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Title:
HYDRONIUM STABILIZED AND DISSOLUBLE SILICIC ACID NANOPARTICLES: PREPARATION, STABILIZATION AND USE
Document Type and Number:
WIPO Patent Application WO/2009/127256
Kind Code:
A1
Abstract:
The present invention relates to hydronium stabilized silicic acid nanoparticles able to dissolve in aqueous environments, to their preparation and use. The present invention provides a stable suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, a molar silicon concentration between 0.035 and 0.65, a free water concentration of at least 30% (w/v) and a ratio between hydronium ion and Si molar concentrations higher than 2 and preferably inferior to 4. The present invention further provides a method for preparing a stable suspension of colloidal silicic acid nanoparticles, which comprises the steps of providing an aqueous inorganic or organic silicon solution and quick mixing said aqueous inorganic or organic silicon solution with water containing a strong acidic compound at a temperature inferior at 30°C, preferably comprised between 1 and 25°C, to form a suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, stabilized by hydronium ions, the ratio between hydronium ions and Si molar concentrations being higher than 2 and preferably inferior to 4, for a molar silicon concentration between 0.035 and 0.65 and a free water concentration of at least 30% (w/v).

Inventors:
SUVEE IVO (PE)
TOURGIS GUILLAUME (FR)
Application Number:
PCT/EP2008/054643
Publication Date:
October 22, 2009
Filing Date:
April 17, 2008
Export Citation:
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Assignee:
JISBREY S A (UY)
AQUARIUS INVEST HOLDING SARL (LU)
SUVEE IVO (PE)
TOURGIS GUILLAUME (FR)
International Classes:
C01B33/143; A23K1/175; A23L1/304; A61K33/00; C01B33/12; C05D9/00
Domestic Patent References:
WO2003101915A12003-12-11
Foreign References:
US2588389A1952-03-11
US2408654A1946-10-01
US2392767A1946-01-08
EP1110909A12001-06-27
Attorney, Agent or Firm:
HENNION, Jean Claude (27bis rue du Vieux Faubourg, Lille, FR)
Download PDF:
Claims:

CLAIMS

1. A stable suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, a molar silicon concentration between 0.035 and 0.65, a free water concentration of at least 30% (w/v) and a ratio between hydronium ion and Si molar concentrations higher than 2.

2. A suspension according to claim 1 wherein the suspension particles pass through a 0.1 micron filter but are not filterable on a MW 20.000 filter.

3. A suspension according to claim 1 for which 29 Si NMR shows a typical colloidal silica spectrum with a separated low Q2 peak having between 5 and 10% of total peak area.

4. A suspension according to claim 1, further comprising an organic sulfur compound such as MSM (dimethylsulfonylmethane) or DMSO (dimethylsulfoxide) as stabilizer, in concentrations varying from 0.01 to 5% (w/v).

5. A suspension according to anyone of claims 1 to 4 further comprising a secondary stabilizer showing the following characteristics: good water solubility, strong hydronium attracting, and neutralizer of ROS (reactive oxygen species) inducing polymerization.

6. A suspension according to claim 5 wherein the secondary stabilizer, present in concentrations ranging from 0,5% (W/V) to 60% (W/V), most preferably between 20 and 50% (W/V), is selected from the chemical group glycol (propylene glycol, etc..) poly-ether compounds, sulfated polysaccharides, polymers of carboxylic acid and hydroxyl acids or combinations thereof.

7. Formulation comprising mono- and di-silicic acids consisting in the suspension according to anyone of claims 1 to 6 diluted in an aqueous environment at pH between 2.5 and 9.5.

8. Formulation according to claim 7 supplemented with:

i - micro- and macro nutrients such as:

A) soluble salts and sources of macro- and micro and trace elements, different sources (salts, oxides, complexes, etc..) of Ca, K, Na, Mg, Mn, B, Li, Sr, Se, Mo, Fe, Co, Cu, Zn, Ti, Al, Ag, Cr, Si, P, S, N, F, Cl, Br, I or

5 mixtures thereof.

B) nutrients such as sugars, fats, proteins, nucleic acids, vitamins, amino acids, plant extracts, biological macro molecules, primary and secondary plant metabolites, compounds of biological pathways (glucosamine, chondroitin, hyaluronic acid, carnitine, organic acids, acetyl compounds,...) l O and combinations thereof, or mixtures thereof; ii - growth activators, fertilizers, biological active compounds for crop production and protection. iii - hydrophilic and hydrophobic anti-oxidants such as carotenoids (beta- carotene, lutein, lycopene, zeaxanthin,...), flavonoids (quercetin,

15 hesperetin, luteolin, rutin...), accepted food additives, antioxidative enzymes, phenolic acids, lipoic acid, Co-QlO... iv - enzyme inhibitors, hormones, antibiotics, or other pharmaceuticals v - natural and synthetic food colorants, food sweeteners, food emulgators and food flavourings, 0 or mixtures thereof.

9. Method for preparing a stable suspension of colloidal silicic acid nanoparticles according to the claim 1, which comprises the steps of:

- providing an aqueous inorganic or organic silicon solution;

- quick mixing said aqueous inorganic or organic silicon solution with water 5 containing a strong acidic compound at a temperature inferior at 30 0 C, preferably comprised between 1 and 25°C, to form a suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, stabilized by hydronium ions, the ratio between hydronium ions and Si molar concentrations being higher than 2, preferably inferior to 4, for a molar silicon concentration 0 between 0.035 and 0.65 and a free water concentration of at least 30% (w/v).

10. Method according to claim 9 in which strong mineral acids used are selected among: HCI, H 3 PO 4 , H 2 SO 4 and HNO 3 .

11. Method according to claim 9 in which completely solubilized silicates or silicon salts are used as inorganic silicon compounds.

12. Method according to claim 9 in which organic silicon solutions used are aqueous solutions of hydrolysable organic silicon compounds, most preferably alkoxy silanes or alkylesters of mono silicic acid (Si(OR) 4 ), Si(OR) 3 OH, Si(OR) 2 (OH) 2 , SiOR(OH) 3 in which R is a lower alkyl compound and ROH is a water soluble compound resulting from hydrolysis of the organic compound.

13. Method according to claim 9 in which the stabilized suspension of colloidal silicic acid nanoparticles is further stabilized for periods of time comprised between 4 weeks and 6 months by addition to said suspension of an organic sulfur compound such as MSM (methylsulfonylmethane) or DMSO (dimethylsulfoxide), in concentrations varying from 0.01 to 5% (w/v).

14. Method according to claim 9 in which the stabilized suspension of colloidal silicic acid nanoparticles is further stabilized for longer periods (more than a year) by the addition of a secondary stabilizer, which is a strong hydronium attracting substance, soluble in water and preferably selected from the chemical group glycol (propylene glycol, etc..) poly-ether compounds, sulphated polysaccharides, polymers of carboxylic acid and hydroxy! acids or combinations thereof.

15. Method for preparing the formulation according to claim 7, comprising the step of dissolving in water or aqueous solution the suspension according to claim 1 or claim 4.

16. Use of the stable suspension according to anyone of claims 1 to 4 as source of mono- and di-silicic acid for micro-organisms, plants, animals and humans.

17. Use of the stable suspension according to anyone of claims 1 to 4 for anticorrosive applications as such or in combination with molybdates or other anti- corrosive compounds upon dilution.

18. Use of the formulation according to claim 8 as food supplement, nutraceutical, food additive, pharmaceutical preparation, topical formulation, hygienic formulation, concentrated fertilizer and growth regulator, concentrated plant protection formulation, concentrated bio-available silicon formulation to induce biological processes in plants, animals, humans and micro-organisms.

19. Use of the formulation according to claim 8 to supplement the drinking water of animals and humans or as plant fertilizer aiming to increase the concentration of omega 3 fatty acids in these organisms.

Description:

HYPRONIUM STABILIZED AND DISSOLUBLE SILICIC ACID NANOPARTICLES: PREPARATION. STABILIZATION AND USE

The present invention relates to hydronium stabilized silicic acid nanoparticles able to dissolve in aqueous environments, to their preparation and use.

Silicates are abundant as silicates and alumino silicates. They make up nearly all the earth's crust. Many organisms use silica as protecting or fortification material against predators, infection or extreme environmental conditions. Silica can also participate in metazoan development and may influence enzymatic reactions.

Specific bacteria, protozoa, algae and plants make certain silica structures. They use silicon anions, silicate complexes or mono silicic acid to create specific silica (polymerized) structures, which are normally used as protecting shell layer. Some sponges form spicules allowing anchoring. They make therefore a differentiated cell type producing scaffolding silicatein proteins. Diatoms which are important in the biogenic silicon cycle form silicate frustules as protecting layer against predators.

Silicon is found in plants at concentrations ranging from 0,01 to 10% or more (dry weight basis). This is much higher than most macro nutrients. Multiple studies demonstrated the role of silicon as an alleviator of biotic and abiotic stress induced by other organisms (bacteria, fungi, viruses, protozoa, insects,...) and physical conditions (salt stress, drought stress, water stress, heat stress, osmotic stress, cold stress, etc.). Different parts of the plant may show large variations in silicon uptake. Silica phytoliths are observed in the cell walls or lumina of plant cells. There are also associations visible with cell wall components (polysaccharides, pectins, lignins, proteins, etc.). Non polymerized silica as mono and disilicic acid, the precursors of biogenic silica, may also play an active role in certain enzymatic systems involved in oxidative stress and in the biosynthesis and metabolism of certain macro molecules important in biochemical pathways (ref. 22, 23).

Humans are continuously exposed to different sources of silicon as dust (silica, silicates), soil particles (silicates, silica) dissolved silica in water, health products, inert silicon dioxide in pharmaceuticals and cosmetics, organic silicon compounds in medical implants and devices, dietary additives (inert silicates), dietary supplements (colloidal gels, dissoluble organic silicon compounds), plant extracts (phytolytic), cosmetics and toiletries (insoluble silicates), detergents, etc. Typically none of these products are highly bio-available. Only dissoluble silica and mono or disilicic acid in drinking water and in food or dietary supplements are bio-available for human. Most silicon compounds are taken up by diet and drinking water. The dietary intake in a Western diet is about 15-60 mg Si/day. Higher consumption of plants results in a higher intake up to 200 mg Si/day. Beer also is an interesting source of bio available silicon.

The gastro intestinal absorption of silicon depends mainly on the presence of absorbable species of silicic acid and silicates. Only soluble silicates (or silicate complexes) and mono- or disilicic acid from dissolution of silica compounds are readily absorbed and excreted.

Moreover, silicon is still a risk factor in human diseases (ref. 24, 25, 26, 27, 28). More specifically crystalline (sands) or amorphous (natural or synthetic) silica is active through macrophage activation and release of cytokines, growth factors and oxidants (ROS). Some concerns have even been expressed on a possible association between silica and esophageal cancer. It is therefore important to produce a silica sol compound which is soluble, hydrated and preferably quickly dissoluble upon dilution. Stable and purified synthetic sol particles could be harmful. Soluble silica compounds are not at all toxic. Crystalline silica may release free radicals in solution (ROS) in combination with soluble iron and may damage directly the epithelial cell layer. It is important that the stabilizing agent is able to scavenge the ROS radicals, which are also inducing polymerization. It is therefore crucial not to use dried or evaporated silica which dissolutes very slowly.

Silicon is not yet recognized as an essential element although it is essential for specific bacteria, fungi, diatoms and plants related to survival and replication.

Silicon plays also an important role in the growth and strength of animals and

humans. Silicon is strongly related to the development of connective tissue and the activity of cells present in the extra cellular matrix and could play an important therapeutic role in the maintenance and prevention or treatment of extra cellular matrix related diseases such as arteriosclerosis, arthritis, osteoarthritis, osteoporosis, skin - hair and nail diseases, reduced mineralization of bone, reduced collagen synthesis, reduced skeleton growth, joint diseases, healing of fractures, etc.... It is also important in detoxification of aluminum ions and other toxic metals. Several recent publications show the importance of silicon in bone health and especially in the synthesis of collagen. It is therefore important to have access to an acceptable technology and a formulation of bio available silicon for plants, animals and humans.

The following patents: US 1233933, US 3867304, W002/051748, US 2356774, US 2391255 and US 3083167 deal with silica sol formation in acid medium. These documents disclose silica sols stabilized by means of ionic transfer or by use of organic silicic acid complexing compounds.

Many silicic acid compositions have been proposed as silicon suppletion products for plants, animals and humans, but they deal with non colloidal silicon or stabilized monosilicic acid.

US 4037019 discloses acidic hydrosols and process for coating therewith. Metal silicates or hydrous magnesium silicate and optionally a magnesium compound and a boron compound are mixed in acidic medium. The obtained sols are resistant for at least 15-20 minutes. This invention describes mixtures of silicate (solid powders) which are not at all soluble in acidic medium.

US 6335457 describes a complex containing biologically assimilable orthosilicic acid, wherein orthosilicic acid is complexed with a polypeptide and under solid, stable and concentrated form.

EP 743922 describes the preparation of ortho silicic acid (monomer) stabilized with a quaternary ammonium compound by dissolving a silicon compound in the solution containing the stabilizing agent. Silicon molar concentrations higher than

1.4 are obtained at values under pH 4. No colloidal silicon is formed. The stabilizer must always be present and cannot be omitted.

US 20060178268 teaches an aqueous solution containing boric acid and non- colloidal silicic acid. Boron is present during hydrolysis of the silicon compound in an acidic solution. Boric acid absorbs to the oligomers. Without the presence of a humectant at a high concentration only very low silica (up to 0.0035 mol) and boron concentrations can be obtained. Boron is needed for stabilization of non colloidal oligomers and for the much higher biological activity. Without boron and the humectants the stability is lost at higher molar silicon concentrations at pH values below 2. The small oligomers are not retained on a MW 20.000 filter or filters with higher cut off. Humectants include urea, dextran, polysorbate, glycol, sorbitol, galactose, cellulose, vegetable gum. They must be used at concentrations higher than 30% (W/V). Boron free solutions could not be obtained by this formulation.

US 2006099276 describes a method for the preparation of silicic acid comprising extrudate, said extrudate, its use and a pharmaceutical composition comprising the said extrudate. An extrudate of stabilized silicic acid as mono silicic acid or its oligomers is proposed. These compounds are formed in the presence of quaternary ammonium compounds, amino acids or an amino acid source and mixed with a carrier. This mixture is extruded and dried before use. Mono silicic acid and oligomers up to 40 units could be present at maximum 1.25 mol Si. Pellets are the final result. 29 Si NMR shows QO and Ql peaks, characteristic for mono and disilicic acid.

EP 1110909 describes a method for preparing ortho- or mono silicic acid starting from an acid hydrolysable compound in the presence of a solvent agent in order to prevent polymerization into oligomers and colloidal silica. The solvents for stabilization are glycols, glycerol, DMSO, polysorbate 80 and polyglycols. Mono silicic acid is made in situ. The silicon concentration is in the range of 0.01 to

50% (W/V). Silicic acid remains in its monomeric form. All examples mentioned are performed with glycerol as solvent. The solvent cannot be removed anymore

(high boiling temperature).

There is still a need to produce and stabilize, for longer periods, silicic acid particles in aqueous solutions, which are able to quickly dissolve into the bioavailable forms of silicon, the mono and disilicic acids, upon dilution in an aqueous environment. Such sols are also more important than mono- or di-silicic acid in detoxification reaction of heavy metals.

Silica is ubiquitous in nature. Its precursor molecules (silicate anion, mono and disilicic acid) are present in water at low concentrations. These forms are taken up by plants and all other organisms. Silica particles formed after polymerization under natural pH conditions are negatively charged and interact with all kind of cells in the environment. Very slow dissolution of these particles finally results in mono silicic acid which is taken up by the plant cells or other organisms.

It is generally accepted that polymerization of monosilicic acid occurs at pH values under 7 through formation of siloxane bonds resulting in dimers, trimers, tetramers and larger oligomers. These mostly cyclic oligomers assemble very quickly into large fibrils and form a three-dimensional open network which results by further associations in gel formation. The oligomers show Angstrom (A) dimensions (non colloidal) and subsequent small sols or nano-particles which assemble in nanometer and micrometer fibrils or particles before gel formation. Primary sol particles are formed after active polymerization of hundreds of oligomers (colloidal). Once sol particles are formed it is difficult to inhibit further association and polymerization of these particles into larger particles and fibril associations (micrometer sols).

The silicate anion shows different structures: linear, planar, cyclic and three dimensional. Silicon nuclear magnetic resonance (NMR) spectroscopy provides a basic method for characterizing silicate anion mixtures. It uses the relationship between the silicon atom and its neighbors, counting the number of other silicon atoms to which atom it is connected to through an oxygen atom (QO, Ql, Q2, Q3 and Q4). QO: monomeric (no connections) is typical for mono silicate and Q4 is typical for all atoms in the interior of polymeric colloidal silica (ref. 29, 30,31,32,33, 34, 35).

Colloidal silica shows no QO and Ql peaks but heterogeneous and multiple Q3 and Q4 peaks. Oligomeric structures show distinct homogeneous Ql, Q2 and Q3 peaks. The ratios between the Qs are also different in oligomeric and colloidal silicic acid. Mono and disilicic acids show the same peak characteristics as the mono and disilicate ions.

Mono silicic acid is normally neutral and relatively inert to physical conditions. It may easily cross different membrane structures. Silicate complexes and silica species (negatively loaded) react more on the different mucus layers in the intestines.

There are practically no extensive studies concerning sol and gel formation from monosilicic acid and oligomers at pH values under 1, starting from solutions of inorganic or organic silicon compounds. There are a lot of studies dealing with the formation of silica sol with the intention to make different kinds of gels. Silica sol - gel experiments with different water, silicon and proton concentrations were mainly prepared to study the effect on the gelling time, pore size and characteristics of the gel. (ref. 1 to 20). It was demonstrated that at pH values below the point of zero charge (pH 2) and more specifically at pH values inferior to 1 that the gelation time increases and sol - gels are formed quite rapidly (ref. 21). Surprisingly, the applicants discovered that only in this low pH region, nano particles of silicic acid are formed and stabilized under specific conditions.

Colloidal silica nano particles for industrial use are normally stabilized after purification between pH 2 and 9. At the end of the preparation stabilized concentrated (superior to 0.7 mol Si) and desalted sols are mostly proposed. The situation under pH 2 and more precisely under pH 0.9 is not fully documented. It is proposed that dimeric silicic acid forms quickly siloxane bonds resulting finally in gelation under pH 0.9 because the polymerization time decreases (rate increases) very quickly under pH 2. It is also known that the addition of salts or peroxides (H 2 O 2 precursors of reactive oxygen species), induces polymerization.

The aim of the present invention is to synthesize de novo nano silicic acid particles, stable for long periods and able to dissolve quickly into mono and

disilicic acid (bio available silicon) upon dilution in aqueous environment. It was found that the preparation of such stabilized sols under strict final hydronium ion, silicon, water and salt concentrations is only possible under pH 0.9 and silicon molar concentrations between 0.035 and 0.65.

The applicants have carefully studied the formation of silicic acid under strong acidic conditions in water starting from inorganic or water soluble organic silicon compounds. So they discovered the existence of small colloidal particles passing through a 0.1 micron filter but not filterable on a MW 20.000 filter without adding any stabilizing compound (liquid or solid compound). The experiments were performed under strict conditions of pH and silicon concentration. The stabilization was done by hydronium ions at pH conditions under 0.9 and silicon molar concentrations between 0.65 mol en 0.035. The temperature is preferably between 1 and 25°C. The colloid is formed during the first hour and might be further stabilized for 12 hours at low temperature. It is stable for weeks or months depending on the silicon concentration and the temperature. The free water (non-hydronium, or pure, solute-free water) concentration is minimal 30%. The standard dissolution test was performed with 0.3 molar concentration of silicon by a 50 fold dilution at pH above 3 in water. Quick dissolution occurs after a few hours at pH 4 and 30 0 C, after 30 minutes at pH 4 and 37°C and at pH 6.5 and 30 0 C. Instant dissolution occurs at pH above 8. Narrow peaks of mono and disilicic acid are seen in 29 Si NMR.

According to a first aspect, the present invention provides a stable suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, a molar silicon concentration between 0.035 and 0.65, a free water concentration of at least 30% (w/v) and a ratio between hydronium ion and Si molar concentrations higher than 2 and preferably inferior to 4.

Stabilization of this suspension is at least 3-6 weeks at room temperature for a molar silicon concentration of 0.2 and 6-12 weeks at temperatures under 6°C This corresponds to the period of time during which a visual observation of the suspension shows it is clear (transparent).

29 Si NMR shows a typical colloidal silica spectrum with:

- no QO and Ql peaks for mono silicic acid and disilicic acid;

- separated low Q2 peak, between 5 and 10% of total peak area;

- heterogeneous peak domains around Q3 and Q4.

Other properties of the suspension according to the invention are listed below:

• A yellow complex is formed with H 2 O 2 (at concentration of H 2 O 2 above 0.02%).

• Source of mono- and disilicic acid upon dilution.

• Highly bio available upon dilution for plants, animals and humans.

• Gel formation after addition of certain humectants as glycerol, mono- and disaccharides, polysaccharides, polysorbates, etc.. in concentrations above 10% (W/V).

• Gel formation upon evaporation or drying with loss of more than 20% water.

• Useful as aluminum neutralizer.

• Only high concentrations (molar concentration superior to 3) of monovalent alkali metals cations destabilize the colloidal suspension.

According to another aspect, the present invention further provides a method for preparing a stable suspension of colloidal silicic acid nanoparticles, which comprises the steps of:

- providing an aqueous inorganic or organic silicon solution;

- quick mixing said aqueous inorganic or organic silicon solution with water containing a strong acidic compound at a temperature inferior at 30 0 C, preferably comprised between 1 and 25°C, to form a suspension of colloidal silicic acid nanoparticles having a pH lower than 0.9, stabilized by hydronium ions, the ratio between hydronium ions and Si molar

concentrations being higher than 2 and preferably inferior to 4, for a molar silicon concentration between 0.035 and 0.65 and a free water concentration of at least 30% (w/v).

This suspension is prepared after titration and calculation of the needed stabilizing hydronium concentration. Mono silicic acid and its oligomers polymerize into nano silicic acid particles until stabilization by hydronium ions and do not grow further. They are quickly dissoluble upon dilution.

During the acidification strong mineral acids are used such as HCI, H 3 PO 4 , H 2 SO 4 , HNO 3 , etc... Most preferably HCI and HNO 3 are used.

Completely solubilized silicates or silicon salts are used as inorganic silicon compounds.

Organic silicon solutions used are aqueous solutions of hydrolysable organic silicon compounds, most preferably alkoxy silanes or alkylesters of mono silicic acid (Si(OR) 4 ), Si(OR) 3 OH, Si(OR) 2 (OH) 2 , SiOR(OH) 3 in which R is a lower alkyl compound C 1 -C 4 and ROH is a water soluble compound resulting from hydrolysis of the organic compound.

In a preferred embodiment of this method, the stable suspension of colloidal silicic acid nanoparticles is further stabilized for periods of time comprised between 4 weeks and 6 months by addition to said suspension of an organic sulfur compound such as MSM (methylsulfonylmethane) or DMSO (dimethylsulfoxide), in concentrations varying from 0.01 to 5% (w/v).

Further stabilization of the colloid suspension for longer periods can be obtained by adding a secondary stabilizer showing the following characteristics: good water solubility, strong hydronium attracting, and neutralizer of ROS (reactive oxygen species) inducing polymerization.

Normal humectants as mono- and polysaccharides (glycerol, lactose, maltose, dextrose, sucrose, sorbitol, xylitol, glucose, dextran, cellulose, cellulose derivates, glucans, starch, pectines, alginates, proteins or hydrolysates, polysorbate) are not

useful as secondary stabilizer for the suspension according to the invention and induce on the contrary aggregation of the colloidal particles into gel formation.

This is completely different to the stabilization of monomeric silicic acid and oligomers previously described. Colloidal silicic acid forms nano particles while mono silicic acid and oligomers are Angstrom sized. Inhibition of colloidal silicon formation in the latter preparations can therefore only be successful when the humectants are already present at high concentrations during the preparation and hydrolysis of the precursor, resulting in a complexation with monomeric silicic acid or oligomers.

Stabilization of colloidal silicic acid according to the invention is performed through attraction of the hydronium ions surrounding the silicic acid coils or spheres inhibiting condensation of the nano particles into bigger sols and gel formation. These newly described colloids don't show QO and Ql peaks in 29 Si NMR and Q2 is present. This spectrum resembles biogenic silica but the particles are much more dissoluble. Broad multiple peaks are seen in the Q3 and Q4 region. Mono and disilicic acid show always very narrow peaks QO and Ql and oligomers show distinct narrow Ql, Q2 and Q3 peaks and combinations thereof and a minor Q4 peak.

Dissolution of the colloid occurs quickly after dilution and at pH equal or superior to 3. 29 Si NMR of the dissoluted solution shows clearly a narrow QO and Ql peak. The Ql peak is mostly remarkable high (more than 7% of the concentration).

The stable suspension of colloidal silicic acid nanoparticles is further stabilized for longer periods (more than a year) by the addition of a secondary stabilizer, which, as indicated above, is a strong hydronium attracting substance, soluble in water and preferably selected from the chemical group glycol (propylene glycol, etc..) poly-ether compounds, sulphated polysaccharides, polymers of carboxylic acid and hydroxyl acids or combinations thereof.

With secondary stabilizer, the stable suspension acquires resistance against strong polymerization inducers such as peroxides (H 2 O 2 , peracetic acid and mono

persulfates, etc) and high mineral concentrations (salts of Calcium, Magnesium, Strontium, Iron, Cobalt, Boron, Copper, Zinc, etc.).

Addition of molybdate to this stable suspension results only in a typical marine blue coloration for the mono silicic acid complex formation after more than 1 year at room temperature.

The hydronium attractant is present in concentrations ranging from 0.5% (W/V) to 60% (W/V), most preferably between 20 and 50% (W/V).

The addition of such attractants results in an increased stability of the colloidal suspension for more than 3 years at 4°C and more than 2 years at 37°C.

This suspension is also stable after addition of hydrogen peroxide which normally induces sol and gel formation. Up to 25% hydrogen peroxide could be combined with 0.18 mol Si and results in a stable suspension for 1 year at 25°C.

This suspension quickly dissolves upon dilution in water or an aqueous solution into mono and disilicic acid at pH between 2.5 and 9.5 and forms water insoluble precipitations or gel by reduction of the water content to a final free water content lower than 20% (W/V). This suspension is completely filterable on 0.1 micron filter (more than 98% filterable Si) and non filterable on a MW 20.000 filter (less than 20% filterable Si).

Examples:

1. 500 ml aqueous potassium silicate solution containing 1,4 % silicon was mixed into an equal volume of an aqueous 5% hydrochloric acid solution within one minute under strong stirring. The pH of this solution is under 0.9. This solution is stable for at least 1 week at 20 0 C or 4 weeks at 4 0 C.

2. 500 ml aqueous potassium silicate solution containing 1,4 % silicon was mixed into an equal volume of an aqueous 8% nitric acid solution within one minute under strong stirring. The pH of this solution is inferior to 0.9. This solution is stable for at least 1 week at 2O 0 C or 4 weeks at 4°C.

3. The solution prepared as described in example 1 was supplemented with 0.2% MSM one hour after the mixing. This solution was stored at 15°C for 3 months without loss of stability (no gel formation).

4. 250 ml aqueous potassium silicate solution containing 2.8 % silicon was mixed into an equal volume of an aqueous 10% hydrochloric acid solution under strong stirring. After one hour the solution was diluted with an equal volume of polyethylene glycol 400 as stabilizing agent. This solution was stable for at least 2 years at 25 0 C and 3 years at 4°C.

5. A solution prepared and stabilized as described in example 4 was supplemented with 5 % calcium as calcium chloride, 5% magnesium as magnesium chloride, 0.5% zinc as zinc chloride and 0,2% selenium as selenate. This solution shows the same stability after addition of these salts as the one prepared and stabilized as prescribed in example 4.

6. A solution prepared and stabilized as described in example 4 is supplemented with 1% copper as copper chloride and stored at 25°C during one year without loss of stability.

7. A solution prepared and stabilized as described in example 4 was supplemented with 0.5% taurine. This sol was stored at 25°C during 2 years without loss of stability.

8. A solution prepared and stabilized as described in example 4 was supplemented with 1% L-threonine and stored at 4°C during 18 months. The solution shows no loss of stability.

9. A solution prepared and stabilized as described in example 4 was supplemented with 0.05% lycopene and stored at 20 0 C during one year, without loss of stability and without loss of antimicrobial activity.

10.250 ml aqueous potassium silicate solution containing 2,8 % silicon was mixed very quickly into an equal volume of an aqueous 16% nitric acid solution during strong stirring. After one hour the solution was diluted with

an equal volume of polyethylene glycol 200 as stabilizing agent. This solution is stable for at least 2 years at 25°C.

11. A solution prepared and stabilized as described in example 10 was supplemented with 0.5% taurine and 0.1% folic acid and kept at 4°C during one year. The solution shows no loss of stability.

12.250 ml aqueous potassium silicate solution containing 2.8 % silicon was mixed very quickly into an equal volume of an aqueous 10% hydrochloric acid solution during strong stirring. After one hour the solution was diluted with an equal volume of propylene glycol as stabilizing agent. The solution was stable for at least 2 years at 25°C.

13. A solution prepared and stabilized as described in example 12 was supplemented with 3 % calcium as calcium chloride, 3% magnesium as magnesium chloride, 0.5% zinc as zinc chloride and 0.1% selenium as selenate. The solution was stored at 4°C for 2 years showing no loss of stability.

14.250 ml aqueous potassium silicate solution containing 2.8 % silicon was mixed very quickly into an equal volume of an aqueous 16 % nitric acid solution during strong stirring. After one hour the solution was diluted with an equal volume of propylene glycol as stabilizing agent. This solution was stable for at least 2 years at 25°C.

15. A solution prepared and stabilized as described in example 14 was supplemented with 1% L-lysine and 1% sodium citrate and stored at 25°C. After one year the solution showed no loss of stability.

16.A solution prepared and stabilized as described in example 1 was diluted one hundred fold in tap water and supplemented with an equal volume of an aqueous silicate solution containing 0.005% Si resulting in a bio available silicon formulation.

17.A solution prepared and stabilized as described in example 4 was diluted in the drinking water for a group of pigs during their growth period. The

dilution grade was adapted every week to the mean weight of the animals. The useful concentration was 4 mg Si/ 50 kg body weight/day. The control group of pigs received no silicon supplement. After 6 months of cultivation the pigs were slaughtered and similar samples of their meat were analyzed for global fatty acid composition. Fatty acid analysis demonstrated increased omega 3 fatty acid concentrations in the pig group supplemented with silicon. The ratio omega 6 /omega 3 fatty acids decreased from 11.2 to 3.8 in the silicon treated group.

The hydronium stabilized suspension according to the invention is used as source of bio-available silicon for micro-organisms, plants, animals and humans as such and in:

- All kind of waters (tap, drinking water for humans and animals, mineral, distilled, process, reversed osmosis, rain, fortified, river, ocean, soil, filtered, cooling water, aqueous solutions, suspensions, emulsions and combinations thereof),

- Biological preparations,

- Plant fertilizers,

- Feed additives for animals,

- Food and food supplements, namely dietary food supplements for human consumption,

- Nutritional products,

- Nutritional meal replacement supplements,

- Nutritional drink mixes,

- All kind of beverages,

- Nutraceuticals,

- Vitamin and mineral preparations,

- Nutritional pills in the nature of nutritional supplement,

- Nutritional additives for use in foods,

- Food and food products,

- Medical foods, baby foods and geriatric foods,

- Food for medically restricted diets,

- Drugs,

- Cosmoceuticals and as additive therein,

- Cosmetics, topical and personal care products,

- Pharmaceutical compounds and their different compositions,

- Combination with other compounds such as anti-oxidants, enzyme inhibitors, hormones, etc.

- Combination with different sources (salts, oxides, complexes, etc..) of Ca, K, Na, Mg, Mn, B, Li, Sr, Se, Mo, Fe, Co, Cu, Zn, Ti, Al, Ag, Cr, Si, P, S, N, F, Cl, Br, I.

- Combination with nutrients such as sugars, fats, proteins, nucleic acids, vitamins, amino acids, plant extracts, biological macro molecules, primary and secondary plant metabolites, compounds of biological pathways and combinations thereof.

The hydronium stabilized suspension is also used for anticorrosive applications as such or in combination with molybdates or other anti-corrosive compounds upon dilution.

The hydronium stabilized suspension according to the invention can be supplemented with: i - Micro- and macro nutrients such as:

A) soluble salts and sources of macro- and micro and trace elements, different sources (salts, oxides, complexes, etc..) of Ca, K, Na, Mg, Mn, B, Li, Sr, Se, Mo, Fe, Co, Cu, Zn, Ti, Al, Ag, Cr, Si, P, S, N, F, Cl, Br, I or mixtures thereof. B) nutrients such as sugars, fats, proteins, nucleic acids, vitamins, amino acids, plant extracts, biological macro molecules, primary and secondary plant metabolites, compounds of biological pathways and combinations thereof, or

mixtures thereof; ii - growth activators, fertilizers, biological active compounds for crop production and protection. iii - hydrophilic and hydrophobic anti-oxidants such as carotenoids, flavonoids, accepted food additives, antioxidative enzymes, lipoic acid,... iv - enzyme inhibitors, hormones, antibiotics, or other pharmaceuticals v - natural and synthetic food colorants, food sweeteners and food flavourings or mixtures thereof.

The present invention further provides formulations of the diluted hydronium stabilized suspension, used as food supplement, nutraceutical, feed additive, pharmaceutical preparation, topical formulation, hygienic formulation, concentrated fertilizer and growth regulator, concentrated plant protection formulation, concentrated bio-available silicon formulation to induce biological processes in plans, animals, humans and micro-organisms. Use of these formulations in drinking water of animals and humans or as plant fertilizer with the aim to increase the concentration of omega 3 fatty acids in these organisms, compared to formulation-free controls.

References silicon nano particles :

1. Peterson KP et al. (1998) Proceedings of the Society for experimental Biology and Medicine, vol 218, issue 4 p. 365-369

2. Meixner DL et al. (1998) Langmuir, vol 14, issue 12, p. 3202-3209

3. Geun Chang Hoang and Hyun Soon Lee. (1997) Proceedings of 5 th international Conference of Properties and Applications of dielectric Materials, Cat n) 97CH35794) , IEEE, New York, USA, p.(vol 1) 174-7

4. Breiter M. W. and Falifek G, (1997) Journal of Electroanalytical Chemistry, 433, p. 107-111

5. De Witte B.M.et al., (1996) Journal of Non-Crystallyne Solids, 202, p. 35 - 41

6. Colomer M.T. and Jurado J.R. (2003) Ionics, vol 9, issue 3-4, p.207-213

7. Tleugabulova D. et al., (2003), Journal of Physical Chemistry B, vol 107, issue 37, p.10127 - 10133

8. Miller E. and Miller J.S., (2003), Colloid and Polymer Science, vol.281, issue 8, p.745 - 753

9. Frenkel-Mullerad H. and Avnir D., (2005), Journal of American Chemical Society, vol.127, issue 22, p.8077 - 8081 lO.Zbigniew Adamczyk et al., (2004), Journal of Colloid and Interface Science, 273, p.668 - 674

11. Gupta R., et al.,(2005) Biosensors and Bioelectronics, 21, p.549 - 556 12.Makedonka D. et al.,(2002) Analytica Chemica Acta, 457, p. 47 - 59

13.Juncal Estella et al., (2007), Journal of Non-Crystalline Solids, 353, p. 286- 294

H.Abhijit Bandyopadhyay et al., (2006), Journal Material Sciences, 41, p. 5981-5993

15. Colomer M.T. (2006), Journal of Solid State Electrochemistry, vol. 10, issue 1, p. 54-59

16.Blu.te Irena et al, (2007), Journal of Colloid and Interface Science, 313, p. 645 - 655

17.Golikova E.V. et al., (2007), Glass Physics and Chemistry, vol.33, issue 3, p.l99 - 208 lδ.Feuston B.P. and Garofalini S.H., (1990), Chemical Physics Letters, vol. 170, issue 2-3, p. 264 - 270

19.Ming-Shyong Tsai at al., (2005), Materials Research Bulletin, 40, p.1609 - 1616

20. Sierra L. et al., (2000), Microporous and Mesoporous Materials, 39 (3), p.519-527

21.Curran Matthew D. and Stiegman A.E., (1999), Journal of Non - Crystalline Solids, 249, p.62 - 68

22. Walters D.R. and Bingham IJ., (2007) Annals of Applied Biology, 151, p.307 - 324

23.Currie Heather A. and Perry Carole C, (2007), Annals of Botany 100, p. 1383 - 1389

24. Jugdaohsingh R., (2007), The Journal of Nutrition, Health and Aging, vol. l l, n°2, p.99-110

25. Chen F. et al., (1998), Annals of Clinical and Laboratory Sciences, vol.28, issue 1, p.1-13

26.Li Yi et al., (2006) Progress in Natural Science, vol.16, issue 10, p.1038 - 1044

27.Deshpande A. et al., (2002), Toxicological Sciences, vol.67, issue 2, p.275 - 283

28.Elias Z. et al., (2006), Toxicological Sciences, vol.91, issue 2, p. 510 - 520

29.Yoshiyuki Sugahara et al., (1997), Journal of Material Chemistry, vol 7(l), p.53-59

30.Cataldo Franco et al., (2007), RadiationPhysics and Chemistry, vol 77, issue 3, p. 267 - 272

31.Kinrade S. et al., (2003), Dalton Trans.,p.3713 - 3716

32.Grδger C. et al., (2007) Journal of Structural Biology, vol.161, issue 1, p.

55-63

33. Casey W. H. et al., (2003), Plant, Cell and Environment, 27, p. 51- 54

34.Wijnen P.WJ.G. et al.(1994), Colloid chemistry of silica, vol.234, p.517 - 531

35.Sjδberg Staffan (1996), Journal of Non-Chrystalline Solids, vol 196, p. 51-57

36.Kinrade S.D. (2001), Chemical Communication, p. 1564-1565




 
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