Stable silicic acid solutions

Abstract

The present invention relates to a stable silicic acid solution having a silicon content of 0.01-1.00% w / w. Silicic acid is stabilized by the combination of amino acid bisulfate 1AA, 1b, 1c, amino acid sodium and / or potassium 2aAA, 2bAA, 2c, 2d, 2e, 2f and sodium and / or potassium bisulfate (NaHSO4 and / or KHSO4) in a mixture of diol, 1, 2-propylene glycol (3) and / or polyethylene glycol (4) and purified water. The present invention discloses a method for preparing such a formulation. The composition is used as a food supplement, a functional food ingredient, a feed additive, a functional feed additive, a biostimulant for aquaculture, an active cosmetic ingredient, an active pharmaceutical ingredient, an agrochemical product and the like, and provides high bioavailability silicon (Si).

Description

Technical Field

[0001] The present invention relates to compositions comprising silicic acid, which compositions can be used, for example, as pharmaceuticals, nutraceuticals, cosmetics, veterinary drugs or agrochemical products providing the beneficial effects of silicon (Si) on eukaryotic organisms, including humans, animals, diatoms and plants. Specifically, the present invention solves the technical problem of stabilizing silicic acid to prevent its solution from polymerizing. Background Art

[0002] Silicon (Si) is an important micronutrient that exhibits many beneficial effects in humans, animals and plants.

[0003] The main bioavailable chemical form of silicon is known to be orthosilicic acid (also called monosilicic acid) (OSA). However, the latter readily polymerizes into its oligomers, various types of polymers, and finally into silica gel (SG), see Figure 1 .

[0004] The main chemical form of silicon is orthosilicic acid (H4SiO4; OSA) [1,2]. A saturated solution contains 0.1% w / w silicic acid [2].

[0005]

[0006] In more concentrated solutions, OSA undergoes a polymerization process with the elimination of water (H2O) and the formation of different oligomers and polymers, such as:

[0007] (i) Oligomers, such as HO-[Si(OH)2O] n -H type, where n≤12 and molar mass M<700 [g / mol] (water-soluble):

[0008] (a) linear oligomers, for example, dimerized silicic acid (S2), trimerized silicic acid (S3);

[0009] (b) branched oligomers, for example, branched tetrasilicic acid (bS4);

[0010] (c) cyclic oligomers, for example, cyclic trimer (cS3), cyclic tetramer (cS4);

[0011] (d) cage-type silsesquioxane-like compound SS;

[0012] (ii) General formula [SiO x (OH) 4-2x ] n The polymer, x = 1-2, is as follows:

[0013] (e) Sub-nano silicate (SNSA) with a particle size of 0.3-0.6 nm, n=12-20 and M=700-1,400 [g / mol]; it is readily soluble in water;

[0014] (f) Sub-nano condensed silicate (SNCSA) with a particle size of 0.6-3 nm, n=20-300 and M=1,400-2,000 [g / mol]; it is readily soluble in water;

[0015] (g) larger SNCSA silicic acid with a particle size of 3-5 nm, n=300-2,000 and M=20,000-140,000 [g / mol]; which is still freely or moderately soluble in water;

[0016] (h) polymeric silica nanoparticles (PSNP) with a particle size of 5-50 nm, n=2,000-10,000 and M=140,000-600,000 [g / mol]; and finally ending with,

[0017] (iii) Highly polymerized silicate [(SiO2) with a particle size > 50 nm n ·yH2O; silica gel; SG], n>10,000 and M=>600,000 [g / mol].

[0018] In addition to OSA itself, its water-soluble oligomers and lower polymers (which can release certain amounts of free OSA) represent valuable silicon-containing chemical forms which provide the mentioned beneficial nutritional and pharmacological effects of silicon in humans and animals and also in plant production and protection.

[0019] In contrast, water-insoluble, higher silicic acid polymers and silica gels release very small amounts of orthosilicic acid and are therefore less favorable chemical forms for silicon supplementation or therapeutic use.

[0020] Therefore, much effort has been devoted to developing stable silicic acid solutions that will not form gels (water-insoluble polymers).

[0021] In order to prevent, minimize or slow down the polymerization of OSA (with the concomitant gelation of its oligomers and lower polymers to water-insoluble higher polymers with poor silicon bioavailability), several methods of formulating OSA solutions have been developed and described.

[0022] WO 2011 / 071379 discloses an acidic aqueous solution of microcolloidal silicic acid, boric acid (H3BO3) and a water-absorbing additive, wherein at least 90% of the microcolloidal silicic acid particles have a particle size within the range of 3.5-8nm. The water-absorbing additive or wetting agent is selected from the group consisting of polysorbate, vegetable gum, substituted cellulose, polyethylene glycol (PEG), polydextrose, propylene glycol, propylene glycol alginate, polyoxyethylene glycol esters, pectin, amidated pectin, sucrose fatty acid esters, acetylated or hydroxypropyl starch, starch phosphate, urea, sorbitol, maltitol, vitamins, and a mixture of two or more such wetting agents. WO 2011 / 071379 focuses on the effect of boric acid (H3BO3) to stabilize the silicic acid nanoparticles of size 3.5-8nm. This document does not mention glycine or its salt as a silicic acid stabilizer.

[0023] WO 2012 / 035364 discloses liquid compositions of orthosilicic acid (OSA) stabilized with carnitine salts (e.g. carnitine hydrogen phosphate) in a matrix of, in particular, aqueous glycerol, 1,2-propylene glycol, d-panthenol or glucosamine. A serious disadvantage of the compositions according to WO 2011 / 071379 is the use of tetraethyl orthosilicate (TEOS) as silicon precursor. The use of TEOS is associated with certain safety aspects, and the final product inevitably contains four moles of ethanol per mole of OSA released. The alcohol content makes this method less favorable.

[0024] EP 3141244 A1 discloses the novel composition of stable orthosilicic acid (OSA), and this stable orthosilicic acid is based on the stabilization by being incorporated into the water-in-oil (WO) emulsion.This emulsion contains the stabilizing agent selected from the group consisting of the following in its aqueous phase: polysorbate, vegetable gum, cellulose, polyglycerol ester, polyethylene glycol (PEG), dextrose, propylene glycol and sugar.According to the serious disadvantage of the composition of EP 3141244 A1, it needs to use fat phase and inevitable emulsifier.In the trend of modern nutraceutical product preparation, it is disadvantageous to use emulsifier and other food additives with major health problems.

[0025] WO 03 / 077657 discloses a liquid stable silicic acid solution containing orthosilicic acid (H4SiO4) and oligomers thereof, which is prepared by hydrolysis of silicon tetrachloride (SiCl4) in a 75% aqueous solution of choline chloride (ChCl) in the presence of hydrogen chloride (HCl) in the following molar ratio n / n with water:

[0026] n(SiCl4):n(ChCl)=1:3-5

[0027] The pH value of this solution is obviously very low, less than 0.5. The complex solution of orthosilicic acid (H4SiO4) and ChCl thus obtained is further neutralized with the following substances:

[0028] (i) Calcium carbonate (CaCO3) or betaine [(CH3)3N + CH2COO - ];as well as,

[0029] (ii) an additional "osmotic agent" ultimately selected from the group consisting of: glycine (Gly), taurine, carnitine, inositol, ethanolamine, and their phosphates; monosaccharides such as glucose, xylose and sorbitol; see patent claims on pages 7 and 8.

[0030] The document shows that SiCl4 can be hydrolyzed in a 75% aqueous ChCl solution with water to give a solution which is further neutralized with CaCO3 or betaine. A serious disadvantage of the composition according to WO 03 / 077657 is that it requires the use of highly toxic and corrosive silicon tetrachloride (SiCl4) as a silicon precursor, which inevitably releases large amounts of hydrochloric acid (HCl), which must be neutralized to a certain extent with some suitable base (e.g., with CaCO3), as shown above.

[0031] WO 95 / 21124 discloses a liquid formulation of stable orthosilicic acid (H4SiO4) with a concentration corresponding to 1%-8% silicon (Si) content, prepared by hydrolyzing silicon tetrachloride (SiCl4) as the starting silicon compound in a mixture of water, choline chloride (ChCl) and hydrochloric acid (HCl), followed by partial neutralization of the solution of H4SiO4 and HCl thus obtained with sodium hydroxide (NaOH), followed by addition of glycerol. The pH value of the solution is 1-4; see the patent claims on page 3. Since the final product is an acidic pH value of 1-3 or "less than 4", it is clear to the person skilled in the art that this liquid stable silicic acid solution contains:

[0032] (i) Orthosilicic acid (H4SiO4);

[0033] (ii) choline chloride (ChCl);

[0034] (iii) sodium chloride (NaCl); formed from excess HCl and sodium hydroxide (NaOH) used as a neutralizing agent;

[0035] (iv) glycerol; as a "polyol diluent"; and

[0036] (v) Purified water made up to 100% w / w from the starting ChCl-aqueous solution.

[0037] Similar to WO 03 / 077657, a serious disadvantage of the composition according to WO 95 / 21124 is that it involves the use of SiCl4, a toxic and highly corrosive substance, which needs to be neutralized with a certain base (herein NaOH) and thus inevitably forms the corresponding chloride salt (herein NaCl). In addition, the latter makes the silicic acid solution unstable due to the unnecessary increase in the ionic strength of the resulting solution.

[0038] In general, it is an object of the present invention to provide new and improved ways of stabilizing silicic acid solutions. More specifically, it is an object of the present invention to provide stable silicic acid solutions which do not suffer from any or all of the disadvantages associated with prior art compositions, such as the use of highly toxic silicon precursors, e.g. SiCl4 or TEOS, or unnecessary bases which generate useless salts, such as NaCl or CaCl2, which may also lead to instability of the resulting silicic acid solution. Summary of the invention

[0039] In general, the present invention is based on the discovery that the above-mentioned objects can be achieved at least in part by the stabilizing effect of amino acid hydrogen sulfates 1, sodium and / or potassium amino acid sulfates 2a, b and sodium and / or potassium hydrogen sulfate (MHSO4, where M = Na and / or K) on silicic acid solutions.

[0040] Therefore, in a first aspect, the present invention relates to a stable silicic acid solution comprising:

[0041] (i) silicic acid, in the form of a mixture of:

[0042] - Orthosilicic acid (H4SiO4),

[0043] - water-soluble oligomers, and

[0044] - water-soluble polymers,

[0045] In a percentage equivalent to 0.01-1.00% w / w silicon (Si),

[0046] (ii) one or more amino acid hydrogen sulfate salts 1AA, 1b and 1c in a total amount of 0.015-21.53% w / w,

[0047]

[0048] (iii) one or more of the amino acid sulphates sodium and / or potassium 2aAA, 2bAA, 2c, 2d, 2e and 2f in a total amount of 0.00-24.24% w / w,

[0049]

[0050] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K) in an amount of 0.00-9.70% w / w,

[0051] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0052]

[0053] or a mixture thereof, relative weight ratio:

[0054] w(3):w(4)=1.00-99.00:99.00-1.00,

[0055] The percentage in the composition is 5-50% w / w, and

[0056] (vi) water, made up to 100% w / w of the composition,

[0057] The proviso is that at least one of (iii) and (iv) is present.

[0058] In a preferred embodiment, the present invention relates to a stable silicic acid solution, wherein the one or more amino acids of 1AA, 2aAA and / or 2bAA are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit) and salts thereof.

[0059] In another preferred embodiment, the stable silicic acid solution according to the present invention, wherein the term 'water-soluble oligomer' refers to a linear, branched or cyclic oligomer formed by the polycondensation of 2 to 12 orthosilicic acid (OSA) molecules, and the term 'water-soluble polymer' refers to a polymer of the general formula [SiO x (OH) 4-2x ] n A polymer wherein x=1-2 is selected from the group consisting of:

[0060] - Subnanosilicic acid (SNSA) with a particle size of 0.3-0.6 nm, where n=12-20 and M=700-1,400 [g / mol];

[0061] - Sub-nano (or sub-colloidal) condensed silicic acid (SNCSA) with a particle size of 0.6-3 nm, where n=20-300 and M=1,400-2,000 [g / mol]; and,

[0062] - Larger SNCSA silicic acids with a particle size of 3-5 nm, where n = 300-2,000 and M = 20,000-140,000 [g / mol].

[0063] Preferably, in the stable silicic acid solution, the term 'water soluble' means that a clear aqueous phase containing said oligomers and / or polymers at a level of at least 10 ppm, preferably at least 100 ppm, more preferably at least 1000 ppm can be formed using clear water at neutral pH at room temperature.

[0064] The above-mentioned objects can be achieved in a particularly advantageous manner by the stabilization of silicic acid solutions by glycine hydrogen sulfate (1), sodium and / or potassium glycine sulfate (2a, b) and sodium and / or potassium hydrogen sulfate (MHSO4, where M=Na and / or K).

[0065] Therefore, in a particularly preferred embodiment, the present invention relates to a stable silicic acid solution comprising or consisting of:

[0066] (i) silicic acid, in the form of a mixture of:

[0067] - Orthosilicic acid (H4SiO4; OSA), which

[0068] - water-soluble oligomers, and

[0069] - water-soluble polymers;

[0070] (ii) glycine hydrogen sulfate (1);

[0071]

[0072] (iii) optionally, sodium and / or potassium glycine sulfate (2a, b);

[0073]

[0074] (iv) optionally, sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K);

[0075] (v) a diol selected from the group consisting of: 1,2-propylene glycol (3), polyethylene glycol (PEG; 4);

[0076]

[0077] and mixtures thereof; and

[0078] (vi) water,

[0079] Provided that the composition comprises at least one of (iii) and (iv).

[0080] In another particularly preferred embodiment, the present invention relates to a stable silicic acid solution comprising or consisting of:

[0081] (i) silicic acid in the form of a mixture of orthosilicic acid (H4SiO4; OSA), its water-soluble oligomers and water-soluble polymers, silicon (Si) in a relative amount of 0.01-1.00 parts by weight,

[0082] (ii) glycine hydrogen sulfate (1), in a relative amount of 0.015-6.17 parts by weight,

[0083]

[0084] (iii) sodium and / or potassium glycine sulfate (2a, b), in a relative amount of 0.00-5.64 parts by weight,

[0085]

[0086] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K), in a relative amount of 0.00-9.70 parts by weight, and

[0087] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0088]

[0089] and mixtures thereof, the relative amount being 5-50 parts (by weight), in

[0090] (vi) in water, typically in an amount sufficient to form a solution,

[0091] Provided that the composition comprises at least one of (iii) and (iv).

[0092] In another preferred embodiment, the present invention relates to a stable silicic acid solution comprising or consisting of the following:

[0093] (i) silicic acid, in the form of a mixture of orthosilicic acid (H4SiO4; OSA), its water-soluble oligomers and water-soluble polymers, in percentages corresponding to 0.01-1.00% w / w silicon (Si),

[0094] (ii) glycine hydrogen sulfate (1), 0.015-6.17% w / w,

[0095]

[0096] (iii) sodium and / or potassium glycine sulfate (2a, b), 0.00-5.64% w / w,

[0097]

[0098] (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 0.00-9.70% w / w,

[0099] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0100]

[0101] And mixtures thereof, relative weight ratio:

[0102] w(3):w(4)=1.00-99.00:99.00-1.00,

[0103] The percentage in the composition is 5-50% w / w, and (vi) water, making up to 100% w / w of the composition,

[0104] The conditions are:

[0105] (a) if (iii) is 0.00% w / w, then the percentage of (iv) is > 0.00%, and vice versa, and / or (b) (iii) and (iv) are not both 0.00% w / w.

[0106] Preferably, the stable silicic acid solution according to the present invention comprises or consists of:

[0107] (i) silicic acid, equivalent to 0.10-0.70% w / w silicon (Si),

[0108] (ii) glycine hydrogen sulfate (1), 0.15-4.32% w / w,

[0109] (iii) sodium and / or potassium glycine sulfate (2), 0.00-3.95% w / w,

[0110] (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 0.30-3.62% w / w,

[0111] (v) glycol, 5-45% w / w, and (vi) water, to make up to 100% w / w of the composition.

[0112] More preferably, the stable silicic acid solution according to the present invention comprises or consists of:

[0113] (i) silicic acid, equivalent to 0.40-0.60% w / w silicon (Si),

[0114] (ii) glycine hydrogen sulfate (1), 0.62-3.70% w / w,

[0115] (iii) sodium and / or potassium glycine sulfate (2), 0.00-3.38% w / w,

[0116] (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 1.05-3.10% w / w,

[0117] (v) diols, 30-45% w / w, and

[0118] (vi) Purified water, made up to 100% w / w of the composition.

[0119] The stabilized silicic acid solution according to the invention is prepared from the following starting materials:

[0120] (I) solid or liquid sodium and / or potassium silicates, xM2O·ySiO2, where M = Na and / or K, x = 1 and y = 1-4,

[0121] (II) glycine (5),

[0122]

[0123] (III) Sulfuric acid (H2SO4),

[0124] (IV) diol, and

[0125] (V) purified water;

[0126] in:

[0127] (a) The molar ratio n / n of silicon (Si) to glycine (5; Gly) is:

[0128] n(Si):n(5)=1:0.8-2.4,

[0129] (b) The amount of sulfuric acid (n) is equal to the sum of:

[0130] - the amount of substances of sodium and / or potassium (Na and / or K) from silicates (n); and

[0131] -25%-100% Amount of substance (n) of glycine (5):

[0132] n(H2SO4)=n(M)+0.25-1.00·n(5),

[0133] (c) the product does not contain excess sulfuric acid or any other additional acid; and

[0134] (d) The pH value of the obtained composition is between 0.35 and 3.00.

[0135] In a preferred embodiment, PEG (4) is selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 2000, PEG 3000, PEG 3350, PEG 4000, PEG 6000, PEG 8000, PEG 10000, PEG 12000, PEG 20000, PEG 35000, and mixtures thereof.

[0136] The present invention also relates to a method for preparing the composition according to the invention, comprising the following manufacturing steps:

[0137] A. dissolving one or more amino acids, preferably glycine (5), in a mixture of diol and purified water; this is achieved by stirring at a temperature of 10°C to 50°C for 1 to 30 minutes,

[0138] B. Sulfuric acid (H2SO4) is added separately and gradually to a portion of the purified water at a temperature of 5°C-20°C over a period of 5-30 minutes,

[0139] C. adding the sulfuric acid solution from step B to the solution from step A at a temperature of 5°C-20°C during 1-30 minutes,

[0140] D. Prepare separately a solution of sodium and / or potassium silicate in water by:

[0141] - dissolve the solid material in a portion of purified water, or

[0142] - dilution of liquid substances with a portion of purified water, and

[0143] E. adding the solution from step D dropwise to the cooled solution from step C at a temperature of 5°C-15°C with vigorous stirring during 5-60 minutes,

[0144] A final liquid silicic acid composition according to the present invention is produced.

[0145] Preferably, the one or more amino acids are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit), proline (Pro), β-alanine (βAl) and salts thereof.

[0146] More preferably, in the method of the present invention:

[0147] (a) The molar ratio n / n of silicon (Si) to amino acid (AA) is:

[0148] n(Si):n(AA)=1:0.8-2.4,

[0149] (b) The amount of sulfuric acid (n) is equal to the sum of:

[0150] - the amount of substances of sodium and / or potassium (Na and / or K) from silicates (n); and

[0151] - 25% to 100% of the amount (n) of the corresponding amino acid (AA):

[0152] n(H2SO4)=n(M)+0.25-1.00·n(AA),

[0153] and / or,

[0154] (c) The sodium and / or potassium silicates (xM2O·ySiO2, wherein M=Na and / or K) used in the process are:

[0155] - in solid form with 97-99% w / w sodium or potassium silicate, or

[0156] - in the form of a liquid having a concentration of about 24-47% w / w sodium or potassium silicate,

[0157] It is characterized by the following molar ratios, x:y, n / n: x=1.00, y=1.00; x=1.00, y=1.60-1.70; x=1.00, y=2.00-2.10; x=1.00, y=3.30-3.40; x=1.00, y=3.90-4.00; or mixtures of these substances.

[0158] Preferably, in the method of the present invention, the one or more amino acids are or include histidine (His), arginine (Arg), ornithine (Orn) and / or lysine (Lys), wherein the side chain portion (R) is in the form of a free base, and for an equimolar amount of the AA used, the amount of sulfuric acid substance (n) used in the method is increased to ensure that the corresponding side chain basic functional groups are converted into the corresponding hydrogen sulfate salts.

[0159] The composition according to the present invention is useful as a food supplement, a functional food ingredient, a feed additive, a functional feed additive, a biostimulant for aquaculture, an active cosmetic ingredient (ACI) or an active pharmaceutical ingredient (API), which provides highly bioavailable silicon (Si) and its beneficial nutritional and pharmacological effects.

[0160] Alternatively, the composition according to the present invention is used as an agrochemical product for silicon fertilization, plant growth promotion and plant protection. BRIEF DESCRIPTION OF THE DRAWINGS

[0161] Figure 1 The polymerization of orthosilicic acid (OSA) into various silica oligomers, polymers, and finally silica gel is depicted. S2 = dimer silicic acid; S3 = trimer silicic acid; bS4 = branched tetrasilicic acid; cS3 = cyclic tetrasilicic acid; SS = cage silsesquioxane type oligosilicic acid; SNSA = subnanosilicic acid; SNCSA = subnano condensed silica; PSNP = polymerized silica nanoparticles; SG = silica gel.

[0162] Figure 2 Depicted are possible structures of molecular complexes of orthosilicic acid (OSA) with glycine hydrogen sulfate (1), potassium glycine sulfate (2b), sodium and / or potassium hydrogen sulfate (MHSO4, M = Na and / or K), 1,2-propylene glycol (3) and water (H2O), with a stoichiometric ratio of OSA:glycine = 1:1, stabilized by multiple hydrogen bonds. DETAILED DESCRIPTION

[0163] In a first aspect, the present invention relates to a stable silicic acid solution comprising:

[0164] (i) silicic acid, in the form of a mixture of:

[0165] - Orthosilicic acid (H4SiO4; OSA), which

[0166] - water-soluble oligomers, and

[0167] - Water-soluble polymers

[0168] (ii) one or more amino acid hydrogen sulfate salts 1AA, 1b, 1c,

[0169]

[0170] (iii) optionally one or more amino acid sulfates sodium and / or potassium 2aAA, 2bAA, 2c, 2d, 2e, 2f,

[0171]

[0172] (iv) optionally sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K),

[0173] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0174]

[0175] or a mixture thereof, relative weight ratio:

[0176] w(3):w(4)=1.00-99.00:99.00-1.00,

[0177] as well as

[0178] (vi) water,

[0179] The condition is that at least one of (iii) and (iv) is present.

[0180] In a preferred embodiment of the present invention, a stable silicic acid solution comprises:

[0181] (i) silicic acid, in the form of a mixture of:

[0182] - Orthosilicic acid (H4SiO4),

[0183] - water-soluble oligomers, and

[0184] - water-soluble polymers,

[0185] In a percentage equivalent to 0.01-1.00% w / w silicon (Si),

[0186] (ii) one or more amino acid hydrogen sulfate salts 1AA, 1b, 1c, in a total amount of 0.015-21.53% w / w,

[0187]

[0188] (iii) one or more amino acid sulphates sodium and / or potassium 2aAA, 2bAA, 2c, 2d, 2e, 2f in a total amount of 0.00-24.24% w / w,

[0189]

[0190] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K) in an amount of 0.00-9.70% w / w,

[0191] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0192]

[0193] or a mixture thereof, relative weight ratio:

[0194] w(3):w(4)=1.00-99.00:99.00-1.00,

[0195] The percentage in the composition is 5-50% w / w, and

[0196] (vi) water, made up to 100% w / w of the composition,

[0197] The condition is that at least one of (iii) and (iv) is present.

[0198] In a preferred embodiment, a stable silicic acid solution according to the present invention is provided, wherein the amino acids of 1AA, 2aAA and / or 2bAA are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit) and salts thereof.

[0199] In a particularly preferred embodiment of the present invention, a stable silicic acid solution is provided, which comprises or consists of the following:

[0200] (i) silicic acid, in the form of a mixture of:

[0201] - Orthosilicic acid (H4SiO4; OSA), which

[0202] - water-soluble oligomers, and

[0203] - water-soluble polymers;

[0204] (ii) glycine hydrogen sulfate (1);

[0205]

[0206] (iii) optionally sodium and / or potassium glycine sulfate (2a, b);

[0207]

[0208] (iv) optionally sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K); and

[0209] (v) a diol selected from the group consisting of: 1,2-propylene glycol (3) and / or polyethylene glycol (PEG; 4);

[0210]

[0211] and mixtures thereof; and

[0212] (vi) purified water;

[0213] Provided that the composition comprises at least one of (iii) and (iv).

[0214] In another particularly preferred embodiment, the present invention relates to a stable silicic acid solution comprising or consisting of:

[0215] (i) silicic acid in the form of a mixture of orthosilicic acid (H4SiO4; OSA), its water-soluble oligomers and water-soluble polymers, silicon (Si) in a relative amount of 0.01-1.00 parts by weight,

[0216] (ii) glycine hydrogen sulfate (1), in a relative amount of 0.015-6.17 parts by weight,

[0217]

[0218] (iii) sodium and / or potassium glycine sulfate (2a, b), in a relative amount of 0.00-5.64 parts by weight,

[0219]

[0220] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K), in a relative amount of 0.00-9.70 parts by weight, and

[0221] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0222]

[0223] and mixtures thereof, the relative amount being 5-50 parts (by weight), in

[0224] (vi) in water, typically in an amount sufficient to form a solution,

[0225] Provided that the composition comprises at least one of (iii) and (iv).

[0226] Unless specifically stated otherwise, amounts expressed as '% w / w' refer to the weight of a given component relative to the total weight of the stable silicic acid-containing solution.

[0227] As used herein, in the context of the present application, the term 'water-soluble' refers to the property that the compound can dissolve in water, even if it may be in small amounts and rather slowly in a given case. Typically, this means that a clear aqueous phase containing the compound at a level of at least 10 ppm, preferably at least 100 ppm, more preferably at least 1000 ppm can be formed at room temperature. It should be noted that the solubility is pH-dependent and, according to the present definition, the solubility is given for clear water (i.e. neutral pH, such as water at a pH of about 7) and is determined using it.

[0228] According to the present invention, these compositions preferably comprise silicic acid oligomers and polymers in sub-colloidal form. Solutions comprising such sub-colloidal particles typically pass through a 0.1 micron filter. In a particularly preferred embodiment of the present invention, water-soluble silicic acid oligomers and polymers are in the form of sub-colloidal particles with a size in the range of 0.1-10 nm, more preferably in the range of 0.2-8 nm, still more preferably 0.3-6 nm, most preferably 0.3-5 nm.

[0229] Can be used 29 Si NMR spectroscopy, TEM and / or SEM are used for particle size determination. In preferred embodiments of the present invention, at least 50%, more preferably at least 60%, even more preferably at least 70%, even more preferably at least 75%, even more preferably at least 80%, even more preferably at least 85%, even more preferably at least 90%, even more preferably at least 95%, even more preferably at least 97%, even more preferably at least 98%, most preferably at least 99% of the silicic acid-containing particles in these compositions have a particle size within the above size range.

[0230] In a particularly preferred embodiment of the present invention, the term 'water-soluble oligomer' refers to a linear, branched or cyclic oligomer formed by the polycondensation of 2-12 orthosilicic acid (OSA) molecules such as S2, S3, bS4, cS4, SS and Figure 1 Similar oligomers.

[0231] As used herein, the term 'water-soluble polymer' refers to a polymer having the general formula [SiO x (OH) 4-2x ] n Polymer, x = 1-2, such as:

[0232] - Subnanosilicic acid (SNSA) with a particle size of 0.3-0.6 nm, n=12-20 and M=700-1,400 [g / mol]; it is readily soluble in water;

[0233] - Subnano (or subcolloidal) condensed silicic acid (SNCSA) with a particle size of 0.6-3 nm, n=20-300 and M=1,400-2,000 [g / mol], which is readily soluble in water; and,

[0234] - Larger SNCSA silicic acid with a particle size of 3-5 nm, n = 300-2,000 and M = 20,000-140,000 [g / mol]; which is still freely or moderately soluble in water, but may eventually give the solution a slightly milky color upon long term storage.

[0235] In preferred embodiments of the invention, the silicic acid oligomers and polymers are water soluble and produce substantially clear solutions when the total silicon concentration is in the range of 0.01-1.00% w / w. The invention encompasses solutions that become slightly milky after prolonged storage. These solutions are stable and are not prone to significant further polymerization, which would be accompanied by gelation and gel formation.

[0236] In a preferred embodiment, (i) is present in a percentage equivalent to 0.01-1.00% w / w silicon (Si), more preferably 0.10-0.70% w / w, most preferably 0.40-0.60% w / w.

[0237] In a preferred embodiment, (ii) is present in an amount of 0.015-6.17% w / w, more preferably 0.15-4.32% w / w, most preferably 0.62-3.70% w / w, based on the total weight of the silicic acid-containing solution.

[0238] In a preferred embodiment, (iii) is present in an amount of 0.00-5.64% w / w, more preferably 0.00-3.95% w / w, most preferably 0.00-3.38% w / w, based on the total weight of the silicic acid-containing solution.

[0239] The relative amounts of (iii) and (iv) are typically inversely proportional, and their absolute values ​​depend on the amount of sulfuric acid used to neutralize the mixture of amino acids (preferably glycine) and sodium and / or potassium silicate in the process disclosed below. A higher relative amount of (iii) means a lower relative amount of (iv), and vice versa. In the extreme case, if (iii) is 0.00% w / w, the percentage of (iv) has the largest relative value within the defined stoichiometric range of sulfuric acid used in the process described below, in any case > 0.00% w / w. In the other extreme case, if (iv) is 0.00% w / w, (iii) is the largest relative value, and its absolute value depends on the stoichiometric ratio of sulfuric acid used in the process disclosed below. In this way, there is no situation where both (iii) and (iv) are 0.00% w / w.

[0240] In a preferred embodiment, (iv) is present in an amount of 0.00-9.70% w / w, more preferably 0.30-3.62% w / w, most preferably 1.05-3.10% w / w, based on the total weight of the silicic acid-containing solution.

[0241] In a preferred embodiment, (v) is present in an amount of 5-50% w / w, more preferably 10-45% w / w, most preferably 30-45% w / w, based on the total weight of the silicic acid-containing solution.

[0242] In a preferred embodiment, 1,2-propylene glycol (3) is used as the sole diol. In case a mixture of 3 and 4 is used, the preferred weight ratio of these components is 1 / 99% w / w to 99 / 1% w / w, more preferably 10 / 90% w / w to 90 / 10% w / w, most preferably 20 / 80% w / w to 80 / 20% w / w.

[0243] In a preferred embodiment of the invention, the water is selected from the group consisting of tap water, demineralized water, deionized water, distilled water, reverse osmosis purified water, or water that has been purified in any other way, such as to make it substantially free of free ions. In a preferred embodiment of the invention, the water is demineralized water, deionized water, distilled water, or purified water. In a particularly preferred embodiment of the invention, the water is purified water according to Ph.Eur. or similar pharmacopoeial standards.

[0244] Preferably, the composition according to the present invention, which is a stable silicic acid solution, comprises or consists of:

[0245] (i) silicic acid in an amount equivalent to 0.01-1.00% w / w silicon (Si);

[0246] (ii) an amino acid hydrogen sulfate, preferably glycine hydrogen sulfate (1), in an amount in the range of 0.015-6.17% w / w;

[0247] (iii) sodium and / or potassium amino acid sulfate, preferably sodium and / or potassium glycine sulfate (2), in an amount ranging from 0.00-5.64% w / w;

[0248] (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na or K) in an amount ranging from 0.00-9.70% w / w;

[0249] (v) diols in an amount ranging from 5-50% w / w; and

[0250] (vi) water, made up to 100% w / w of the composition;

[0251] The conditions are:

[0252] (a) if (iii) is 0.00% w / w, then the percentage of (iv) is > 0.00%, and vice versa, and / or

[0253] (b) (iii) and (iv) are not both 0.00% w / w.

[0254] More preferably, the composition according to the present invention which is a stable silicic acid solution comprises or consists of:

[0255] (i) silicic acid in an amount corresponding to 0.10-0.70% w / w silicon (Si);

[0256] (ii) amino acid hydrogen sulfate 1AA, 1b, 1c, preferably glycine hydrogen sulfate (1), in an amount in the range of 0.15-4.32% w / w;

[0257] (iii) sodium and / or potassium sulfate of amino acids 2aAA, 2bAA, 2c, 2d, 2e, 2f, preferably sodium and / or potassium glycine sulfate (2), in an amount in the range of 0.00-3.95% w / w;

[0258] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K) in an amount ranging from 0.30-3.62% w / w;

[0259] (v) diols in an amount ranging from 10-45% w / w; and

[0260] (vi) Water, made up to 100% w / w of the composition.

[0261] Most preferably, the composition according to the present invention which is a stable silicic acid solution comprises or consists of:

[0262] (i) silicic acid in an amount corresponding to 0.40-0.60% w / w silicon (Si);

[0263] (ii) amino acid hydrogen sulfate 1AA, 1b, 1c, preferably glycine hydrogen sulfate (1), in the range of 0.62-3.70% w / w;

[0264] (iii) sodium and / or potassium sulfate of amino acids 2aAA, 2bAA, 2c, 2d, 2e, 2f, preferably sodium and / or potassium glycine sulfate (2), in the range of 0.00-3.38% w / w;

[0265] (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K) in the range of 1.05-3.10% w / w;

[0266] (v) diols in the range of 30-45% w / w; and

[0267] (vi) Water, made up to 100% w / w of the composition.

[0268] In another preferred embodiment, the present invention relates to a stable silicic acid solution comprising or consisting of the following:

[0269] (i) silicic acid in the form of a mixture of orthosilicic acid (H4SiO4; OSA), its water-soluble oligomers and water-soluble polymers, silicon (Si) in a relative amount of 0.01-1.00 part by weight, more preferably 0.10-0.70 part by weight, most preferably 0.40-0.60 part by weight,

[0270] (ii) amino acid hydrogen sulfate 1AA, 1b, 1c, preferably glycine hydrogen sulfate (1), in a relative amount of 0.015-6.17 parts (by weight), more preferably 0.15-4.32 parts (by weight), most preferably 0.62-3.70 (parts by weight),

[0271]

[0272] (iii) sodium and / or potassium sulfate of amino acids 2aAA, 2bAA, 2c, 2d, 2e, 2f, preferably sodium and / or potassium glycine sulfate (2a, b), in a relative amount of 0.00-5.64 parts (by weight), more preferably 0.00-3.95 parts (by weight), most preferably 0.00-3.38 parts (by weight),

[0273]

[0274] (iv) sodium and / or potassium hydrogen sulfate (MHSO4, wherein M = Na and / or K), in a relative amount of 0.00-9.70 parts (by weight), more preferably 0.30-3.62 parts (by weight), most preferably 1.05-3.10 parts (by weight), and

[0275] (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4),

[0276]

[0277] and mixtures thereof, in a relative amount of 5-50 parts (by weight), more preferably 10-45 parts (by weight), most preferably 30-45 parts (by weight),

[0278] (vi) In water, typically in an amount sufficient to form a solution.

[0279] The stabilized silicic acid solution according to the invention is typically made from the following starting materials:

[0280] (i) solid or liquid sodium and / or potassium silicates, xM2O·ySiO2, where M = Na and / or K, x = 1 and y = 1-4,

[0281] (ii) an amino acid, preferably glycine (5),

[0282]

[0283] (iii) Sulfuric acid (H2SO4),

[0284] (iv) a diol, preferably a diol as defined above, and

[0285] (v) water;

[0286] in:

[0287] (a) The molar ratio n / n of silicon (Si) to amino acid (preferably glycine (5)) is:

[0288] n(Si):n(5)=1:0.8-2.4,

[0289] (b) The amount of sulfuric acid (n) is equal to the sum of:

[0290] - the amount of substances of sodium and / or potassium (Na and / or K) from silicates (n); and

[0291] -25% to 100% of the amount (n) of amino acid (preferably glycine (5)):

[0292] n(H2SO4)=n(M)+0.25-1.00·n(5),

[0293] (c) the product does not contain excess sulfuric acid or any other additional acid; and

[0294] (d) The pH value of the obtained composition is between 0.35 and 3.00.

[0295] According to a preferred embodiment, the sodium and / or potassium silicate (xM2O·ySiO2, wherein M=Na and / or K) used to prepare the composition according to the invention is:

[0296] - in solid form with 97-99% w / w sodium or potassium silicate, or

[0297] - in the form of a liquid having a concentration of about 24-47% w / w sodium or potassium silicate,

[0298] It is characterized by the following molar ratio x:y, n / n:

[0299] -x=1.00, y=1.00;

[0300] -x=1.00, y=1.60-1.70;

[0301] -x=1.00, y=2.00-2.10;

[0302] -x=1.00, y=3.30-3.40;

[0303] -x=1.00, y=3.90-4.00;

[0304] Or a mixture of these substances. Sodium and / or potassium silicates of this type are generally commercially available products throughout the world.

[0305] According to a preferred embodiment, the 1,2-propylene glycol (3) used to prepare the composition according to the present invention is a food or pharmaceutical grade purity product, which is also commercially available all over the world.

[0306] According to a preferred embodiment, the type of PEG (4) is selected from the group consisting of: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 2000, PEG 3000, PEG 3350, PEG 4000, PEG 6000, PEG 8000, PEG 10000, PEG 12000, PEG 20000, PEG 35000, or a mixture of these substances. According to a preferred embodiment, PEG is a food or pharmaceutical grade purity product, which is commercially available from different manufacturers and distributors around the world.

[0307] Sulfuric acid (H2SO4) used to prepare the compositions according to the invention may be of various concentrations, most practically 50% to 96% w / w, and is preferably of food or pharmaceutical grade quality.

[0308] The amino acids, preferably glycine (5), used to prepare the compositions according to the invention may be of various origins, either synthetically produced or isolated from animal or plant protein hydrolysates, but are preferably of food or pharmaceutical grade quality. Such grades are widely available from various manufacturers and distributors around the world.

[0309] A second aspect of the present invention relates to a method for preparing a stable silicic acid solution, preferably a stable silicic acid solution as defined above, the method comprising the following steps:

[0310] A. dissolving one or more amino acids in a mixture of glycol and purified water; this is achieved by stirring at a temperature of 10°C to 50°C for 1 to 30 minutes,

[0311] B. Sulfuric acid (H2SO4) is added separately and gradually to a portion of the purified water at a temperature of 5°C-20°C over a period of 5-30 minutes,

[0312] C. adding the sulfuric acid solution from step B to the solution from step A at a temperature of 5°C-20°C during 1-30 minutes,

[0313] D. Prepare separately a solution of sodium or potassium silicate in water by:

[0314] - dissolve the solid material in a portion of purified water, or

[0315] - dilution of liquid substances with a portion of purified water, and

[0316] E. Add the solution from step D dropwise to the cooled solution from step C at a temperature of 5°C-15°C with vigorous stirring over a period of 5-60 minutes to produce the final liquid silicic acid composition.

[0317] In a preferred embodiment, there is provided a method as defined herein, wherein:

[0318] (a) The molar ratio n / n of silicon (Si) to amino acid (AA) is:

[0319] n(Si):n(AA)=1:0.8-2.4,

[0320] (b) The amount of sulfuric acid (n) is equal to the sum of:

[0321] - the amount of substances of sodium and / or potassium (Na and / or K) from silicates (n); and

[0322] - 25% to 100% of the amount (n) of the corresponding amino acid (AA):

[0323] n(H2SO4)=n(M)+0.25-1.00·n(AA),

[0324] and / or

[0325] (c) The sodium and / or potassium silicates (xM2O·ySiO2, wherein M=Na and / or K) used in the process are:

[0326] - in solid form with 97-99% w / w sodium or potassium silicate, or

[0327] - in the form of a liquid having a concentration of about 24-47% w / w sodium or potassium silicate,

[0328] It is characterized by the following molar ratios, x:y, n / n: x=1.00, y=1.00; x=1.00, y=1.60-1.70; x=1.00, y=2.00-2.10; x=1.00, y=3.30-3.40; x=1.00, y=3.90-4.00; or mixtures of these substances.

[0329] The method according to claim 12, wherein the one or more amino acids are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit), proline (Pro), β-alanine (βAl) and salts thereof.

[0330] In a preferred embodiment, a method as defined herein is provided, wherein the one or more amino acids are or include histidine (His), arginine (Arg), ornithine (Orn) and / or lysine (Lys), wherein the side chain moiety (R) is in the form of a free base, and for an equimolar amount of said AA used, the amount of substance (n) of sulfuric acid used in the method is increased to ensure that the corresponding side chain basic functional group is converted into the corresponding bisulfate.

[0331] In a preferred embodiment, there is provided a method for preparing a stable silicic acid solution as defined herein, the method comprising the following steps:

[0332] A. dissolving glycine (5) in a mixture of diol and purified water; this is achieved by stirring at a temperature of 10°C to 50°C for 1 to 30 minutes,

[0333] B. Sulfuric acid (H2SO4) is added separately and gradually to a portion of the purified water at a temperature of 5°C-20°C over a period of 5-30 minutes,

[0334] C. adding the sulfuric acid solution from step B to the solution from step A at a temperature of 5°C-20°C during 1-30 minutes,

[0335] D. Prepare separately a solution of sodium and / or potassium silicate in water by:

[0336] - dissolve the solid material in a portion of purified water, or

[0337] - dilution of liquid substances with a portion of purified water, and

[0338] E. adding the solution from step D dropwise to the cooled solution from step C at a temperature of 5°C-15°C with vigorous stirring during 5-60 minutes,

[0339] A final liquid silicic acid composition according to the present invention is produced.

[0340] Using glycine (Gly; 5) as an example, the reactions that occur during the manufacturing process are as follows:

[0341] (1) During step C, neutralization of glycine with sulfuric acid occurs, producing glycine bisulfate (1) containing excess residual unreacted H2SO4; see Equation 1a:

[0342] (2) During step E, when sodium or potassium silicate solution is added to the glycine bisulfate (1)-sulfuric acid system, the "sodium or potassium oxide" in the corresponding silicate is neutralized to obtain the corresponding sodium or potassium bisulfate and orthosilicic acid (H4SiO4); see equation 2a:

[0343]

[0344] (3) In the case of using a lower molar excess of sulfuric acid, for example, if the amount of substance (n) of H2SO4 is equal to the amount of substance of sodium (Na) and / or potassium (K) in the silicate plus 0.25 of the amount of substance of glycine (5) is less than 1.00, for example 0.50 (50%), then there is not enough sulfuric acid for quantitative conversion of the glycine base into glycine hydrogen sulfate (1). In this case, sodium and / or potassium hydrogen sulfate (MHSO4, M = Na and / or K) reacts with the excess unreacted glycine (free base) to produce a mixed salt of sodium or potassium glycine sulfate (2a, b); see equations 1b and 2b:

[0345]

[0346] In addition, if the amount of H2SO4 is equal to the sum of the amount of sodium (or potassium) in the silicate and the amount of glycine, a mixture of sodium (or potassium) hydrogen sulfate and glycine hydrogen sulfate (1) is formed. In this case, no mixed salt glycine sodium sulfate (2a) or glycine potassium sulfate (2b) is formed.

[0347] The quantitative composition of the stabilizing components glycine hydrogen sulfate (1), sodium or potassium glycine sulfate (2a or 2b) and sodium and / or potassium hydrogen sulfate (MHSO4; M = Na and / or K) can be easily calculated from the amounts of sodium or potassium silicate, glycine (5) and sulfuric acid (H2SO4) used, taking into account that sodium or potassium hydroxide (from the sodium or potassium silicate) is a stronger base than glycine. In this way, the first amount of sulfuric acid is used to neutralize the hydroxide (OH) radicals from the sodium or potassium silicate. - ) anions to form water (H2O) and sodium and / or potassium bisulfate (MHSO4; M = Na and / or K), while all excess sulfuric acid used is used to neutralize glycine into its salt, glycine bisulfate (1). In the case if sulfuric acid is used in a lower molar excess necessary to neutralize both NaOH or KOH (from silicate) and glycine base, then mainly sodium and / or potassium bisulfate (MHSO4; M = Na and / or K) formed neutralizes the excess glycine base, yielding sodium or potassium glycine sulfate (2a or 2b).

[0348] In a preferred embodiment of the present invention, the mixture of glycol and purified water in step A. comprises glycol and purified water in a ratio of 1:1 to 3:1 w / w.

[0349] In a preferred embodiment of the present invention, in step A., an amino acid, preferably glycine (5) is dissolved in a mixture of the diol and purified water to a concentration in the range of 0.01-5.00% w / w.

[0350] In a preferred embodiment of the present invention, in step B., sulfuric acid having an initial concentration of 50-96% w / w is added to partially purified water to a concentration in the range of 0.01-40.00% w / w.

[0351] In a preferred embodiment of the present invention, in step D., a sodium or potassium silicate solution is prepared, the solution comprising sodium or potassium silicate in a concentration range of 0.02-16.00% w / w.

[0352] Typical experimental procedures for preparing products based on the compositions of the present invention are described in Examples 7-35.

[0353] The results of a stability study of a typical formulation according to the invention compared with a formulation which can be considered as the closest prior art solution (the products according to Comparative Examples 1-6) are described in Example 36.

[0354] A third aspect of the present invention relates to a stable silicic acid solution obtainable in any of the methods as defined above. The present inventors understand that the composition obtained by said method has the characteristics of the product defined above, but the present invention is not limited by any such theory.

[0355] The composition according to the present invention can be used as a food supplement, a functional food ingredient, a feed additive, a functional feed additive, an active cosmetic ingredient (ACI) or an active pharmaceutical ingredient (API), which provides highly bioavailable silicon (Si) and its beneficial nutritional and pharmacological effects.

[0356] When used as a food supplement, a functional food ingredient, a feed additive, a functional feed additive, an active cosmetic ingredient (ACI), or as an active pharmaceutical ingredient (API), the composition according to the present invention is used as a functional ingredient providing beneficial nutritional and pharmacological effects selected from the group consisting of: antioxidant, anti-inflammatory, anti-osteoporotic, stimulation of collagen biosynthesis, stimulation of cartilage and connective tissue formation, stimulation of hair, nail and skin strength and growth, vitamin D mimetic activity - because it stimulates calcium absorption, stimulation of bone mineralization and growth, stimulation of skin repair and regeneration, anti-wrinkle effect, wound healing effect, immune system modulating effect, neuroprotective effect by preventing aluminum accumulation in the brain, anti-atherosclerotic effect, antihypertensive effect, antidiabetic effect, antihistamine effect, analgesic effect and diuretic effect.

[0357] More specifically, the composition according to the invention can be used as an active pharmaceutical ingredient for the prevention and / or treatment of medical disorders or diseases selected from the group consisting of: skin ulcers, including decubitus ulcers, diabetic skin ulcers, burn ulcers, traumatic ulcers or foot ulcers, surgical site wounds or diabetic gangrene; cancer diseases, including melanoma; allergies; osteoporosis, bone fractures, osteoarthritis, and other disorders and diseases of bone and cartilage; prevention and treatment of inflammatory diseases: dermatitis, arthritis, osteoarthritis, otitis (including otitis media), gastritis, gastroenteritis, inflammatory bowel disease (including Crohn's disease), sinusitis, sinusitis, pharyngitis, laryngitis, lower respiratory tract inflammation and other inflammatory diseases; periodontitis; poor peripheral blood circulation; paresthesia; hypertension; diabetes; atherosclerosis; vertigo; headache; tinnitus; insomnia; diarrhea; constipation; hemorrhoids; kidney stones; urinary tract infections; low back pain; excessive female secretions; abscesses and ulcers in the genital area and cervix and mastitis; alopecia.

[0358] When used as a food supplement, a functional food ingredient, a functional feed additive, an active cosmetic ingredient (ACI) or an active pharmaceutical ingredient (API), the composition according to the present invention can be used in a dosage equivalent to 0.1-30 mg silicon (Si) per day, preferably in a dosage equivalent to 1-15 mg Si per day, most preferably in a dosage equivalent to 3-12 mg Si per day.

[0359] When used as a feed additive, the composition according to the invention is preferably used in a dosage equivalent to 0.001-0.5 mg silicon (Si) / kg animal body weight per day, preferably 0.01-0.2 mg Si / kg / day, most preferably 0.05-0.15 mg Si / kg / day.

[0360] Alternatively, the composition according to the present invention can be used as an agrochemical product for silicon fertilization, plant growth promotion and plant protection.

[0361] More specifically, the compositions according to the invention can be used as active agrochemical agents which promote plant growth and increase crop yield, improve strength, reduce climatic stress (including drought resistance), provide resistance to mineral stress, and increase resistance to attack by insect pests, nematodes and diseases (including fungal diseases).

[0362] When used as an agrochemical product, the composition according to the invention is preferably used in a concentration providing 5-500 ppm of silicon (Si), depending on the type of application, which may for example involve drip fertigation or foliar spraying, such as 10-100 ppm or 25-50 ppm.

[0363] Alternatively, the composition according to the invention may be used in aquaculture, typically as a fertilizer, as a feed additive and / or as a biostimulant, in order to increase productivity and / or reduce its environmental impact.

[0364] More precisely, the composition according to the invention can be used in aquaculture with one or more of the following purposes and / or results:

[0365] - Promote the growth of aquatic animals;

[0366] - Accelerate the growth of aquatic animals;

[0367] - Increase the weight of aquatic animals;

[0368] - Shorten harvest time;

[0369] - Improve overall productivity;

[0370] - Improve feed utilization;

[0371] - Improve feed conversion rate;

[0372] - Improve water quality;

[0373] - Increase dissolved oxygen levels and / or maintain dissolved oxygen levels;

[0374] - reduce ammonia concentrations and / or prevent ammonia concentrations from rising;

[0375] - Improve the pH of water and / or maintain the pH at an appropriate level;

[0376] - reduce salinity and / or prevent salinization and / or hypersalinization;

[0377] - Promote / stimulate the growth of phytoplankton, especially diatoms, in the water; and

[0378] -Reduce the ecological impact of aquaculture.

[0379] When used in aquaculture, the composition of the present invention is preferably added to the water in which the aquatic species are reared, and its dosage is such that the silicon (Si) level in the water is at least 0.1ppm, preferably at least 0.5ppm, at least 1ppm, at least 2.5ppm, at least 5ppm, at least 10ppm, or at least 25ppm. Alternatively, the composition of the present invention can be added to the feed, typically in an amount such that the silicon (Si) level in the feed is at least 0.001ppm, preferably at least 0.005ppm, at least 0.01ppm, at least 0.025ppm, at least 0.05ppm, at least 0.10ppm, or at least 0.25ppm.

[0380] As will be apparent to the skilled person, based on the present teaching, many of the envisaged uses (such as those defined above) will require dilution of the stable silicic acid solution of the present invention, typically by simply adding water, for example before application to crops or before application to animals. Therefore, another aspect of the present invention relates to a method for providing a diluted and / or ready-to-use silicic acid composition, the method comprising the steps of combining an amount of the stable silicic acid solution of the present invention with an amount of water (such as ordinary tap water), for example in a ratio in the range of 1:1 to 1:50000, 1:2 to 1:1000 or 1:5 to 1:500, depending on the envisaged application. Yet another aspect of the present invention relates to a diluted and / or ready-to-use composition obtainable by said method.

[0381] Examples

[0382] General information

[0383] All percentage (%) values ​​of materials are expressed as parts by weight (% w / w). The term "room temperature" (rt) relates to a temperature range of 20°C-25°C. Mixing speeds are expressed in revolutions per minute (rpm) of the stirring element.

[0384] Starting materials were purchased from the following suppliers:

[0385] (1) 1,2-propylene glycol (3), Essential, Ph. Eur.; pharmaceutical grade; Merck KGaA, Darmstadt (Germany);

[0386] (2) polyethylene glycol 400 (4; PEG 400), Essential, Ph. Eur.; Pharmaceutical grade; Merck KgaA, Darmstadt (Germany);

[0387] (3) Polyethylene glycol 1000 (4; PEG 1000), used for synthesis; Merck KGaA, Darmstadt (Germany);

[0388] (4) Sorbitol, anhydrous; Acros Organics, Haier (Belgium);

[0389] (5) Sorbitol, 70% w / w solution; Carlo Erba, Milan (Italy);

[0390] (6) Clear PQ sodium silicate solution; composition: 8.9% w / w Na2O, 28.7% SiO2, 37.60% w / w total solids; PQ Company (USA);

[0391] (7) -6 type potassium silicate solution; composition: 12.7% w / w K2O, 26.5% SiO2, 39.21.0% w / w total solids; PQ Company (USA);

[0392] (8) Food grade amino acids, 98.5%-101.5%; Gonmisol (Spain); such as glycine (Gly), L-leucine (Leu), L-proline (Pro), L-serine (Ser), L-threonine (Thr), L-aspartic acid (Asp), L-glutamic acid (Glu), L-phenylalanine (Phe), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His), L-arginine (Arg), L-glutamine (Glu), L-ornithine hydrochloride (Orn·HCl), L-lysine hydrochloride (Lys·HCl), L-methionine (Met), L-cysteine ​​hydrochloride monohydrate (Cys·HCl·H2O), L-citrulline DL-malate (Cit·Mal) and β-alanine (βAl).

[0393] (9) Sulfuric acid 95%-97%, analytical grade ISO;Merck KgaA, Darmstadt (Germany);

[0394] All other starting materials and laboratory consumables were purchased from local suppliers.

[0395] Example 1 (Comparative). Preparation of a 0.6% w / w silicon (Si) based on glycine (Gly), glycerol and hydrochloric acid (HCl) Comparative composition of silicic acid

[0396] Starting materials (for 100 g solution):

[0397] (1) 10.00% w / w (10.00 g) glycine (Gly); n(Gly) = 0.1332 mol;

[0398] (2) 40.00% w / w (40.00 g) glycerol;

[0399] (3) 30.74% w / w (30.74 g) purified water;

[0400] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0401] (5) 14.41% w / w (14.41 g) hydrochloric acid, 37%; 5.33 g HCl, n(HCl) = 0.1462 mol.

[0402] Total: 100% w / w (100.00 g)

[0403] preparation : Glycine was dissolved in a mixture of purified water (10.00 g) and glycerol by stirring at rt for 5 min. Separately, hydrochloric acid (37%) was added dropwise to purified water (5.74 g) over 5 min under external cooling at 15°C-20°C, and the dilute hydrochloric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture of purified water (10.00 g) and glycerol by stirring at rt for ... -6 was added to purified water (15.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrochloride-hydrochloric acid in aqueous glycerol solution at 12-17° C. over a period of 25-30 min.

[0404] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 0.80 / 20°C; the composition of the product is as follows:

[0405] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0406] (2) 14.86% w / w glycine hydrochloride;

[0407] (3) 0.98% w / w potassium chloride (KCl);

[0408] (4) 40.00% w / w glycerol; and

[0409] (5) Make up to 100% w / w with purified water.

[0410] Example 2 (Comparative). Preparation of a 0.6% w / w silicon (Si) based on glycine (Gly), sorbitol and hydrochloric acid Comparative composition of silicic acid (HCl)

[0411] Starting materials (for 100 g solution):

[0412] (1) 10.00% w / w (10.00 g) glycine (Gly); n(Gly) = 0.1332 mol;

[0413] (2) 57.14% w / w (40.00g) sorbitol, 70% w / w solution;

[0414] (3) 13.60% w / w (13.60 g) purified water;

[0415] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0416] (5) 14.41% w / w (14.41 g) hydrochloric acid, 37%; 5.33 g HCl, n(HCl) = 0.1462 mol.

[0417] Total: 100% w / w (100.00 g)

[0418] preparation : Glycine was suspended in sorbitol 70% solution by stirring at rt for 5 min. Separately, hydrochloric acid (37%) was added dropwise to purified water (3.60 g) during 5 min at 15°C-20°C with external cooling, and the dilute hydrochloric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the solution. -6 was added to purified water (10.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrochloride-hydrochloric acid in aqueous sorbitol solution at 12-17° C. over a period of 25-30 min.

[0419] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 0.70 / 20°C; the composition of the product is as follows:

[0420] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0421] (2) 14.86% w / w glycine hydrochloride;

[0422] (3) 0.98% w / w potassium chloride (KCl);

[0423] (4) 40.00% w / w sorbitol; and

[0424] (5) Make up to 100% w / w with purified water.

[0425] Example 3 (Comparative). Preparation of a 0.6% w / w silicon (Si) based on glycine (Gly), glycerol and phosphoric acid (H3PO4) The control composition of silicic acid

[0426] Starting materials (for 100 g solution):

[0427] (1) 5.00% w / w (5.00 g) glycine (Gly); n(Gly) = 0.0666 mol;

[0428] (2) 40.00% w / w (40.00 g) glycerol;

[0429] (3) 40.72% w / w (40.72 g) purified water;

[0430] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0431] (5) 9.43% w / w (9.43 g) phosphoric acid, 85%; 8.02 g H3PO4, n(H3PO4) = 0.0818 mol.

[0432] Total: 100% w / w (100.00 g)

[0433] preparation : Glycine was suspended in a mixture of purified water (10.00 g) and glycerol by stirring at rt for 5 min. Separately, phosphoric acid (85%) was added dropwise to purified water (10.72 g) within 5 min under external cooling at 15°C-20°C, and the dilute phosphoric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture of purified water (10.00 g) and glycerol by stirring at rt for 5 min. Separately, phosphoric acid (85%) was added dropwise to purified water (10.72 g) under external cooling at 15°C-20°C within 5 min. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine dihydrogen phosphate-phosphoric acid in aqueous glycerol solution at 12-17° C. over a period of 25-30 min.

[0434] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 2.23 / 20°C; the composition of the product is as follows:

[0435] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0436] (2) 11.53% w / w glycine dihydrogen phosphate;

[0437] (3) 1.78% w / w potassium dihydrogen phosphate (KH2PO4);

[0438] (4) 40.00% w / w glycerol; and

[0439] (5) Make up to 100% w / w with purified water.

[0440] Example 4 (Comparative). Preparation of a polyol based on glycine (Gly), sorbitol and phosphoric acid with 0.6% w / w silicon (Si) Comparative composition of silicic acid (H3PO4)

[0441] Starting materials (for 100 g solution):

[0442] (1) 5.00% w / w (5.00 g) glycine (Gly); n(Gly) = 0.0666 mol;

[0443] (2) 40.00% w / w (40.00 g) sorbitol, anhydrous;

[0444] (3) 40.72% w / w (40.72 g) purified water;

[0445] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0446] (5) 9.43% w / w (9.43 g) phosphoric acid, 85%; 8.02 g H3PO4, n(H3PO4) = 0.0818 mol.

[0447] Total: 100% w / w (100.00 g)

[0448] preparation : Glycine was dissolved in a mixture of purified water (10.00 g) and sorbitol by stirring at rt for 5 min. Separately, phosphoric acid (85%) was added dropwise to purified water (10.72 g) during 5 min at 15°C-20°C with external cooling, and the dilute phosphoric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine dihydrogen phosphate-phosphoric acid in aqueous sorbitol solution at 12-17° C. over a period of 25-30 min.

[0449] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 2.01 / 20°C; the composition of the product is as follows:

[0450] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0451] (2) 11.53% w / w glycine dihydrogen phosphate;

[0452] (3) 1.78% w / w potassium dihydrogen phosphate (KH2PO4);

[0453] (4) 40.00% w / w sorbitol; and

[0454] (5) Make up to 100% w / w with purified water.

[0455] Example 5 (Comparative). Preparation of a 0.6% w / w silicon (Si) based on glycine (Gly), glycerol and sulfuric acid (H2SO4) The control composition of silicic acid

[0456] Starting materials (for 100 g solution):

[0457] (1) 5.00% w / w (5.00 g) glycine (Gly); n(Gly) = 0.0666 mol;

[0458] (2) 40.00% w / w (40.00 g) glycerol;

[0459] (3) 42.01% w / w (42.01 g) purified water;

[0460] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0461] (5) 8.14% w / w (8.14 g) sulfuric acid, 96%; 7.81 g H2SO4, n(H2SO4) = 0.0818 mol.

[0462] Total: 100% w / w (100.00 g)

[0463] preparation : Glycine was dissolved in a mixture of purified water (10.00 g) and glycerol by stirring at rt for 5 min. Separately, sulfuric acid (96%) was added dropwise to purified water (12.01 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture of purified water (10.00 g) and glycerol by stirring at rt for 5 min. Separately, sulfuric acid (96%) was added dropwise to purified water (12.01 g) over 5 min at 15°C-20°C with external cooling. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine dihydrogen sulfate-sulfuric acid in aqueous glycerol solution at 12°C-17°C during 25-30 min.

[0464] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 2.01 / 20°C; the composition of the product is as follows:

[0465] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0466] (2) 11.53% w / w glycine dihydrogen sulfate (1);

[0467] (3) 1.78% w / w potassium dihydrogen sulfate (KHSO4);

[0468] (4) 40.00% w / w glycerol; and

[0469] (5) Make up to 100% w / w with purified water.

[0470] Example 6 (Comparative) Preparation of a polyol based on glycine (Gly), sorbitol and sulfur with 0.6% w / w silicon (Si) Comparative composition of silicic acid (H2SO4)

[0471] Starting materials (for 100 g solution):

[0472] (1) 5.00% w / w (5.00 g) glycine (Gly); n(Gly) = 0.0666 mol;

[0473] (2) 57.14% w / w (57.14 g) sorbitol, 70% w / w solution;

[0474] (3) 24.87% w / w (24.87 g) purified water;

[0475] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0476] (5) 8.14% w / w (8.14 g) sulfuric acid, 96%; 7.81 g H2SO4, n(H2SO4) = 0.0818 mol.

[0477] Total: 100% w / w (100.00 g)

[0478] preparation : Glycine was suspended in a mixture of purified water (4.87 g) and sorbitol 70% solution by stirring at rt for 5 min. Separately, sulfuric acid (96%) was added dropwise to purified water (10.00 g) over 5 min under external cooling at 15°C-20°C, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (10.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine dihydrogen sulfate-sulfuric acid in aqueous sorbitol solution at 12-17° C. over a period of 25-30 min.

[0479] The product thus obtained is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 2.01 / 20°C; the composition of the product is as follows:

[0480] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0481] (2) 11.53% w / w glycine dihydrogen sulfate (1);

[0482] (3) 1.78% w / w potassium dihydrogen sulfate (KHSO4);

[0483] (4) 40.00% w / w sorbitol; and

[0484] (5) Make up to 100% w / w with purified water.

[0485] Example 7. Preparation of a 1,2-propanediol (3)-based cellulose having 0.6% w / w silicon (Si) according to the present invention. Composition of the invention

[0486] Starting materials (for 100 g solution):

[0487] (1) 1.61% w / w (1.61 g) glycine (Gly); n(Gly) = 0.02145 mol;

[0488] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0489] (3) 50.01% w / w (50.01 g) purified water;

[0490] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0491] (5) 3.53% w / w (3.53 g) sulfuric acid, 96%; 3.39 g H2SO4, n(H2SO4) = 0.03455 mol.

[0492] Total: 100% w / w (100.00 g)

[0493] preparation : Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.01 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0494] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 0.98 / 22° C.; the composition of the product is as follows:

[0495] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0496] (2) 3.71% w / w glycine hydrogen sulfate (1);

[0497] (3) 0.00% w / w potassium glycine sulfate (2b);

[0498] (4) 1.78% w / w potassium hydrogen sulfate (KHSO4);

[0499] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0500] (6) Make up to 100% w / w with purified water.

[0501] Example 8. Preparation of a 0.6% w / w silicon (Si) based on glycine (Gly) and polyethylene glycol 400 (PEG400) The composition according to the invention

[0502] Starting materials (for 100 g solution):

[0503] (1) 1.61% w / w (1.61 g) glycine (Gly); n(Gly) = 0.02145 mol;

[0504] (2) 40.00% w / w (40.00 g) polyethylene glycol 400 (4; PEG 400);

[0505] (3) 50.01% w / w (50.01 g) purified water;

[0506] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0507] (5) 3.53% w / w (3.53 g) sulfuric acid, 96%; 3.39 g H2SO4, n(H2SO4) = 0.03455 mol.

[0508] Total: 100% w / w (100.00 g)

[0509] preparation : Glycine was dissolved in a mixture of purified water (20.00 g) and polyethylene glycol 400 (4; PEG 400) by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.01 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in aqueous PEG solution at 15-20°C during 20-30 min.

[0510] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.13 / 20° C.; the composition of the product is as follows:

[0511] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0512] (2) 3.71% w / w glycine hydrogen sulfate (1);

[0513] (3) 0.00% w / w potassium glycine sulfate (2b);

[0514] (4) 1.78% w / w potassium hydrogen sulfate (KHSO4);

[0515] (5) 40.00% w / w polyethylene glycol 400 (4; PEG 400); and

[0516] (6) Make up to 100% w / w with purified water.

[0517] Example 9. Preparation of a composition according to the invention based on glycine (Gly) with 0.01% w / w silicon (Si)

[0518] Starting materials (for 100 g solution):

[0519]

[0520] Total: 100% w / w (100.00 g)

[0521] preparation : Glycine was dissolved in a mixture of purified water (49.765 g), 1,2-propylene glycol (3) and polyethylene glycol 1000 (4; PEG 1000) by stirring at rt for 15 min. Separately, sulfuric acid was added dropwise to the above glycine solution at 15°C-20°C over 1 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol-PEG aqueous solution at 15°C-20°C during 25-30 min.

[0522] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.40 / 20° C.; the composition of the product is as follows:

[0523] (1) Silicic acid; equivalent to 0.01% w / w silicon (Si);

[0524] (2) 0.125% w / w glycine hydrogen sulfate (1);

[0525] (3) 0.000% w / w potassium glycine sulfate (2b);

[0526] (4) 0.030% w / w potassium hydrogen sulfate (KHSO4);

[0527] (5) 15.00% w / w 1,2-propylene glycol (3);

[0528] (6) 15.00% w / w polyethylene glycol 1000 (4; PEG 1000); and

[0529] (7) Make up to 100% w / w with purified water.

[0530] Example 10. Preparation of a composition according to the invention based on glycine (Gly) with 0.1% w / w silicon (Si)

[0531] Starting materials (for 100 g solution):

[0532]

[0533] Total: 100% w / w (100.00 g)

[0534] preparation : Glycine was dissolved in a mixture of purified water (50.00 g), 1,2-propylene glycol and PEG400 by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (13.39 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, a sodium silicate solution was added dropwise to the mixture. Clear was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute sodium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol-PEG aqueous solution at 15-20° C. over a period of 20-30 min.

[0535] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.30 / 20° C.; the composition of the product is as follows:

[0536] (1) Silicic acid; equivalent to 0.10% w / w silicon (Si);

[0537] (2) 0.62% w / w glycine hydrogen sulfate (1);

[0538] (3) 0.00% w / w sodium glycine sulfate (2a);

[0539] (4) 0.26% w / w sodium bisulfate (NaHSO4);

[0540] (5) 10.00% w / w 1,2-propylene glycol (3);

[0541] (6) 5.00% w / w polyethylene glycol 400 (4; PEG 400); and

[0542] (7) Make up to 100% w / w with purified water.

[0543] Example 11. Preparation of a composition according to the invention based on glycine (Gly) with 0.4% w / w silicon (Si)

[0544] Starting materials (for 100 g solution):

[0545]

[0546] Total: 100% w / w (100.00 g)

[0547] preparation : Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (13.36 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 25-30 min.

[0548] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.07 / 20° C.; the composition of the product is as follows:

[0549] (1) Silicic acid; equivalent to 0.40% w / w silicon (Si);

[0550] (2) 2.47% w / w glycine hydrogen sulfate (1);

[0551] (3) 0.00% w / w potassium glycine sulfate (2b);

[0552] (4) 1.18% w / w potassium hydrogen sulfate (KHSO4);

[0553] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0554] (6) Make up to 100% w / w with purified water.

[0555] Example 12. Preparation of a composition according to the invention based on glycine (Gly) with 0.5% w / w silicon (Si)

[0556] Starting materials (for 100 g solution):

[0557]

[0558] Total: 100% w / w (100.00 g)

[0559] preparation : Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (12.59 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 25-30 min.

[0560] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.70 / 20° C.; the composition of the product is as follows:

[0561] (1) Silicic acid; equivalent to 0.40% w / w silicon (Si);

[0562] (2) 1.55% w / w glycine hydrogen sulfate (1);

[0563] (3) 1.88% w / w potassium glycine sulfate (2b);

[0564] (4) 0.28% w / w potassium hydrogen sulfate (KHSO4);

[0565] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0566] (6) Make up to 100% w / w with purified water.

[0567] Example 13. Preparation of a composition according to the invention based on glycine (Gly) with 0.6% w / w silicon (Si)

[0568] Starting materials (for 100 g solution):

[0569]

[0570] Total: 100% w / w (100.00 g)

[0571] preparation: Glycine was dissolved in a mixture of purified water (15.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.56 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (15.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0572] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.43 / 21° C.; the composition of the product is:

[0573] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0574] (2) 2.79% w / w glycine hydrogen sulfate (1);

[0575] (3) 1.13% w / w potassium glycine sulfate (2b);

[0576] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0577] (5) 50.00% w / w 1,2-propylene glycol (3); and

[0578] (6) Make up to 100% w / w with purified water.

[0579] Example 14. Preparation of a composition according to the invention based on glycine (Gly) with 1.0% w / w silicon (Si)

[0580] Starting materials (for 100 g solution):

[0581]

[0582] Total: 100% w / w (100.00 g)

[0583] preparation: Glycine was dissolved in a mixture of purified water (15.00 g) and polyethylene glycol 400 (4; PEG 400) by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (14.28 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (15.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in aqueous PEG solution at 15°C-20°C during 25-30 min.

[0584] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.47 / 20° C.; the composition of the product is as follows:

[0585] (1) Silicic acid; equivalent to 1.00% w / w silicon (Si);

[0586] (2) 6.18% w / w glycine hydrogen sulfate (1);

[0587] (3) 1.89% w / w potassium glycine sulfate (2b);

[0588] (4) 1.75% w / w potassium hydrogen sulfate (KHSO4);

[0589] (5) 40.00% w / w polyethylene glycol 400 (4; PEG 400); and

[0590] (6) Make up to 100% w / w with purified water.

[0591] Example 15. Preparation of a composition according to the invention based on glycine (Gly) with 0.6% w / w silicon (Si)

[0592] Starting materials (for 100 g solution):

[0593]

[0594] Total: 100% w / w (100.00 g)

[0595] preparation: Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.65 g) over 5 min under external cooling at 10°C-15°C, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 10°C-17°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0596] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 2.20 / 20° C.; the composition of the product is:

[0597] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0598] (2) 0.93% w / w glycine hydrogen sulfate (1);

[0599] (3) 2.76% w / w potassium glycine sulfate (2b);

[0600] (4) 0.00% w / w potassium hydrogen sulfate (KHSO4);

[0601] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0602] (6) Make up to 100% w / w with purified water.

[0603] Example 16. Preparation of a composition according to the invention based on glycine (Gly) with 0.6% w / w silicon (Si)

[0604] Starting materials (for 100 g solution):

[0605]

[0606]

[0607] Total: 100% w / w (100.00 g)

[0608] preparation: Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.65 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17° C. over a period of 25-30 min.

[0609] The product thus obtained, the stabilized silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.65 / 20° C.; the composition of the product is:

[0610] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0611] (2) 1.85% w / w glycine hydrogen sulfate (1);

[0612] (3) 2.27% w / w potassium glycine sulfate (2b);

[0613] (4) 0.32% w / w potassium hydrogen sulfate (KHSO4);

[0614] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0615] (6) Make up to 100% w / w with purified water.

[0616] Example 17. Preparation of a composition according to the invention based on glycine (Gly) with 0.6% w / w silicon (Si)

[0617] Starting materials (for 100 g solution):

[0618]

[0619]

[0620] Total: 100% w / w (100.00 g)

[0621] preparation: Glycine was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (10.56 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above glycine solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of glycine hydrogen sulfate (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17° C. over a period of 25-30 min.

[0622] The product thus obtained, the stabilized silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.65 / 20° C.; the composition of the product is:

[0623] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0624] (2) 2.79% w / w glycine hydrogen sulfate (1);

[0625] (3) 1.13% w / w potassium glycine sulfate (2b);

[0626] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0627] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0628] (6) Make up to 100% w / w with purified water.

[0629] Example 18. Preparation of 0.6%, 0.3% and 0.25% w / w silicon (Si)-containing eighteen different amino acids Compositions according to the invention

[0630] Starting materials (for 100 g solution):

[0631]

[0632]

[0633] Total: 100% w / w (100.00 g)

[0634] The amounts of m1-m4 used in these experiments are as follows:

[0635]

[0636]

[0637] a The amount of each amino acid (AA) is equimolar to silicon: n(Si):n(AA)=1:1.

[0638] b The amount of sulfuric acid used is equal to the sum of:

[0639] (a)K + The amount of substance (from K2O) and

[0640] (b) 75% of the amount of substance of the corresponding amino acid (AA) unless otherwise stated.

[0641] c Potassium silicate solution ( The amount of 6) corresponds to a silicon (Si) content in the final product equal to 0.60% w / w Si.

[0642] d The amount of sulfuric acid used in these cases is equal to the sum of:

[0643] (i) the amount of the corresponding AA substance required to neutralize the side chain basic imidazole (His) or guanidine (Arg) group;

[0644] (ii) 75% of the amount of the corresponding AA substance required to partially neutralize the remaining α-amino groups; and

[0645] (iii) All K2O (from 6) K required for conversion to KHSO4 + The amount of substance (from K2O).

[0646] e L-Ornithine and L-Lysine are only available as hydrochloride salts, while L-Citrulline is available as DL-malate (2:1). Therefore, the amount of sulfuric acid in these cases is equal to the sum of:

[0647] (i)K + the amount of substance (from K2O); and

[0648] (ii) 75% of the amount of the substance of the corresponding amino acid (AA).

[0649] f L-cysteine ​​is available in the form of its hydrochloride monohydrate salt. In this case, the amount of sulfuric acid used is equal to K + The amount of substance (from K2O).

[0650] preparation: Amino acids (AA) according to column m1 were added to 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid (m3) was added dropwise to purified water (m2) within 1 min under stirring, and the dilute sulfuric acid solution thus obtained was added dropwise to the above AA solution at 15°C-20°C during 15 min. Separately, potassium silicate solution -6 (4.85 g) was added to purified water (m4) and homogenized by stirring for 5 min. The dilute potassium silicate solution thus obtained was added dropwise to the above solution of amino acid (AA)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17°C during 25-30 min.

[0651] The product thus obtained, the stable silicic acid solution according to the present invention, exhibits the following key features:

[0652]

[0653]

[0654]

[0655] Example 19: Preparation of 0.6%, 0.3% and 0.25% w / w Silicon (Si)-containing 18 different amino acids Compositions according to the invention

[0656] Starting materials (for 100 g solution):

[0657]

[0658]

[0659] Total: 100% w / w (100.00 g)

[0660] The amounts of m1-m4 used in these experiments are as follows:

[0661]

[0662]

[0663] preparation : Amino acids (AA) according to column m1 were added to 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid (m3) was added dropwise to purified water (m2) within 1 min under stirring, and the dilute sulfuric acid solution thus obtained was added dropwise to the above AA solution at 15°C-20°C during 15 min. Separately, potassium silicate solution -6 (4.85 g) (2.43 g for Experiment 29 and 2.02 g for Experiment 32) was added to purified water (m4) and homogenized by stirring for 5 min. The dilute potassium silicate solution thus obtained was added dropwise to the above solution of amino acid (AA)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13°C-17°C during 25-30 min.

[0664] The product thus obtained, the stable silicic acid solution according to the present invention, exhibits the following key features:

[0665]

[0666]

[0667] Example 20: Preparation of five selected amino groups with 0.25% w / w silicon (Si) and 50% w / w 1,2-propylene glycol Compositions according to the invention of acid analogs

[0668] Starting materials (for 100 g solution):

[0669]

[0670] The amounts of m1-m4 used in these experiments are as follows:

[0671]

[0672] preparation : Amino acids (AA) according to column m1 were added to 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid (m3) was added dropwise to purified water (m2) within 1 min under stirring, and the dilute sulfuric acid solution thus obtained was added dropwise to the above AA solution at 15°C-20°C during 15 min. Separately, potassium silicate solution -6 (2.02 g) was added to purified water (m4) and homogenized by stirring for 5 min. The dilute potassium silicate solution thus obtained was added dropwise to the above solution of amino acid (AA)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17°C during 25-30 min.

[0673] The product thus obtained, the stable silicic acid solution according to the present invention, exhibits the following key features:

[0674]

[0675] Example 21: Preparation of analogs with five selected amino acids, 0.60% w / w silicon (Si) and 1,2 propanediol Compositions according to the invention

[0676] Starting materials (for 100 g solution):

[0677]

[0678]

[0679] Total: 100% w / w (100.00 g)

[0680] The amounts of m1-m4 used in these experiments are as follows:

[0681]

[0682] preparation : Amino acids (AA) according to column m1 were added to 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid (m3) was added dropwise to purified water (m2) within 1 min under stirring, and the dilute sulfuric acid solution thus obtained was added dropwise to the above AA solution at 15°C-20°C during 15 min. Separately, potassium silicate solution -6 (4.85 g) was added to purified water (m4) and homogenized by stirring for 5 min. The dilute potassium silicate solution thus obtained was added dropwise to the above solution of amino acid (1)-sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17° C. over 25-30 min.

[0683] The product thus obtained, the stable silicic acid solution according to the present invention, exhibits the following key features:

[0684]

[0685] Example 22: Preparation of L-tyrosine (Tyr) based Compositions according to the invention

[0686] (Test 48) Starting materials for 100 g of a solution of the product with 0.10% w / w Si and 40% w / w 1,2-propylene glycol:

[0687]

[0688] Total: 100% w / w (100.00 g)

[0689] (Test 49) Starting materials for 100 g of a solution of the product with 0.05% w / w Si and 5% w / w 1,2-propylene glycol:

[0690]

[0691] Total: 100% w / w (100.00 g)

[0692] preparation: L-Tyrosine (0.30 g) was added to 1,2-propylene glycol and 85.00 g of water by stirring at rt for 5 min. Sulfuric acid was added dropwise to the mixture under stirring for 1 min, and the reaction mixture so obtained was stirred at 15°C-20°C for 15 min. Separately, to purified water (8.96 g), potassium silicate solution was added -6 and homogenized by stirring for 5 min. The dilute potassium silicate solution thus obtained was added dropwise to the above reaction mixture - sulfuric acid in 1,2-propylene glycol aqueous solution at 13-17°C during 25-30 min.

[0693] The product thus obtained, the stable silicic acid solution according to the present invention, exhibits the following key features:

[0694]

[0695]

[0696] Example 23. Preparation of a 1,2-propanediol (3)-based L-alanine (Ala) and 0.6% w / w silicon (Si) Compositions of the present invention

[0697] Starting materials (for 100 g solution):

[0698] (1) 1.91% w / w (1.91 g) L-alanine (Ala); n(Ala) = 0.02144 mol;

[0699] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0700] (3) 49.71% w / w (49.71 g) purified water;

[0701] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0702] (5) 3.53% w / w (3.53 g) sulfuric acid, 96%; 3.39 g H2SO4, n(H2SO4) = 0.03452 mol.

[0703] Total: 100% w / w (100.00 g)

[0704] preparation: L-alanine (Ala) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.71 g) over 5 min under external cooling at 15°C-20°C, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-alanine (Ala) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-alanine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0705] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 0.95 / 22° C.; the composition of the product is as follows:

[0706] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0707] (2) 4.01% w / w L-alanine hydrogen sulfate (1Ala);

[0708] (3) 0.00% w / w L-alanine potassium sulfate (2bAla);

[0709] (4) 1.78% w / w potassium hydrogen sulfate (KHSO4);

[0710] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0711] (6) Make up to 100% w / w with purified water.

[0712] Example 24. Preparation of a 0.6% w / w silica-containing (Si) The composition according to the present invention

[0713] Starting materials (for 100 g solution):

[0714] (1) 1.91% w / w (1.91 g) L-alanine (Ala); n(Ala) = 0.02144 mol;

[0715] (2) 40.00% w / w (40.00 g) polyethylene glycol 400 (4; PEG 400);

[0716] (3) 49.71% w / w (49.71 g) purified water;

[0717] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0718] (5) 3.53% w / w (3.53 g) sulfuric acid, 96%; 3.39 g H2SO4, n(H2SO4) = 0.03455 mol.

[0719] Total: 100% w / w (100.00 g)

[0720] preparation : L-alanine (Ala) was dissolved in a mixture of purified water (20.00 g) and polyethylene glycol 400 (4; PEG 400) by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.71 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-alanine (Ala) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the purified water (9.71 g) under external cooling at 15°C-20°C. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-alanine hydrogen sulfate-sulfuric acid in aqueous PEG solution at 15°C-20°C during 20-30 min.

[0721] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.10 / 20° C.; the composition of the product is as follows:

[0722] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0723] (2) 4.01% w / w L-alanine hydrogen sulfate (1Ala);

[0724] (3) 0.00% w / w L-alanine potassium sulfate (2bAla);

[0725] (4) 1.78% w / w potassium hydrogen sulfate (KHSO4);

[0726] (5) 40.00% w / w polyethylene glycol 400 (4; PEG 400); and

[0727] (6) Make up to 100% w / w with purified water.

[0728] Example 25. Preparation of a 1,2-propanediol (3)-based L-leucine (Leu)-containing 0.6% w / w silicon (Si) Compositions of the present invention

[0729] Starting materials (for 100 g solution):

[0730] (1) 2.81% w / w (2.81 g) L-leucine (Leu); n (Leu) = 0.02142 mol;

[0731] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0732] (3) 49.36% w / w (49.36 g) purified water;

[0733] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0734] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0735] Total: 100% w / w (100.00 g)

[0736] preparation : L-leucine (Leu) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.36 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-leucine (Leu) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-leucine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0737] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.24 / 20° C.; the composition of the product is:

[0738] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0739] (2) 3.69% w / w L-leucine hydrogen sulfate (1Leu);

[0740] (3) 1.43% w / w L-leucine sulfate potassium (2bLeu);

[0741] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0742] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0743] (6) Make up to 100% w / w with purified water.

[0744] Example 26. Preparation of a 1,2-propanediol (3)-based L-proline (Pro) having 0.6% w / w silicon (Si) Compositions of the present invention

[0745] Starting materials (for 100 g solution):

[0746] (1) 2.47% w / w (2.47 g) L-proline (Pro); n(Pro) = 0.02145 mol;

[0747] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0748] (3) 49.70% w / w (49.70 g) purified water;

[0749] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0750] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0751] Total: 100% w / w (100.00 g)

[0752] preparation : L-proline (Pro) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.70 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-proline (Pro) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-proline hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0753] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.10 / 20° C.; the composition of the product is:

[0754] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0755] (2) 3.43% w / w L-proline hydrogen sulfate (1Pro);

[0756] (3) 1.35% w / w L-proline potassium sulfate (2bPro);

[0757] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0758] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0759] (6) Make up to 100% w / w with purified water.

[0760] Example 27. Preparation of a 1,2-propanediol (3)-based L-serine (Ser)-based 1,2-propanediol (3)-based 1,2-propanediol (3)-based 1,2-propanediol (3)-based Compositions of the present invention

[0761] Starting materials (for 100 g solution):

[0762] (1) 2.25% w / w (2.25 g) L-serine (Ser); n(Ser) = 0.02141 mol;

[0763] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0764] (3) 49.92% w / w (49.92 g) purified water;

[0765] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0766] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0767] Total: 100% w / w (100.00 g)

[0768] preparation : L-serine (Ser) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.92 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-serine (Ser) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-serine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15°C-20°C during 20-30 min.

[0769] The product thus obtained, the stabilized silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.15 / 20° C.; the composition of the product is:

[0770] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0771] (2) 3.26% w / w L-serine hydrogen sulfate (1Ser);

[0772] (3) 1.29% w / w L-serine potassium sulfate (2bSer);

[0773] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0774] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0775] (6) Make up to 100% w / w with purified water.

[0776] Example 28. Preparation of a 1,2-propanediol (3)-based L-glutamic acid (Glu) with 0.6% w / w silicon (Si) Compositions of the present invention

[0777] Starting materials (for 100 g solution):

[0778] (1) 3.15% w / w (3.15 g) L-glutamic acid (Glu); n (Glu) = 0.02141 mol;

[0779] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0780] (3) 49.02% w / w (49.02 g) purified water;

[0781] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0782] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0783] Total: 100% w / w (100.00 g)

[0784] preparation : L-glutamic acid (Glu) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (9.02 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-glutamic acid (Glu) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-glutamic acid hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0785] The product thus obtained, the stabilized silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.20 / 20° C.; the composition of the product is:

[0786] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0787] (2) 3.94% w / w L-glutamic acid hydrogen sulfate (1Glu);

[0788] (3) 1.52% w / w L-glutamic acid potassium sulfate (2bGlu);

[0789] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0790] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0791] (6) Make up to 100% w / w with purified water.

[0792] Example 29. Preparation of a radical based on L-phenylalanine (Phe) and 1,2-propylene glycol (3) with 0.6% w / w silicon (Si) The composition according to the present invention

[0793] Starting materials (for 100 g solution):

[0794] (1) 3.54% w / w (3.54 g) L-phenylalanine (Phe); n(Phe) = 0.02143 mol;

[0795] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0796] (3) 48.63% w / w (48.63 g) purified water;

[0797] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0798] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0799] Total: 100% w / w (100.00 g)

[0800] preparation : L-phenylalanine (Phe) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (8.63 g) over 5 min under external cooling at 15°C-20°C, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-phenylalanine (Phe) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-phenylalanine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15°C-20°C during 20-30 min.

[0801] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.28 / 20° C.; the composition of the product is:

[0802] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0803] (2) 4.23% w / w L-phenylalanine hydrogen sulfate (1Phe);

[0804] (3) 1.61% w / w L-phenylalanine sulfate potassium (2bPhe);

[0805] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0806] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0807] (6) Make up to 100% w / w with purified water.

[0808] Example 30. Preparation of a 1,2-propanediol (3)-based L-tryptophan (Trp)-based 1,2-propanediol (3 ... Compositions of the present invention

[0809] Starting materials (for 100 g solution):

[0810] (1) 4.37% w / w (4.37 g) L-tryptophan (Trp); n(Trp) = 0.02140 mol;

[0811] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0812] (3) 47.80% w / w (47.80 g) purified water;

[0813] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0814] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0815] Total: 100% w / w (100.00 g)

[0816] preparation: L-tryptophan (Trp) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (7.80 g) over 5 min under external cooling at 15°C-20°C, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-tryptophan (Trp) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-tryptophan hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0817] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.28 / 20° C.; the composition of the product is:

[0818] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0819] (2) 4.85% w / w L-tryptophan hydrogen sulfate (1Trp);

[0820] (3) 1.82% w / w L-tryptophan potassium sulfate (2bTrp);

[0821] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0822] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0823] (6) Make up to 100% w / w with purified water.

[0824] Example 31. Preparation of a root based on L-histidine (His) and 1,2-propanediol (3) with 0.6% w / w silicon (Si) The composition according to the present invention

[0825] Starting materials (for 100 g solution):

[0826] (1) 3.32% w / w (3.32 g) L-histidine (His); n(His) = 0.02140 mol;

[0827] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0828] (3) 46.66% w / w (46.66 g) purified water;

[0829] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0830] (5) 5.17% w / w (5.17g) sulfuric acid, 96%; 4.96g H2SO4, n(H2SO4)=0.0506mol.

[0831] Total: 100% w / w (100.00 g)

[0832] preparation : L-histidine (His) was dissolved in a mixture of purified water (15.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (16.66 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-histidine (His) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (15.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-histidine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15°C-20°C during 20-30 min.

[0833] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 0.81 / 20° C.; the composition of the product is:

[0834] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0835] (2) 5.64% w / w L-histidine dihydrogen sulfate [1His·H2SO4];

[0836] (3) 2.08% w / w L-histidine sulfate potassium bisulfate (2bHis·H2SO4);

[0837] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0838] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0839] (6) Make up to 100% w / w with purified water.

[0840] Example 32. Preparation of a root product based on L-ornithine (Orn) and 1,2-propylene glycol (3) with 0.6% w / w silicon (Si) The composition according to the present invention

[0841] Starting materials (for 100 g solution):

[0842] (1) 3.61% w / w (3.61 g) L-ornithine hydrochloride (Orn·HCl); n(Orn) = 0.02141 mol;

[0843] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0844] (3) 48.56% w / w (48.56 g) purified water;

[0845] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0846] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0847] Total: 100% w / w (100.00 g)

[0848] preparation : L-Ornithine hydrochloride (Orn·HCl) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (8.56 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-ornithine (Orn) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-ornithine hydrochloride hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15°C-20°C during 20-30 min.

[0849] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.12 / 20° C.; the composition of the product is:

[0850] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0851] (2) 4.28% w / w L-ornithine hydrogen sulfate hydrochloride (1Orn·HCl);

[0852] (3) 1.63% w / w L-ornithine sulfate potassium (2bOrn);

[0853] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0854] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0855] (6) Make up to 100% w / w with purified water.

[0856] Example 33. Preparation of a 1,2-propanediol (3)-based L-lysine (Lys)-based Compositions of the present invention

[0857] Starting materials (for 100 g solution):

[0858] (1) 3.92% w / w (3.92 g) L-lysine hydrochloride (Lys·HCl); n(Lys) = 0.02146 mol;

[0859] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0860] (3) 48.25% w / w (48.25 g) purified water;

[0861] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0862] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0863] Total: 100% w / w (100.00 g)

[0864] preparation: L-Lysine hydrochloride (Lys·HCl) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (8.25 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-lysine (Lys) solution at 15°C-20°C over 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-lysine hydrochloride hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15°C-20°C during 20-30 min.

[0865] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.09 / 20° C.; the composition of the product is:

[0866] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0867] (2) 4.52% w / w L-lysine hydrogen sulfate hydrochloride (1Lys·HCl);

[0868] (3) 1.71% w / w L-lysine potassium sulfate (2bLys);

[0869] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0870] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0871] (6) Make up to 100% w / w with purified water.

[0872] Example 34. Preparation of a β-alanine (βAl) and 1,2-propanediol (3)-containing 0.6% w / w silicon (Si) Compositions of the present invention

[0873] Starting materials (for 100 g solution):

[0874] (1) 1.91% w / w (1.91g) β-alanine (βAl); n (βAl) = 0.02144mol;

[0875] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0876] (3) 50.26% w / w (50.26 g) purified water;

[0877] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0878] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0879] Total: 100% w / w (100.00 g)

[0880] preparation : β-Alanine (βAl) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (8.25 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above β-alanine (βAl) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of β-alanine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0881] The product thus obtained, the stable silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.28 / 20° C.; the composition of the product is:

[0882] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0883] (2) 3.01% w / w β-alanine hydrogen sulfate (1βAl);

[0884] (3) 1.21% w / w β-alanine potassium sulfate (2bβAl);

[0885] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0886] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0887] (6) Make up to 100% w / w with purified water.

[0888] Example 35. Preparation of a radical based on L-methionine (Met) and 1,2-propanediol (3) with 0.6% w / w silicon (Si) The composition according to the present invention

[0889] Starting materials (for 100 g solution):

[0890] (1) 3.20% w / w (3.20 g) L-methionine (Met); n(Met) = 0.02145 mol;

[0891] (2) 40.00% w / w (40.00 g) 1,2-propylene glycol (3);

[0892] (3) 48.97% w / w (48.97 g) purified water;

[0893] (4) 4.85% w / w (4.85 g) potassium silicate solution, -6 type; containing 12.7% w / w K2O and 26.5% w / w SiO2; equivalent to: 0.616g K2O, n (K2O) = 0.00654mol; 1.285g SiO2, n (SiO2) = 0.02139mol;

[0894] (5) 2.98% w / w (2.98 g) sulfuric acid, 96%; 2.86 g H2SO4, n(H2SO4) = 0.02916 mol.

[0895] Total: 100% w / w (100.00 g)

[0896] preparation : L-methionine (Met) was dissolved in a mixture of purified water (20.00 g) and 1,2-propylene glycol by stirring at rt for 5 min. Separately, sulfuric acid was added dropwise to purified water (8.97 g) over 5 min at 15°C-20°C with external cooling, and the dilute sulfuric acid solution thus obtained was added dropwise to the above L-methionine (Met) solution at 15°C-20°C during 5 min. Separately, potassium silicate solution was added dropwise to the mixture. -6 was added to purified water (20.00 g) and homogenized by stirring for a short time (1 min). The dilute potassium silicate solution thus obtained was added dropwise to the above solution of L-methionine hydrogen sulfate-sulfuric acid in 1,2-propylene glycol aqueous solution at 15-20° C. over a period of 20-30 min.

[0897] The product thus obtained, the stabilized silicic acid solution according to the invention, is in the form of an odorless, colorless, clear, slightly viscous solution; pH = 1.22 / 20° C.; the composition of the product is:

[0898] (1) Silicic acid; equivalent to 0.60% w / w silicon (Si);

[0899] (2) 3.98% w / w L-methionine hydrogen sulfate (1Met);

[0900] (3) 1.53% w / w L-methionine sulfate potassium (2bMet);

[0901] (4) 1.05% w / w potassium hydrogen sulfate (KHSO4);

[0902] (5) 40.00% w / w 1,2-propylene glycol (3); and

[0903] (6) Make up to 100% w / w with purified water.

[0904] Example 36. Stability study of the composition according to the invention compared to a control sample possibly obtained from the prior art. Research

[0905] Six (6) control samples (from Examples 1-6) and two (2) compositions according to the invention (from Examples 7 and 8) were tested. All compositions had a stable silicic acid concentration corresponding to a silicon (Si) content of 0.6% w / w.

[0906] Stability studies were performed according to the International Conference on Harmonization (ICH) Q1A(R2) guideline for accelerated stability testing of pharmaceutical products (see: Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH Tripartite Harmonized Guideline: Stability Testing of New Drug Substances and Drug Products Q1A(R2); Current Version Step 4, February 6 (2003)). The studies were performed under accelerated stability testing conditions of 40°C-42°C / 70% relative humidity (RH). The purpose of the study was to determine the gel time (t G T ; expressed in [days]), which is the time period required for a freshly prepared liquid composition to transform into a clear to slightly opalescent semi-gel (which is no longer a liquid). G It actually represents the shelf life of the product.

[0907] From the t of the test sample and the control sample thus obtained G The relative stability is calculated to numerically represent the relative stability of the composition according to the invention relative to the stability of the control formulation. The relative stability is calculated by dividing the gel time (t G ) divided by the result obtained with any reference formulation. It represents a numerical value describing how many times more stable the formulation of the invention is than each reference formulation obtained from the prior art.

[0908] The results of this stability study are presented in the table below.

[0909] The composition according to the present invention is compared with six (6) prior art documents and general knowledge. d Stability test of the control formulation obtained by combining the above a result.

[0910]

[0911]

[0912] The results show that the concept of "water-absorbing additives" or stabilizing effects of wetting agents as defined in prior art document 17 is fundamentally incorrect. Specifically, it is apparent that not all wetting agents exhibit a stabilizing effect on orthosilicic acid (OSA). For example, samples based on sorbitol are relatively very unstable and gel after only 2-4 days under accelerated test conditions. Samples based on glycerol are much more stable, but still 6-12x less stable than the compositions according to the invention.

[0913] The results show that the compositions of the present invention exhibit significantly higher stability towards the polymerization of orthosilicic acid (H4SiO4), its oligomers and low water-soluble polymers contained therein, compared to any control formulation that could be obtained from the closest prior art documents identified, such as references 23 and / or 24, whether or not combined with the general knowledge of all corresponding chemical fields related to this scientific field.

[0914] The present invention thus provides a solution to the defined technical problem in a new and inventive way.

[0915] Possible stabilization mechanisms of orthosilicic acid (H4SiO4), its oligomers and low water-soluble polymers may include the formation of a molecular complex of orthosilicic acid (OSA) with 1,2-propylene glycol (3) [or polyethylene glycol 400 (4; PEG 400)], glycine hydrogen sulfate (1), sodium or potassium glycine sulfate (2a, b), sodium or potassium hydrogen sulfate (MHSO4, M = Na and / or K) and water, which is stabilized by hydrogen bonds. Figure 2 Possible chemical substances are shown which may lead to a significant increase in the stability of orthosilicic acid (OSA) in the product solution according to the invention.

[0916] Figure 2 Possible chemistries are demonstrated which may lead to a significant increase in the stability of orthosilicic acid (OSA) (and its lower polymers) in the product solutions according to the invention.

[0917] in conclusion

[0918] The compositions according to the invention show a significantly higher stability to the polymerization of orthosilicic acid (H4SiO4), its oligomers and low-water-soluble polymers than any control formulation that could be obtained from the closest prior art document identified, whether or not combined with the general knowledge of all corresponding chemical fields related to this scientific field. The present invention therefore provides a solution to the defined technical problem in a new and inventive way.

Claims

1. A stable silicic acid solution comprising: (i) silicic acid, in the form of a mixture of: - Orthosilicic acid (H4SiO4), - water-soluble oligomers, and - water-soluble polymers, In a percentage equivalent to 0.01-1.00% w / w silicon (Si), (ii) one or more amino acid hydrogen sulfate salts 1AA, 1b, 1c, in a total amount of 0.015-21.53% w / w, (iii) one or more amino acid sulphates sodium and / or potassium 2aAA, 2bAA, 2c, 2d, 2e, 2f, in a total amount of 0.00-24.24% w / w, (iv) sodium and / or potassium bisulfate (MHSO4, wherein M = Na and / or K) in an amount of 0.00-9.70% w / w, (v) a diol selected from the group consisting of: 1,2-propylene glycol (3), polyethylene glycol (PEG; 4), or a mixture thereof, relative weight ratio: w(3):w(4)=1.00-99.00:99.00-1.00, The percentage in the composition is 5-50% w / w, and (vi) water, made up to 100% w / w of the composition, The proviso is that at least one of (iii) and (iv) is present.

2. The stable silicic acid solution according to claim 1, wherein The amino acids of 1AA, 2aAA and / or 2bAA are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit) and salts thereof.

3. The stable silicic acid solution according to claim 1 or 2, wherein: The term 'water-soluble oligomer' refers to a linear, branched or cyclic oligomer formed by the polycondensation of 2 to 12 orthosilicic acid (OSA) molecules, and the term 'water-soluble polymer' refers to a polymer of the general formula [SiO x (OH) 4-2x ] n A polymer wherein x=1-2 is selected from the group consisting of: - Subnanosilicic acid (SNSA) with a particle size of 0.3-0.6 nm, where n=12-20 and M=700-1,400 [g / mol]; - Sub-nano (or sub-colloidal) condensed silicic acid (SNCSA) with a particle size of 0.6-3 nm, where n=20-300 and M=1,400-2,000 [g / mol]; and, - Larger SNCSA silicic acid with a particle size of 3-5 nm, where n=300-2,000 and M=20,000-140,000 [g / mol].

4. The stable silicic acid solution according to any one of claims 1 to 3, wherein These water-soluble silicic acid oligomers and polymers are in the form of sub-colloidal particles having a size in the range of 0.1-10 nm.

5. The stable silicic acid solution according to claim 1 or 2, wherein: The term 'water-soluble' means that a clear aqueous phase comprising said oligomers and / or polymers at a level of at least 10 ppm, preferably at least 100 ppm, more preferably at least 1000 ppm can be formed using clear water at neutral pH at room temperature.

6. The stable silicic acid solution according to any one of the preceding claims, comprising: (i) silicic acid, in the form of a mixture of: - Orthosilicic acid (H4SiO4), - water-soluble oligomers, and - water-soluble polymers, In a percentage equivalent to 0.01-1.00% w / w silicon (Si), (ii) glycine hydrogen sulfate (1), 0.015-6.17% w / w, (iii) sodium and / or potassium glycine sulfate (2a, b) 0.00-5.64% w / w, (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 0.00-9.70% w / w, (v) a diol selected from the group consisting of 1,2-propylene glycol (3), polyethylene glycol (PEG; 4), or a mixture thereof, relative weight ratio: w(3):w(4)=1.00-99.00:99.00-1.00, The percentage in the composition is 5-50% w / w, and (vi) water, made up to 100% w / w of the composition, The proviso is that at least one of (iii) and (iv) is present.

7. The stable silicic acid solution according to claim 6, comprising: (i) silicic acid, equivalent to 0.10-0.70% w / w silicon (Si), (ii) glycine hydrogen sulfate (1), 0.15-4.32% w / w, (iii) sodium and / or potassium glycine sulfate (2), 0.00-3.95% w / w, (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 0.30-3.62% w / w, (v) diols, 10-45% w / w, and (vi) Water, made up to 100% w / w of the composition.

8. The stable silicic acid solution according to claim 6, comprising: (i) silicic acid, equivalent to 0.40-0.60% w / w silicon (Si), (ii) glycine hydrogen sulfate (1), 0.62-3.70% w / w, (iii) sodium and / or potassium glycine sulfate (2), 0.00-3.38% w / w, (iv) sodium and / or potassium bisulfate (MHSO4, where M = Na and / or K), 1.05-3.10% w / w, (v) diols, 30-45% w / w, and (vi) Water, made up to 100% w / w of the composition.

9. The stable silicic acid solution according to any one of the preceding claims, wherein Polyethylene glycol (PEG; 4) is selected from the group consisting of PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 2000, PEG 3000, PEG 3350, PEG 4000, PEG 6000, PEG 8000, PEG 10000, PEG 12000, PEG 20000, PEG 35000 and mixtures thereof.

10. A method for preparing a stable silicic acid solution, the method comprising the following steps: A. dissolving one or more amino acids in a mixture of glycol and purified water; this is achieved by stirring at a temperature of 10°C to 50°C for 1 to 30 minutes, B. Sulfuric acid (H2SO4) is added separately and gradually to a portion of the purified water at a temperature of 5°C-20°C over a period of 5-30 minutes, C. adding the sulfuric acid solution from step B to the solution from step A at a temperature of 5°C-20°C during 1-30 minutes, D. Prepare separately a solution of sodium or potassium silicate in water by: - dissolve the solid material in a portion of purified water, or - dilution of liquid substances with a portion of purified water, and E. Add the solution from step D dropwise to the cooled solution from step C at a temperature of 5°C-15°C with vigorous stirring over a period of 5-60 minutes to produce the final liquid silicic acid composition.

11. The method according to claim 10, wherein: The one or more amino acids are selected from the group consisting of glycine (Gly), alanine (Ala), valine (Val), norvaline (Nva), leucine (Leu), isoleucine (Ile), norleucine (Nle), serine (Ser), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), phenylglycine (Phg), phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), histidine (His), arginine (Arg), asparagine (Asn), glutamine (Gln), ornithine (Orn), lysine (Lys), methionine (Met), cysteine ​​(Cys), citrulline (Cit), proline (Pro), β-alanine (βAl), and salts thereof.

12. The method according to claim 10 or 11, wherein: (a) The molar ratio n / n of silicon (Si) to amino acid (AA) is: n(Si):n(AA)=1:0.8-2.4, (b) The amount of sulfuric acid (n) is equal to the sum of: - the amount of substances of sodium and / or potassium (Na and / or K) from silicates (n); and - 25% to 100% of the amount (n) of the corresponding amino acid (AA): n(H2SO4)=n(M)+0.25-1.00·n(AA), as well as, (c) The sodium and / or potassium silicates used in the process, xM2O·ySiO2, wherein M=Na and / or K, are: - in solid form with 97-99% w / w sodium or potassium silicate, or - in the form of a liquid having a concentration of about 24-47% w / w sodium or potassium silicate, It is characterized by the following molar ratios, x:y, n / n: x=1.00, y=1.00; x=1.00, y=1.60-1.70; x=1.00, y=2.00-2.10; x=1.00, y=3.30-3.40; x=1.00, y=3.90-4.00; or mixtures of these substances.

13. The method according to claim 12, wherein: The one or more amino acids are or include histidine (His), arginine (Arg), ornithine (Orn) and / or lysine (Lys), wherein the side chain portion (R) is in the form of a free base, and for an equimolar amount of the AA used, the amount of sulfuric acid substance (n) used in the method is increased to ensure that the corresponding side chain basic functional group is converted into the corresponding hydrogen sulfate.

14. A method for preparing the stable silicic acid solution according to claim 10, comprising the following steps: A. dissolving glycine (5) in a mixture of diol and purified water; this is achieved by stirring at a temperature of 10°C to 50°C for 1 to 30 minutes, B. Sulfuric acid (H2SO4) is added separately and gradually to a portion of the purified water at a temperature of 5°C-20°C over a period of 5-30 minutes, C. adding the sulfuric acid solution from step B to the solution from step A at a temperature of 5°C-20°C during 1-30 minutes, D. Prepare separately a solution of sodium or potassium silicate in water by: - dissolve the solid material in a portion of purified water, or - dilution of liquid substances with a portion of purified water, and E. Add the solution from step D dropwise to the cooled solution from step C at a temperature of 5°C-15°C with vigorous stirring over a period of 5-60 minutes to produce the final liquid silicic acid composition.

15. A stable silicic acid solution obtainable by a process as defined in any one of claims 10 to 14.

16. Use of the stable silicic acid solution according to any one of claims 1 to 9 and 15 as a food supplement, a functional food ingredient, a feed additive, a functional feed additive, an active cosmetic ingredient, or as an active pharmaceutical ingredient to provide highly bioavailable silicon (Si) and its beneficial nutritional and pharmacological effects.

17. Use of the stable silicic acid solution according to claim 16 as a functional ingredient providing beneficial nutritional and pharmacological effects selected from the group consisting of: antioxidant, anti-inflammatory, anti-osteoporotic, stimulation of collagen biosynthesis, stimulation of cartilage and connective tissue formation, stimulation of hair, nail and skin strength and growth, vitamin D mimetic activity - because it stimulates calcium absorption, stimulates bone mineralization and growth, stimulates skin repair and regeneration, anti-wrinkle effects, wound healing effects, immune system modulating effects, neuroprotective effects by preventing aluminum accumulation in the brain, anti-atherosclerotic effects, antihypertensive effects, antidiabetic effects, antihistamine effects, analgesic effects and diuretic effects.

18. Use of the stable silicic acid solution according to claim 16 as an active pharmaceutical ingredient for preventing and / or treating a medical disorder or disease selected from the group consisting of: Skin ulcers, including decubitus ulcers, diabetic skin ulcers, burn ulcers, traumatic ulcers or foot ulcers, surgical site wounds or diabetic gangrene; cancerous diseases, including melanoma; allergies; osteoporosis, fractures, osteoarthritis, and other disorders and diseases of bone and cartilage; prevention and treatment of inflammatory diseases: dermatitis, arthritis, osteoarthritis, ear inflammation - including otitis media, gastritis, gastroenteritis, inflammatory bowel disease - including Crohn's disease, sinusitis, sinusitis, pharyngitis, laryngitis, lower respiratory tract inflammation and other inflammatory diseases; periodontitis; poor peripheral blood circulation; paresthesia; hypertension; diabetes; atherosclerosis; vertigo; headache; tinnitus; insomnia; diarrhea; constipation; hemorrhoids; kidney stones; urinary tract infection; low back pain; excessive female discharge; abscesses and ulcers in the genital area and cervix and mastitis; hair loss.

19. Use of the stable silicic acid solution according to any one of claims 1 to 9 and 15 as an agrochemical product for silicon fertilization, plant growth promotion and plant protection.

20. Use of the stabilized silicic acid solution according to claim 19 as an active agrochemical agent to promote plant growth and increase crop yield, improve strength, reduce climatic stress including drought resistance, provide resistance to mineral stress, increase resistance to attack by insect pests, nematodes and diseases including fungal diseases.

21. Use of the stabilized silicic acid solution according to any one of claims 1 to 9 and 15 as fertilizer, as feed additive and / or as biostimulant in aquaculture.

22. The use of the stable silicic acid solution according to claim 19, wherein: The use has one or more of the following purposes and / or results in one or more of the following: - Promote the growth of aquatic animals; - Accelerated growth of aquatic animals; - Increased weight of aquatic animals; - Shortened harvesting time; - Improved overall productivity; - Improved feed utilization; - Improved feed conversion rate; - Improved water quality; - Increased dissolved oxygen levels; - Reduced ammonia concentration; - Improved water pH; - Reduced water salinity; - Promote the growth of phytoplankton, especially diatoms, in the water; and - Reduced ecological impact of aquaculture.

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