HRP20100460A2 - Formulation based on source of ortho-silicon acid insoluble in water and aspartic acid as efficient inhibitor of its polymerization - Google Patents

Abstract

High bioavailability silicone formulation consisting of: (i) one or more water-insoluble sources of silicic acid such as zeolite, amorphous silica, magnesium silicate or calcium silicate; in an amount of 1-50% w / w, preferably 10-40% w / w; (ii) aspartic acids (1); in an amount of 0.01-10% w / w, preferably 0.1-5% w / w; (iii) one or more excipients with which they form a form that enables the desired formulation to be desired: oral suspension, tablets, capsules, liquid powder (topical suspension), paste, shampoo, suspension concentrate and wettable powder; and of one or more additional pharmaceutical, cosmetic or agrochemical active substances which support the basic biological activities of silicic acid; up to a total of 100% w / w. Its use effectively achieves all known positive therapeutic effects of silicic acid: stimulation of the immune system; allergy treatment; adjuvant in the treatment of infectious diseases; strengthening the structure and elasticity of arterial, venous and capillary walls, and reducing their permeability; stimulation of joint and ligament function; osteoblast stimulation and bone mineralization; prevention of osteoporosis; reducing the absorption of aluminum from the digestive tract and thus preventing the onset of neurodegenerative diseases such as Alzheimer's or Parkinson's disease; improving the structure of connective tissue and soft tissue building proteins such as the liver, lungs, and brain; anti-inflammatory in the treatment of acute and chronic inflammatory diseases; treatment of various dermatoses such as skin irritations, eczema, seborrheic dermatitis, neurodermitis, psoriasis; treatment of decubitus, wounds and burns; stimulation of collagen and elastin biosynthesis; slowing skin aging; reducing wrinkles; stimulation of hair growth; stimulation of nail growth. In plants, application of the formulation increases yields, resistance to stress conditions such as drought or hail, and resistance to fungal diseases.

Description

Field of invention

The present invention relates to a silicon (Si) formulation with high bioavailability that is used in medicine, cosmetics, veterinary medicine and agriculture.

The essence of invention

The subject invention solves the technical problem of obtaining an improved pharmaceutical, cosmetic, veterinary or agrochemical product that is used as a source of silicon with high bioavailability.

The product formulation consists of:

(i) one or more water-insoluble sources of silicic acid such as zeolite, amorphous silica, magnesium silicate or calcium silicate; in an amount of 1-50% m/m, preferably 10-40% m/m;

(ii) aspartic acid (1);

[image]

in an amount of 0.01-10% m/m, preferably 0.1-5% m/m;

(iii) one or more auxiliary substances with which they form the form that enables the desired application of the formulation in question: oral suspension, tablets, capsules, liquid powder (suspension for topical application), paste, shampoo, concentrate for suspension and wet powder;

and from one or more additional pharmaceutical, cosmetic or agrochemical active substances that support the basic biological effects of silicic acid; in the amount up to a total of 100% m/m.

Applying the formulation achieves all the known positive therapeutic effects of silicon on the human, animal or plant organism.

Prior art

Silicon (Si) is an important biogenic microelement that has a number of important roles in the human and animal organism:

(i) helps resorption of calcium and participates in its turnover; stimulates osteoblasts; stimulates bone mineralization; in traumatological cases it affects the acceleration of bone healing; helps prevent osteoporosis [E. M. Carlisle: A requirement for silicon for bone growth in culture, Fed. Proc. 37 (1978) 1123; E. M. Carlisle: A relationship between silicon and calcium in bone formation, Fed. Proc. 29 (1970) 265; E. M. Carlisle: Silicon: a requirement in bone formation independent of vitamin D, Calcif. Tissue Int. 33 (1981) 27; D. M. Reffitt, N. Ogston, R. Jugdaohsingh: Orthosilicic acid stimulates collagen type I synthesis and osteoblast-like cells in vitro, Bone 32 (2003) 127; S. Spripanyakorn, R. Jungdaohsingh, R. P. H. Thompson, J. J. Powell: Dietary silicon and bone health, Nutr. Bull. 30 (2005) 222];

(ii) participates in the structure of the connective tissue and the formation of the functional tertiary structure of the building proteins of soft organs such as the liver, lungs, and brain; participates in the structure of arterial, venous and capillary walls, increases the elasticity and strength of blood vessels, reduces their permeability [E. M. Carlisle, D. L. Garvey: The effect of silicon on formation of extra-cellular matrix components by chondrocytes in culture, Fed. Proc. 41 (1982) 461; E.M. Carlisle, C. Suchil: Silicon and ascorbate interaction in cartilage formation in culture, Fed. Proc. 42 (1983) 398];

(iii) acts as a cross-linking agent for glucosaminoglycans and mucopolysaccharides in joints, ligaments and synovial fluid [K. Schwartz: A bound form of silicon in glycosaminoglycans and polyuronides, Proc. Nat. Acad. Sci. USA 70 (1973) 1608; A. Lassus: Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy and onychopathy. A pilot study. J. Int. Honey. Crisp. 25 (1997) 206];

(iv) stimulates the immune system [A. Schiano, F. Eisinger, P. Detolle: Silicium, tissu osseux et immunité, Revue du Rhumatisme 46 (1979) 483];

(v) exhibits an anti-inflammatory effect; for example, it has a beneficial effect on various inflammatory skin disorders such as psoriasis, seborrheic dermatitis, neurodermatitis, skin irritations, accelerates wound healing, alleviates decubitus and other skin disorders and diseases [A. Lassus: Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females, J. Int. Honey. Crisp. 21 (1993) 209; A. Lassus: Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy and onychopathy. A pilot study. J. Int. Honey. Crisp. 25 (1997) 206];

(vi) in its oligomeric form, silicic acid reduces the resorption of aluminum (Al3+) from the digestive tract and, with its antioxidant effect, has a preventive effect on the occurrence of neurodegenerative diseases such as Alzheimer's disease [J. D. Birchall, J. S. Chappell: The chemistry of aluminum and silicon in relation to Alzheimer's disease, Clin. Chem. 34 (1980) 265; R. Jugdaohsingh: Soluble silica and aluminum bioavailability, PhD Thesis (1999) University of London; R. Jugdaohsingh, S. H. Anderson, K. L. Tucker: Dietary silicon intake and absorption, Am. J. Clin. Nutr. 75 (2002) 887; R. Jugdaohsingh, D. M. Reffitt, C. Oldham: Oligomeric but not monomeric silica prevents aluminum absorption in humans, Am. J. Clin. Nutr. 71 (2000) 944; D. M. Reffitt, R. Jugdaohsingh, R. P. H. Thompson: Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminum excretion, J. Inorg. Biochem. 76 (1999) 141];

(vii) stimulates the biosynthesis of building proteins of the skin: collagen and elastin [C. D. Seaborn, F. H. Nielsen: Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver, Biol. Trace Element Res. 89 (2002) 251; M. R. Calomme, D. A. V. Berghe: Supplementation of calves with stabilized orthosilicic acid effect on the Si, Ca, Mg and P concentration in serum and the collagen concentration in skin and cartilage, Biol. Trace Element Res. 56 (1997) 153]; you

(viii) stimulates the growth of hair and nails [A. Lassus: Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females, J. Int. Honey. Crisp. 21 (1993) 209].

In plants, silicon shows the following effects [H. A. Currie, C. C. Perry: Silica in Plants: Biological, Biochemical and Chemical Studies, Ann. Botany (2007) 1]:

(i) stimulates the process of photosynthesis and increases the utilization of nutrients, which leads to increased yields;

(ii) improves water management, thereby increasing resistance to stressful conditions such as drought; you

(iii) increases resistance to attacks by insects and fungal diseases.

The biologically available form of silicon is ortho-silicic acid (H4SiO4). However, it is described in the literature that excessive doses of silicic acid can cause damage to the liver and kidney, which is the most important organ through which silicon is excreted [J. W. Dobbie, M. J. Smith: Silicate nephrotoxicity in the experimental animal: the missing factor in analgesic nephropathy, Scottish Med. J. 27 (1982) 10].

The average expert in the field knows that silicic acid in its monomeric, ortho-form (H4SiO4) is not stable, but at higher concentrations undergoes polymerization with the formation of dimers (H6Si2O7), trimers (H8Si3O10), linear unbranched oligomers (S1) which are still soluble in leads. Chain polymers of silicic acid (S1) are subjected to further polymerization, whereby three-dimensional, branched polymers (S2) are formed, which are not significantly soluble in water but form an opalescent gel. The polymerization process continues with the formation of hydrated silica (silica gel; SiO2•xH2O). The course of silicic acid polymerization is shown in Scheme 1.

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Scheme 1.

In addition to monomeric ortho-silicic acid (H4SiO4), its lower water-soluble oligomers are also biologically available, because partial hydrolysis releases the original H4SiO4 (oligomerization is reversible). That is, under certain concentration conditions, a balance is established between ortho-silicic acid and its lower oligomers.

Branched polymers of silicic acid are not biologically available [H. Yokoi, S. Enomoto: Effect of degree of polymerization of silicic acid on the gastrointestinal absorption of silicate in rats, Chem. Pharm. Bull. 27 (1979) 1733; K. Van Dyck, R. Van Cauwenbergh, H. Robberecht: Bioavailability of silicon from food and food supplements, Fresenius J. Anal. Chem. 363 (1999) 541].

By using natural foods that are as little refined as possible (e.g. cereals in the form of whole grains), sufficient amounts of silicon are usually introduced into the body. However, with the use of highly processed and unhealthy food, silicon deficiency conditions often occur. Such conditions, along with possible other factors, can often be the cause of the appearance of one of the mentioned diseases or disorders in which silicon plays an important role.

For this reason, the development of a stabilized form of silicic acid in which its polymerization and thus its bioavailability is prevented is of great importance. Such products can be used as effective food supplements or as therapeutic agents for the aforementioned diseases or disorders. For use in pharmaceuticals and cosmetics, only pharmacologically acceptable forms of silicic acid are considered.

All non-toxic forms of silicic acid with high bioavailability are also considered for use in agriculture.

The most well-known product used as a dietary supplement to add silicon is "BioSil", which is based on choline chloride-stabilized ortho-silicic acid [S. R. Bronder, U.S. 5,922,360 (1999); V. Berghe, D. A. Richard, E.P. 1 371 289 A1 (2002), assigned to Bio Pharma Sciences B.V., Belgium].

Furthermore, the patent literature mentions other stabilizers that prevent (inhibit) the polymerization of ortho-silicic acid, such as humectants such as polyethylene glycol, polysorbate, vegetable gums, substituted cellulose, propylene glycol, pectin, ethoxylated derivatives of higher fatty acids, acetylated or hydroxypropyl-derivatized starch , starch phosphate, urea, sorbitol, maltitol, vitamins [W. A. Cross, U.S. 2006/0178268 A1], proline, serine, lysine, arginine, glycine, their mixtures, polypeptides or protein hydrolysates [V. Berghe, D.A. Richard, WO 2004/016551 A1 (Bio Pharma Sciences B.V.)].

In addition to silicic acid stabilized with choline chloride, various food supplements containing silicon in the form of amorphous or colloidal silicon dioxide (SiO2) can be found on the market. Such products are characterized by very low bioavailability [R. Jugdaohsingh: Silicon and bone health, J. Nutr. Health Aging 11 (2007) 99].

Somewhat effective (bioavailable) sources of silicic acid are also various herbal drugs such as horsetail extracts (Equisetum arvense), nettle (Urtica dioica) and some other plants. However, it is known that the proportion of soluble (and thus bioavailable) silicic acid in these medicinal plants usually does not exceed 1/10 of the total amount. All remaining silicic acid is insoluble and as such is not biologically available [D. Kuštrak: Pharmacognosy and phytopharmacy, Golden marketing-Technical book, Zagreb (2005)].

The authors of this innovation previously described the micronized zeolite clinoptilolite as an effective source of silicon with high bioavailability based on the finding that it releases certain amounts of ortho-silicic acid in contact with (neutral) water [I. Cepanec, A. Lelas: Formulation based on micronized clinoptilolite as therapeutic agent providing highly bioavailable silicon, PCT/HR2008/000030].

In agriculture, preparations based on silicon as auxiliaries for increasing plant resistance to stress (in the case of drought or hail) and to fungal diseases have only recently found application. The most well-known are products containing horsetail extract (Equisetum arvense) or ground quartz sand (silicon dioxide; SiO2) in organic, and potassium silicate solution (30% K2SiO3) in conventional cultivation (most often in viticulture; e.g. "Sil-Matrix") . These preparations are usually applied foliarly.

The subject invention is the technical problem of obtaining an improved product that shows the effects of bioavailable silicon based on the effective stabilization of ortho-silicic acid (H4SiO4) which is released in equilibrium upon contact in water with an insoluble source of silicic acid (such as amorphous silica, zeolite or magnesium and calcium silicate) with water or hydrochloric acid (HCl) of gastric juice, solved in a new and significantly more favorable way as will be demonstrated in the detailed description of the invention.

Detailed description of the invention

The subject invention represents an improved pharmaceutical, cosmetic or agrochemical formulation that is an effective source of silicon with high bioavailability.

The formulation consists of:

(i) one or more water-insoluble sources of silicic acid such as zeolite, amorphous silica, magnesium silicate or calcium silicate; in an amount of 1-50% m/m, preferably 10-40% m/m;

(ii) aspartic acid (1);

[image]

in an amount of 0.01-10% m/m, preferably 0.1-5% m/m;

(iii) one or more auxiliary substances with which they form the form that enables the desired application of the formulation in question: oral suspension, tablets, capsules, liquid powder (suspension for topical application), paste, shampoo, concentrate for suspension and wet powder;

and from one or more additional pharmaceutical, cosmetic or agrochemical active substances that support the basic biological effects of silicic acid; in the amount up to a total of 100% m/m.

As a water-insoluble source of silicic acid can be used:

(i) pharmaceutical acceptable types of zeolites such as synthetic zeolite A [Na2O•Al2O3•2SiO2•4.5H2O] or natural zeolite clinoptilolite [Ca/Mg/(K/Na)2Al2Si7O18•xH2O], wherein the cation in the zeolite structure is chosen from groups consisting of calcium (Ca2+), magnesium (Mg2+), potassium (K+) or sodium (Na+);

(ii) amorphous anhydrous or hydrated silicon dioxide (SiO2);

(iii) calcium silicates [xCaO•ySiO2•zH2O; y=1, x= 1-3, z= 1-2; eg CaSiO3•H2O]; you

(iv) non-fibrous forms of magnesium silicate [MgO•SiO2; 2MgO•SiO2; 2MgO•3SiO2]; or mixtures thereof.

The mentioned compounds in contact with water or stomach acid (HCl) release a greater or lesser amount of ortho-silicic acid (H4SiO4) [Y. Mauras, J.C. Renier, A. Tricard, P. Allain: Demonstration of the gastrointestinal absorption of silicon from an alumino-silicate compound, Therapie 38 (1983) 175; E. A. Cefali, J. C. Nolan, W. R. McConnell: Pharmacokinetic study of Zeolite A, sodium aluminosilicate, magnesium silicate and aluminum hydroxide in dogs, Pharm. Crisp. 12 (1995) 270].

In the case of contact with (neutral) water, equilibrium dissociation of the silicate skeleton occurs with the release of small amounts of H4SiO4, whereby the concentration determined by the solubility product constant (Ks) for the given compound is reached. Considering the high biological activity of ortho-silicic acid, even such small amounts of it can be used quite effectively to meet the nutritional needs of humans, animals or plants for silicon. The only prerequisite is that, in addition to the mentioned solid source of silicon, a specific stabilizer of ortho-silicic acid is also present in the system. Its task is to prevent (inhibit) its polymerization to biologically unavailable polymers and finally to almost unusable hydrated silicon dioxide (SiO2•xH2O). Therefore, if ortho-silicic acid (H4SiO4) is not stabilized immediately upon formation (in situ), the process of its polymerization occurs with the loss of biological availability. In the case of the presence of a suitable H4SiO4 stabilizer (that is, an inhibitor of its polymerization), a silicic acid complex with high bioavailability is obtained. As an example, the reaction of hydrochloric acid (HCl) of gastric juice with calcium silicate (CaSiO3) is shown in Scheme 2.

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Scheme 2

Completely unexpectedly, L-(+)-aspartic acid (1) was found to act effectively as a stabilizer of ortho-silicic acid (H4SiO4). The effect was found and tested on a model complex of sodium silicate (Na2SiO3) and aspartic acid in a molar ratio of 1:0.5 (disodium asparaginate-H4SiO4 complex; 2).

Chemically pure sodium silicate was prepared by base-catalyzed hydrolysis of tetraethyl orthosilicate [Si(OC2H5)4; TEOS] with sodium hydroxide (NaOH). The hydrolysis reaction and formation of complex 2 with aspartic acid is shown in Scheme 3.

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Scheme 3

The test of the stabilizing effect of aspartic acid was carried out under conditions that are known to lead to rapid polymerization of ortho-silicic acid (H4SiO4), which is a pH value close to neutral. Under the mentioned conditions, for example between pH= 6-7, a relatively fast polymerization of H4SiO4 occurs with the formation of its polymers, which is accompanied by the formation of an opalescent gel. In more concentrated systems, the change from the solution phase (which is initially clear and then opalescent) to the (opalescent) gel phase is relatively fast, so it can be used for analytical purposes to determine the rate of gelation (polymerization) of H4SiO4.

By mixing an equal volume of the solution of complex 2 and phosphate buffer (pH= 4.5), a test solution was prepared, which was followed by the time it takes for it to turn from the initial clear solution into an opalescent gel. This time is called the gelation or polymerization time (tG). Longer gelation time (tG) means slower polymerization indicating a more stable complex.

In addition to complex 2 from the present invention, as control samples, sodium silicate solution (Na2SiO3) as a standard, and solutions of complexes with choline chloride [(CH3)3N+(CH2CH2OH) Cl-] and serine, which are in the state of the art, were tested in the same way they state as stabilizers H4SiO4 [S. R. Bronder: Stabilized orthosilicic acid comprising preparation and biological preparation, WO95/21124 (1994)].

The complex with L-(+)-glutamic acid (3), which is a higher analog of aspartic acid, and L-(+)-histidine were also tested. The results are presented in Table 1.

Table 1. Inhibitory effect of L-(+)-aspartic acid on the polymerization of ortho-silicic acid (H4SiO4) at pH= 6.5.a

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a The test solution was prepared by mixing 2 mL of the sample and 2 mL of 1.5 M phosphate buffer pH= 4.5. The final pH value of all solutions after mixing the respective sample and buffer was 6.5.

b Time from the moment of mixing the sample and the phosphate buffer (clear solution) to the moment of the formation of the opalescent gel, expressed in minutes.

c "Relative stability" expressed as a numerical parameter, a coefficient that describes the stability of ortho-silicic acid in a given sample compared to a standard [sodium silicate solution (Na2SiO3)]. It shows a stabilizing or destabilizing effect on ortho-silicic acid, i.e. on its polymerization (gelation).

d Prepared by stirring 1.2 mL of TEOS (1.12 g; 0.0054 mol) in a solution of 0.44 g (0.011 mol; 2.05 eq.) of NaOH in 6 mL of distilled water for 6 h, with subsequent dilution with more 7.4 mL of distilled water [total 15.00 g; contains 150 mg (1% m/m) Si].

e Samples were prepared by adding 0.0054 mol of choline chloride (0.75 g), L-serine (0.57 g) or L-histidine (0.84 g) to a hydrolyzed solution of sodium silicate (6 mL of distilled water + 0, 44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water to a total of 15.00 g [150 mg (1% m/m) Si].

f The samples were prepared by adding 0.0027 mol of aspartic (0.36 g) or glutamic (0.40 g) acid to a hydrolyzed sodium silicate solution (6 mL distilled water + 0.44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water to a total of 15.00 g [containing 150 mg (1% m/m) Si]. Aspartic and glutamic acids are dibasic acids, so 0.5 molar equivalents were used - analogous to experiments 2 and 3.

From the obtained results, it was concluded that choline chloride, which is declared in the literature as a "stabilizer" of ortho-silicic acid, actually acts as a catalyst for its polymerization in physiological conditions where the pH value is around 7 (experiment 2). More precisely, choline chloride can obviously be considered as a "stabilizer" of silicic acid in the formulation where the pH is very low, lower than pH= 3, whereby it stabilizes the ortho-silicic acid from the polymerization process. So it is actually a "stabilizer" in the technological sense that helps to stabilize the finished product based on H4SiO4 in terms of long-term storage of the product.

Furthermore, the amino acid serine, which is also reported to stabilize ortho-silicic acid, indeed shows a slight stabilizing effect, however, the effect is negligible as the recorded gelation time is only 10% longer than that of the standard (experiment 3).

L-(+)-Aspartic acid and its higher analog L-(+)-glutamic acid have been shown to be very effective stabilizers of ortho-silicic acid. L-(+)-glutamic acid, with about 71% increased gelation time (experiment 5), proved to be a less effective stabilizer than L-(+)-aspartic acid, where the recorded tG was even 86% longer than the standard ( experiment 4).

This undoubtedly proved the fact that ortho-silicic acid (H4SiO4) creates relatively stable complexes with dicarboxylic amino acids such as aspartic acid, which leads to a much slower equilibrium dissociation with the release of free H4SiO4, which then at a pH close to neutral (pH= 6.5) undergoes polymerization (gelation) with the formation of silica gel. A more stable complex means a longer gelation time.

An interesting result with the amino acid L-histidine, which was confirmed to act not as a stabilizer but as a catalyst for the polymerization of ortho-silicic acid. The gelation time in that case was shorter than in the case of the standard (experiment 6). The catalytic effect of the imidazole ring (strong nucleophile and base) of histidine on the polymerization of ortho-silicic acid in natural processes of (bio)silicification is known in the literature [M.-K. Liang, S. V. Patwardhan, E. N. Danilovtseva, V. V. Annenkov, C. C. Perry: Imidazole catalyzed silica synthesis: Progress toward understanding the role of histidine in (bio)silicification, J. Mater. Crisp. 24 (2009) 1700].

Based on the obtained results, aspartic acid was selected as the most effective for the preparation of the formulation of the present invention. Since chirality has no influence on its aforementioned property, racemic DL-(±)-aspartic acid or its unnatural D-(-)-enantiomer can also be used in the formulation of the present invention.

Therefore, the key basis of the subject innovation is the use of a combination of:

(i) aspartic acid (1); which has been proven by the present invention to unexpectedly efficiently stabilize ortho-silicic acid (H4SiO4) from polymerization; you

(ii) a pharmaceutically acceptable, water-insoluble source of silicic acid such as zeolite, amorphous anhydrous or hydrated silica, calcium silicate or non-fibrous forms of magnesium silicate; which are known to release ortho-silicic acid on contact with water or hydrochloric acid (HCl) of gastric juice;

which unexpectedly achieved the key prerequisites for the biological effect of silicon as a microelement from sources that are otherwise insoluble in water:

(i) its availability in the form of ortho-silicic acid (H4SiO4); you

(ii) its simultaneous (in situ) stabilization.

In humans and animals, the subject formulation is used in all medical, cosmetic and veterinary indications for which silicon (Si) is known to have a positive effect:

(i) helps calcium resorption; participates in its circulation, stimulates osteoblasts, stimulates bone mineralization, accelerates bone healing; in the prevention of osteoporosis;

(ii) participates in the structure of arterial, venous and capillary walls, increases elasticity and strength of blood vessels, reduces their permeability; it also participates in the structure of connective tissue and the formation of the functional tertiary structure of building proteins of soft organs such as the liver, lungs, and brain;

(iii) stimulates the immune system; thereby increasing the natural ability of the organism to fight against microorganisms in infectious diseases, and in all other disorders and diseases that occur in states of weakened immunity, such as various allergic diseases;

(iv) anti-inflammatory effect; therapy of various acute and chronic inflammatory diseases, for example, it has a beneficial effect on various skin disorders such as psoriasis, seborrheic dermatitis, neurodermatitis, eczema, skin irritations, burns, wound healing, alleviates decubitus, scalp dandruff, and other skin disorders and diseases; it also works favorably in other inflammatory diseases such as rheumatoid arthritis ("rheumatism");

(v) acts as a cross-linking agent for glucosaminoglycans and mucopolysaccharides and thus supports the functioning of joints, ligaments and the formation of synovial fluid;

(vi) reduces the resorption of aluminum (Al3+) from the digestive tract and, with its antioxidant effect, has a preventive effect on the occurrence of neurodegenerative diseases such as Alzheimer's or Parkinson's disease;

(vii) stimulates the biosynthesis of building proteins of the skin: collagen and elastin; for the treatment of wrinkles and their prevention; thereby helping to slow down skin aging;

(viii) stimulates the growth of hair and nails; it is used for the treatment of hair and nails, whereby they become stronger and the hair shines.

The average expert in the field knows that silicon exhibits analogous biological effects in animals, and thus the formulation of the subject invention is also used in veterinary medicine in all the indicated indications.

In plants, supplementing with silicon enables:

(i) increase in yield (due to stimulation of photosynthesis due to better utilization of nutrients added through basic fertilization);

(ii) resistance to stressful conditions (eg during drought or after hail); you

(iii) resistance to fungal diseases.

Composition of the formulation according to the invention

The formulation of the subject invention consists of:

(i) one or more water-insoluble sources of silicic acid such as zeolite, amorphous silica, magnesium silicate or calcium silicate; in an amount of 1-50% m/m, preferably 10-40% m/m;

(ii) aspartic acid (1);

[image]

in an amount of 0.01-10% m/m, preferably 0.1-5% m/m;

(iii) one or more auxiliary substances with which they form the form that enables the desired application of the formulation in question: oral suspension, tablets, capsules, liquid powder (suspension for topical application), paste, shampoo, concentrate for suspension and wet powder;

and from one or more additional pharmaceutical, cosmetic or agrochemical active substances that support the basic biological effects of silicic acid; in the amount up to a total of 100% m/m.

As water-insoluble sources of silicic acid can be used:

(i) pharmaceutical acceptable types of zeolites such as synthetic zeolite A [Na2O•Al2O3•2SiO2•4.5H2O] or natural zeolite clinoptilolite [Ca/Mg/(K/Na)2Al2Si7O18•xH2O], wherein the cation in the zeolite structure is chosen from groups consisting of calcium (Ca2+), magnesium (Mg2+), potassium (K+) or sodium (Na+);

(ii) amorphous anhydrous or hydrated silicon dioxide (SiO2);

(iii) calcium silicates [CaO•SiO2; 3CaO•2SiO2; 2CaO•SiO2; 3CaO•SiO2; and their hydrates]; you

(iv) non-fibrous forms of magnesium silicate [MgO•SiO2; 2MgO•SiO2; 2MgO•3SiO2]; or mixtures thereof.

For greater efficiency, the mentioned water-insoluble sources of silicic acid are used in micronized form, with average particle sizes of less than 10 μm, preferably below 3 μm.

The formulation of the subject invention intended for medical, cosmetic and veterinary use is in the following dosage forms:

(i) oral suspension;

(ii) tablets;

(iii) capsules;

(iv) liquid powder (suspension for topical application);

(v) paste;

(vi) shampoo;

while in agriculture it is applied in the form of:

(vii) concentrate for suspension; and

(viii) urine powder;

For their preparation, various auxiliary substances are used which are known to the average expert in the field as: diluents, fillers, binders, disintegrators, lubricants, emollients, emulsifiers, surfactants, humectants, thickeners, preservatives, antioxidants, stabilizers, and other auxiliary substances such as colors, fragrances , pH control agents, etc.

In the liquid form of the oral suspension, the diluent is selected from the group consisting of purified water, glycerol, 1,2-propylene glycol, liquid polyethylene glycols (e.g. PEG 400), liquid polyglycerols, sorbitol, ethanol, vegetable oils such as sunflower, soybean or almond oil, or mixtures of these substances.

In the case of liquid forms of liquid powder or concentrate for suspension (SC), in addition to the listed diluents, the following can also be used: 1,3-propylene glycol; hexylene glycol; 1,3-butanediol; liquid polypropylene glycols; isopropanol; butanol; isosorbide dimethyl ether; methyl and ethyl ethers of mono-, di- and triethyleneglycol; ethyl lactate; triethylhexanoin; mineral oil; dimethylsulfoxide; or mixtures of these substances.

For solid oral forms such as tablets and capsules, microcrystalline cellulose, lactose monohydrate, calcium hydrogen phosphate, calcium sulfate dihydrate, crystallized sorbitol, starch, modified starches, inulin, etc. can be used as fillers.

The following can be used as fillers for liquid powder or wet powder: talc, kaolin, bentonite, montmorillonite, calcium carbonate, basic magnesium carbonate, aluminum hydroxide, or mixtures of the above substances.

Gelatin, lactose monohydrate, sorbitol, sucrose, xylitol, maltitol, starch, modified starches, cellulose, methylcellulose, 2-hydroxyethyl cellulose, 2-hydroxypropylcellulose, sodium carboxymethylcellulose, polyethylene glycols, polyvinylpyrrolidone, carrageenans, or mixtures of the above substances.

Starch, cellulose, methylcellulose, sodium carboxymethylcellulose, 2-hydroxyethylcellulose, 2-hydroxypropylcellulose, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone, sodium starch glycolate, or mixtures of these substances can be used as disintegrators in solid oral forms.

Metal soaps such as magnesium stearate, calcium stearate, zinc stearate can be used as lubricants; stearic acid; talc; silicon dioxide; or mixtures of these substances.

Emollients as basic ingredients of the topical form of the paste are chosen from the group consisting of: paraffin; vaseline; mineral oil; ozokerite; yellow or white beeswax; synthetic esters of higher fatty acids such as isopropyl myristate, isopropyl palmitate, trimethylolpropane tristearate, glyceryl tricaprylate; synthetic waxes such as lauryl laurate; liquid natural waxes such as jojoba oil; various vegetable oils or fats such as soybean oil, almond oil, sunflower oil, fish oil, olive oil, wheat germ oil, corn germ oil, avocado oil, palm oil, coconut oil; higher fatty alcohols such as cetanol, stearol, oleyl alcohol; or mixtures of the mentioned fatty substances.

The following can be used as emulsifiers in pastes that are emulsions or other liquid preparations such as liquid powder or shampoo: sodium lauryl sulfate; sodium laurylethylene glycol sulfate; sodium lauryl diethylene glycol sulfate; fatty alcohol ethoxylates such as, for example, polyoxyethylene (2) lauryl ether, polyoxyethylene (10) lauryl ether, polyoxyethylene (23) lauryl ether and others, where the numbers 2, 10 and 23 indicate the average number of ethylene glycol units attached to a higher fatty alcohol; ethoxylates of higher fatty acids such as, for example, polyoxyethylene(2) laurate, polyoxyethylene(10) stearate, polyoxyethylene(23) oleate, where the numbers 2, 10 and 23 indicate the average number of ethylene glycol units attached to the higher fatty acid; then sorbitan esters such as polyoxyethylene sorbitan monolaurate; lanolin; lanolin ethoxylates; glycerol monostearate; beeswax ethoxylates; or mixtures of these substances.

As surfactants in the subject formulation in the form of shampoo, the following can be used: sodium lauryl sulfate; sodium laurylethylene glycol sulfate; sodium lauryl diethylene glycol sulfate; ammonium lauryl sulfate; ammonium laurylethylene glycol sulfate; ammonium lauryl diethylene glycol sulfate; sodium cocoamphopropionate; disodium cocoamphodiacetate; disodium cocoamphodipropionate; polyoxyethylene(10) lauryl ether, polyoxyethylene(23) lauryl ether, polyoxyethylene(10) stearyl ether, polyoxyethylene(23) stearyl ether, polyoxyethylene(10) oleyl ether, polyoxyethylene(23) oleyl ether, other ethoxylates of higher fatty alcohols to which H.L.B. factor ≥ 10; polyoxyethylene(10) laurate, polyoxyethylene(23) laurate, polyoxyethylene(10) stearate, polyoxyethylene(23) stearate, polyoxyethylene(10) oleate, polyoxyethylene(23) oleate, or other higher fatty acid ethoxylates that H.L.B. factor ≥ 10; then sorbitan esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate; mono or diethanolamides of higher fatty acids or their mixtures such as cocoamidopropyl betaine; glycosides of higher fatty alcohols such as cocoglucoside; sodium or calcium di(2-ethylhexyl) sulfosuccinate; disodium 2-ethylhexylsulfosuccinate; cationic surfactants such as cetyltrimethylammonium bromide, didecyldimethylammonium chloride, benzalkonium chloride, cetylbenzyldimethylammonium chloride, cetylpyridinium chloride; metal salts of higher fatty acids such as the sodium or potassium salt of lauric, myristic, palmitic, stearic, oleic, ricinoleic acids; or mixtures of these substances.

Forms of the formulation of the subject invention for use in agronomy: suspension concentrate and wettable powder, in addition to surfactants (with H.L.B.>12), also contain smaller amounts of wetting agents, surfactants with a slightly lower H.L.B. with a value in the range of 8-10. Examples of such substances are sodium 1,4-bis-(2-ethylhexyl)-sulfosuccinate or calcium di[1,4-bis-(2-ethylhexyl)-sulfosuccinate] (sodium or calcium docusate).

Humectants are selected from the group consisting of: glycerol, 1,2-propylene glycol, 1,3-propylene glycol, hexylene glycol, 1,3-butanediol, polyethylene glycols, polypropylene glycols, polyglycerols, sorbitol, d-panthenol, sodium hyaluronate, or mixtures of these substances.

In the formulation of the present invention in the form of a paste, auxiliary substances selected from the group consisting of: polyacrylic acid or its salts with sodium, potassium, ammonium hydroxide, or triethanolamine can be used for thickening; methylcellulose; sodium carboxymethylcellulose; 2-hydroxyethyl cellulose; 2-hydroxy propyl cellulose; starch; modified starches; polyglycerols, polyethylene glycols; gelatin; pectin; agar agar; carrageenans; gum arabic; alginic acid or sodium alginate; or mixtures thereof.

Methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sorbic acid, benzoic acid, or mixtures of these substances are used as preservatives to preserve the microbiological purity of the formulation of the subject invention, in all cases where the content of the aqueous phase is relatively high.

In topical forms of liquid powder, paste and shampoo, in addition to the mentioned preservatives, the following are also used: ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, triclosan, chlorhexidine salts, diimidazolidinyl urea, 2-bromo-2-nitropropane-1,3-diol, 4 -chlor-m-cresol, thymol, eugenol, extracts of plants with a significant content of thymol, eugenol such as thyme (Thymus vulgaris), cloves (Syzygium aromaticum), lavender (Lavandula officinalis), pine (Juniperus communis), or a mixture of the above substances.

One or more compounds selected from the group consisting of: 2,6-di-tert-butyl-4-methylphenol (BHT), tert-butylhydroxyanisole (BHA), tocopherol, tocopheryl acetate, ascorbic acid can be used as antioxidants in the formulation of the present invention. , ascorbyl palmitate, in standard concentrations as is customary in the art.

Compounds such as disodium ethylenediamine tetraacetate (Na2EDTA·2H2O) can be used as stabilizers in the formulation of the present invention. The latter act as ligands for transition metals, which, converting them into complexes, stabilize the formulation in the long term against possible metal-catalyzed decomposition of the organic ingredients of the formulation.

Additional pharmaceutical, cosmetic, veterinary or agrochemical active substances can be used in the formulation of the present invention, which can help or enhance the primary biological action of silicic acid (H4SiO4) on the human, animal or plant organism, and to the average expert in the field they are known as:

(i) anti-inflammatory and/or antiphlogistics;

(ii) immunostimulants;

(iii) antioxidants;

or in agronomy as:

(iv) fungicides.

The use of these additional active substances in the formulation of the subject invention is optional.

An anti-inflammatory and/or antiphlogistic is selected from the group consisting of: paracetamol; metamizole sodium; acetylsalicylic acid and its salts with pharmaceutically acceptable bases; salicylic acid or its salts with pharmaceutically acceptable bases; salsalate; methyl salicylate; ethyl salicylate; benzyl salicylate; 2-hydroxyethyl salicylate; salicylamide; phenylbutazone sodium or other salts of phenylbutazone with pharmaceutically acceptable bases; propyphenazone; oxyphenbutazone; mofebutazone; bumadisone calcium; clofezone; phenazone; ethenamide; etofenamate; succibusone; azapropazone; proquazone; tolmetin sodium; ketoprofen or its salts with pharmaceutically acceptable bases; ibuprofen or its salts with pharmaceutically acceptable bases; naproxen; flurbiprofen; pyrprofen; mefenamic acid; flufenamic acid; tiaprofenic acid; diclofenac sodium or other salts of diclofenac with pharmaceutically acceptable bases; indomethacin; piroxicam; meloxicam; oxaceprol; codeine and its salts with pharmaceutically acceptable acids; caffeine; papaverine and its salts with pharmaceutically acceptable acids; ortho-carbamoylphenyloxyacetic acid and its salts with pharmaceutically acceptable bases; extract of St. John's wort (Hypericum perforatum), azulene or chamomile extract (Matricaria recutita); calendula flower extract (Calendula officinalis); arnica extract (Arnica montana); willow bark extract (Salix alba); capsaicin or paprika extract (Capsici Fruct.); seeder extract (Euphrasia officinalis); rabbit thorn extract (Ononis spinosa); menthol; essential oil or mint extract (Menta piperita); eucalyptol, essential oil or eucalyptus extract (Eucalyptus globulus); essential oil or extract of rosemary (Rosmarinus officinalis); lavender essential oil or extract (Lavandula officinalis); purified turpentine oil; camphor; pinene; bornyl acetate; terpineol; terpenyl acetate; eugenol; lemon essential oil (Citrus limonum); essential oil of orange (Citrus aurantium); pine essential oil (Juniperus communis); clove essential oil (Syzygium aromaticum); green tea extract (Camellia sinensis); rooibos extract (Aspalathus linearis); nettle extract (Urtica dioica); horse chestnut extract (Hippocastani sem.); mulberry extract (Verbascum phlomoides); holly extract (Ilex aquifolium); borage extract (Borago officinalis); burdock extract (Arctium lappa); plantain extract (Plantago lanceolata); agave extract (Agave americana); wormwood extract (Lycopodium clavatum); methyl nicotinate; benzyl nicotinate; other nicotinic acid esters; glucosamine sulfate; L-histidine; chondroitin sulfate; hyaluronidase; heparin sodium; coumarin; choline and its salts; sulfur; extracts with a significant content of silicic acid (H4SiO4) such as field horsetail green (Equisetum arvense), lungwort (Pulmonaria officinalis), oleander green (Polygonum aviculare), creeping sedge (Agropyron repens), turkey (Agrimonia eupatoria), oats (Avena sativa), dandelion root (Taraxaci radix); anti-inflammatory corticosteroids such as cortisone, hydrocortisone, dexamethasone, betamethasone, alclomethasone, fluprednide, prednisone, prednisolone, triamcinolone, methylprednisolone, paramethasone, clobetasol, diflorazone, fluocinolone, clocortolone, flumethasone, halomethasone, fluocortolone, diflucortolone, mono- or diesters of the said synthetic steroids on 17 - and/or 21-position, or 16,17-acetonide derivatives such as hydrocortisone acetate, hydrocortisone-17-butyrate, betamethasone-17-valerate, betamethasone 17,21-dipropionate, alclomethasone-17,21-dipropionate, fluprednide-21- acetate, triamcinolone-16α,17α-acetonide, clobetasol-17-propionate; then γ-linolenic acid or vegetable oils with a dominant content of linolenic acid such as fish, linseed or soybean oil; or mixtures of these substances.

The immunostimulant was chosen from the group consisting of: acemannan or aloe vera extracts (Aloe barbadensis); echinacea extract (Echinacea angustifolia); ginseng extract (Panax ginseng, Panax quinquefolium); amiprilose or its salts with pharmaceutically acceptable acids; bucilamine or its salts with pharmaceutically acceptable bases; salts of diethyldithiocarbamic acid with pharmaceutically acceptable bases; inosine pranobex; interleukin-2; lentinan or Shiitake mushroom extracts (Lentinus edodes); levamisole or its salts with pharmaceutically acceptable acids; romurtide; Platonist; procodazole or its salts with pharmaceutically acceptable bases; pidotimod or its salts with pharmaceutically acceptable bases; imiquimod or its salts with pharmaceutically acceptable acids; thymomodulin or thyroid extracts rich in thymomodulin; thymopentin or extracts rich in thymopentin; ubenimex or enriched extracts containing ubenimex from Streptomyces olivoreticuli; or mixtures of these substances.

The antioxidant was chosen from the group consisting of: α-lipoic acid in all optical forms; resveratrol; superoxide dismutase (SOD); green tea extract (Camellia sinensis); rooibos extract (Aspalathus linearis); nettle extract (Urtica dioica); silymarin; sycamore fruit extract (Silybum marianum); ascorbic acid; salts, esters and other derivatives of ascorbic acid; tocopherol; tocopheryl acetate and other tocopherol esters; niacinamide; routine; quercetin; plant extracts with a significant content of rutin or quercetin; cyanidin or blueberry extract (Vaccinium myrtillus); hesperedin; diosmin; orange extract (Citrus aurantium); lycopene; extracts with a significant content of lycopene; resveratrol; tetrahydrocurcumin; rosmarinic acid; rosemary extract (Rosmarinus officinalis); hypericin; extract of St. John's wort (Hypericum perforatum); ellagic acid; chlorogenic acid; oleuropein; olive leaf extract (Olea europea); grape seed extract; pycnogenol; carnosine; glutathione; extracts of herbal drugs with a significant content of silicic acid, such as field horsetail (Equisetum arvense), lungwort (Pulmonaria officinalis), oleander (Polygonum aviculare), creeping sedge (Agropyron repens), turkey (Agrimonia eupatoria), oats (Avena sativa) ), dandelion root (Taraxaci radix); or compatible mixtures of said substances.

In addition to the above, other active substances whose beneficial or protective effects on sensitive skin, scalp, nails or other organs in the human or animal body are known to the average expert in the field can be used in the formulation of the subject invention for topical or oral use: for example, vitamins or provitamins such as retinol palmitate, β-carotene, d-panthenol, calcium pantothenate, folic acid, riboflavin, pyridoxine or its derivatives; then protein hydrolysates; algae extracts; chlorophyll; various plant extracts such as sedge (Erythraea centaurum), mulberry (Verbascum phlomoides), holly (Ilex aquifolium), ivy leaf (Hedera helix); further urea, coenzyme Q10; and α- and β-hydroxy acids such as glycolic, lactic, malic, citric, tartaric and salicylic acids; zinc pyrithione, zinc oxide, UVA/UVB filters such as octyl 4-methoxycinnamate or titanium dioxide, or a compatible mixture of these substances.

In agriculture, where the formulation of the subject invention is used in the treatment of plants primarily to increase resistance to stressful conditions (due to hail or drought) and fungal diseases, as an active substance that can support the basic biological effects of silicon, it is selected from the group consisting of fungicides: propiconazole, miconazole , fluconazole, ketoconazole, other related imidazole derivatives and their salts, undecylenic acid and its salts, calcium propionate, zinc propionate, pyrithione, zinc pyrithione, copper(II) pyrithione, thiophanate methyl, iprodione, triflumizole, fenarimol, triadimefon, myclobutanil, mefenoxam , piperalin, flutolanil, azoxystrobin, kresozyme methyl, trifloxystrobin, fludioxonil, etridiazole, dimethomorph, phenhexamide, chlorthalonil, cineb, mancozeb, ciram, fosetyl aluminum, phosphitic acid, copper(II) sulfate (CuSO4·5H2O), copper(II) hydroxide [Cu(OH)2], copper(I) oxide (Cu2O), basic copper chloride or sulfate, and other copper salts, then garlic extract (Allium sativu m), thymol, thyme essential oil (Thymus vulgaris), methyl salicylate or wintergreen essential oil (Gaultheria species), rosemary essential oil (Rosmarinus officinalis), lavender essential oil (Lavandula officinalis), neem oil (Melia azadirachta), terpineol, essential tea tree oil (Melaluca alternifolia), sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3), sodium hydrogen phosphate (Na2HPO4), potassium hydrogen phosphate (K2HPO4), ammonium hydrogen phosphate [(NH4)2HPO4], calcium polysulfide (CaSx; x= 3-5), sulfur, sodium or potassium silicate (M2SiO3; M= Na,K), hydrogen peroxide (H2O2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), or compatible mixtures the mentioned substances.

It is clear to the average expert in the field that in the case of the application of a combination of individual relatively reactive pharmaceutical, cosmetic or agrochemical active substances or plant extracts, their mutual chemical compatibility and compatibility with excipients used for the production of the final dosage form of the formulation is key.

Preparation of the formulation of the subject invention

The formulation of the subject invention can be in the form:

(i) oral suspension, tablet, capsule, liquid powder (suspension for topical application), paste or shampoo; for use in medicine, cosmetics or veterinary medicine; you

(ii) suspension concentrate or wet powder for use in agriculture.

The formulation is prepared by the usual procedures that are known to the average expert in the field of pharmaceutical, cosmetic or chemical technology.

Tablets are prepared by wet granulation of a mixture of L-aspartic acid (1) and a solid source of silicic acid (zeolites, amorphous SiO2, magnesium or calcium silicate) with the addition of auxiliary substances from the group of fillers, binders, disintegrants, lubricants, and others. The granulate thus prepared is subjected to the tableting process.

Capsules are produced by encapsulating granules or a homogenized dry mixture of L-aspartic acid (1) and a solid source of silicic acid according to the invention, and one or more auxiliary substances, in gelatin or vegetable capsules.

The formulation of the subject invention in the form of an oral suspension is prepared by homogenizing L-aspartic acid (1) and a solid source of silicic acid according to the subject invention, in a pharmaceutically acceptable diluent such as glycerol, 1,2-propylene glycol, purified water or their mixtures. The suspension may also contain other auxiliary substances such as fragrances, flavoring agents, emulsifiers, and others.

The liquid powder (suspension for topical application) is produced in a similar way to the oral suspension, except that the active substances according to the invention are added to a previously prepared basic lotion, which can be:

(i) water- or oil-based solution; or

(ii) liquid emulsion of oil-in-water (O-W) or water-in-oil (W-O) type.

The paste is produced by homogenizing L-aspartic acid (1) and a solid source of silicic acid according to the present invention, in a carrier that can be an ointment, emulsion/cream (either O-W or W-O emulsion) or a water-based gel.

The shampoo is produced by homogenizing the active ingredients according to the invention in a previously prepared viscous solution of one or more anionic and nonionic, or one or more cationic and nonionic surfactants, with the subsequent addition of other functional ingredients such as thickeners, dyes, fragrances.

The suspension concentrate for use in agriculture is produced by homogenizing L-aspartic acid (1) and a solid source of silicic acid according to the present invention, in a suitable diluent such as:

(i) mineral or vegetable (sunflower, rapeseed) oil; or

(ii) purified water, glycerol, 1,2-propylene glycol or their mixtures;

with the addition of wetting agents and/or surfactants such as polyoxyethylene sorbitan monostearate. The formulation may also contain other auxiliary substances such as preservatives, thickeners, etc.

The wet powder is prepared by dry homogenization of the active substances according to the invention with an inert filler (e.g. calcium carbonate or kaolin), with the addition of small amounts of solid lubricant (e.g. talc), wetting agent (e.g. calcium dioctyl sulfosuccinate; calcium docusate), surfactant (polysorbate 60 ), and anti-dust agents (eg mineral oil).

Alternatively, the formulation in the form of a wettable powder can be granulated into the form of wettable granules with the addition of suitable binders.

Examples of embodiments of the invention

General remarks

The term room temperature refers to the temperature interval: 20-25 oC. All percentages (%) of ingredients are made as mass (m/m).

Example 1

Preparation of a standard solution of pure sodium silicate and a complex of sodium silicate with choline chloride and selected amino acids

Preparation of a standard sodium silicate solution with a concentration of 1% m/m silicon (Si): Tetraethyl orthosilicate ( TEOS; 1.2 mL; 1.12 g; 0.0054 mol). The reaction mixture was stirred at room temperature for 6 h. After that, distilled water (7.5 mL) was added to the total mass of the reaction mixture of 15.00 g. The content of silicon in the thus prepared standard solution is 150 mg (1% m/m).

Preparation of a complex of sodium salts of amino acids and ortho-silicic acid with a concentration of 1% m/m silicon (Si). General procedure: To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 mol equiv.) in distilled water (6 mL) was added tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0 .0054 mol). The reaction mixture was stirred at room temperature for 6 h. After that, 0.0054 mol of the appropriate amino acid or choline chloride was added to the reaction mixture containing sodium silicate in an amount equivalent to 150 mg (0.0054 mol) of silicon (Si):

(i) 0.75 g (0.0054 mol) choline chloride;

(ii) 0.57 g (0.0054 mol) of L-serine;

(iii) 0.36 g (0.0027 mol; 0.0054 mol COOH group) of L-aspartic acid;

(iv) 0.40 g (0.0027 mol; 0.0054 mol COOH group) of L-glutamic acid; you

(v) 0.84 g (0.0054 mol) of L-histidine.

Each solution was then mixed at room temperature for 30 minutes, and then distilled water was added to each to a total mass of 15.00 g. The silicon content in each solution of the complex was 150 mg (1% m/m). The pH of the solution was 12.0-12.5.

Example 2

Examination of the influence of sodium silicate complexes with choline chloride and selected amino acids on the stability of ortho-silicic acid (H4SiO4) in solution. Influence of L-(+)-aspartic acid on the stability of H4SiO4 in solution.

Determination of the gelation (polymerization) time of ortho-silicic acid in the presence of different amino acids. General procedure: 2 mL of 1.5 M phosphate buffer pH = 4.5 and 2 mL of sample or standard solution were mixed in a test tube. The pH values of all solutions were 6.5. The time from the moment of mixing with the phosphate buffer (t0; all solutions at the time of preparation are clear) to the formation of an opalescent (immobile) gel was determined with the mixtures thus prepared. This time period is designated as "gelation (polymerization) time", tG, and is expressed in minutes. The obtained results for tG are expressed in relation to the sodium silicate solution as a standard. The results are presented in Table 1.

Preparation of 1.5 M phosphate buffer pH= 4.5 for testing purposes: Sodium dihydrogen phosphate (NaH2PO4; 18.00 g; 0.15 mol) was quantitatively transferred into a 100 mL volumetric flask and dissolved by stirring at room temperature in 80-85 mL distilled water. The resulting solution was made up to the mark of 100 mL with distilled water.

Example 3

Preparation of the formulation of the subject invention in the form of an oral suspension with 30% micronized clinoptilolite zeolite, 0.3% L-(+)-aspartic acid and 3% DL-α-lipoic acid

Composition (100 g of oral suspension): (a) Micronized zeolite clinoptilolite (30.00 g; 30% w/w), (b) L-(+)-aspartic acid (0.30 g; 0.3% w/w) m), (c) DL-α-lipoic acid (3.00 g; 3.0% m/m), (d) 1,2-propylene glycol (64.93 g; 64.93% m/m), (e) polyoxyethylene sorbitan monostearate (0.70 g; 0.7% m/m), (f) DL-α-tocopheryl acetate (0.07 g; 0.07% m/m), (g) trans- anethole (1.00 g; 1.0% w/w).

Procedure: (c) was added to (d) with vigorous stirring, and stirring was continued for 15 minutes with the formation of a lemon yellow clear solution. Then (e), (f) and (g) were added and homogenized by mixing at room temperature for 15 minutes. To the resulting cloudy yellow solution, (a) was added in portions for 5 minutes, then (b), and stirred at room temperature for 1 hour. A dark green viscous suspension with good precipitation stability was obtained. The smell is pleasant, like fennel.

Example 4

Preparation of the formulation of the subject invention in the form of tablets with 20% calcium silicate and 5% L-(+)-aspartic acid

Composition (1000 g tablet mixture): (a) calcium silicate (CaSiO3; 200.00 g; 20% m/m), (b) L-(+)-aspartic acid (50.00 g; 5.0% m /m), (c) microcrystalline cellulose (500.00 g; 50% m/m), (d) lactose monohydrate (196.00 g; 19.6% m/m), (e) polyvinylpyrrolidone (20.00 g; 2.0% w/w), (f) sodium starch glycolate (25.00 g; 2.5% w/w), (g) magnesium stearate (9.00 g; 0.9% w/w ).

Procedure: Ingredients (a), (b), (c), (d), (e) and (f) were ground and homogenized by mixing at room temperature for 30 minutes. Then ground (g) was added, and the mixture was homogenized in a V-blender for an additional 15 minutes. The homogenous mixture thus prepared was subjected to tableting with the formation of approx. 2000 tablets (500 mg each). The average weight of the tablet was 506 mg.

Each tablet contains 100 mg of calcium silicate and 25 mg of L-(+)-aspartic acid.

Example 5

Preparation of the formulation of the subject invention in the form of capsules with 25% magnesium silicate and 2.5% L-(+)-aspartic acid

Composition (1000 g of encapsulation mixture): (a) Magnesium silicate (magnesium trisilicate; 2MgO·3SiO2; 250.00 g; 25% m/m), (b) L-(+)-aspartic acid (25.00 g ; 2.5% w/w), (c) inulin (715.00 g; 71.5% w/w), (d) talc (10.00 g; 1.0% w/w).

Procedure: Ingredients (a), (b), (c) and (d) were ground and homogenized in a V-blender at room temperature for 30 minutes. The resulting powdery homogeneous mixture was filled into gelatin capsules of size "0" (Lukaps d.d., Ludbreg, Croatia) with the help of a manual laboratory capsule maker. Approximately 2500 capsules with a gross weight of 510 mg and a net weight of 410 mg were obtained. Each capsule contains approximately 100 mg of magnesium silicate and 10 mg of L-(+)-aspartic acid.

Example 6

Preparation of the formulation of the subject invention in the form of a liquid powder (suspension for topical application) with 15% zeolite A and 0.15% L-(+)-aspartic acid

Composition (100 g of liquid powder): (a) Zeolite A (15.00 g; 15% m/m), (b) L-(+)-aspartic acid (0.15 g; 0.15% m/m) ), (c) white petroleum jelly (8.50 g; 8.5% w/w), (d) glycerol monostearate (4.00 g; 4.0% w/w), (e) cetyl alcohol (2, 00 g; 2.0% m/m), (f) cetyl palmitate (0.80 g; 0.8% m/m), (g) beeswax (2.50 g; 2.5% m/m ), (h) ceteareth-20 (0.90 g; 0.9% m/m), (i) ceteareth-12 (0.60 g; 0.6% m/m), (j) dimethicone (0 .50 g; 0.5% m/m), (k) almond oil (3.00 g; 3.0% m/m), (l) jojoba oil (1.00 g; 1.0% m/ m), (m) tocopherol acetate (0.5 g; 0.5% m/m), (n) retinol palmitate (0.05 g; 0.05% m/m), (o) niacinamide (0, 20 g; 0.2% m/m), (p) isopropyl myristate (1.20 g; 1.2% m/m), (q) methyl 4-hydroxybenzoate (0.20 g; 0.2% m /m), (r) propyl 4-hydroxybenzoate (0.10 g; 0.1% m/m), (s) carbopol 934P (0.40 g, 0.4% m/m), (t) sodium hydroxide (0.60 g 20% aqueous solution; 0.6% w/w), (u) 1,2-propylene glycol (0.50 g, 0.5% w/w), (v) glycerol (2, 50 g, 2.5% m/m), (z) lavender essential oil:lemon essential oil (1.00 g; 2:1, m/m ; 1.0% w/w), (x) purified water (53.80 g; 53.80% w/w).

Procedure: Ingredients of the oil phase (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m) and ( p) they were melted with gentle heating to 55-60 oC, and the obtained melt was heated to 70-75 oC with gentle stirring. The melts were then added in order (o), (q) and (r), and stirring was continued at this temperature for 5 minutes. The aqueous phase was then added dropwise for 30 minutes at 70-75 oC with intensive stirring. The aqueous phase was previously prepared by dissolving (s), (u) and (v) in (x). Then (t) was added to the emulsion with intensive mixing. Then the active substances (a) and (b) were added. The resulting suspension was intensively stirred at temperatures from 70 oC to 50 oC for 20-30 minutes. Then further at 50 oC for 30 minutes, and then slowly cooled to 40 oC. (n) and (z) were added and stirring was continued to room temperature for 30 minutes. The product was additionally homogenized by intense mixing at room temperature for 30 minutes. A liquid powder in the form of a white viscous suspension [basically an oil-in-water (O-W) emulsion] with a pleasant refreshing lavender scent was obtained.

Example 7

Preparation of the formulation of the subject invention in the form of a paste with 20% micronized clinoptilolite zeolite and 1% L-(+)-aspartic acid

Composition (100 g of paste): (a) Micronized zeolite clinoptilolite (20.00 g; 20% m/m), (b) L-(+)-aspartic acid (1.00 g; 1.0% m/m) ), (c) white petrolatum (20.00 g; 20% w/w), (d) thick mineral oil (47.40 g; 47.4% w/w), (e) almond oil (10.00 g; 10% m/m), (f) sorbitan trioleate (1.00 g; 1.0% m/m), (g) d-panthenol (0.50 g; 0.5% m/m), (h) tocopheryl acetate (0.10 g; 0.1% w/w).

Procedure: (c) heated to 60 oC with gentle stirring, then (d), (e), (f), (g) and (h) added in order. The mixture was stirred at that temperature for 10-15 minutes until a clear melt formed in the form of a thick oily pale yellowish liquid. Then (a) and (b) were added, and stirring at 60 oC was continued for the next 15 minutes. The resulting paste, while still warm (>50 oC), with gentle stirring, was poured into small containers of 25 g each. A dark green (the color comes from zeolite clinoptilolite) semi-solid odorless paste was obtained.

Example 8

Preparation of the formulation of the subject invention in the form of a shampoo with 20% amorphous silicon dioxide, 0.5% L-(+)-aspartic acid and 1% zinc pyrithione

Composition (100 g of shampoo): (a) Amorphous silicon dioxide (20.00 g; 20% m/m), (b) L-(+)-aspartic acid (0.50 g; 0.5% m/m) ), (c) zinc pyrithione (1.00 g; 1.0% m/m), (d) sodium lauryl sulfate (5.00 g; 5.0% m/m), (e) cocoamidopropyl betaine (2, 00 g; 2.0% w/w), (f) cocodiethanolamide (1.00 g; 1.0% w/w), (g) polyoxyethylene(23) lauryl ether (2.00 g; 2.0% w /m), (h) polysorbate 60 (2.00 g; 2.0% m/m), (i) disodium lauryl sulfosuccinate (3.00 g; 3.0% m/m), (j) methylcellulose (0 .25 g; 0.25% m/m), (k) glycerol (3.00 g; 3.0% m/m), (l) disodium edetate (0.20 g; 0.2% m/m), (m) citric acid (0.20 g; 0.2% m/m), (n) sodium benzoate (0.20 g; 0.2% m/m), (o) potassium sorbate (0.30 g ; 0.3% m/m), (p) fragrance, mixture of lavender and lemon essential oils (3:1 m/m; 1.00 g; 1.0% m/m), (q) purified water (58 .35 g; 58.35% m/m).

Procedure: First, (j) is dissolved in cold (10-15 oC) (q) with intense mixing for 30 minutes. (d), (e), (f), (g), (h) and (i) were added to the resulting viscous solution, and dissolved by stirring at 40-45 oC for 30 minutes. Then (k), (l), (m), (n), and (o) were added in order, and dissolved by stirring at 40-45 oC for 10 minutes. Then active substances (a), (b), and (c) were added and homogenized by mixing at the same temperature for 30 minutes. Then the fragrance (p) was added. The resulting thick viscous suspension was gradually cooled to room temperature with stirring for 30 minutes. The resulting shampoo is in the form of a white viscous fine stable suspension with a pleasant lavender scent.

Example 9

Preparation of the formulation of the subject invention in the form of a suspension concentrate for use in agriculture with 30% micronized zeolite clinoptilolite and 3% L-(+)-aspartic acid

Composition (100 g of suspension concentrate): (a) Micronized zeolite clinoptilolite (30.00 g; 30% m/m), (b) L-(+)-aspartic acid (3.00 g; 3.0% m /m), (c) sunflower oil (59.00 g; 59% m/m), (d) polysorbate 80 (7.00 g; 7.0% m/m), (e) bentonite (1.00 g; 1.0% m/m).

Procedure: (d) and (e) were added to (c) and homogenized by mixing at room temperature for 15 minutes. Then (a) and (b) were added, and the mixture was stirred at 40-50 oC for 1 h. A viscous dark green suspension with good settling stability was obtained. It suspends/emulsifies nicely in water with the formation of a pale green diluted suspension with good stability during foliar application.

Example 10

Preparation of the formulation of the subject invention in the form of a wet powder for use in agriculture with 25% micronized zeolite A, 2.5% L-(+)-aspartic acid and 10% sulfur

Composition (100 g of wet powder): (a) Micronized zeolite A (25.00 g; 25% w/w), (b) L-(+)-aspartic acid (2.50 g; 2.5% w/w) m), (c) sulfur, micronized (10.00 g; 10% m/m), (d) kaolin (54.50 g; 64.5% m/m), (e) bentonite (6.00 g ; 6.0% m/m), (f) sodium 1,4-bis-(2-ethylhexyl)-sulfosuccinate (1.00 g; 1.0% m/m), (g) light mineral oil (1 .00 g; 1.0% m/m).

Procedure: Ingredients (a)-(f) were added to the homogenizer and mixed in a V-blender for 30 minutes. (g) was then added and stirred at room temperature for an additional 30 minutes. A very fine, yellow-green powder was obtained. It is not dusty during application. In a working concentration of 0.5-2% in water, it creates a relatively stable suspension that is suitable for spraying with the help of classic sprayers without any particular difficulties.

Claims (40)

1. Formulation as a source of biologically available silicon, characterized by the fact that it consists of: (i) one or more water-insoluble sources of silicic acid such as zeolite, amorphous silica, magnesium silicate or calcium silicate; in an amount of 1-50% m/m, preferably 10-40% m/m; (ii) aspartic acid (1); [image] in an amount of 0.01-10% m/m, preferably 0.1-5% m/m; (iii) one or more auxiliary substances with which they form the form that enables the desired application of the formulation in question: oral suspension, tablets, capsules, liquid powder (suspension for topical application), paste, shampoo, concentrate for suspension and urine powder; and from one or more additional pharmaceutical, cosmetic or agrochemical active substances that support the basic biological effects of silicic acid; in the amount up to a total of 100% m/m. 2. Formulation as a source of biologically available silicon according to claim 1, characterized in that the water-insoluble source of silicic acid is selected from the group consisting of: (i) pharmaceutical acceptable types of zeolites such as synthetic zeolite A [Na2O•Al2O3•2SiO2•4.5H2O] or natural zeolite clinoptilolite [Ca/Mg/(K/Na)2Al2Si7O18•xH2O], wherein the cation in the zeolite structure is chosen from groups consisting of calcium (Ca2+), magnesium (Mg2+), potassium (K+) or sodium (Na+); (ii) amorphous anhydrous or hydrated silicon dioxide (SiO2); (iii) calcium silicates [CaO•SiO2; 3CaO•2SiO2; 2CaO•SiO2; 3CaO•SiO2; and their hydrates]; you (iv) non-fibrous forms of magnesium silicate [MgO•SiO2; 2MgO•SiO2; 2MgO•3SiO2]; or mixtures thereof. 3. Formulation as a source of biologically available silicon according to claims 1 and 2, characterized by the fact that the auxiliary substance is one or more substances selected from the groups consisting of: diluents, fillers, binders, disintegrants, lubricants, emollients, emulsifiers, surfactants/wetting agents, humectants , thickeners and preservatives. 4. Formulation as a source of biologically available silicon according to claims 1-3, characterized in that the excipient is a diluent selected from the group consisting of: water; glycerol; 1,2-propylene glycol; 1,3-propylene glycol; hexylene glycol; 1,3-butanediol; liquid polyethylene glycols; liquid polyglycerols; liquid polypropylene glycols; ethanol; isopropanol; butanol; isosorbide dimethyl ether; methyl and ethyl ethers of mono-, di- and tri-ethylene glycol; ethyl lactate; triethylhexanoin; dimethylsulfoxide; sorbitol; mineral oil; vegetable oils; or mixtures of these substances. 5. Formulation as a source of biologically available silicon according to claims 1-4, characterized in that the auxiliary substance is a filler selected from the group consisting of: microcrystalline cellulose, lactose monohydrate, calcium hydrogen phosphate, calcium sulfate dihydrate, crystallized sorbitol, starch, modified starches, inulin , talc, kaolin, bentonite, montmorillonite, calcium carbonate, basic magnesium carbonate, aluminum hydroxide, or mixtures of these substances. 6. Formulation as a source of biologically available silicon according to claims 1-5, characterized in that the auxiliary substance is a binder selected from the group consisting of: gelatin, lactose monohydrate, sorbitol, sucrose, xylitol, maltitol, starch, modified starches, cellulose, methylcellulose, 2-hydroxyethylcellulose, 2-hydroxypropylcellulose, sodium carboxymethylcellulose, polyethylene glycols, polyvinylpyrrolidone, carrageenans, or mixtures of the aforementioned substances. 7. Formulation as a source of biologically available silicon according to claims 1-6, characterized in that the auxiliary substance is a disintegrant selected from the group consisting of: starch, cellulose, methylcellulose, sodium carboxymethylcellulose, 2-hydroxyethylcellulose, 2-hydroxypropyl cellulose, polyvinylpyrrolidone, polyvinylpyrrolidone copolymers , sodium starch glycolate, or mixtures of these substances. 8. Formulation as a source of biologically available silicon according to claims 1-7, characterized in that the auxiliary substance is a lubricant selected from the group consisting of: magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, silicon dioxide, or mixtures of the aforementioned substances. 9. Formulation as a source of biologically available silicon according to claims 1-8, characterized in that the auxiliary substance is an emollient selected from the group consisting of: paraffin; vaseline; mineral oil; ozokerite; yellow or white beeswax; synthetic esters of higher fatty acids such as isopropyl myristate, isopropyl palmitate, trimethylolpropane tristearate, glyceryl tricaprylate; synthetic waxes such as lauryl laurate; liquid natural waxes such as jojoba oil; various vegetable oils such as soybean oil, almond oil, sunflower oil, fish oil, olive oil, wheat germ oil, corn germ oil, avocado oil, palm oil, coconut oil; higher fatty alcohols such as cetanol, stearol, oleyl alcohol; or mixtures of these substances. 10. Formulation as a source of biologically available silicon according to claims 1-9, characterized in that the auxiliary substance is an emulsifier selected from the group consisting of: sodium lauryl sulfate; sodium laurylethylene glycol sulfate; sodium lauryl diethylene glycol sulfate; fatty alcohol ethoxylates such as polyoxyethylene (2) lauryl ether, polyoxyethylene (10) lauryl ether or polyoxyethylene (23) lauryl ether where the numbers 2, 10 and 23 indicate the average number of ethylene glycol units attached to the higher fatty alcohol; ethoxylates of higher fatty acids such as polyoxyethylene(2) laurate, polyoxyethylene(10) stearate or polyoxyethylene(23) oleate, where the numbers 2, 10 and 23 indicate the average number of ethylene glycol units attached to the higher fatty acid; sorbitan esters such as polyoxyethylene sorbitan monolaurate; lanolin; lanolin ethoxylates; glycerol monostearate; beeswax ethoxylates; or mixtures of these substances. 11. Formulation as a source of biologically available silicon according to claims 1-10, characterized in that the excipient is a surfactant/wetting agent selected from the group consisting of: sodium lauryl sulfate; sodium laurylethylene glycol sulfate; sodium lauryl diethylene glycol sulfate; ammonium lauryl sulfate; ammonium laurylethylene glycol sulfate; ammonium lauryl diethylene glycol sulfate; sodium cocoamphopropionate; disodium cocoamphodiacetate; disodium cocoamphodipropionate; polyoxyethylene(10) lauryl ether, polyoxyethylene(23) lauryl ether, polyoxyethylene(10) stearyl ether, polyoxyethylene(23) stearyl ether, polyoxyethylene(10) oleyl ether, polyoxyethylene(23) oleyl ether, other ethoxylates of higher fatty alcohols to which H.L.B. factor ≥ 10; polyoxyethylene(10) laurate, polyoxyethylene(23) laurate, polyoxyethylene(10) stearate, polyoxyethylene(23) stearate, polyoxyethylene(10) oleate, polyoxyethylene(23) oleate, or other higher fatty acid ethoxylates that H.L.B. factor ≥ 10; then sorbitan esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate; mono or diethanolamides of higher fatty acids or their mixtures such as cocoamidopropyl betaine; glycosides of higher fatty alcohols such as cocoglucoside; sodium or calcium di(2-ethylhexyl) sulfosuccinate; disodium 2-ethylhexylsulfosuccinate; cationic surfactants such as cetyltrimethylammonium bromide, didecyldimethylammonium chloride, benzalkonium chloride, cetylbenzyldimethylammonium chloride, cetylpyridinium chloride; metal salts of higher fatty acids such as the sodium or potassium salt of lauric, myristic, palmitic, stearic, oleic, ricinoleic acids; sodium 1,4-bis-(2-ethylhexyl)-sulfosuccinate; calcium di[1,4-bis-(2-ethylhexyl)-sulfosuccinate]; or mixtures of these substances. 12. Formulation as a source of biologically available silicon according to claims 1-11, characterized in that the auxiliary substance is a humectant selected from the group consisting of: glycerol, 1,2-propylene glycol, 1,3-propylene glycol, hexylene glycol, 1,3-butanediol, polyethylene glycols, polypropylene glycols, polyglycerols, sorbitol, d-panthenol, sodium hyaluronate, or mixtures of the aforementioned substances. 13. Formulation as a source of biologically available silicon according to claims 1-12, characterized in that the auxiliary substance is a thickener selected from the group consisting of: polyacrylic acid or its sodium, potassium, ammonium or triethanolamine salts; methylcellulose; sodium carboxymethylcellulose; 2-hydroxyethyl cellulose; 2-hydroxy propyl cellulose; starch; modified starches; polyglycerols, polyethylene glycols; gelatin; pectin; agar agar; carrageenans; gum arabic; alginic acid or sodium alginate; or mixtures thereof. 14. Formulation as a source of biologically available silicon according to claims 1-13, characterized in that the auxiliary substance is a preservative selected from the group consisting of: methyl 4-hydroxybenzoate, ethyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, sorbic acid , benzoic acid, triclosan, chlorhexidine salts such as chlorhexidine diacetate, diimidazolidinyl urea, 2-bromo-2-nitropropane-1,3-diol, 4-chloro-m-cresol, thymol, eugenol, essential oils of thyme (Thymus vulgaris), cloves (Syzygium aromaticum), lavender (Lavandula officinalis), juniper (Juniperus communis), or a mixture of these substances. 15. Formulation as a source of biologically available silicon according to claims 1-14, characterized in that the additional pharmaceutical, cosmetic or agrochemical active substance that supports one or more basic biological effects of silicic acid is selected from one or more groups consisting of: (i) anti-inflammatory and/or antiphlogistics; (ii) immunostimulants; (iii) antioxidants; you (iv) fungicides. 16. Formulation as a source of biologically available silicon according to claims 1-15, characterized by the fact that an additional pharmaceutical, cosmetic or agrochemical active substance that supports one or more basic biological effects of silicic acid is an anti-inflammatory/antiphlogistic selected from the group consisting of: paracetamol; metamizole sodium; acetylsalicylic acid and its salts with pharmaceutically acceptable bases; salicylic acid or its salts with pharmaceutically acceptable bases; salsalate; methyl salicylate; ethyl salicylate; benzyl salicylate; 2-hydroxyethyl salicylate; salicylamide; phenylbutazone sodium or other salts of phenylbutazone with pharmaceutically acceptable bases; propyphenazone; oxyphenbutazone; mofebutazone; bumadisone calcium; clofezone; phenazone; ethenamide; etofenamate; succibusone; azapropazone; proquazone; tolmetin sodium; ketoprofen or its salts with pharmaceutically acceptable bases; ibuprofen or its salts with pharmaceutically acceptable bases; naproxen; flurbiprofen; pyrprofen; mefenamic acid; flufenamic acid; tiaprofenic acid; diclofenac sodium or other salts of diclofenac with pharmaceutically acceptable bases; indomethacin; piroxicam; meloxicam; oxaceprol; codeine and its salts with pharmaceutically acceptable acids; caffeine; papaverine and its salts with pharmaceutically acceptable acids; ortho-carbamoylphenyloxyacetic acid and its salts with pharmaceutically acceptable bases; extract of St. John's wort (Hypericum perforatum), azulene or chamomile extract (Matricaria recutita); calendula flower extract (Calendula officinalis); arnica extract (Arnica montana); willow bark extract (Salix alba); capsaicin or paprika extract (Capsici Fruct.); seeder extract (Euphrasia officinalis); rabbit thorn extract (Ononis spinosa); menthol; essential oil or mint extract (Menta piperita); eucalyptol, essential oil or eucalyptus extract (Eucalyptus globulus); essential oil or extract of rosemary (Rosmarinus officinalis); lavender essential oil or extract (Lavandula officinalis); purified turpentine oil; camphor; pinene; bornyl acetate; terpineol; terpenyl acetate; eugenol; lemon essential oil (Citrus limonum); essential oil of orange (Citrus aurantium); pine essential oil (Juniperus communis); clove essential oil (Syzygium aromaticum); green tea extract (Camellia sinensis); rooibos extract (Aspalathus linearis); nettle extract (Urtica dioica); horse chestnut extract (Hippocastani sem.); mulberry extract (Verbascum phlomoides); holly extract (Ilex aquifolium); borage extract (Borago officinalis); burdock extract (Arctium lappa); plantain extract (Plantago lanceolata); agave extract (Agave americana); wormwood extract (Lycopodium clavatum); methyl nicotinate; benzyl nicotinate; other nicotinic acid esters; glucosamine sulfate; L-histidine; chondroitin sulfate; hyaluronidase; heparin sodium; coumarin; choline and its salts; sulfur; extracts with a significant content of silicic acid (H4SiO4) such as horsetail green (Equisetum arvense), lungwort (Pulmonaria officinalis), oleander green (Polygonum aviculare), creeping heather (Agropyron repens), turkey (Agrimonia eupatoria), oats (Avena sativa), dandelion root (Taraxaci radix); cortisone; hydrocortisone; dexamethasone; betamethasone; alclomethasone; flupredniden; prednisone; prednisolone; triamcinolone; methylprednisolone; paramethasone; clobetasol; diflorazone; fluocinolone; clocortolone; flumethasone; halomethasone; fluocortolone; diflucortolone; mono- or diesters of the said synthetic steroids at the 17- and/or 21-position, or a 16,17-acetonide derivative such as hydrocortisone acetate, hydrocortisone-17-butyrate, betamethasone-17-valerate, betamethasone 17,21-dipropionate, alclomethasone-17 ,21-dipropionate, flupredniden-21-acetate, triamcinolone-16α,17α-acetonide, clobetasol-17-propionate; γ-linolenic acid or vegetable oils with a dominant content of linolenic acid such as fish, linseed or soybean oil; or mixtures of these substances. 17. Formulation as a source of biologically available silicon according to claims 1-16, indicated by the fact that an additional pharmaceutical, cosmetic or agrochemical active substance that supports one or more basic biological effects of silicic acid is an immunostimulant selected from the group consisting of: acemannan or aloe vera extracts (Aloe barbadensis); echinacea extract (Echinacea angustifolia); ginseng extract (Panax ginseng, Panax quinquefolium); amiprilose or its salts with pharmaceutically acceptable acids; bucilamine or its salts with pharmaceutically acceptable bases; salts of diethyldithiocarbamic acid with pharmaceutically acceptable bases; inosine pranobex; interleukin-2; lentinan or Shiitake mushroom extracts (Lentinus edodes); levamisole or its salts with pharmaceutically acceptable acids; romurtide; Platonist; procodazole or its salts with pharmaceutically acceptable bases; pidotimod or its salts with pharmaceutically acceptable bases; imiquimod or its salts with pharmaceutically acceptable acids; thymomodulin or thyroid extracts rich in thymomodulin; thymopentin or extracts rich in thymopentin; ubenimex or enriched extracts containing ubenimex from Streptomyces olivoreticuli; or mixtures of these substances. 18. Formulation as a source of biologically available silicon according to claims 1-17, indicated by the fact that the additional pharmaceutical, cosmetic or agrochemical active substance that supports one or more basic biological effects of silicic acid is an antioxidant selected from the group consisting of: α-lipoic acid in in all optical forms; resveratrol; superoxide dismutase (SOD); green tea extract (Camellia sinensis); rooibos extract (Aspalathus linearis); nettle extract (Urtica dioica); silymarin; sycamore fruit extract (Silybum marianum); ascorbic acid; salts, esters and other derivatives of ascorbic acid; tocopherol; tocopheryl acetate and other tocopherol esters; niacinamide; routine; quercetin; plant extracts with a significant content of rutin or quercetin; cyanidin or blueberry extract (Vaccinium myrtillus); hesperedin; diosmin; orange extract (Citrus aurantium); lycopene; extracts with a significant content of lycopene; resveratrol; tetrahydrocurcumin; rosmarinic acid; rosemary extract (Rosmarinus officinalis); hypericin; extract of St. John's wort (Hypericum perforatum); ellagic acid; chlorogenic acid; oleuropein; olive leaf extract (Olea europea); grape seed extract; pycnogenol; carnosine; glutathione; extracts of herbal drugs with a significant content of silicic acid, such as field horsetail (Equisetum arvense), lungwort (Pulmonaria officinalis), oleander (Polygonum aviculare), creeping sedge (Agropyron repens), turkey (Agrimonia eupatoria), oats (Avena sativa) ), dandelion root (Taraxaci radix); or mixtures of these substances. 19. Formulation as a source of biologically available silicon according to claims 1-15, characterized by the fact that an additional pharmaceutical, cosmetic or agrochemical active substance that supports one or more basic biological effects of silicic acid is a fungicide selected from the group consisting of: propiconazole, miconazole, fluconazole , ketoconazole, other related imidazole derivatives and their salts, undecylenic acid and its salts, calcium propionate, zinc propionate, pyrithione, zinc pyrithione, copper(II) pyrithione, thiophanate methyl, iprodione, triflumizole, fenarimol, triadimefon, myclobutanil, mefenoxam, piperaline , flutolanil, azoxystrobin, kresozyme methyl, trifloxystrobin, fludioxonil, etridiazole, dimethomorph, phenhexamide, chlorthalonil, cineb, mancozeb, ciram, fosetyl aluminum, phosphitic acid, copper(II) sulfate (CuSO4·5H2O), copper(II) hydroxide [Cu (OH)2], copper(I) oxide (Cu2O), basic copper chloride or sulfate, and other copper salts, then garlic extract (Allium sativum), thymol, essential oil t thyme (Thymus vulgaris), methyl salicylate or wintergreen essential oil (Gaultheria species), rosemary essential oil (Rosmarinus officinalis), lavender essential oil (Lavandula officinalis), neem oil (Melia azadirachta), terpineol, tea tree essential oil (Melaluca alternifolia), sodium bicarbonate (NaHCO3), potassium bicarbonate (KHCO3), sodium hydrogen phosphate (Na2HPO4), potassium hydrogen phosphate (K2HPO4), ammonium hydrogen phosphate [(NH4)2HPO4], calcium polysulfide (CaSx; x= 3-5), sulfur, sodium or potassium silicate (M2SiO3; M= Na,K), hydrogen peroxide (H2O2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), or mixtures of the above substances. 20. Preparation of the formulation according to claims 1-19, characterized in that aspartic acid and one or more water-insoluble sources of silicic acid, such as zeolite, amorphous silica, magnesium silicate or calcium silicate, are homogenized by mixing with: (i) one or more excipients; you (ii) one or more additional pharmaceutical, cosmetic or agrochemical active substances that support the basic biological effects of silicic acid; with the formation of a homogeneous mixture which: (a) represents the final form of the subject formulation: oral suspension, liquid powder (suspension for topical application), paste, shampoo, concentrate for suspension and wet powder; or (b) is subjected to a tableting process with the formation of the final tablet form; or (c) filled into gelatin or vegetable capsules with the formation of the final shape of the capsules. 21. Formulation according to claims 1-18, characterized in that it is used as a source of silicon for the human body. 22. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for stimulating the immune system. 23. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment of allergies. 24. Formulation according to claims 1-18, characterized in that it is used as an auxiliary therapeutic agent in infectious diseases. 25. Formulations according to claims 1-18, characterized by the fact that it is used as a therapeutic agent for strengthening the structure and elasticity of arterial, venous and capillary walls, reducing their permeability; and for improving the structure of connective tissue and building proteins of soft organs such as the liver, lungs and brain. 26. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for stimulating the functioning of joints and ligaments. 27. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the stimulation of osteoblasts and bone mineralization and the prevention of osteoporosis. 28. Formulation according to claims 1-18, characterized by the fact that it is used as a therapeutic agent to reduce the resorption of aluminum from the digestive tract and thereby prevent the occurrence of neurodegenerative diseases such as Alzheimer's or Parkinson's disease. 29. Formulation according to claims 1-18, characterized in that it is used as an anti-inflammatory agent in the therapy of acute and chronic inflammatory diseases. 30. Formulations according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment of dermatoses such as: skin irritation, eczema, seborrheic dermatitis, neurodermatitis and psoriasis. 31. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment of dandruff of the scalp. 32. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment of pressure ulcers. 33. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment of burns. 34. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for the treatment and healing of wounds. 35. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for stimulating the biosynthesis of collagen and elastin and thus for the treatment of wrinkles and their prevention. 36. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for slowing skin aging. 37. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for stimulating hair growth, strength and shine. 38. Formulation according to claims 1-18, characterized in that it is used as a therapeutic agent for stimulating growth and increasing nail strength. 39. Formulation according to claims 1-18, characterized in that it is used as a source of silicon for an animal organism. 40. Formulation according to claims 1-15, 19, characterized by the fact that it is used for feeding plants in order to achieve the physiological effects of silicon; and increasing resistance to stress and fungal diseases.