 standard. Turbidity [00137] A nanofibrillar cellulose sample was diluted in water to a concentration below the gel point of said nanofibrillar cellulose, and the turbidity of the diluted sample was measured. The turbidity of the nanofibrillar cellulose samples was measured at a concentration of 0.1%. The HACH P2100 turbidometer with a 50 ml measuring vessel was used for turbidity measurements. The dry matter of the nanofibrillar cellulose sample was determined and 0.5 g of the sample, calculated as dry matter, was loaded into the measuring vessel, which was filled with tap water up to 500 g and vigorously mixed by stirring for about 30 seconds. . Without delay, the aqueous mixture was divided into 5 measuring vessels, which were inserted into the turbidometer. Three measurements in each container were performed. The mean value and standard deviation were calculated from the results obtained, and the final result was given as units of NTU. The new nanofibrillar cellulose product had a typical turbidity below 200, preferably below 150 NTU under the measurement conditions mentioned above. Degree of polymerization (DP) [00138] The length of the nanofibrillar cellulose is related to the degree of polymerization (DP) of the cellulosic chains. The cellulose samples were dissolved in a solution of cupriethylenediamine (CED). From the solutions (starting material and the final product) a viscosity was measured and the number of limit viscosity was calculated. The DP was calculated from the average intrinsic viscosity value using the method of ISO 5351 and the parameters based on the Mark-Houwink equation: [n] = KMa The parameters, a and K, are system dependent and, in this case, the values of K = 2.28 and a = 0.76 were used. Fiber size distribution [00139] The fiber size distribution of the gels was determined using a Metso FS5 fiber analyzer. 1 g of fibrillated cellulose was diluted in two steps to obtain a test sample: 1.60 mg of fibers in 50 ml of water. The sample was fed to the fiber analyzer. The fiber size of the sample is clearly decreased by the treatment. Crystallinity [00140] The analysis by X-ray diffraction (XRD) was performed to define the crystallinity index of the samples. The samples were pressed into tablets before analysis. The diffractograms were recorded with a Philips X'Pert MPD X-ray diffractometer in the powder method in a range of 5 to 40 ° 2θ. Cu Kα radiation monochromatized with graphite (X = 0.1541 nm). The working conditions were 40 kV and 50 mA of tube power. Crystallinity indices were calculated using the Segal method. Field emission scanning electron microscopy [00141] Photographs of the field emission scanning electron microscopy (FE-SEM, Sigma VP, Zeiss GmbH) were taken from the dispersion at a concentration of 0.1% by weight. On the lens, an SE detector was used when viewing in secondary electronic mode. Low acceleration voltages between 1.5 to 2.5 keV were used. The width and length of the nanofibrillar cellulose fibrils were measured from the photographs. Rheological measurements [00142] To verify the success of fibrillation, the rheological measurements of the samples in the form of nanofibrillary cellulose hydrogels were performed with a rotational tension-controlled rheometer (ARG2, TA instruments, UK) equipped with a four-blade propeller geometry. The samples were diluted with deionized water (200 g) to a concentration of 0.5% by weight and mixed with a Waring Blender (LB20E *, 0.5 l) 3 x 10 seconds (20,000 rpm) with a short interval between mixing . The rheometric measurement was performed for the sample. The diameters of the cylindrical sample cup and the helix were 30 mm and 28 mm, respectively, and the length was 42 mm. The steady-state viscosity of the hydrogels was measured using a gradually increasing shear stress from 0.001 to 1000 Pa. After loading the samples into the rheometer, they were left to stand for 5 minutes before the measurement was started, at room temperature. The steady-state viscosity was measured with a gradually increasing shear stress (proportional to the applied torque) and the shear rate (proportional to the angular velocity) was measured. The indicated viscosity (= shear stress / shear rate) at a given shear stress was recorded after reaching a constant shear rate or after a maximum time of 2 minutes. The measurement was interrupted when a shear rate of 1000 s-1 was exceeded. The method was used to determine the zero-shear viscosity. The viscosity properties of the hydrogels were also determined with the frequency sweep in the dynamic oscillation mode of the rheometer (effort of 1% and 10%, frequency of 0.1 to 100, temperature of 25 ° C). The stress sweep was measured in a shear stress range of 0.001 to 100 Pa at the frequency of 0.1 Hz, at 25 ° C. Example 1 Pretreatment of cellulose pulp followed by fibrillation - Sample 1 [00143] 2000 g of wet native cellulose pulp obtained from bleached birch pulp were filtered and the solid mass was diluted with 0.01 M aqueous HCl and to obtain the suspension having a dry matter content of approximately 1% by weight. The suspension was allowed to rest for approximately 15 minutes with occasional stirring. The suspension was then filtered, washed twice with deionized water and filtered. Then, the solid mass was suspended in a 0.005 M aqueous solution of NaHCO3 to obtain the suspension having a dry matter content of approximately 1% by weight, the pH of the obtained suspension was adjusted between 8 and 9 with an aqueous solution 1 M NaOH and the suspension obtained was allowed to rest for 15 minutes with occasional stirring. The suspension was filtered and the solid mass was washed with deionized water until the conductivity of the filtrate was less than 20μS / cm. The final conductivity was 8 μS / cm and the pH 8.4. [00144] The washed pulp was pre-refined with a PFI mill. Standard refining was performed until the target SR value> 75 was reached. The SR value after pre-refining was 80.2. [00145] The sample was diluted to a consistency of 1.7% by weight and followed by fibrillation in a Microfluidics Fluidizer (M-7115-30), once through the APM + 200 μm chambers and through the APM + 100 μm chambers (150 MPa -1500 bar) until turbidity is below the target level of <200 NTU. The final turbidity for the product, Sample 1, was 136 NTU. [00146] The DP of the starting material was 2780 and the DP of the final product Sample 1 was 1580. Table 1 illustrates the fiber size measured by Metso F5. [00147] The crystallinity index of the starting material was 77 and the crystallinity index of the final product Sample 1 was 71. Example 2 Pretreatment of cellulose pulp followed by fibrillation - Sample 2 [00148] 2000 g of wet native cellulose pulp obtained from the bleached birch pulp were filtered and the solid mass was diluted with 0.01M aqueous HCl to obtain the suspension having a dry matter content of approximately 1% by weight. The suspension was allowed to rest for approximately 15 minutes with occasional stirring. The suspension was then filtered, washed twice with deionized water and filtered. Then, the solid mass was suspended in a 0.005 M aqueous solution of NaHCO3 to obtain the suspension having a dry matter content of approximately 1% by weight, the pH of the obtained suspension was adjusted between 8 and 9 with aqueous solution 1 M of NaOH and the suspension obtained was allowed to rest for 15 minutes with occasional stirring. The suspension was filtered and the solid mass was washed with deionized water until the conductivity of the filtrate was less than 20 μS / cm. [00149] The washed pulp was pre-refined with a PFI mill. Standard refining was performed until a target SR value> 75 was reached. The SR value after pre-refining was 86.0. [00150] The pre-refined sample was diluted to a consistency of 1.5% by weight and followed by fibrillation in a Microfluidics Fluidizer (M-110Y), once through APM chambers + 200 μm and through APM chambers +100 μm (150 KPa - 1500 bar) until turbidity is below the target level of <200 NTU. The final turbidity for the product, Sample 2, was 127 NTU. [00151] The DP of the starting material was 2833 and the DP of the final product Sample 2 was 1640. [00152] The crystallinity index of the starting material was 75 and the crystallinity index of the final product Sample 2 was 66. Example 3 Measurement of the FE-SEM size [00153] The width and length of the nanofibrillary cellulose fibrils in Sample 1 were measured from the FE-SEM photographs. The distribution of the width of the fibril was measured with an automatic image analysis routine of 5 images, magnification of 50,000 x. Figure 2 as an example. The analysis data are illustrated in Figure 3. The numerical mean diameter is between 2 and 15 nm. The length of the fibril is measured / estimated by following the fibrils with a microscope from frame to frame, 5,000 x magnification and 10,000 x magnification. The average numerical length is between 2 and 20 μm. Figures 4 and 5 are presented as examples. Based on the results, the average aspect ratio l / w was calculated. The average aspect ratio was greater than 500. Example 4 Properties of the gel by rheological measurements [00154] To check the preferred gel properties, the rheological measurements of the samples in the form of nanofibrillary cellulose hydrogels were performed with a controlled tension rotational rheometer. Figure 6 shows the flow profiles of the dispersions of Sample 1 and Sample 2 as a function of the applied shear stress. Both samples are measured as such and then diluted to 0.5% by weight of consistency. [00155] The frequency sweep measurement of Sample 1 was performed at 0.5% by weight to verify that the resistance of the gel is sufficient, that is, a loss tangent (tanδ) is less than 0.3. The frequency sweep is illustrated in Figure 7. The loss tangent (tanδ) was 0.20 and the storage module (G ') was 2 Pa at a frequency of 1 rad / s, 1% effort. The frequency sweep at 0.5% by weight using 10% constant voltage was also measured, Figure 8. [00156] Figure 9 shows the Stress Sweep of the dispersions of Sample 1 and Sample 2 at 0.5% by weight of consistency. The loss tangent of Sample 1 (tanδ) was 0.21 and the storage module (G ') was 1.5 Pa at a shear stress of 0.1 Pa, frequency of 0.1 Hz. loss of Sample 2 (tanδ) was 0.18 and the storage module (G ') was 2.7 Pa at a shear stress of 0.1 Pa, frequency 0.1 Hz. References Bhattacharya M. ET AL. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. J. Control. Release 164 (2012) 291-298. Paakko M. et al. Enzymatic hydrolysis combined with mechanical shearing and hig-pressure homogenization for nanoscale cellulose fibrils and strong gels. Biomacromolecules 8 (2007) 1934-1941.
权利要求:
Claims (26) [0001] 1. Nanofibrillar cellulose, characterized by the fact that said nanofibrillar cellulose is in the form of a hydrogel or a membrane, has an average degree of polymerization greater than 1000, and a storage module between 0.3 and 20 Pa when dispersed at a concentration of 0.5% by weight in water, and in which the said nanofibrillar cellulose is of delaminated cellulose pulp of vegetable origin, in which the nanofibrillar cellulose has a numerical average diameter between 2 and 15 nm. [0002] 2. Nanofibrillar cellulose according to claim 1, characterized by the fact that said nanofibrillar cellulose has an average degree of polymerization greater than 1150. [0003] Nanofibrillar cellulose according to either of claims 1 or 2, characterized by the fact that said nanofibrillar cellulose is of wood origin. [0004] 4. Nanofibrillar cellulose according to any one of claims 1 to 3, characterized by the fact that said nanofibrillar cellulose is native cellulose. [0005] Nanofibrillar cellulose according to any one of claims 1 to 4, characterized in that said nanofibrillar cellulose has a turbidity of 200 NTU or less in water at a concentration of 0.1% by weight. [0006] 6. Nanofibrillar cellulose according to any one of claims 1 to 5, characterized by the fact that the crystallinity of the nanofibrillar cellulose is 60% to 80%. [0007] 7. Nanofibrillar cellulose according to any one of claims 1 to 6, characterized by the fact that the nanofibrillar cellulose has a hemicellulose content greater than 10% by weight. [0008] 8. Nanofibrillar cellulose according to any one of claims 1 to 7, characterized by the fact that the nanofibrillar cellulose has an average numerical length between 2 and 20 μm. [0009] 9. Nanofibrillar cellulose according to any one of claims 1 to 8, characterized by the fact that the nanofibrillar cellulose has an average aspect ratio greater than 500. [0010] 10. Nanofibrillary cellulose according to any one of claims 1 to 9, characterized by the fact that the nanofibrillary cellulose has a zero shear viscosity in the range of 100 to 8,000 Pa ^ s when dispersed at a concentration of 0.5% in weight in water. [0011] 11. Nanofibrillar cellulose according to any one of claims 1 to 10, characterized by the fact that the nanofibrillar cellulose has a loss tangent of less than 0.3 when dispersed at a concentration of 0.5% by weight in water. [0012] 12. Nanofibrillar cellulose according to any one of claims 1 to 11, characterized by the fact that more than 90% by weight of the nanofibrillar cellulose is in the fiber fraction of 0 to 0.2 mm. [0013] 13. Nanofibrillar cellulose according to claim 1, characterized by the fact that it is for use as a pharmaceutical product. [0014] 14. Nanofibrillary cellulose according to claim 1, characterized in that it is for use in or as a matrix for drug release, cell release, tissue engineering, wound treatment, or implants, or as a healing agent of wounds, an anti-inflammatory agent, or a hemostatic agent. [0015] 15. Nanofibrillar cellulose according to claim 1, characterized by the fact that the cellulose pulp includes cations, said cations having substituted cations present in the native cellulose pulp, the cellulose pulp having a freedom of at least 60 ° SR (Schopper -Riegler). [0016] 16. Method for the manufacture of nanofibrillar cellulose, the method characterized by the fact that it comprises the steps of providing an aqueous suspension of cellulose pulp of vegetable origin, preferably of wood origin, more preferably of birch; ion exchange at least part of the carboxyl groups present in the cellulose pulp, preferably with Na +; pre-refining said cellulose pulp exchanged in ions; subjecting said pre-refined cellulose pulp to a high-pressure mechanical disintegration to obtain nanofibrillar cellulose; and optionally sterilizing said nanofibrillar cellulose, preferably by autoclaving or irradiation; and / or optionally forming a nanofibrillar cellulose membrane. [0017] 17. Method according to claim 16, characterized by the fact that the method further comprises modifying said cellulose pulp, said ion-exchanged cellulose pulp, or said pre-refined cellulose pulp by the physical or chemical incorporation of a desired chemistry, excluding chemical modifications aimed at enhancing disintegration, and / or in which the method comprises modifying said nanofibrillar cellulose by incorporating a desired chemical, preferably functional side groups, hydrophobization, amination, and / or labeling. [0018] Method according to either of claims 16 or 17, characterized in that the ion exchange comprises adjusting the pH of the aqueous cellulose pulp suspension to a value below 5.0 using an organic or inorganic acid; removing water to produce solid matter, washing the solid matter with water, and forming an aqueous suspension of the solid matter; adding at least one water-soluble salt of NH4 +, alkali metal or alkaline earth metal or metal to the formed suspension; adjust the pH of the suspension to a value above 7.0 using an inorganic base; removing water to produce solid matter, washing the solid matter with water, preferably distilled or deionized water, to produce the cellulose pulp exchanged in ions; and forming an aqueous suspension of the ion-exchanged cellulose pulp. [0019] 19. Method according to any of claims 16 to 18, characterized in that the cellulose pulp exchanged in ions is pre-refined until a freedom of at least 75 ° SR (Schopper-Riegler), preferably at least minus 80 ° SR, is obtained. [0020] 20. Method according to any one of claims 16 to 19, characterized in that the pre-refinement comprises subjecting the ion-exchanged cellulose pulp to delamination using a PFI mill or a refiner equipped with fibrillation blades. [0021] 21. Method according to any one of claims 16 to 20, characterized in that the pre-refined cellulose is subjected to high pressure mechanical disintegration until NTU of 200 or less, preferably 150 or less, is obtained. [0022] 22. Method according to either of claims 16 or 21, characterized in that the high-pressure mechanical disintegration is conducted using a pressure-type homogenizer, preferably a high-pressure homogenizer or high-pressure fluidizer. [0023] 23. Method according to any of claims 16 to 22, characterized in that the membrane is formed by filtration, vacuum filtration, pressure filtration, molding, film coating, rotating vessel coating, electrospinning, wet spinning , dry spinning, wet spinning with spinning, melt spinning, gel spinning, electrospray, spraying, spray drying, molding, pressing or extrusion, or other suitable methods, optionally followed by drying. [0024] 24. Membrane, characterized by the fact that it comprises nanofibrillar cellulose as defined in claim 1. [0025] 25. Use of nanofibrillary cellulose as defined in claim 1, characterized by the fact that it is in a cosmetic, a composition for personal care, a flocculating or water treatment system, a composite, a bulking agent, a thickener, a modifier of rheology, a food additive, an ink additive, a paper, cardboard or pulp additive, or in or as a matrix for cell or tissue culture. [0026] 26. Product, characterized by being pharmaceutical, cosmetic, food, agrochemical, paint, coating, paper, cardboard, pulp, filter, composite product, adhesive, canvas, personal care composition, toothpaste, or culture matrix cell or tissue, or cell or tissue release matrix comprising the nanofibrillary cellulose as defined in claim 1.
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引用文献:
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法律状态:
2019-10-15| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. | 2020-08-04| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]| 2020-09-24| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]| 2021-03-09| B09A| Decision: intention to grant [chapter 9.1 patent gazette]| 2021-03-30| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 04/05/2015, OBSERVADAS AS CONDICOES LEGAIS. |
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