DK3058022T3 - Tredimensionelt cellulose-formlegeme, fremgangsmåde til fremstilling af samme samt brug af samme - Google Patents

Description

THREE-DIMENSIONAL CELLULOSE MOULDED BODY, METHOD FOR THE PRODUCTION THEREOF AND USE OF THE SAME

The present invention describes a novel type of cellulose II particles as well as suitable methods of preparation. The properties of these particles make them especially suitable for use in cosmetic and pharmaceutical applications. The particles are characterized by an inner sponge-like fine structure, which is surrounded by a compact outer shell.

State of the art:

Cellulosic powders and other systems containing particulate cellulose have been known for a long time, although there have been new developments in this area, especially in recent years. The most widespread are dry fibrous powders which are formed by the comminution of pulp by means of suitable aggregates. Depending on the pulp used and the type of preparation (comminution and any modifications), a wide variety of qualities may be produced. As a variant, not pulp, but plants (parts) are directly comminuted. In addition to the cellulose, the particles obtained also contain other substances such as lignin or hemicelluloses in higher proportions and exhibit greater fluctuations with respect to homogeneity. Because of the macro-molecular structure of the cellulose, all the powders described so far are fibrous, i.e. the particles comprise a pronounced L/D ratio. A further widespread class of cellulose powders are the so-called microcrystalline celluloses (MCC). In the production of MCC from pulp, treatment with acid is also performed, in addition to mechanical comminution, wherein the amorphous portions of the cellulose are degraded and a material with a high crystalline content is formed. Depending on the method, the individual crystallites may be made into different shapes. Thus, in addition to fibrous particles, aggregates /agglomerates of approximately spherical shape are also possible. In the case of MCC or conventional fibrous cellulose powder, the possibilities of incorporating or applying additional materials into the particles are limited. The application of additives is only possible as a coating or as a deposit in the aggregates or agglomerates. A frequently used method is granulation, wherein the desired final particles are built up from smaller particles. To a certain extent, these starting particles themselves will have previously been prepared by comminution, which makes the entire process complex.

All the materials described so far have the same microstructure, i.e. an arrangement of the cellulose molecules, which is referred to as a structure type in the specialist literature, in this case the cellulose-1 structure. This type is that which is formed from plants and is not changed by the methods which are used in the production of the particles already described.

In addition to cellulose-1, there is still another common structure type, called cellulose-ll, which is the thermodynamically more stable form. The two types of structures may be easily distinguished radiographically or also by NMR. Cellulose-1 may be converted into cellulose-ll by dissolving it in suitable solvents and subsequent regeneration. This process is also used in industrially-used methods for fiber production, such as, for example, in Viscose and. Lyocell methods. Recently, there have also been a large number of publications on the topic of "ionic liquids as a solvent for cellulose", although large-scale technical implementation is still pending. An advantage of all these methods is that by the dissolution and subsequent regeneration of the cellulose, a significantly more variable shaping of the particles is possible. In this way, native spherical particles are actually possible without the latter having to be constructed from sub-units, as in the case of MCC. A further advantage is that, during the course of the methods, additional substances may also be incorporated directly into the particles and, of course, may also be applied superficially.

In addition to these dry powders of fibrous or spherical particles there are also suspensions of cellulosic particles, often also referred to as cellulose gels. The simplest method for their preparation is to disperse a suitable cellulose powder in water. However, the trend is clearly moving to more sophisticated processes and materials. Recently, microscale and nanoscale cellulosic suspensions have been the focus of interest. They are available under a wide variety of designations, such as microfibrillated cellulose (MFC) or nanocellulose. Such materials may now again be prepared either on the basis of cellulose-1 or cellulose-ll. The methods of production here are usually very complex and energy-intensive, and may only be transferred to larger scales to a limited extent.

As this rough overview already shows, a number of cellulosic particle systems are known to the person skilled in the art and from which a system may be selected. The fields of application for cellulosic particles are now also varied, ranging from the construction sector to plastics’ reinforcement, to pharmacy and cosmetics. The known particles may be used to cover many applications, but this is partly associated with additional complexity since the requirements of the existing materials are not completely fulfilled and additional processing steps (modifications) are necessary.

In addition to pure cellulose, some cellulosic derivatives (such as, for example, methylcellulose or carboxymethylcellulose), some of which are water-soluble, are also used (especially also in cosmetics). In addition, there are a large number of particles on a mineral or synthetic base, especially in the case of the latter, wherein the possibilities for modification are much more diverse. Particularly complex cosmetic products contain a variety of ingredients to achieve the desired effects, which, of course, also makes the formulation a complex process. US 2010/0297445 describes the production of beads from polymers, inter alia, cellulosic spheres from a cellulose solution in so-called organic solvents such as 1 -ethyl-3-methylimidazolium acetate using an underwater granulator. The beads are then dried by means of a solvent exchange. Nothing is revealed about the inner structure of these beads. The processing of the beads after shaping, such as washing or the removal of residual solvents, is also not specified in detail. WO 2009/036480 A1 discloses the preparation of spherical cellulose particles from a cellulose solution which is as amorphous as possible, wherein several comminution steps take place. This document discloses that an underwater granulator may be used in the first comminution stage as well as other aggregates. The structure of the intermediate product thus produced is not disclosed. Subsequently, the thus produced intermediate product is further comminuted in the never-dried state. WO 2009/037146 also discloses cellulose beads. These are cross-linked by various methods to increase strength. The cross-linking also causes an almost complete loss of the swelling capacity of the cellulose beads. WO 02/57319 discloses monodisperse cellulose beads, but does not make any quantitative statements about their internal structure. These beads are prepared from solutions with a maximum of 10 wt.-% of cellulose; In the examples, however, a maximum of 4 wt.-% of cellulose is used, which suggests that the use of more concentrated cellulose solutions with the invention according to WO 02/57319 was not possible. US 2004/011690 describes the preparation of cellulose beads for use in cosmetics, pharmaceutics or similar fields. The cellulose beads are formed through agglomeration of microcrystalline cellulose with additional additives. The cellulose beads are, therefore, rather a microgranulate or agglomerate and not compact cellulose particles. The structure of the cellulose beads is not disclosed in detail. A review of cellulose beads is to be found in "M. Gericke et al., Functional Cellulose Beads: Preparation, Characterization and Applications." Chemical Reviews 113, 2013, pp. 4512-4836”. However, the preparation methods described are largely restricted to laboratory methods. Different morphologies are mentioned, but not described in detail, and the connections between production and structure are only indicated. The bulk of the article deals with the further functionalization of cellulose beads. A more detailed description of the relationships between the preparation of cellulose beads and their structure may be found in "J. Trygg et al., Physicochemical design of the morphology and ultrastructure of cellulose beads. Carbohydrate Polymers 93, 2013, p.291-299”. The solvent system NaOH-urea with cellulose concentrations up to 6% is described. Under certain conditions, core/shell structures may be produced according to this document, wherein the envelope is in fact usually only a few pm thick. Only under extreme regeneration conditions (10 molar nitric acid) may the thickness of the skin be increased to 50 pm; otherwise it has little influence. A more precise characterization of the shell (for example compared to the core) does not take place.

In summary, therefore, it must be stated that, in the prior art, only cellulosic particles with functional properties such as slow controlled release (“slow release”) of pharmaceutical or cosmetic active ingredients, changes the properties through external action, for example, pressure ("stimuli response") and ("sensoric booster") properties were known in oil-water emulsions, which had been produced by the agglomeration of even smaller particles. Such a multi-stage method is correspondingly complex and thus expensive. Among other things, the comminution step for producing the sub-particles is very energy-intensive. On the other hand, cellulosic particles which already have the particle size required for the above applications are already known in the prior art, but these particles do not have the above-mentioned functional properties.

Statement of the problem

In view of this prior art, there is still a need for cellulose particles with correspondingly improved properties, especially in the higher-value fields of application of cosmetics and pharmaceutics. The particles should already contribute these properties in themselves, and should not need to be obtained by an additional step in the production process or by the addition of further auxiliary agents, as is now necessary in some cases. The following characteristics are of particular interest: slow, controlled release (slow release) of active substances (pharmaceutic or cosmetic), alteration of the properties by external action (stimuli response, for example, pressure), improved swelling capability, defined inner structure (for example, a clearly defined reproducible core/shell structure) and defined surface quality. These and, if appropriate, further functionalities are to be introduced in a defined manner during the production of the particles. In addition, the production methods should be as simple as possible and thus readily attainable industrially. As a result of the multi-functionality of these particles, the formulation and production of the end products is also to be simplified in the ideal case, since fewer ingredients are necessary overall. A further advantage could arise if synthetic materials were also to be replaced by such novel cellulose particles. This could take into account the increased demand for products from renewable raw materials.

The solution according to the invention of the above-described object is to build up the cellulose particles not from sub-particles but to produce them in one step. Special attention is given here to the selection of the corresponding method parameters since the properties of the particles are already defined by these.

Description of the invention

This object has now been achieved by a three-dimensional cellulosic molded body according to claim 1, which has an optically detectable core/shell structure, wherein the shell has a higher density and a lower crystallinity than the core, while the core has a sponge-like structure. In the context of this invention, "optically detectable" means that the core/shell structure may be determined by means of light microscopy, X-ray and/or NMR spectroscopy. Microscopy is suitable for both dry and swollen specimens. On the other hand, radiography is restricted to dry, in particular air-dried, samples, while NMR spectroscopy is restricted to molded bodies in the swollen state. This is due to the need for sample preparation. Since the molded bodies according to the invention are produced from a cellulose solution, they always have the cellulose-ll type structure.

The shell of the molded body according to the invention has a relative density of 65% to 85%, while the core has a relative density of 20% to 60%. The relative density is based on compact cellulose.

The shell thickness is between 50 pm and 200 pm.

The ratio of the shell thickness to the total diameter of the molded body is between 1 : 5 and 1 : 50.

The molded bodies according to the invention are preferably substantially spherical, but may also be cylindrical, ellipsoidal or ovoid. The ratio of the semi-axes (length : diameter) of the molded body does not exceed 3 : 1.

Depending on the intended use, the molded bodies according to the invention may either be dried or re-used in the never-dried state, wherein the never-dried variant of the cellulose beads preferably comprises a moisture content of 25 - 300 wt.-%, based on the amount of cellulose.

Depending on the intended use, the molded bodies according to the invention may contain additive substances incorporated during their preparation. These additive substances are preferably selected from the group consisting of ZnO, T1O2, CaCC>3, CaCl2, kaolin, Fe2C>3, aluminum hydroxide, color pigments based on plastic, activated carbon, super-absorbent materials, phase-change materials, flame- retardants, biocides, chitosan, as well as further polymers and biopolymers.

Furthermore, molded bodies according to the invention have a high water retention capacity (WRC). The WRC is, for example, typically in the range from 70 - 90 wt.-%, and, in the case of supercritical CC>2-dried or freeze-dried cellulose beads, typically in the range from 120 - 150 wt.-%, after 2 hours of swelling in demineralized water for cellulose beads dried at standard pressure.

The present invention furthermore relates to a process for the preparation of the above-described three-dimensional cellulosic molded body according to the invention with an optically-detectable core/shell structure, characterized in that it comprises the following production steps: a. Dissolving the cellulose according to a Lyocell process to obtain a solution containing 10 to 15 wt.-% of cellulose; b. Extrusion of the polymer obtained in step a. with no air gap directly in a precipitation bath; c. Regeneration process, wherein, upon entry of the cellulose solution into the precipitation bath, the difference between the NMMO concentrations of the cellulose solution and the precipitation bath are 15 - 78 wt.-%, preferably 40 -70 wt.-%, and the difference in temperature between the cellulose solution and the precipitation bath should be 50 - 120K, preferably 70-120 K, more preferably 80- 120 K; d. Washing process according to the percolation principle with at least one alkaline washing step, preferably at pH 9 -13; e. Optionally a drying process wherein the outer skin of the formed bodies is not abrasively harmed; wherein the washing mentioned in point d. is preferably carried out in several stages and in counter-current, and contains at least one alkaline step.

Suitable dissolving processes are, for example, the Viscose, the Lyocell or the cuprammonium method; It is also possible to dissolve the cellulose in NaOH or suitable ionic liquids. In general, the invention is not restricted to particular solvents or processes, but the structure of the particles obtained may additionally be influenced by the use of different methods. However, preference is given to the Lyocell method known in principle to a person skilled in the art, and described, inter alia, in EP 0356419. Additional substances may also be incorporated into the spinning mass during its preparation, but, in any event, prior to extrusion, as already described above.

Starting from the cellulose solution, the molding takes place, wherein, especially in the precipitation process, care must be taken that no fibrous structures are formed. This is not a trivial requirement, since cellulose, due to its macromolecular structure, strives to form fibrous domains. This problem is solved by the fact that the cellulose solution is first brought into the desired form without substantial shearing, and the regeneration conditions are subsequently selected accordingly. It is absolutely necessary that the cellulose solution is directly extruded into a precipitation bath, i.e. without air gap, and the comminution of the solution strand takes place in a manner which gives substantially equal-sized particles. Suitable aggregates for this step are, for example, underwater or strand granulators, wherein, in addition to spherical particles, cylinders, ellipsoids of revolution and ovoids may also be produced.

The above-mentioned aggregates also fulfill the additional requirements for the manufacturing process. The particles produced should be as uniform as possible, wherein the properties may be controlled via the method parameters. At the same time, the method should have a high throughput.

Granules of different sizes may be produced from Lyocell spinning mass, for example with an underwater granulator of the EUP50 type from the company Econ. Depending on the design of the perforated plate and nozzle hole, high throughputs of 2 to 30 kg/h are calculated for 100% cellulose, NMMO-free washed and dried end product, are possible. The produced beads may be separated from the process water by a mechanical centrifugal dryer. In other embodiments, such solid-liquid separations may be effected e.g. by means of hydrocyclones, thrust centrifuges or also by sieves. Granulators are available in various sizes on the market and, due to the simplicity of the method for the comminution of spinning mass, upscaling to an industrial scale is relatively simple. For example, with a single granulator of the EUP 3000 type, about 5000 tons of beads per year may be produced. Furthermore, there are still significantly larger machines available from other manufacturers.

In a further embodiment, cellulosic strands may also be produced with special Lyocell nozzles with nozzle hole diameters of 0.5 to 5 mm, which are fed to a strand granulator after a washing line. The washing, feeding and entry of the individual strands into the strand granulator are critical in this respect, since the strands are very flexible. In this way, cylindrical granules may be obtained.

The viscosity of the cellulose solution also has a considerable influence on the properties of the particles obtained, since this usually also dominates the viscosity difference between the cellulose solution and the precipitation bath. The precipitation bath is preferably aqueous (with a viscosity in the region of 1 Pa.s), but the viscosity of the precipitation bath may also be significantly increased by the addition of thickeners (polymers). A lower viscosity difference results in a thinner shell. According to the invention, a difference in viscosity between the cellulose solution and the precipitation bath is at least 600 Pa.s, preferably in the range 750 - 1200 Pa.s (based on the zero viscosity).

The thickness of the shell is decisively influenced by the NMMO concentration difference when the cellulose solution enters the precipitation bath. The larger this is, the thicker is the shell of the moldings produced according to the invention. The concentration difference is maximized when pure water is used as a precipitation bath and the precipitation bath is mixed so well at the entry point of the cellulosic solution that all emerging NMMO is immediately transported away.

The thickness of the shell is also influenced by the temperature difference at the entry of the cellulose solution into the precipitation bath. The larger this is, the thicker is the shell of the granulates produced according to the invention.

In addition to the possibility of underwater granulation in a liquid precipitation bath, there is also the possibility of coagulation in a gaseous medium.

The preferred method principle for the washing out of the molded bodies according to the invention on an industrial scale, is counter-current washing in order to keep the required quantity of washing water and the recovery costs within limits. In order to achieve the required purity of the molded bodies, 10 to 12 washing steps are necessary for this purpose. At low NMMO residual contents, an increase in the washing water temperature is also advantageous. A washing water temperature of from 60°C to 100°C is preferred. In order to also efficiently remove small amounts of degradation products of the solvent, an alkaline step is additionally required, with preference being given to using pH values of 9 -13.

As a method for industrial scale washing according to the invention, in principle all types of solid-liquid extractions are suitable in continuous or batch operation. However, methods according to the percolation principle, i.e. with cross-counter-current washing, are preferred. Suitable devices for this purpose are, inter alia, carousel extractors or extractors of the De-Smet, Crown or Bollmann type. Cascades are also suitable for this purpose. Such extractors are also used, for example, in maceration. Thrust centrifuges would, in principle, also be suitable, but it is important for the method according to the invention that shearing or pressure loading of the granules is avoided as far as possible, so centrifuges are not suitable. Also suitable, are columns according to the ion exchanger principle, wherein the solvent for cellulose is preferably displaced from the top downwards via the column. These may also again be arranged in cascades.

In view of the wide range of applications of the products produced according to the invention, it is important to remove the NMMO as completely as possible, since NMMO may have an oxidizing effect on some active substances which are subsequently introduced into the products.

After the granulate washing, the excess adhering moisture should be removed from the particles to minimize drying costs and make the granules free-flowing. Suitable aggregates for this purpose are centrifuges and decanters as well as belt filters which may be operated continuously or discontinuously.

As an additional process step, steam sterilization may also follow after washing the granules. The water retention capacity of the never-dried cellulose beads is reduced by the steam sterilization, and the pre-dewatering before the drying may be more efficient.

In view of the use in cosmetics where many products are aqueous formulations or emulsions, never-dried particles with a defined moisture are a preferred embodiment of this invention. As a result, the very open pore structure obtained after the regeneration and the washing out of the solvent means the cellulose particles are very receptive and accessible.

Furthermore, a core/shell structure is formed by the coagulation of the spinning mass with the aid of the above-mentioned aggregates. This core/shell structure is shown by a compact transparent outer skin (shell) and a sponge-like white inner (core) of the beads.

This structure is responsible for the controlled-release properties of the molded bodies according to the invention for the delivery of cosmetic or pharmaceutic active ingredients, since the active substances, which are readily available in the sponge-like interior, have to overcome the very compact outer skin upon delivery. The release of the active substances is thus delayed. The thickness and structure of this outer skin of the beads may be altered by changing the precipitation medium parameters.

An enzyme treatment may take place between intermediate step d. and step e. in order to impart functional properties corresponding to the molded body according to the invention, as will be described in detail below. For this purpose, preference is given to using one or more enzymes selected from the group comprising exo- and endo-1,4-b-glumayases, glucosidases and xylanases. Surprisingly, the enzymatic treatment of the particles according to the invention not only attacks the surface (which is smoothed) but also the porous structure inside. From this, it may be concluded that enzymes may migrate into the interior of the particle. According to the invention, the strength of the particle may thus be infinitely adjusted by means of enzyme treatment. Furthermore, this shows that enzymes or proteins may penetrate into the interior of the beads and a loading of the thus more easily accessible beads with these substances is possible. The enzyme treatment of the beads also shows that both enzymes and proteins may be absorbed by the beads. With appropriate drying, these may also be encapsulated or immobilized.

The formation of this core/shell structure makes it possible to also produce beads with so-called stimuli-response properties. Thus, on the one hand, the elasticity of the beads may be drastically changed by the variable molding of the outer skin. On the other hand, however, the inside of the beads as well as the outer skin thereof, may be so modified by chemical or enzymatic modification, or variation of the precipitation medium parameters, that the beads may already be crushed under low pressure between the fingers, thus deliberately releasing their contents (for example, by forming a hydrogel). The hydrogel resulting from the crushing of the beads has very interesting cosmetic properties. Thus no stickiness, greasiness or oiliness of this hydrogel is detectable. The particle size and granularity may also be individually adjusted by the duration of the chemical modification, enzymatic treatment or, also, modification of the precipitation bath parameters. As a result, the beads may also be used as texture-forming agents in cosmetics.

This stimuli-response effect is particularly important for the cosmetic or pharmaceutical sector, since e.g. cosmetic or pharmaceutical active substances, but also color pigments or paints of decorative cosmetics, which have been introduced into the beads, may thus be specifically released. Furthermore, the beads may be used as for peeling or as exfoliants with stimuli-response effect. In this case, these beads may contain abrasive pigments or else enzymes which may be released by bursting when the beads are rubbed and thus achieve the desired peeling effect. The stimuli-response effect of the beads may be individually adjusted by the duration of the chemical modification, the enzymatic treatment, or, also, by changing the precipitation medium parameters.

If particles having only a low moisture content are advantageous for certain applications, particles according to the invention may also be dried by means of various drying methods. In a preferred embodiment of the method according to the invention, the drying process is carried out by means of standard pressure drying, flow drying, fluidized bed drying, freeze drying or supercritical CO2 drying. Drying is a challenge because the product moisture is very high. In the case of the cellulose beads, moisture content of 70 -75 wt.-% has to be overcome, wherein the mixture has to be dried for some applications from 10-13 wt.-% or to < 5 wt.-%. To preserve the product, the drying should be carried out according to the invention as far as possible without contact.

Surprisingly, drying in the fluidized bed process has proved particularly gentle and efficient. Through the permanent circulation and loosening of the material, the expulsion of moisture is strongly favored. In addition, the drying is very product-friendly with respect to abrasion. In addition, high throughputs and short drying times may be achieved. These, in turn, lead to the fact that the yellowing, which normally occurs by the action of elevated temperatures, is extremely low. The process may also be operated continuously. High deposits of the material, as they occur to some extent in some other drying processes, would cause the moisture to stay between the grains for a very long time, as a result of which the drying time would increase enormously and the long temperature effect would additionally entail the risk of yellowing. Examples which may be mentioned here are, for example, dryers or crystallisers. The agitation also creates high shear on the product in these aggregates, which rubs the outer skin and creates a lot of dust. Furthermore, the thickness of the shell layer is also altered or destroyed by this abrasion, thus reducing the controlled-release properties of the product. These aggregates are therefore not suitable for the method according to the invention.

As an alternative to fluidized bed drying according to the invention, it is also possible to consider vibration dryers which offer similar advantages in drying. These may be advantageous for certain incorporated products, since the drying takes place under vacuum at low temperatures. A further advantage of the fluidized bed process is that the granules may be both dried and coated with an additional substance in one process step. The possibilities in the coating process are manifold. For example, the granules may be colored, or functional substances such as, for example, biopolymers (for example, chitosan, etc.), synthetic polymers, active cosmetic or pharmaceutical substances, enzymes, proteins and release agents, and comminution agents may be applied. A chemical modification of the surface of the beads in the fluidized bed is also possible. By coating in the fluidized bed, the distribution of the coating over the surface and over the individual particles is very homogeneous. Surprisingly, it has been found that the coated molded bodies according to the invention, dried by means of the fluidized bed, still have very good swelling behavior.

The pore structure and the density of the molded bodies according to the invention may also be significantly influenced by selecting appropriate drying processes. During normal pressure drying at 60°C in a circulating air drying cabinet, the sponge-like structure of the never-dried beads collapses completely and a virtually transparent, compact, much smaller bead is formed, which, however, retains its ellipsoidal shape. This effect of collapsing the structure inside the beads is, however, partly reversible since the beads reswell in water. At normal pressure, the fluidized bed drying showed that the sponge-like structure of the never-dried beads was best recovered by subsequent swelling in water, as already explained above.

However, the sponge-like structure could be improved a little when the beads were prepared by shock-drying the never-dried beads in liquid nitrogen and then freeze-drying. It was found that these dried beads were no longer transparent but white. This is an indication of the pore structure. However, the surface and shape of the beads changed very strongly during drying. Although the product so obtained substantially retained its ellipsoidal shape, dents and craters had formed on the surface like a lunar landscape. The bead thus showed a raisin-like appearance. Further, the density of these beads was lower than water.

As a further type of drying, the supercritical CO2 drying was selected for the drying of the never-dried beads during the preceding solvent exchange. In particular, the water in the beads was exchanged for acetone and the supercritical CO2 drying was then begun. The original shape and porosity of the never-dried beads could be best obtained with this drying method. These beads had an ellipsoidal shape with a smooth surface. The fine pore structure was characterized by the white color of the beads. These beads also had a lower density than water. A further object of the present invention is also the use of the molded bodies according to the invention, wherein, because of their unique structure, they may be loaded with a wide variety of active substances.

According to the invention, the molded bodies may be used for the production of an active substance-loaded carrier material, wherein the molded body is impregnated with a solution of the active compound and subsequently washed and dried.

Furthermore, they may be used for the production of an active substance-loaded carrier material with controlled-release properties for cosmetic and pharmaceutical applications. For this purpose, a prior comminution of the molded bodies according to the invention is necessary under certain circumstances, wherein the controlled-release properties remain to a certain extent; particularly preferred are the following applications: natural product emulsions, gel emulsions, men's care products, health care products, sun protection products, cosmetic serums, deodorizing applications, make-up bases and color cosmetics. The active substances may be, for example, enzymes and peptides for cosmetic and technical applications, e.g. the coenzyme Q10.

According to the invention, the molded bodies may also be used as abrasive material in cosmetic products, for example for peeling or as exfoliates, wherein the average size of the molded bodies is 150 - 800 pm, preferably 200 - 800 pm, more preferably 300 -550 pm.

Likewise, the molded bodies may be used according to the invention as optical effect beads in cosmetic products, preferably shampoos and creams.

The molded bodies may also be used according to the invention, both in the never-dried as well as in the dried state, as starting materials for the production of spherical cellulosic powders which have sensoric booster properties in oil-water emulsions. The molded bodies are preferably comminuted by means of various comminution methods to particle sizes of preferably dso = 5 pm. They are then used for cosmetic and personal care products. Their advantages consist mainly in the fact that the end products have less stickiness and lubricity as well as an improved absorption of lotions into the skin. Particular preference is given here to natural product emulsions, gel emulsions, men's care products, face care products, sun protection products, cosmetic serums, deodorizing applications, make-up bases and color cosmetics.

In the technical field, the molded bodies described above may be used according to the invention as column material in chromatography, in particular in normal phase, reverse phase, ion exchange, affinity and size exclusion chromatography. The molded bodies may also be chemically modified, for example by means of acetylation, methoxylation or like method.

Furthermore, the molded bodies described above may be used according to the invention for the immobilization of enzymes, or peptides in order to increase their enzymatic activity or stability. Particularly preferred for this is use in the cosmetic and technical field. Likewise, the molded bodies described above may be used according to the invention for the immobilization of cells of human, animal or plant origin (bacteria, fungi, tissue, algae, etc.).

The molded bodies described above may be made manageable in various ways. A preferred variant according to the invention is the introduction into nonwovens. The nonwovens themselves may be produced by the methods known in the prior art such as carding, spun-bonding, melt-blowing or air-laid methods. The introduction may take place in the various stages of the production of the nonwoven fabric and/or on the finished nonwoven fabric: a. Before nonwoven formation: In air-laid and wet-laid methods, the molded bodies according to the invention may be mixed with the other starting materials before the nonwoven formation stage. In wet-laid methods, they may be dispersed, for example, in liquids or foam. b. During nonwoven formation: In extrusion processes, such as melt-blowing or spun-bonding methods, the molded bodies according to the invention may be added during, or directly after, filament formation when the filament strands are deposited on the screen belt or the screen drum. The introduction of the molded bodies may be carried out, for example, by spraying into the filament curtain or spraying on or before the filament curtain is laid down on the screen belt or sieve drum. c. After nonwoven formation, but before the solidification step. d. After the solidification step (online), wherein the solidification may be carried out by methods known from the prior art, for example by means of thermal bonding, chemical cross-linking, air-through bonding, ultrasonic bonding, needle punching, spun-lacing and also combinations of two or more of these methods. e. On pre-consolidated nonwovens, for example before the application of a second nonwoven layer. The pre-consolidated nonwoven fabric may, for example, also be fed from a roll in a discontinuous process. f. In methods which comprise a combination of the above-described variants a. to e.

The molded bodies according to the invention are preferably fixed in all these methods by means of a binder, for example an adhesive.

With these methods, the most diverse layer structures may be produced from the molded bodies (A) and nonwovens (B) according to the invention: nonwoven fabrics coated on one side (A-B) or both sides (B-A-B) with molded bodies, sandwich structures of two nonwovens with internal molded body layer (A-B-A), or multi-layered systems which alternately have nonwoven and molded body layers (A-B-A-B, A-B-A-B-A, ...). A likewise possible variant is the application of the molded bodies according to the invention to plastic films. The molded bodies are also preferably fixed by means of adhesive.

Examples

The following examples serve to illustrate and better understand the particles according to the invention as well as their method of preparation. However, the invention itself is not limited only to these exemplary embodiments.

Example 1 - Preparation of cellulose beads A standard Lyocell spun mass having the following composition: 13 wt.-% of cellulose (100% of Saiccor), 75.3 wt.-% of NMMO, 11.7 wt.-% of water and traces of stabilizer were used as starting material for the preparation of the cellulose beads. The spinning mass was maintained at 120 - 125°C and processed by means of an ECON EUP 50 underwater granulator. Through-hole perforated plates with 12 holes and 4 knives were used. The starting valve and the perforated plate were heated to a constant 120°C, and the water tank to 20°C, Table 1 summarizes the parameters which were varied during tests V1 to V6.

Table 1

The cellulose beads prepared by means of an underwater granulator were precipitated in pure deionized water (demineralized water) and subsequently subjected to demineralized hot water in a column. The fine washing followed with sodium hydroxide solution (pH 11). After the sodium hydroxide washing, the beads were washed with neutralized water at a temperature of 80°C and centrifuged to a residual moisture content of about 70 wt.-%.

The structure of the never-dried particles from the tests V1 to V6 was examined under an optical microscope (type Zeiss Discovery V12, Olympus DP71). It was found that all particles have a pronounced core/shell structure. Figure 1 shows a particle from V6 as an example.

Using the software Analysis 5.0 from Olympus, the thickness of the shell was measured, wherein five measurements were performed and averaged. The results are also summarized in Table 1. A clear dependence of the shell thickness on the regeneration conditions was found. The thickness of the outer layer decreases with increasing NMMO concentration in the precipitation bath or with an increase in the temperature.

Furthermore, it may be seen that the outer skin is transparent, while the inside of the beads is white. This clearly shows the different structuring of the material. The transparent layer is very dense, whereas the white interior of the cellulose beads has a sponge-like structure. A detailed characterization of the core/shell structure may be found in Example 5.

Example 2 - Loading with active substance 20 g of non-dried cellulose beads V1 from Example 1 (68.3 wt.-% of residual moisture), 40 ml of a 5 wt.-% of paracetamol (Merck), heated to 30°C, were dissolved in ethanol p.a. solution. This suspension was stirred at 100 rpm for 120 min. The loaded cellulose beads were filtered off by suction and washed with 10 ml of deionized water and then dried in a vacuum drying cabinet at 40°C, 150 mbar, for about 8 h. The weight of the dried cellulose beads was 5.915 g. The loading of the cellulose beads with paracetamol was 8.48 % wt.-% (weight increase).

The following materials were used as comparative substances: Tencel® CP 4 (spherical cellulose powder, manufacturer Lenzing AG), Tencel® gel (cellulose suspension, Lenzing AG) and Vivapur 105 (MCC, manufacturer J. R &amp; Sohne). Suspensions with paracetamol in ethanol were likewise prepared analogously to the cellulose beads according to the invention, wherein the ratio of cellulose to paracetamol was always kept constant. The comparative materials, however, were not dried in a vacuum drying cabinet because this would have led to clogging due to the fine particles, but by means of Buchi B290 spray dryers. Table 2 summarizes the properties of the loaded particles.

Table 2

Example 3 - Release tests

The re-release rate of paracetamol from the loaded particles prepared in Example 2 was determined according to the method described below. For this purpose, 100 mg of the particles were introduced into 500 ml of aqueous hydrochloric acid (0.1 M, pH 1.2) and stirred at 100 rpm (stirring apparatus: Erweka Dissolution Tester DT 820). Samples were taken at regular intervals and the absorbance at 243 nm was measured against a reference (pure aqueous hydrochloric acid) (Perkin Buimer Lambda 950 UVNIS spectrometer). Figure 2 shows the release curves of the different particles.

It is clear that the cellulose beads according to the invention show a significant retarding effect on the active ingredient paracetamol. This retarding effect is much more pronounced compared to powdered particles which are loaded by spray drying. In the case of the particles which have been produced from the cellulose gel, the highest loading may be achieved on account of the more open structure, although the release occurs in this case as well. Only the cellulose beads according to the invention have slow-release properties due to their internal structure.

Example 4 - Drying (including coating)

The never-dried cellulose beads V1 from Example 1 (residual moisture 63.83%) were subjected to different drying processes in order to examine their influence on the structure of the dried particles:

• Drying cabinet at 60°C

• Fluidized bed drying (in a fluidized bed dryer DMR WFP-8) at 100°C • Drying with supercritical CO2 (Natex 5I laboratory apparatus) after solvent exchange to acetone ("SC-CO2 drying") • Freeze drying (Labconco Freezone 2.5 liters, vacuum 0 mbar) after shock freezing in liquid N2

In the fluidized bed drying, coating tests were also carried out. For this purpose, corresponding aqueous dye solutions (Waco blue, Waco pink, SepiCoat 3213 Yellow + Sepifilm Gloss, Sepicoat 3404 Green + Sepifilm Gloss, Sepicoat 5901 Brown + Sepifilm Gloss) were introduced into the fluidized bed dryer. All the particles obtained showed a homogeneous coloration on the surface.

In all drying processes, a shrinkage of the particles was observed. For example, the cellulose beads had a bulk density of 0.74 g/ml after drying in the drying cabinet, while the never-dried cellulose beads still had a bulk density of 0.72 g/ml. The increase in the material density directly indicates a decrease in the particle size. Figure 3 shows typical structures obtained from the various drying processes: • Left: drying cabinet - transparent to slightly opaque cellulose beads with a rough surface • Middle: SC-CO2 drying - white cellulose beads with a smooth surface • Right: freeze-drying - white cellulose beads with smooth but deformed surface

However, the drying process does not only have an influence on the external appearance of the particles, but also on their internal structure. For this purpose, the BET surface area of the particles was determined by means of N2 adsorption (BELsorp mini 11 measuring apparatus). For the cellulose beads dried in the drying cabinet, no BET surface area could be determined with this measurement, which means that the inner pore structure had completely collapsed. For the SC-CO2 dried sample, a BET surface area of θβετ = 174 m2/g was obtained, which indicates a substantial preservation of the pore structure which is never dried. With θβετ = 45 m2/g, the freeze-dried pattern lies as expected between the other two methods. In Fig. 3a. The pore size distribution of the sc-CC>2-dried cellulose beads is determined by means of B.J.H. plotting (calculated from the N2 adsorption/desorption), which mainly lies in the range of 25 nm.

Furthermore, helium pyknometry (Pycnomatic ATC from the company ThermoFisher/Porotec) proved that the sc-C02-dried cellulose beads have an open-pored structure, while the freeze-dried cellulose beads show a closed-pore structure.

Example 5 - Characterization of the core/shell structure

On the never-dried samples V4 and V6 from Example 1, which have a significantly different thickness to that of the shell (75 pm and 182 pm, respectively), 13 C CP-MAS-NMR measurements were carried out (Bruker Avance DPX 300 NMR spectrometer, 7.05T magnetic field strength Ultrashield (SB), 2 rf channels, 100/300 W 1H/BB amplifier, 4 mm 1H/BB solid state CP-MAS-NMR sample head). From these measurements, the method described in "G. Zuckerståtter et al., Novel insight into cellulose supramolecular structure through 13 C CP-MAS-NMR spectroscopy and paramagnetic relaxation enhancement,

Carbohydrate Polymers 93 (2013), p. 122-128”, describes methods to determine innercrystalline (IC), surfacecrystalline (SC) and disordered portions (DIS).

It may be clearly seen from the results shown in Fig. 4 that a lowering of the precipitation bath temperature from 50°C (V4) to 10°C (V6) and a lowering of the NMMO concentration in the precipitation bath from 44.6 wt.-% NMMO (V4) to 0 wt.-% NMMO (V6) increases the disordered ranges from 37.4% to 29.3%. As a result, the inner-crystalline part has to decrease correspondingly since the surface-crystalline part remains constant. Therefore it may be said that the thickness of the skin is correlated with the disordered parts, and one may clearly identify the outer skin as an amorphous part of the bead. Computer tomography measurements clearly show that this amorphous outer skin consists of denser material than the core.

These X-ray computed tomography measurements were performed with a GE Phoenix/X-ray nanotome device and a voxel size of 4.5 pm, the measurement time was 121 min and a total of 1700 projections were recorded. The complete freeze-dried cellulose beads (from Example 4) and the commercially-available compact cellulose beads (Sprayspheres-SE White, Umang) were obtained by measuring whole cellulose beads (not crushed). Measurement of the wet cellulose beads was not possible. By means of the VG Studio MAX 2.2 software, (virtual) cuts through the particles were made and evaluated according to the gray scale (corresponding to the scattered density). A relative density of 0% was defined for air (particle interspaces) and a relative density of 100% for compact cellulose (sprayspheres). Table 3 shows the values obtained for the dried Tencel® beads.

Table 3

Example 6 - Source behavior dried cellulose beads

The (uncoated) cellulose beads from Example 4, dried by means of a fluidized bed, were examined for their swelling behavior in water. As reference material, commercial cellulose beads (Spraysphere SE White, Umang) prepared by spray granulation were again used. 10 g of particles were each added to 100 ml of water and allowed to swell without further agitation (stirring or the like) until equilibrium occurred. Table 4 summarizes the results of these experiments.

Table 4

It is found that the Tencel beads according to the invention have a significantly better swelling behavior than comparable commercial cellulose particles. This may, in turn, be traced back to the inner structure already described in the previous examples.

Example 7 - Variation of the strength of the particles by enzymatic and chemical treatment

The never-dried cellulose beads V1 from Example 1 were subjected to both an enzymatic and an oxidative treatment, wherein the following parameters were used: A solution of the enzymes Celluclast 1.5L and Econase HC 400 (Novozyme) was prepared in a buffer solution (pH 4) in the ratio 2 : 1. A further possibility of enzyme treatment results from the use of Novozyme FiberCare R or FiberCare D in a buffer solution of pH 6.5. The cellulose beads were each introduced into a buffer solution (40°C) and the respective enzyme solution was then added in a dosage corresponding to 1 ml per gram of dry cellulose beads. The reaction time was 10 min and 60 min, after which the reaction was stopped by enzyme deactivation and the cellulose beads were rinsed several times with deionised water.

The oxidation was carried out by means of the known TEMPO reaction, wherein the reaction time here was 4h at 80°C. After stopping the reaction by addition of EtOH and thorough washing of the cellulose beads with demineralized water, post-oxidation was carried out in 0.1 M Na-acetate buffer (pH = 4.5) for 48 h. After the reaction, the particles were filtered off, washed thoroughly and stored in the refrigerator.

The strength of the cellulose beads was examined by means of various stamps of different weights, which were applied to a defined quantity of cellulose beads. Furthermore, microscopy images of the particles were prepared again to analyze changes in the morphology.

Enzymatically-treated, never-dried cellulose beads (10 min and 60 min reaction time) are crushed by the dead weight of a 100 g heavy stamp. Untreated cellulose beads are only reversibly deformed by the weight of this stamp. Untreated cellulose beads (blank value) are irreversibly deformed only from a stamp with a dead weight of 3 kg and crushed from 5 kg. The crushed enzymatically-treated cellulose beads show a hydrogel-like consistency and are neither tacky nor greasy.

Similar to the enzymatic treatment, the structural integrity of the beads has also been greatly reduced by TEMPO oxidation. Thus, these beads may already be irreversibly deformed with a 1 kg stamp with crack formation. Starting from a 2 kg stamp, there shows a strong crack formation and with a 5 kg stamp, the cellulose beads are already completely crushed.

In addition to these simple tests for the determination of the hardness, the microhardness was also determined from selected samples by means of a Shimadzu EZ Test X curing test device. The test was carried out with a 10 mm stamp and the deformation against the applied force was recorded. Figure 5 shows the deformation curves for enzyme-treated and TEMPO-oxidized samples.

The enzymatically-treated samples showed a drastic change in morphology. In addition to smoothing the surface, the core/shell structure also disappeared. This shows that both the dense outer skin and the interior of the cellulose beads are accessible to the enzymes and are degraded. There was no longer any difference between the outer skin and the interior of the cellulose beads; Both are components of a hydrogel.

These morphological changes in TEMPO oxidation and enzyme treatment are also confirmed by NMR investigations (see Fig. 6) as described in Example 5. Thus, the disordered cellulose content decreases in the enzyme treatment and the inner-crystalline portion thereby necessarily increases. In the TEMPO oxidation, the surface-crystalline fraction decreases strongly, as a result of which the inner-crystalline portion increases.

Example 8 - Incorporation of inorganic pigments A 33 wt.-% ZnO suspension (Type Pharma 4, dso = 1.2 pm) in 60 wt.-% of aqueous NMMO was used to prepare a Lyocell spun mass. The finished spinning mass consisted of 12.2 wt.-% of cellulose (type Bacell), 73.9 wt.-% of NMMO, 11.5 wt.-% of water, 2.4 wt.-% of ZnO and traces of stabilizer. Cellulose beads were then prepared from this spun mass as described in Example 1, V1. The outer appearance of the cellulose beads corresponded to that of the cellulose beads without ZnO addition. The ZnO content of the particles was determined to be 16.7 wt.-% (impregnation of the beads at 850°C and gravimetric evaluation of the residue against the blank value of a bead without ZnO) and the distribution by means of SEM (Hitachi S-4000 Field Emission SEM) with a built-in EDX (Oxford EDX Detector). Fig. 7 shows the very even Zn distribution in such a half Tencel bead.

Claims (14)

1. TREDIMENSIONELT CELLULOSE-FORMLEGEME, FREMGANGSMÅDE TIL FREMSTILLING AF SAMME SAMT BRUG AF SAMME

   1. Tredimensionalt cellulose-formlegeme, der har en visuelt detekterbar kerne/skal-struktur, hvor skalstrukturen har en højere densitet og lavere krystalinitet end kernen, og hvor kernen har en svampelignende struktur, kendetegnet ved, at skallen har en relativ densitet på fra 65% til 85%, og kernen har en relativ densitet på fra 20% til 60% - i forhold til kompakt cellulose - skaltykkelsen er mellem 50 mp og 200 mp, forholdet mellem skaltykkelsen og formlegemets totale diameter er mellem 1:5 og 1:50, og forholdet mellem formlegemets halvakser ikke overstiger 3:1.
2. 2. Formlegeme ifølge krav 1, hvor den aldrig-tørre variant af celluloseperlerne har et fugtindhold på 25 - 300 vægt-% i forhold til cellulosemængden.
3. 3. Formlegeme ifølge krav 1, hvor formlegemet indeholder additivsubstanser, som er blevet inkorporeret under fremstillingen, og at disse additivsubstanser er valgt fra gruppen, som indeholder ZnO, T1O2, CaCCb, kaolin, Fe2C>3, farvepigmenter på kunststofbasis, aktiv kul, superabsorptionsmaterialer, faseændringsmaterialer, flammehæmmende midler, biocider, chitosan samt andre polymerer eller biopolymerer.
4. 4. Fremgangsmåde til fremstilling af et tredimensionelt cellulose-formlegeme, som har en visuelt detekterbar kerne-/skalstruktur, en kerne, der har en svampelignende struktur, og et forhold mellem formlegemets halvakser, der ikke er større end 3:1, kendetegnet ved, at den omfatter følgende fremstillingstrin: a. opløsning af cellulosen ifølge en lyocelleproces for at opnå en opløsning, der har 10 til 15 vægt-% cellulose; b. ekstrudering af den i trin a. opnåede celloluseopløsning uden luftspalte direkte i et udfældningsbad; c. en regenereringsproces, hvor - efter at celluloseopløsningen er kommet i udfældningsbadet - forskellen mellem NMMO-koncentrationerne af celluloseopløsningen og udfældningsbadet skal være 15-78 vægt-%, fortrinsvis 40 -70 vægt-%, og forskellen mellem temperaturen af celluloseopløsningen og udfældningsbadet skal være 50 til 120 K, fortrinsvis 70 - 120 K, mere fortrinsvis 80 -120 K; d. vaskeproces ifølge perkolationsprincippet med mindst ét alkalisk vasketrin, fortrinsvis ved pH 9 - 13; e. evt. en tørreproces, som ikke skuremæssigt beskadiger formlegemernes udvendige hud; hvor den i pkt. d.) nævnte vaskeproces fortrinsvis sker i flere trin og modstrøms og indeholder mindst ét alkalisk trin.
5. 5. Fremgangsmåde ifølge krav 4, hvor tørreprocessen sker via normaltryks-tørring, strømningstørring, båndtørring, hvirvellagstørring, frysetørring eller superkritisk CO2-tørring.
6. 6. Fremgangsmåde ifølge krav 4, hvor der sker en enzymbehandling mellem trin d og trin e.
7. 7. Fremgangsmåde ifølge krav 6, hvor der anvendes en eller flere enzymer, som er valgt fra gruppen, der omfatter exo- og endo-1,4-b-glucanaser, glucosidaser og zylanaser.
8. 8. Brug af formlegemerne ifølge krav 1 til fremstilling af et bæremateriale, der er ladet med aktivt middel, hvor formlegemet vædes med en opløsning af det aktive middel og derefter vaskes og tørres.
9. 9. Brug af formlegemerne ifølge krav 1 til fremstilling af et bæremateriale, der er ladet med et aktivt middel, med controller-release-egenskaber, navnlig til kosmetiske og farmaceutiske anvendelser.
10. 10. Brug af formlegemerne ifølge krav 1 som et skurende materiale i kosmetiske produkter såsom peelings eller exfoliator-blandinger, hvor den gennemsnitlige størrelse af formlegemet er 150 - 800 pm, fortrinsvis 200 - 800 pm, mere fortrinsvis 300 - 550 pm.
11. 11. Brug af formlegemerne ifølge krav 1 som små visuelle effektkugler i kosmetiske produkter, fortrinsvis shampoo og cremer.
12. 12. Brug af formlegemerne ifølge krav 1 som udgangsmateriale til fremstilling, via slibning, af sfærisk cellulosepulver, som har sensoriske booster-egenskaber til kosmetiske produkter i olie/vand-emulsioner.
13. 13. Brug af formlegemerne ifølge krav 1 som udgangsmateriale til fremstilling af sfærisk cellulosepulver, der kan anvendes til control-release-partikler eller som kerne for control-release-partikler.
14. 14. Brug af formlegemerne ifølge krav 1 som søjlemateriale i kromatografi, navnlig i normalfase-, vendefase-, ionombytnings-, affinitets- og størrelses-eksklusionskromatografi.