Water-soluble silicon-containing granules

Abstract

Formula Y x Si(OH) 4-x A water-soluble silicon-containing granule comprising a silicon compound or an oligomer thereof of the formula: [wherein Y is an optionally substituted (C1-C4) alkyl, (C2-C5)-alkenyl, (C1-C4)-alkoxy, or amino, and x is 0 to 2], and a cold water-soluble starch material.

Description

[Technical field]

[0001] The present invention relates to formulations comprising silicon compounds in a bioavailable form, their preparation process and their use. [Background technology]

[0002] Bioavailable forms of inorganic silicon are available at dilute concentrations, i.e., <10 -3 M is chemically stable orthosilicic acid (OSA) (Iler, 1979). At higher concentrations, polycondensation of OSA occurs, resulting in the formation of oligomers and polymers. These polycondensed forms of the monomer are not absorbed by humans (Jugdaohsingh et al., 2000), but should be converted to OSA by gastric acid to allow absorption in the digestive tract. Stabilizers may be used to inhibit the polycondensation. The result is silicic acid in a bioavailable form, also known as bioavailable silicon compounds. Monoalkyltrisilanol compounds, such as monomethyltrisilanol, have also been proposed as bioavailable silicon compounds.

[0003] Both liquid and solid formulations of stabilized silicic acid have been invented by the applicant and developed into commercial products. A liquid formulation is disclosed in EP0743922 and a solid formulation prepared by extrusion-spheronisation technique is disclosed in EP1551763. The solid formulation is in the form of beadlets with a particle size between 800 and 1200 μm and is used to fill hard capsules. These products have been tested in various clinical trials and beneficial results have been found regarding bone, cartilage, hair, nails and skin. It has also been found that after oral ingestion of stabilized silicic acid, the ingested silicon compounds are mainly detected as orthosilicic acid in blood and urine.

[0004] It is desirable to provide a bioavailable solid formulation of silicic acid suitable for food, feed and pharmaceutical applications, with a predefined dosage and easily solubilized in liquids or beverages to give a low-viscosity, easy-to-drink formulation. Such a formulation contributes to patient compliance and facilitates use when the patient is traveling. The solid formulation can also be blended with other nutrients, flavors and / or sweeteners without the risk of separation and can replace beads made by extrusion-spheronization technology. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] EP0743922 [Patent Document 2] EP1551763 [Non-patent literature]

[0006] [Non-Patent Document 1] MJ Jivan et al., J. Food Science Technology (March 2014), 51(3), pp. 601-605 Summary of the Invention [Problem to be solved by the invention]

[0007] It is a first object of the present invention to provide such an improved solid formulation that contains bioavailable silicon compounds.Therefore, it is a first object of the present invention to provide a method for producing an improved solid formulation of bioavailable silicon compounds.It is a further object of the present invention to provide a dosage form that can be solubilized in liquid and has a predefined effective dosage.It is yet another object of the present invention to provide a use as a food or feed supplement.It is another object of the present invention to provide a formulation for use as a medicine. [Means for solving the problem]

[0008] The first objective is to x Si(OH) 4-x The water-soluble silicon-containing granules include a silicon compound of the formula: wherein Y is an optionally substituted (C1-C4)-alkyl, (C2-C5)-alkenyl, (C1-C4)-alkoxy, amino, and x is 0-2, or an oligomer thereof; and (2) a cold water-soluble starch material.

[0009] The second objective is to A method for providing the water-soluble silicon-containing particulate of the present invention, comprising the steps of: - Expression Y x Si(OH) 4-x [wherein Y is an optionally substituted (C1-C4) alkyl, (C2-C5) alkenyl, (C1-C4) alkoxy, or amino, and x is 0-2, preferably x=0], or a solution of a silicon compound or an oligomer thereof; - providing a cold water soluble starch material; - mixing the liquid agent with a cold water soluble starch material, and adsorbing the silicon compound onto the starch material to form silicon-containing granules; This is achieved in a method comprising:

[0010] The first object is also achieved with a granule obtainable by the method of the invention. Further objects are achieved in galenic or nutritional compositions, such as dosage forms or packages comprising the granule of the invention, in its use as a food or feed supplement, and in the granule for use in the prevention, inhibition and / or treatment of diseases associated with bone loss and cartilage degeneration, loss of hair and nail quality, alopecia, and skin aging diseases.

[0011] Further objects are further achieved in a method for preventing, inhibiting and / or treating bone loss and cartilage degeneration-related diseases, hair and nail quality deterioration, alopecia, and skin aging diseases, comprising the use of the water-soluble silicon-containing granule of the present invention and / or any dosage form or package containing said granule.In one preferred embodiment, the granule or the solid dosage form thereof is dissolved or dispersed in a beverage before its oral administration to a consumer or patient.

[0012] The inventors of the present invention have discovered that water-soluble granules containing silicon compounds such as orthosilicic acid or its oligomers can be prepared by mixing a liquid formulation of silicon compounds with cold water-soluble starch materials. This is a practical method, which avoids the use of a separate binder solution for the solid portion that is put into the granulation process. Moreover, the granules are in a suitable form for integration with other nutrients and / or solid food products. Moreover, the resulting granules prove to be very advantageous, since the customer or patient can dissolve the granules in a beverage before use. In this respect, the taste of the silicon compounds is suppressed by the taste of the beverage. Moreover, the inventors were surprised that the silicic acid in the granules does not further polymerize into a form that cannot be further absorbed by the digestive tract.

[0013] The term "cold water soluble starch" is known per se in the field of starch and relates to starch materials which, when added to water at room temperature, demonstrate a complete collapse of the granular structure and the formation of a colloidal dispersion or even a solution or an apparent solution. Non-limiting examples of modification processes are esterification, optionally combined with salt formation; alcohol-alkali treatment, as disclosed, for example, in MJ Jivan et al., J. Food Science Technology (March 2014), 51(3), pp. 601-605; mixing of starch in aqueous alcohol at high temperature and pressure; hydrolysis of starch using a mixture of sodium hydroxide and urea as hydrolysis agents; dextrinification.

[0014] Suitably, the modified starch material has a percent solubility at room temperature (25° C.) of at least 50 wt.%, more preferably at least 60 wt.%, or even at least 70 wt.%. The percent solubility is measured based on a 1 wt.% aqueous suspension of the modified starch, produced by mixing at 1,000 rpm at room temperature using a rotary shaker for 45 minutes. A supernatant is separated from the suspension using a centrifuge process (1,200 g for 15 minutes), followed by drying the supernatant (105° C., 6 hours). The percent solubility is calculated by multiplying the ratio of the mass of solids in the supernatant to the mass of the sample by 100%.

[0015] Preferred carrier materials include one or more chemically modified starch materials, such as dextrin, acid-treated starch, alkali-modified starch, bleached starch, oxidized starch, enzyme-treated starch. Preferred types of modified starch materials are esterified starches, such as monostarch phosphate, distarch glycerol, distarch phosphate esterified with sodium trimetaphosphate, phosphated distarch phosphate, acetylated distarch phosphate, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated distarch adipate, acetylated distarch glycerol, starch sodium octenyl succinate, and / or combinations thereof. Hydroxypropyl starch, hydroxypropyl distarch phosphate, hydroxypropyl distarch glycerol may also be suitable. The modified and esterified starches may furthermore be used in the form of their salts, such as the sodium salts.

[0016] More preferably, a combination of a first and a second modified starch material is used, for example the first modified starch material having a higher molecular weight than the second starch material. Good experimental results have been obtained herewith. Most preferably, both modified starch materials are so-called cold water soluble starches. It has been found experimentally that the second starch material can be incorporated in the formation of granules with a size in the range of 100-600 μm to an extent of at least 80 wt%, preferably at least 90 wt%, and in particular the amount of granules smaller than 100 μm can be reduced. A preferred combination is a combination of esterified starch with dextrin or maltodextrin. The esterified starch is more preferably a salt. The most preferred combination is a combination of starch sodium octenyl succinate and dextrin. It is considered preferable that the mass proportion of the first modified starch is present in an amount of 50-75% and the second modified starch in an amount of 25-50 wt%. More preferably, the mutual mass ratio of the first modified starch to the second modified starch is between 1.5 and 2.5, such as between 1.8 and 2.2.

[0017] The starch material may be of any desired origin, including, for example, wheat starch, maize starch, corn starch, potato starch, cassava starch, tapioca starch, etc. When a first and second modified starch are used, it is not necessary that both are derived from the same starch origin.

[0018] Preferably, silicon compounds are used in combination with a stabilizer that inhibits the polymerization of silicon compounds. The inhibition is more specifically such that it prevents the formation of water-insoluble and no longer hydrolyzable silicon polymers. Such silicon polymers are not bioavailable, i.e., the body cannot absorb silicon in absorbable forms, especially silicic acid monomers of orthosilicic acid, their oligomers and presumably certain variants thereof, such as silanols and silicates, even when consuming silicon polymers. Stabilization can be obtained by using amino acids, other organic acids, such as salicylic acid, sorbitol acid, ascorbic acid, lactic acid and caproic acid, peptides, carnitine, phenolic or polyphenolic compounds such as vanillin (4-hydroxy-3-methoxybenzaldehyde), quaternary ammonium compounds such as betaine and choline, and their derivatives. Choline compounds are preferred and are selected from, for example, choline chloride, choline bitartrate, choline hydroxide, choline dihydrogen citrate, choline 2-4-dichlorophenoxyacetate (2,4D choline salt), choline acetate, choline carbonate, choline citrate, choline tartrate, choline lactate, choline dibutyl phosphate; choline O,O'-diethyldithiophosphate, choline dihydrogen phosphate; and choline phosphate.

[0019] Good results have been found with choline chloride. When the stabilizer is a quaternary ammonium compound such as choline chloride, the liquid formulation is characterized by an unpleasant taste and unpleasant odor that can be described as fishy and bitter, which negatively impacts product compliance. This problem is overcome by using a carrier such as microcrystalline cellulose to obtain a solid pelleted formulation or a liquid-filled polysaccharide capsule. However, both of these solid dosage formulations are not water-soluble. The use of the solid formulation of the present invention overcomes this drawback.

[0020] In the most preferred embodiment, the silicic acid compound is a silicic acid monomer and / or its oligomer, known as orthosilicic acid. This corresponds to the value x=0 in formula (I). The bioavailability of orthosilicic acid has been directly proven in several scientific studies and has also been approved by the European Food Safety Authority (EFSA). Moreover, it is a natural component, compared to monomethyltrisilanol, which does not occur in nature but is a man-made synthetic compound.

[0021] Preferably, in the present invention, silicic acid substantially comprises oligomers and / or monomers of orthosilicic acid. Oligomers are, for example, oligomers that contain less than 1000 monomers, preferably less than 100 monomers per molecule. More preferably, oligomers are those in which at least 80%, preferably at least 90%, of silicon atoms are bonded to a maximum of three other silicon atoms via silicon-oxygen-silicon bridges. The term substantially herein suitably refers to at least 95wt%, preferably at least 98wt%, more preferably at least 99wt%. Silicic acid preparations that are polymerized to the extent that their hydrolysis into monomers, dimers and trimers is feasible in the digestive tract are simply referred to as bioavailable silicon. Silicic acid in such preparations can be absorbed by the human body.

[0022] In an alternative embodiment, a trisilanol compound is used as the silicon compound, such as monomethyltrisilanol. This corresponds to the option of x=1 in formula I. Trisilanol compounds may further be used in blends of silicon compounds according to formula (I) where x=0-2, preferably x=0, 1. One preferred side group Y is C1-C4 alkyl, such as methyl.

[0023] More preferably, the solid agent is particulate, with at least 80 wt% of the particles having a size in the range of 100-800 μm, as determined by sieve analysis. A preferred example sieve analysis shows the possibility of reaching a distribution in which 90% of the granules are smaller than 600 μm. Optionally, sieving can be applied to select a fraction of the granules with a specific narrow particle size distribution, or to remove particles with a size >600 μm. More preferably, the particle size distribution is such that the particles smaller than 100 μm are a fraction that represents at most 15 wt% of the particles, more preferably at most 10 wt% of the particles or even at most 5 wt% of the particles.

[0024] In a further embodiment, the silicon concentration of the dry granule is in the range of 0.002wt% to 2.0wt%. In order to limit the volume of the granule to reach the daily dose known from clinical studies, the silicon concentration is preferably at least 0.01wt%, more preferably at least 0.1wt%. Most preferably, the silicon concentration is higher than 0.5%w / w. The latter can be achieved by combining the silicon compound with a stabilizer such as, for example, a choline compound. In one advantageous embodiment, a high silicon concentration of at least 0.5%w / w in the granule is achieved by using orthosilicic acid and / or its oligomer as the silicon compound.

[0025] In a preferred embodiment, the resulting granules are dried after they are formed to a predetermined moisture content, for example up to 5 wt%, although alternatively moisture levels up to 4 wt% or up to 3 wt% can be selected.

[0026] According to an important embodiment, the granule is a fluidized granule. More specifically, it is obtained by a method comprising the steps of: (1) preparing a liquid formulation of silicon compound; (2) introducing a particulate carrier comprising starch material into a fluidized bed granulator; and (3) spraying said liquid formulation into the fluidized bed granulator while the fluidized bed granulator is in operation, the liquid acting as binder causes the carrier particles to aggregate into granules. The fluidized bed granulation process ensures a uniform distribution of the liquid silicon formulation through the carrier material. Furthermore, a good size distribution is found, and the fluidization process results in a granule with a relatively low density and porosity, which is considered to be favorable for dissolution (including the production of a colloidal solution, which is a formally dilute suspension). This embodiment is particularly important in that it combines the use of orthosilicic acid and / or oligomer as silicon compound with the presence of a stabilizer for silicon compound, more specifically a choline compound as stabilizer. For this particular silicon compound with stabilizing agent, it has proven more difficult to produce granules with uniform granule size using other wet granulation methods.

[0027] In a preferred embodiment, the granules of the present invention have a density of 0.25 to 0.60 g / cm 3 , more preferably 0.30 to 0.55 g / mol, for example, 0.33 to 0.36 g / cm 3 or a density in the range of 0.40 to 0.53 g / mol. This density is typically 0.75 g / cm 3 This is clearly lower than the density obtained by extrusion-spheronization, which results in a density of more than

[0028] In a preferred embodiment, the drying step is carried out in a fluidized bed granulator, where granules are produced. The three different steps of spraying, granulation and drying can be carried out by fluidized bed granulation and are carried out in one run in a single granulator unit. Such fluidized bed granulation units are known per se, for example from the company Glatt, equipped with various accessories for the different process steps. Fluidized bed granulation units usually contain spray nozzles that can be adjusted in terms of position and spray rate. Preferably, so-called top nozzles are used. Suitable spray rates are in the range of 500 to 2000 g / min.

[0029] In a further embodiment, the resulting granules may be provided with a coating, which is preferably applied by fluidized bed granulation. If a coating is desired, such a coating may be applied in a single unit in the same fluidized bed granulation process. Coatings may be made to alter flavor or aroma, to protect against oxidation, to alter visual appearance, or for enteric coating. Examples of coatings are film coating, enteric coating, delayed release coating, hot melt coating.

[0030] In yet a further embodiment, the fluidized bed granulation is carried out using a carrier gas, preferably air, heated above room temperature. The preferred temperature of the carrier gas is at least 50°C and not more than 120°C, preferably in the range of 70-100°C. The heated carrier gas further results in drying of the material. In a preferred embodiment, 25-40 wt% stabilized silicic acid is sprayed onto a carrier material such as 60-75 wt% modified starch, e.g. esterified starch. Several types of modified starch can be combined to vary the particle size distribution of the resulting granules. The preferred ratio between the liquid stabilized silicic acid formulation and the carrier material is 1:2.

[0031] In a further embodiment, the granules are administered and mixed into beverages and liquid foods. Thus, in one embodiment, the granules of the present invention are blended with at least one of nutrients, plant-based extracts, proteins and various bioactive molecules, and then packaged. Such blends are also known under the name "superfoods". Preferably, granules are used with a particle size distribution such that at least 90 wt%, preferably at least 95 wt% or even 100% of the particles have a diameter of at most 600 μm. Such a specific particle size distribution allows perfect blending to be obtained. The absence of large particles (>600 μm) minimizes the risk of separation of the blend components.

[0032] The customer can prepare the nutritional composition before consumption by mixing the blend and / or granules with water, dairy products (liquids such as milk and semi-liquids such as yogurt), juice, protein drinks or other drinks. Alternatively, the granules can be filled into sachets or stick packs or another type of unidose packaging. The contents are mixed with a drink and / or semi-liquid food and consumed immediately. The unidose packaging facilitates the consumer to take the product when traveling. In a further application, the granules are used as a raw material for use in the manufacture of other solid dose galenic forms, such as tablets, chewable tablets, effervescent tablets, and hard gelatin or vegetable capsules.

[0033] In further embodiments, any of these dosage forms or packages may further comprise conventional additives and nutrients, such as, for example, sweeteners; flavorings; excipients, such as anti-caking agents; trace elements, such as at least one of magnesium, boron, calcium, selenium, zinc; vitamins, such as at least one of vitamin C, vitamin D, vitamin K, etc.

[0034] For the sake of completeness, it is observed that any of the above mentioned embodiments are considered to be related to any of the aspects according to the present invention.

[0035] These and other aspects of the invention will be further elucidated with reference to the examples and figures. [Brief description of the drawings]

[0036] [Figure 1A] Figure 1 shows the silicon concentration (elemental silicon) of dissolution medium measured by GFAAS. 500mg of stabilized silicic acid granules (lot I-160713) are incubated in a dissolution apparatus with 500ml of dissolution medium at 37°C and a mixing speed of 1000rpm. After 240 minutes, the silicon concentration is 1.01% (GFAAS) w / v. [Figure 1B] Figure 1 shows the silicon concentration of dissolution medium measured by molybdenum blue colorimetry (specific for monomeric silicic acid).500mg of stabilized silicic acid granules (lot I-160713) are incubated in a dissolution apparatus with 500ml of dissolution medium at 37°C and a mixing speed of 1000rpm.After 240 minutes, the silicon concentration is 0.95% (colorimetry) w / v. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS EXAMPLES

[0037] In all examples, percentages refer to weight percentages unless otherwise specified.

[0038] Example 1 Choline chloride is treated with dry hydrochloric acid. Silicon(IV) tetrachloride is added to the formed choline solution (ratio of SiCl4 to choline chloride: 1 mole per 1-5 moles). The resulting solution is hydrolyzed by adding water (ice / ice water) while cooling to a temperature range of -10 to -30 °C. The solution is neutralized by adding sodium hydroxide, maintaining the temperature below 0 °C. The final pH is between 1 and 1.5. The pH was measured using a Stratos, type MS A405 pH analyzer from Knick, equipped with a Memosens pH electrode with an Ag / AgCl2 reference system and liquid KCl electrolyte. Following clarification with activated carbon, the precipitate is removed by filtration together with the activated carbon. The concentration of water is reduced by distillation under vacuum until a formulation containing 2.0-4% silicon by volume, 60-80% choline chloride by mass, and 15-30% water by mass is obtained. The precipitate formed during the distillation is removed by filtration.

[0039] A mixture of 65.67% sodium starch octenyl succinate (Emarusta Al, Matsutani Chemical Industry Co., Ltd., Japan) and 1% tricalcium phosphate is added to a Flowcoater FLO-120 (Freund Bldg, Japan) fluid bed system. The fluid bed granulation process is started by setting the inlet air temperature at 85°C, and when the product reaches a temperature of 50°C, 33.33% liquid choline stabilized silicic acid is sprayed onto the modified starch. Following spraying, drying of the fluidized granules is automatically started in the FLO-120 unit at a product temperature of 50°C until a moisture content of less than 3% is obtained in the granules. An example of particle size distribution measured by sieve analysis is given in Table 1, showing that 96% of the particles have a size smaller than 595 μm (30 mesh). The density is between 0.408 and 0.525 g / ml. The dried granules have an elemental silicon concentration between 0.75% and 1.5% (w / w) as measured by graphite furnace atomic absorption spectrometry (GFAAS).

[0040] [Table 1]

[0041] The dried granules have an elemental silicon concentration between 0.75% and 1.5% (w / w) measured by graphite furnace atomic absorption spectrometry. Surprisingly, analysis of dissolution medium containing 500 mg of granules in 500 ml of dissolution medium shows identical profiles when analyzed by GFAAS analysis or by molybdenum blue colorimetry (see Figure 1). The latter is only reactive towards monomeric silicic acid. This indicates that the granulation process does not result in polycondensation of the stabilized silicic acid, which is quickly released from the starch carrier into the aqueous environment.

[0042] When incubated in a closed container at 40° C. and 75% relative humidity for 6 months, the silicon concentration, measured by the molybdenum blue colorimetric method, does not change significantly (see Table 2), indicating that the granules have excellent stability.

[0043] [Table 2]

[0044] Example 2 The silicic acid granules prepared according to Example 1 are mixed with sweeteners, salt and flavors using the following recipe:

[0045] [Table 3]

[0046] The blend has excellent flow properties and can be easily filled into single dose stick packs (4 g per stick pack). The filled stick packs were incubated at 40° C. for 6 months to test the stability of the flavor granules. As shown in Table 3, excellent stability was found and no interactions occurred between the stabilized silicic acid and the added compounds.

[0047] [Table 4]

[0048] Example 3 Choline chloride is treated with dry hydrochloric acid. Silicon(IV) tetrachloride is added to the formed choline solution (ratio of SiCl4 to choline chloride: 1 mole per 1-5 moles). The resulting solution is hydrolyzed by addition of water (ice / ice water) while cooling to a temperature range of -10 to -30 °C. The solution is neutralized by adding sodium hydroxide and the temperature is maintained below 0 °C. The final pH is between 1 and 1.5. The pH was measured using a Stratos, type MS A405 pH analyzer from Knick, equipped with a Memosens pH electrode with an Ag / AgCl2 reference system and liquid KCl electrolyte. Following clarification with activated carbon, the precipitate is removed by filtration together with the activated carbon. The water concentration is reduced by distillation under vacuum until a formulation containing 2.0-4% silicon by volume, 60-80% choline chloride by mass and 15-30% water by mass is obtained. The precipitate formed during the distillation is removed by filtration.

[0049] Modified starches, namely octyl-succinate starch commercially available as Capsul HS (Ingredion) and dextrin (Crystal Tex 626, Ingredion) and combinations thereof, are used as carriers for liquid choline-stabilized silicic acid (ch-OSA) in a laboratory-scale fluidized bed equipment type GPCG1.1 (Glatt). The formulation is shown in Table 4. A hot inlet air flow of 80-100°C fluidizes the dried starch and dextrin, resulting in a maximum product temperature in the range of 60-70°C. The choline-stabilized silicic acid is sprayed onto the carrier using a top nozzle, resulting in the formation of granules that are dried in the same equipment until a loss on drying of less than 3.5% is obtained. Depending on the formulation, the density of the dried granules is 330-360 g / l. Sieving analysis shows that more than 90% of the particles are smaller than 600 μm (see Table 5). The use of dextrin results in less dust (ie particles less than 100 μm) and improves the processability and flowability of the resulting granules.

[0050] [Table 5]

[0051] [Table 6]

[0052] Example 4 Example 3 is repeated in a larger pilot-scale GPCG15 system (Glatt) with a mixture of 8 kg Capsul HS and 4 kg Crystal Tex 626 used as a carrier for 6 kg choline-stabilized silicic acid, but with an inlet air flow of only 65° C., resulting in a maximum product temperature of 53° C. Again, at these conditions, the pilot-scale fluidized bed process results in a granulate with more than 90% of the particles having a size smaller than 600 μm (see Table 6). Experiment A47-06 uses a higher spray rate than experiment A47-05, in the range of 500-2000 g / mol, so the granules are coarser and very fine particles (dust, <100 μm) are removed.

[0053] [Table 7]

[0054] The silicon concentration of all formulations, both laboratory and pilot scale, is between 0.99-1.05% (w / w). The water content of the formulations is between 2-3% (w / w).

[0055] Example 5 Example 4 was repeated at industrial level. 140.8 kg Capsul HS and 70.4 kg Crystal Tex626 were used as carriers for 105.6 kg choline-stabilized silicic acid in a GPCG300 fluidized bed system equipped with top spray nozzles. Using an inlet air temperature of 65°C, the solid materials were heated to 53°C, and the choline-stabilized silicic acid was then sprayed into the fluidized bed at a spray rate of 540-1800 g / min and a pressure of 2 bar. The same temperature as the inlet air was used for drying, resulting in a final granule moisture content of 3-4%.

[0056] The bulk density of the resulting granules was 0.356 g / cm 3 with 93% of the particles having a size less than 600 μm and 94% having a size of at least 125 μm. The particle size distribution is shown in Table 7 and demonstrates that the particle size distribution obtained in the industrial scale experiment does not differ significantly from the laboratory scale experiment. The total output of the process was 293 kg of granules.

[0057] Random samples were taken to check for uniformity. The results summarized in Table 8 demonstrate the formation of a uniform product. This confirms that the industrial granulation process does not result in polycondensation of stabilized silicic acid, as GFAAS and molybdenum analysis revealed no difference in silicon concentration.

[0058] [Table 8]

[0059] [Table 9]

[0060] Example 6 The granules obtained in Example 1 were mixed with the following formulation: - 200 mg Choline-stabilized Silica Granules - 90.01 mg microcrystalline cellulose - 6mg calcium stearate - 3.99 mg tricalcium phosphate - 3mg shellac The tablets were compressed using

[0061] When packed into alu / alu foil and incubated at 40° C. and 75% relative humidity for 3 months, the tablets were found to be stable as GFAAS and molybdenum analysis revealed no difference in silicon concentration and disintegration times remained the same over time (Table 9).

[0062] [Table 10]

[0063] Example 7 The granules obtained in Example 1 were mixed with the following formulation: - 500mg Choline-stabilized Silica Granules - 1.25g microcrystalline cellulose - 650mg of Advantose - 10mg sucralose - 300mg maltodextrin - 100mg Magnesium Stearate - 30mg ginger-lemon flavoring - 30mg banana flavoring - 45mg Ascorbic Acid The mixture was compressed into chewable tablets using a 500 ml 500 ml mixer.

[0064] When packed in alu / alu foil and incubated at 40° C. and 75% relative humidity for 3 months, the tablets were found to be stable as GFAAS and molybdenum analysis also revealed that the silicon concentration was no different and remained unchanged over time (Table 10).

[0065] [Table 11]

Claims

1. - silicic acid or its oligomers, or monoethyltrisilanol, and - Cold water soluble starch materials Also includes The composition further comprises a stabilizer that inhibits polymerization of the silicon compound, the stabilizer being a choline compound; the choline compound is selected from choline, choline chloride, choline bitartrate, choline hydroxide, choline dihydrogen citrate, choline 2-4-dichlorophenoxyacetate, choline acetate, choline carbonate, choline citrate, choline tartrate, choline lactate, choline dibutyl phosphate, choline O,O'-diethyldithiophosphate, choline dihydrogen phosphate, and choline phosphate; Water-soluble silicon-containing granules.

2. 2. The water-soluble granular material according to claim 1, wherein the silicon compound is orthosilicic acid.

3. 0.30 to 0.60 g / cm 3 The water-soluble granule according to claim 1 or 2, having a density in the range of

4. 4. A water-soluble granule according to any one of claims 1 to 3, wherein at least 90 wt% of the granules have a diameter of at most 600 μm and at least 80 wt% of the granules have a diameter of at least 100 μm.

5. 5. The water soluble granule according to any one of claims 1 to 4, wherein the cold water soluble starch material comprises starch chemically modified to an esterified starch with an organic acid or a salt thereof.

6. 6. The water-soluble granule according to claim 5, wherein the organic acid is selected from phosphoric acid, acetic anhydride, adipic acid, and octenylsuccinic acid.

7. 7. The water-soluble granule according to claim 5 or 6, wherein the esterified starch or its salt is starch octyl succinate or its alkali salt.

8. 8. The water soluble granule according to claim 1, wherein the cold water soluble starch material comprises dextrin or maltodextrin.

9. 9. The water-soluble granule according to claim 1, wherein the silicon concentration is in the range of 0.5 to 2.0 wt. % based on the total mass of the granule.

10. A method for preparing a water-soluble silicon-containing particulate material, comprising the steps of: - preparing a solution of silicic acid or an oligomer thereof, or monomethyltrisilanol, further comprising a stabilizer that inhibits polymerization of the silicon compound, the stabilizer being a choline compound; - providing a solid cold water soluble starch material; - mixing said liquid agent with said solid cold water soluble starch material, whereby silicic acid or its oligomers, or monomethyltrisilanol, is adsorbed onto the starch material to form water soluble silicon-containing granules. Including, The method of claim 1, wherein the choline compound is selected from choline, choline chloride, choline bitartrate, choline hydroxide, choline dihydrogen citrate, choline 2-4-dichlorophenoxyacetate, choline acetate, choline carbonate, choline citrate, choline tartrate, choline lactate, choline dibutyl phosphate, choline O,O'-diethyldithiophosphate, choline dihydrogen phosphate, and choline phosphate.

11. 11. The method of claim 10, wherein the starch material is provided into a fluid bed granulator and fluidized, and the liquid is sprayed into the fluid bed granulator while the fluid bed granulator is running, the liquid acting as a binder to cause the starch material particles to aggregate into granules.

12. A galenical or nutritional composition, such as a package or dosage form, comprising a granulate according to any one of claims 1 to 9.

13. 13. A method for preparing a nutritional composition according to claim 12 as a food or feed supplement by dissolving and / or dispersing a granulate according to any one of claims 1 to 9 in water, a beverage and / or other aqueous solution or dispersion.

14. A galenical composition according to claim 12 for use in the prevention, inhibition and / or treatment of diseases associated with bone loss and cartilage degeneration, loss of hair and nail quality, alopecia and skin ageing diseases.

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