ortho-Silicic Acid : Health Effects & Patents ![](0logo.gif) [**rexresearch.com**](http://rexresearch.com/)[**rexresearch1.com**](http://rexresearch1.com/) --- **ortho-Silicic Acid** **Health Effects & Patents** --- **![](Orthosilicicacid3D.png) ![](Orthosilicicacid5.png)** --- ******[**https://pubchem.ncbi.nlm.nih.gov/compound/Orthosilicic-acid**](https://pubchem.ncbi.nlm.nih.gov/compound/Orthosilicic-acid)[**https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546016/**](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546016/)**Nutr Metab (Lond). 2013; 10: 2.**** **Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy** **Lela Munjas JurkiA, et al** Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources. Silicon (Si) is the most abundant element (27.2%) present in the earth's crust following oxygen (45.5%) [1]. Silicon is known for a number of important chemical and physical properties, i.e. semiconductor property that are used in various scientific and technical applications. These Si features, along with structural complexity of its compounds, have attracted researchers from the earliest times [2]. In particular, silicon dioxide or silica (SiO2) is the most studied chemical compound following water, and the most important Si-containing inorganic substance [1]. Formally, silica (SiO2) is a silicic acid anhydride of monomeric ortho-silicic acid (H4SiO4), which is water soluble and stable in highly diluted aqueous solutions. Moreover, several alowera hydrated forms of ortho-silicic acid exist in aqueous solutions as well including meta-silicic acid (H2SiO3 or lower oligomers like di-silicic (H2Si2O5) and tri-silicic acids (H2Si3O7) including their hydrated forms pentahydro-silicic (H10Si2O9), and pyro-silicic acids (H6Si2O7) [1]. These are water soluble, formed in reversible equilibrium reactions from H4SiO4 and stable in diluted aqueous solutions. During a prolonged storage period, at increased concentration or in an acidic environment, these low molecular silicic acids undergo further condensation by cross-linking and dehydration. This process results in formation of poly-silicic acids chains of variable composition [SiOx(OH)4-2x and complex structure [1]. The end product is a jelly-like precipitate, namely hydrated silica (SiO2A*xH2O; often referred as acolloidal silicic acida or ahydrated silica gela). Further condensation follows which is accompanied by dehydration yielding less hydrated silicon dioxide (SiO2) phases, also known as asilica gela or aamorphous silicon dioxidea. Lower molecular forms, especially the ortho-silicic acid (H4SiO4; Figure aFigure1),1), play a crucial role in delivering silicon to the living organismsa cells and thus represent major sources of silicon for both humans and animals. Most of the silica in aqueous systems and oceans is available in the form of H4SiO4, which makes it an important compound in environmental silicon-chemistry and biology [3]. In this paper, we critically review the most recent findings on biological effects of Si and ortho-silicic acid on animals and human beings. Moreover, we propose that previously observed positive biological effects of various colloidal silicic acids (various hydrated silica gels) as well as some zeolites [4-6], e.g. zeolite A (Figure a(Figure2)2) and clinoptilolite (Figure a(Figure3),3), might be, at least partially, ascribed to the ortho-silicic acid-releasing property. Presently, many biological roles of silicon remain unknown [13]. Consequently, the recommended daily silicon intake (RDI) has not yet been set [13,14]. Considering the risk assessment of amorphous silicon dioxide as common silicon source (e.g. food additive E551), the safe upper intake level (UIL) may be estimated as 700 mg/day for adults, that is the equivalent to 12 mg silicon/kg bw/day for a 60 kg adult [15]. These numbers refer to the amorphous silicon dioxide form and only small amounts of silicon (as H4SiO4) are actually released in the gastrointestinal (GI) tract and subsequently absorbed in the systemic circulation. Due to lack of data, it is difficult to set a recommended upper intake level for silicon. Moreover, little information on the intake of dietary silicon by humans is available. A mean intake of daily silicon has been reported in Finland [16], (29 mg silicon/day) and in a typical British diet (20a50 mg silicon/day) [17-19]. This corresponds to 0.3-0.8 mg/silicon/kg bw/day for a 60 kg person. These data are in the same range as the estimated mean intakes of silicon in the USA (30 and 33 mg silicon/day in men, and 24 and 25 mg silicon/day in women, respectively) [8]. Silicon intake decreases with age to less than 20 mg silicon/day (18.6 A+/- 4.6 mg silicon/day for elderly British woman in an unrelated randomised controlled intervention study) [20]. Generally, silicon is abundantly present in foods derived from plants such as: cereals, oats, barley, white wheat flour, and polished rice. In contrast, silicon levels are lower in animal foods including meat or dairy products. Furthermore, silicon is present in drinking waters, mineral waters, and in beer as well [17]. However, Jugdaohsingh et al. [21] raised some doubt on utilisation of silicon from drinking water in an animal rat study as no significant differences were found in the silicon bone concentration when the drinking water was supplemented with silicon in the ortho-silicic acid form. Indeed, the major sources of silicon in the typical Western hemisphere diet comes from cereals (30%), followed by fruits, beverages and vegetables, which altogether comprise around 75% of total silicon intake [20]. Even though plant food contains high levels of silicon, its bioavailability from these sources is questionable, due to poor solubility of actual silicon forms present in these foods [18,19,22]. Efficient absorption in the GI tract would require their breakdown to soluble species such as ortho-silicic acid, present in drinking and mineral waters in the range of 2 to 5 mg silicon/L [23] and in beer ranging from 9 to 39 mg silicon/L [18,24]. Absorption studies indicate that the ortho-silicic acid is a main readily bioavailable source of silicon for humans, whereas its higher polymers are not of significant absorbability [25]. In a placebo-controlled study on eight volunteers, Jugdaohsingh et al. [25] showed that 53% of administered ortho-silicic acid is excreted in the urine, whereas the ingestion of polymeric silicic acid causes only a marginal increase of silicon in the urine. This result substantiates the statement that polymeric silicic acids and amorphous silicon dioxide are of poor bioavailability. Besides the ortho-silicic acid, water soluble silicates are bioavailable silicon forms as well. For instance, pharmaceutically acceptable alkali metals silicates (M2SiO3; M= Na, K) in adequately diluted aqueous solutions, release ortho-silicic acid (H4SiO4) upon contact with stomach hydrochloric acid (HCl). Popplewell et al. [26] employed a tracer dose of radiolabelled ammonium silicate to measure total uptake and urine excretion. Their results revealed that 36% of ingested dose was absorbed and completely excreted in urine within 48h. However, elimination occurred in two steps where the major dose (90%) has been excreted within the first 2.7 hours. They suggested that excess silicon is eliminated from the body through two distinct processes, differing significantly in the duration. The aslower processa is thought to include the intracellular uptake and release of silicon, whilst the afaster processa probably includes retention of silicon in the extracellular fluids [26]. These data report on increased silicon levels in serum upon consumption of silicon-rich food [7,27], showing that at least some silicon is available from food as well. Indeed, selective silicon deprivation in rats showed a significant drop of urinary silicon excretion and fasting silicon serum concentration, suggesting that the rats actively regulate silicon levels via urinary conservation, perhaps through renal re-absorption [21]. Most of silicon present in the serum is filtered by the kidney [7,28] suggesting the kidney as its major excretion route; silicon levels in serum correlate with those in urine. However, it is still not clear how and if the body can efficiently retain adequate doses of silicon. In concentrated solutions, ortho-silicic acid (H4SiO4) has to be stabilized to avoid its polymerization into poly-silicic acids and eventually into silica gel, resulting in a decreased silicon bioavailability. This issue has been solved in the field of pharmaceutical technology by use of choline chloride in aqueous glycerol solution. This resulted in development of a liquid formulation known as choline-stabilized ortho-silicic acid (ch-OSA). Choline chloride-stabilized ortho-silicic acid is not a new chemical entity of ortho-silicic acid, but a complex of H4SiO4 and choline chloride formed by several possible hydrogen bonds between these two compounds. Subsequently, from the standpoint of nutrition and pharmacology, the effects of ch-OSA must involve effects of both H4SiO4 and choline chloride rather than a new chemical entity. Due to a possible impact of choline chloride on the chemical stability of H4SiO4, certain specific biological effects different from those of a pure ortho-silicic acid or its immediate releasing compounds (e.g. sodium silicate), must be taken in account. Ch-OSA has been approved for human consumption and is known to be non-toxic. Its lethal doses (LD) exceed 5000 mg/kg bw in humans [29] and 6640 mg/kg bw in animals [30]. The ch-OSA represents the most bioavailable source of silicon [22,29]. Moreover, in a randomized placebo-controlled study [29], the bioavailability of ch-OSA during maternal transfer to the offspring was investigated in a supplementation study with pigs. The authors correlated significantly higher silicon concentrations in the serum of weanling piglets from supplemented sows and maternal transfer of absorbed silicon between sows and their offspring during lactation with high bioavailability of silicon from ch-OSA. Importantly, highly bioavailable silicon from ch-OSA did not altered calcium, phosphorus and magnesium levels in blood. Therapeutic and biological effects of ortho-silicic acid and certain ortho-silicic acid-releasing compounds It was reported that silicon is connected with bone mineralization and osteoporosis [31], collagen synthesis and ageing of skin [11], condition of hair and nails [32], atherosclerosis [33,34], Alzheimer disease [9,35,36], as well as with other biological effects and disorders. Trace minerals are known to generally play a vital role in the human body homeostasis [37] and the serum levels of silicon are similar to other trace elements, i.e. of iron, copper, and zinc [38]. Silicon is excreted through the urine in similar orders of magnitude as calcium. Some researches claim that silicon does not act as a protein-bounding element in plasma and is believed to exist almost entirely as un-dissociated monomeric ortho-silicic acid [28]. While early analyses showed that serum contains 50a60 I1/4g silicon/dL [38,39], more recent analyses indicate that human serum contains 11a25 I1/4g silicon/dL, or levels ranging between 24 and 31 I1/4g/dL (8.5 and 11.1 I1/4mol/L), detected by absorption spectrometry in large population groups [40]. Interestingly, pregnant women had very low serum silicon concentrations (3.3-4.3 I1/4g/dL) in comparison with infants that have high concentrations between 34 and 69 I1/4g/dL [27,41]. Moreover, silicon concentrations in serum showed a statistically significant age and sex dependency, as it seems that silicon concentrations decrease with age, especially in woman [40]. Biological importance of silicon might be analysed in the context of its bio-distribution in the body. For example, the highest silicon concentration has been measured in connective tissues, especially in the aorta, tracheas, bone, and skin. Low levels of silicon in the form of ortho-silicic acid [42-44] may be found in liver, heart, muscle, and lung [45]. It is therefore plausible to assume that observed decrease of silicon concentration in the ageing population may be linked to several degenerative disorders, including atherosclerosis. Supplementation of the regular diet with bioavailable forms of silicon may therefore have a therapeutic potential including prevention of degenerative processes. Several experiments have already confirmed this hypothesis. For example, in a controlled animal study, spontaneously hypertensive rats had lower blood pressure upon supplementation with soluble silicon [44], whilst silicon deficiency in animals has been found to be connected with bone defects and impaired synthesis of connective tissue compounds, such as collagen and glycosaminoglycans [46-48]. It is therefore reasonable to assume that silicon deficiency or lower bioavailability may be linked to problems with bone structure and collagen production. Moreover, silicon was shown to be uniquely localized in active growth areas in young bones of animals where a close relationship between silicon concentration and the degree of mineralization has been assessed [46,49]. Studies confirmed the essential role of silicon in the growth and skeletal development of chicks that during silicon deprivation showed significantly retarded skeletal development [50]. Experimental silicon deprivation in rats [51-53] and chicks [46,47] demonstrated striking effects on skeletal growth and bone metabolism as well. On the other hand, the controlled animal study of Jugdaohsingh et al. [21] showed no profound effects of a silicon-deficient diet on the bone growth and skeletal development in rats. Silicon concentrations in the tibia and soft tissues did not differ from those in rats on a silicon-deficient diet where the silicon was supplemented in drinking water. Nevertheless, silicon levels in tibia were much lower compared to the reference group fed by a silicon rich diet. Body and bone lengths were also found to be lower in comparison with the reference group, while reduction in bone growth plate thickness was found in silicon deprived rats [21]. Moreover, Reffit et al. [54] found that ortho-silicic acid stimulates collagen type 1 synthesis in human osteoblast-like cells and skin fibroblasts and enhances osteoblastic differentiation in the MG-63 cells in vitro. Ortho-silicic acid did not alter collagen type 1 gene expression, but it modulated the activity of prolyl hydroxylase, an enzyme involved in the production of collagen [55]. Similarly, SchA1/4tze et al. [56] reported that the zeolite A stimulated DNA synthesis in osteoblasts and inhibited osteoclast-mediated bone resorption in vitro. This is probably attributable to the ortho-silicic acid-releasing property of zeolite A. The mechanism underlying observed biological effects of silicon may probably be ascribed to its interrelationships with other elements present in the body such as molybdenum [57] aluminium [9,35,58,59], and calcium [46,49,50]. For instance, it was proven that silicon levels are strongly affected by molybdenum intake, and vice versa[59]. Furthermore, silicon accelerates the rate of bone mineralization and calcification as shown in controlled animal studies, in a similar manner that was demonstrated for vitamin D [11,50]. It is well known that vitamin D increases the rate of bone mineralization and bone formation [60], and that its deficiency leads to less mature bone development. Vitamin D is known to be important in calcium metabolism, but silicon-deficient cockerelsa skulls in a controlled animal study showed lower calcification and collagen levels irrespective of the vitamin D dietary levels suggesting a vitamin D-independent mechanism of action [61]. Jugdaohsingh et al. [21] found that silicon supplementation in drinking water did not significantly altered silicon concentrations in bones and suggested that some other nutritional co-factor is required for maximal silicon uptake into bone and that this co-factor was absent in rats fed with a low-silicon diet compared to the reference group fed by a silicon-rich diet. They suggested vitamin K as such co-factor, which is important in bone mineralisation through carboxylation of osteocalcin, and whose deficiency might influence incorporation of minerals such as silicon in the bones. **Osteoporosis**Osteoporosis is among leading causes of morbidity and mortality worldwide [62]. It is defined as a progressive skeletal disorder, characterised by low bone mass (osteopenia) and micro-architectural deterioration [63]. Interestingly, the administration of silicon in a controlled clinical study induced a significant increase in femoral bone mineral density in osteoporotic women [31]. Direct relationship between silicon content and bone formation has been shown by Moukarzel et al. [64]. They found a correlation between decreased silicon concentrations in total parenterally fed infants with a decreased bone mineral content. This was the first observation of a possible dietary deficiency of silicon in humans. A randomized controlled animal study on aged ovariectomized rats revealed that long-term preventive treatment with ch-OSA prevented partial femoral bone loss and had a positive effect on the bone turnover [65]. Dietary silicon is associated with postmenopausal bone turnover and bone mineral density at the women's age when the risk of osteoporosis increases. Moreover, in a cohort study on 3198 middle-aged woman (50a62 years) it was shown that silicon interacts with the oestrogen status on bone mineral density, suggesting that oestrogen status is important for the silicon metabolism in bone health [66]. **Skin and hair**Typical sign of ageing skin is fall off of silicon and hyaluronic acid levels in connective tissues. This results in loss of moisture and elasticity in the skin. Appearance of hair and nails can also be affected by lower silicon levels, since they are basically composed of keratin proteins. As previously discussed, ortho-silicic acid may stimulate collagen production and connective tissue function and repair. For example, Barel et al. [67] conducted experiments on females, aged between 40a65 years, with clear clinical signs of photo-ageing of facial skin. Their randomized double-blinded placebo-controlled study illustrates positive effects of ch-OSA taken as an oral supplement on skin micro relief and skin anisotropy in woman with photo-aged skin. Skin roughness and the difference in longitudinal and lateral shear propagation time decreased in the ch-OSA group, suggesting improvement in isotropy of the skin. In addition, ch-OSA intake positively affected the brittleness of hair and nails. Oral supplementation with ch-OSA had positive effects on hair morphology and tensile strengths, as shown in a randomized placebo-controlled double blind study by Wickett et al. [68]. **Alzheimer disease**Aluminium (as Al3+ ion) is a well-known neurotoxin. Aluminium salts may accelerate oxidative damage of biomolecules. Importantly, it has been detected in neurons bearing neurofibrillary tangles in Alzheimer's and Parkinson's disease with dementia as shown in controlled studies [69,70]. Amorphous aluminosilicates have been found at the core of senile plaques in Alzheimer's disease [69,71], and have consequently been implicated as one of the possible causal factors that contribute to Alzheimeras disease. Since aluminosilicates are water insoluble compounds, the transport path to the brain is still not well understood. By reducing the bioavailability of aluminium, it may be possible to limit its neurotoxicity. Consumption of moderately high amounts of beer in humans and ortho-silicic acid in animals has shown to reduce aluminium uptake from the digestive tract and slow down the accumulation of this metal in the brain tissue [36,72]. Silicic acid has also been found to induce down-regulation of endogenous antioxidant enzymes associated with aluminium administration and to normalize tumour necrosis factor alpha (TNFI+/-) mRNA expression [35]. Although the effect of silicic acid on aluminium absorption and excretion from human body produced conflicting results so far as shown in an open-label clinical study [7], in a controlled clinical study it was shown that silicic acid substantially reduces aluminium bioavailability to humans [73]. In fact, it was already found that silicon reduces the aluminium toxicity and absorption in some plants and animals that belong to different biological systems [74-76]. This is possible as silicon competes with aluminium in biological systems such as fresh water, as suggested by Birchall and Chappell study perfomed on the geochemical ground [77], and later confirmed by Taylor et al. in randomized double blind study [78]. They found that soft water contains less silicic acid and more aluminium, while hard waters contain more silicic acid and less aluminium. Removal of aluminium from the body and its reduced absorption by simultaneous administration of silicic acid was tested and proven by Exley et al. in controlled clinical study [59]. They showed reduced urinary excretion of aluminium along with unaltered urinary excretion of trace elements such as iron in persons to whom silicic acid-rich mineral water was administered. Moreover, they documented that regular drinking of a silicon-rich mineral water during a period of 3 months significantly reduced the body burden of aluminium. Similar results were obtained by Davenward et al. [79] who showed that silicon-rich mineral waters can be used as a non-invasive method to reduce the body burden of aluminium in both Alzheimer's patients and control group by facilitating the removal of aluminium via the urine without any concomitant effect. They also showed clinically relevant improvements of cognitive performances in at least 3 out of 15 individuals with Alzheimer disease. This implies a possible use of ortho-silicic acid as long-term non-invasive therapy for reduction of aluminium in Alzheimer's disease patients. The mechanism through which aluminium bioavailability reduction occurs involves interaction between aluminium species and ortho-silicic acid where highly insoluble hydroxyaluminosilicates (HAS) forms are produced [77,80]. This process makes aluminium unavailable for absorption. **Immunostimulatory effects**Quartz as a form of crystalline silicon dioxide has been connected with severe negative biological effects. However, in controlled studies on mouse and rats it was shown that sub-chronic and short-term exposure to this compound can actually have beneficial effects on respiratory defence mechanisms by stimulating immune system through the increase of neutrophils, T lymphocytes and NK cells. It also activates phagocytes and consequently additional ROS production [81-83] which can help the pulmonary clearance of infectious agents. In rats, crystalline silica caused proliferation and activation of CD8+ T cells and, to a lesser amount, of CD4+ T cells. Recently, an aanionic alkali mineral complexa BarodonA(r) has shown immunostimulatory effects in horses [84], pigs [85] and other animals. BarodonA(r) is a mixture of sodium silicate (M2SiO3, M= Na,K) and certain metal salts in an alkaline solution (pH= 13.5), where sodium-silicate (sodium water glass) represents 60% of the total content. In a placebo-controlled experiment in pigs, the immunostimulatory effect of BarodonA(r) was assessed by measurement of proliferation and activation of porcine immune cells, especially CD4+ CD8+ double-positive (dpp) T lymphocytes in peripheral blood and in the secondary lymphoid organ [85]. As this type of T lymphocyte cells are characterized by a specific memory cell marker CD29, they may play a role during activation of secondary immune responses as shown in a cross-sectional and longitudinal study on pigs [86]. Moreover, BarodonA(r) acted mainly on the lymphoid organs, implying a role in antigenic stimulation of immune tissues [85]. BarodonA(r) induced increased levels of MHC-II lymphocytes and non-T/non-B (N) cells as well along with increased stimulatory mitogen activity including the activity of PHA, concanavalin A, and pokeweed mitogen [85,87]. In a placebo-controlled experiment on pigs, it was shown that this mineral complex exerts an adjuvant effect with hog cholera and Actinobacillus pleuropneumoniae vaccines by increasing the antibody titres and immune cell proportions [88]. Moreover, BarodonA(r) showed nonspecific immunostimulating effects in racing horses and higher phagocytic activity against Staphylococcus equi subsp. equi and Staphylococcus aureus as well in a controlled study [84]. Administration of BarodonA(r) in horse herds reduced many clinical complications, including stress-induced respiratory disease, suggesting activation of immune cell populations similarly to the treatment with inactivated Propionibacterium acnes[89,90]. The exact mechanism of BarodonA(r) immunostimulatory effect is not known, although it has been suggested that sodium silicate, the main mineral ingredient, might be responsible for the observed immune-enhancing properties. Indeed, sodium silicate is known to decompose quantitatively into bioavailable ortho-silicic acid (H4SiO4) in the acidic gastric juice (HCl), and as such being absorbed in the body. In this manner, presumably all observed pharmacological effects of BarodonA(r) are actually originated from the ortho-silicic acid. Pure sodium metasilicate (Na2SiO3) also bears immunostimulatory effects and acts as a potent mitochondria activator [91]. Dietary silicon in the form of sodium metasilicate activates formation of ammonia by elevating mitochondrial oxygen utilisation as shown in a controlled animal experiment [91]. These findings further corroborate the hypothesis that sodium silicate might be responsible for immunostimulatory effects of BarodonA(r). Once again, the pharmacologically active species was ortho-silicic acid released upon the action of stomach hydrochlorid acid on sodium metasilicate. Zeolites are a class of aluminosilicates of general formula (Mn+)x/n[(AlO2)x(SiO2)yA*mH2O, wherein M represents a positively charged metal ion such as sodium (Na+), potassium (K+), magnesium (Mg2+), or calcium (Ca2+). Zeolites are crystalline aluminosilicates with open 3D framework structures built of SiO4 and AlO4 tetrahedra linked to each other by sharing all the oxygen atoms to form regular intra-crystalline cavities and channels of molecular dimensions [92]. The positively charged metal ions (e.g. Na+, K+, Ca2+, Mg2+) are positioned in these cavities of aluminosilicate skeleton which are termed as micro- (2a20 A), meso- (20a50 A), and macro-(50a100 A) -pores. These ions are readily exchangeable in contact with aqueous solution of other positively charged ions (e.g. heavy metal ions like Hg2+). This structural characteristic of zeolites is the base of their ion (cation)-exchange property [93]. At present, 191 unique zeolite frameworks have been identified [94], while over 40 naturally occurring zeolite frameworks have been described. Zeolites have been widely employed in chemical and food industries, agriculture, and environmental technologies as adsorbents, absorbents, adsorbent filter-aids, ion-exchangers, catalysts, active cosmetic and pharmaceutical ingredients, soil improvers, etc. [95-103]. Besides, zeolites exhibit a number of interesting biological activities [5,104,105] (Figure a(Figure4).4). For example, nontoxic natural zeolite clinoptilolite affects tumour cells proliferation in vitro and might act as an adjuvant in cancer therapy [105]. Katic et al. [106] confirmed that clinoptilolite influences cell viability, cell division, and cellular stress response that results in antiproliferative effect and apoptosis induction in vitro. Obtained results demonstrated that clinoptilolite biological effect on tumour cells growth inhibition might be a consequence of adsorptive and ion-exchange characteristics that cause adsorption of some serum components by clinoptilolite [106]. Similarly, clinoptilolite showed antiviral effects in vitro and a potential in antiviral therapy either for local skin application against herpesvirus infections or oral treatment of adenovirus or enterovirus infections [107]. The antiviral mechanism is probably non-specific and is based on adsorption of viral particles on external cavities at the clinoptilolite surface rather than a consequence of ion-exchange properties. Each zeolite particle acts like a large inorganic molecule and acts as a molecular sieve with a potential in molecular medicine in molecular medicine. Their pores are indeed, rather small (less than 2 nm to 50 nm) [108], and these structural similarities between the cages of zeolites and binding sites of enzymes resulted in development of zeolite structures that mimic enzyme functions [108], e.g. haemoglobin, cytochrome P450 or iron-sulphur proteins [109]. Important data on biological zeolites fate (Figure a(Figure5)5) and effects in vivo have been widely reported so far in the scientific literature. For example, it was shown that zeolites bear detoxifying and decontaminant properties when added to animal diets, reducing levels of heavy metals (e.g. lead, mercury, and cadmium) and various organic pollutants, i.e. radionuclides (Figure a(Figure6)6) and antibiotics [108]. Furthermore, zeolites have been successfully utilized for haemodialysis, for cartridges in haemoperfusions, for wound healing, and surgical incisions [108]. For instance, QuikClot and Zeomic formulations are already being marketed for haemorrhage control [110] and dental treatment [5], respectively. The fate of isotope labelled activated clinoptilolite-zeolite in the gastro-intestinal tract (by courtesy from Application of natural zeolites in medicine and cosmetology a ZEOMEDCOS.SWB, Baku-London, 2010). Several toxicological studies proved that certain natural zeolite, e.g. clinoptiolite are non-toxic and completely safe for use in human and veterinary medicine [105]. In vitro and in vivo controlled animal studies have shown that clinoptilolite is an inert substance that may cause, in some instances, only moderate but not progressive fibrosis or mesothelioma [111]. This effect might be attributed to side-substances present in natural zeolites, e.g. silica or clay aluminosilicates [112]. It should be also stated that some zeolites might be extremely dangerous for human health and exert negative biological effects. For example, erionite, a fibrous type of natural zeolite, causes a high incidence of mesotheliomas and fibrosis in humans and experimental animals [113]. Animal studies have also shown the possibility of zeolite A (sodium aluminosilicate) as a viable source of silicon [4,6,114]. The latter is one of known zeolites that breaks down into bioavailable ortho-silicic acid (H4SiO4) in the digestive system. This property arises from the structure of zeolite A which is characterized by the same number of aluminium and silicon atoms in zeolite A [115]. Zeolite A is hydrolysed at low pH (stomach hydrochloric acid) into ortho-silicic acid (H4SiO4) and aluminium ions (Al3+). These are combined back to the amorphous aluminosilicate. Such process readily provides additional source of bioavailable silicon to the organism [114,116]. Indeed, randomized placebo-controlled studies on dogs [114] proved that silicon is absorbed upon oral administration of zeolite A. Comparable results have been obtained in a randomized placebo-controlled research on horses as well [6]. Addition of zeolite A to the diet of young racing quarter horses have resulted in decreased skeletal injury rates and better training performance [117]. However, increased bone formation was found in randomized controlled studies on broodmare horses [118], but not in yearling horses [119]. Food supplementation with zeolite A in calves showed no changes in bone architecture or mechanical properties [120]. However, in a controlled study Turner et al. [120] showed increased aluminium content in the bone and cartilage of zeolite A-fed calves which is an important safety issue for the zeolite A therapeutic usage. **Conclusion**In conclusion, we believe that ortho-silicic acid (H4SiO4) might be a prominent therapeutic agent in humans. Some potential therapeutic and biological effects on bone formation and bone density, Alzheimer disease, immunodeficiency, skin, hair, and nails condition, as well as on tumour growth, have already been documented and are critically discussed in the presented paper. Acid forms of ortho-silicic acid include: choline-chloride-stabilized ortho-silicic acid (ch-OSA) as a specific pharmaceutical formulation of H4SiO4, simple water soluble silicate salts such as sodium silicate (E550; Na2SiO3) or potassium silicate (E560; K2SiO3), and certain water-insoluble forms that, upon contact with stomach juice (HCl), release small, but biologically significant amounts of ortho-silicic acid. The latter involves: colloidal silicic acid (hydrated silica gel), amorphous silicon dioxide (E551), certain types of zeolites such as zeolite A (sodium aluminosilicate, E554; potassium aluminosilicate, E555; calcium aluminosilicate, E556), and the natural zeolite clinoptilolite. However, for some of the above-proposed therapeutic perspectives of both ortho-silicic acid and ortho-silicic acid -releasing derivatives, additional insights into biological mechanisms of action and larger studies on both animals and humans are required. **References** Greenwood NN, Earnshaw A. 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Biol Trace Elem Res. 2008;121(2):149a159. doi: 10.1007/s12011-007-8040-4. --- [**https://en.wikipedia.org/wiki/Orthosilicic\_acid**](https://en.wikipedia.org/wiki/Orthosilicic_acid) **Orthosilicic acid** IUPAC name Silicic acid[1] Other names Orthosilicic acid Identifiers CAS Number 10193-36-9 check CHEBI:26675 check ChemSpider 14236 check ECHA InfoCard 100.030.421 EC Number 233-477-0 Gmelin Reference 2009 PubChem CID 14942 UNII 623B93YABH check CompTox Dashboard (EPA) DTXSID5058721 Chemical formula Si(OH)4 Molar mass 96.113 gA*mola1 Orthosilicic acid (/EEErI,EsEaElEasEak/) is an inorganic compound with the formula Si(OH)4. Although rarely observed, it is the key compound of silica and silicates and the precursor to other silicic acids [H2xSiOx+2]n. Silicic acids play important roles in biomineralization and technology.[2][3][4] **Isolation**Structure of Si(OH)4 stabilized by two chloride anions. Typically orthosilicic acid is assumed to be a product of the hydrolysis of its esters, Si(OR)4, where R stands for organyl group, as is practiced in sol-gel syntheses.[2] These conditions are however too vigorous to allow isolation of the parent acid. Orthosilicic acid can be produced by Pd-catalyzed hydrogenolysis of tetrabenzoxysilicon:[5] Si(OCH2Ph)4 + 4 H2 a Si(OH)4 + 4 PhCH3 The acid was crystallized from a solution of dimethylacetamide and tetrabutylammonium chloride. As established by X-ray crystallography, the chloride anions interact with the acid via hydrogen bonds. Otherwise, the structure consists of the expected tetrahedral silicon center. **Reactions**Chemical structure of cyclo-tetrasilicic acid. Silicic acid readily condenses to give "higher" silicic acids including disilicic (pyrosilicic) and cyclo-tetrasilicic acid, (aOaSi(OH)2a)4:[5] 2 Si(OH)4 a O(Si(OH)3)2 + H2O 4 Si(OH)4 a (aOaSi(OH)2a)4 + 4 H2O These derivatives have also been characterized crystallographically. **Orthosilicic acid in plants**Silicon has been explored as a nutrient for plant growth, with silica comprising up to 10% of plant weight on a dry matter basis.[6] Orthosilicic acid is of particular interest as it is thought to be the form in which plants uptake silicon from the soil,[7][8] before being deposited as phytoliths throughout the plant, leading to research in the application of orthosilicic acid through foliar sprays to supplement plant growth.[9] Studies have demonstrated that foliar application of stabilized orthosilicic acid can alleviate abiotic stressors such as drought,[10][11] heavy metal toxicity,[12][13] and salinity,[14] resulting in increased yields.[15] Additionally, applications of orthosilicic acid have been demonstrated to reduce fungal infections and disease in plants,[16] suggesting the possibility of using stabilized orthosilicic acid as an alternative or complement to existing disease control measures. The mechanisms by which orthosilicic acid alleviates abiotic stress and controls diseases is not well understood; current theories advanced include the activation of plant defense reactions[17] and the precipitation of silica in the apoplast of the plant.[18] --- [**https://impellobio.com/blogs/inoculants/how-silicic-acid-promotes-plant-growth-and-stress-resilience**](https://impellobio.com/blogs/inoculants/how-silicic-acid-promotes-plant-growth-and-stress-resilience) **How Silicic Acid Promotes Plant Growth and Stress Resilience** --- [**https://www.onlymyhealth.com/orthosilicic-acid-skincare-benefits-know-how-this-compound-is-second-to-oxygen-for-the-skin-1618287863**](https://www.onlymyhealth.com/orthosilicic-acid-skincare-benefits-know-how-this-compound-is-second-to-oxygen-for-the-skin-1618287863) **Orthosilicic Acid Skincare Benefits: Know How This Compound Is Second To aOxygena For The Skin** the benefits of ortho-silicic acid: inhibits the aging process in tissues can help maintain a youthful skin tone and increase collagen levels stimulates cell metabolism and cell formation, has mild disinfecting properties, and is an anti-inflammatory helps strengthen connective tissues Aids in articular cartilage connective tissue Helps to retain moisture in the tissue under the skin which can help prevent wrinkles --- **STABILIZED SOLUTION OF ORTHO-SILICIC ACID BASED ON SALICYLIC ACID AS EFFECTIVE INHIBITOR OF ITS POLYMERIZATION, ITS PREPARATION AND USE** **WO2012032364** ****[ [PDF](WO2012032364A1.pdf) ]**** The present invention discloses a formulation that serves as a highly bioavailable silicon (Si) source consisting of: (i) ortho-silicic acid (H4SiO4), from 0.01-8% w/w; (ii) salicylic acid (1), from 1-2 molar equivalents to H4SiO4; (iii) pharmaceutically acceptable acid, from 0.1-4 molar equivalents to H4SiO4; or pharmaceutically acceptable base, in amounts of 2 molar equivalents to salicylic acid (1); and (iv) diluent, selected from the group consisting of: purified water, 1, 2-propylene glycol, glycerol, ethanol, or their mixtures, in amounts of up to 100% w/w of the formulation. The present invention discloses the preparation and the use of the formulation that provides all known positive therapeutic effects of ortho-silicic and salicylic acid in human and animals, and benefits of use for plants. The present invention solves technical problem of effective stabilization of ortho-silicic acid (H Si04) , which is used as nutritional and therapeutic source of highly bioavailable silicon Formulation of the product is in the form of a solution comprising: (i) ortho-silicic acid (H4Si04) , from 0.01-8% w/w; (ii) salicylic acid (1) , from 1-2 molar equivalents to H4Si04; (iii) pharmaceutically acceptable acid, from 0.1-4 molar equivalents to H4Si04; or pharmaceutically acceptable base, in amounts of 2 molar equivalents to salicylic acid (1) ; and (iv) diluent, selected from the group consisting of: purified water, 1, 2-propylene glycol, glycerol, ethanol, or their mixtures, in amounts of up to 100% w/w of the formulation. The use of the formulation provides all positive therapeutic effects of silicon in human, animal or plant organism. Prior art Silicon (Si) is important biogenic microelement which exhibits several important roles in human and animal organism: (i) helps resorption of calcium and takes part in its metabolism; stimulates osteoblasts; stimulates bone mineralization; in traumatic cases, influences faster bone healing; helps in prevention of osteoporosis [E. M. Carlisle: A requirement for silicon for bone growth in culture, Fed. Proc. 37 (1978) 1123; E. M . Carlisle: A relation 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) takes part in the structure of connective tissue and formation of functional tertiary structure of building proteins of soft organs such as liver, lung, and brain; takes part in structure of arterial, vein, and capillary walls, increases elasticity and hardness of blood vessels, decreases 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 cross-linking agent for glucosaminoglycans and mucopolysaccharides in joints, ligaments, and sinovial fluid [ . 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. Med. Res. 25(1997) 206]; (iv) stimulates immune system [A. Schiano, F. Eisinger, P. Detolle: Silicium, tissu osseux et immunite, Revue du Rhumatisme 46 (1979) 483] ; (v) exhibits antiinflammatory effect; e.g. helps at various inflammatory diseases like rheumatoid arthritis, muscle inflammation, skin disorders such as psoriasis, seborrheic dermatitis, neurodermitis, skin irritations, accelerates wound healing, soothes decubitus and other skin disorderds and diseases [A. Lassus: Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females, J. Int. Med. Res. 21 (1993) 209; A. Lassus: Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy and onychopathy. A pilot study. J. Int. Med. Res. 25 (1997) 206]; (vi) in oligomeric form, silicic acid inhibits resorption of aluminum (Al<3+>) from gastrointestinal tract, and beside antioxidative action, preventively influences on development of neurodegenerative diseases like Alzheimer disease [J. D. Birchall, J. S. Chappell: The chemistry of aluminium and silicon in relation to Alzheimer's disease, Clin. Chem. 34 (1980) 265; R. Jugdaohsingh : Soluble silica and aluminium 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 aluminium absorption in human, Am. J. Clin. Nutr. 71 (2000) 944; D. . Reffitt, R. Jugdaohsingh, R. P. H. Thompson: Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion, J. Inorg. Biochem. 76 (1999) 141] ; (vii) stimulates biosynthesis of skin building proteins: collagen and elastin [C. D. Seaborn, F. H. Nielsen: Silicon deprivation decreases colagen 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 stabilised 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]; and (viii) stimulates 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. Med. Res. 21 (1993) 209] . At plants, silicon shows the following effects [H. A. Currie, C. C. Perry: Silica in Plants: Biological, Biochemical and Chemical Studies, Ann. Botany 100 (2007) 1383-1389] : (i) stimulates photosynthesis process and enhances utility of nutrients, what resuts in increased crop yields; (ii) improves water management, thus increases resistance to stress events like drought; and (iii) enhances resistance to attacks of insects and fungal diseases. Biologically available form of silicon is ortho-silicic acid (H Si04) . However, in literature, there is described that too large doses of silicic acid can cause damages of liver and kidney which is the most important organ for excretion of silicon [J. W. Dobbie, M. J. Smith: Silicate nephrotoxicity in the experimental animal: the missing factor in analgesic nephropathy, Scotish Med. J. 27 (1982) 10] . A person skilled in the art knows that silicic acid in its monomeric form, ortho-form (H4Si04) , is not stable and at higher concentration, but undergoes polymerization with formation of dimer (H6Si207) , trimer (H8Si3O10) , and linear chain oligomers (SI) which are still water soluble. Linear chain polymers of silicic acid (SI) undergo further polymerization yielding tridimensional, branched polymers (S2) which are not of significant water solubility but form opalescent gel. The polymerization process proceeds further with formation of hydratized silicon dioxide (silica gel; Si02'xH20) . The course of polymerization of silicic acid is given in Scheme 1 (at the end of the specification) . Beside monomeric ortho-silicic acid (HSi04) , biologically available forms are also its lower oligomers soluble in water, due to partial hydrolysis that release starting HSi0 (oligomerization is reversible) . In other words, under certain conditions of concentration, the equilibrium between ortho-silicic acid and its lower oligomers is established. 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, as less as possible refined food (e.g. whole grain cereals), usual intakes of silicon in organism are sufficient. However, at use of highly refined and unhealthy food, silicon deficiencies occur quite often. Such conditions, with eventual other factors, often can cause development of diseases or disorders where silicon plays important role. Because of this reason, it is of a great importance development of stabilized form of silicic acid where its polymerization is inhibited and, in this way, lost its bioavailability. Such products can be used as effective food supplements or therapeutic agents at diseases and disorders caused by silicon deficiency. For application in pharmacy, cosmetics, and veterinary, only pharmaceutically acceptable forms of silicic acid can be employed. For use in agriculture, also, only non-toxic forms of silicic acid of high bioavailability can be applied. The most known product used as food supplement for silicon supplementation is aBioSil", 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 Al (2002), the holder is BioPharma Sciences B.V., Belgium] . Except choline chloride, in the patent literature there are mentioned also other stabilizers that prevent (inhibit) polymerization of ortho-silicic acid such as humectants like polyethylene glycol, polysorbates, plant gums, substituted cellulose, 1 , 2-propylene glycol, pectin, ethoxylated derivatives of higher fatty acids, acetylated or hydroxypropyl-derivatized starch, starch phosphate, urea, sorbitol, maltitol, vitamins [W. A. Kros, U.S. 2006/0178268 Al] , as well as proline, serine, lysine, arginine, glycine, their mixtures, polypeptides or protein hydrolyzates [V. Berghe, D. A. Richard, WO 2004/016551 Al (Bio Pharma Sciences B.V.) ] . Beside choline chloride-stabilized silicic acid, on the market exist various food supplements which contain silicon in the forms of amorphous or colloidal silicon dioxide (Si02) . However, 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 plant drugs like extracts of horsetail (Equisetum arvense) , nettle (Urtica dioica) , and some other plants. However, it is known that portions of soluble (and thus bioavailable) silicic acid from these healing plants usually do not exceed 1/10 of total amounts. All remained silicic acid is not soluble and, as such, not bioavailable [D. Kustrak: Pharmacognosy and phytopharmacy (in Croatian) Golden marketing-Tehnicka knjiga, Zagreb, Croatia (2005)]. In agriculture, silicon based products are used for only a few years. They are used for increasing resistance of plants to stress (at drought or hail) and against fungal diseases. It seems that they also pasively protect from insect attacks by forming thin hard barrier of silicon dioxide on the plant leaves. The most known product are those based on horsetail {Equisetum arvense) extract or finelly milled quartz sand (silicon dioxide; Si02) in organic, and solution of potassium silicate (30% K2Si03) in conventional agriculture (mainly at grape; e.g. aSil-Matrix" ) . These products are usually applied by foliar spraying. Salicylic acid (1) is a well known pharmaceutically active substance which, as such, or in forms of its derivatives (e.g. salicylamide, acetylsalicylic acid) , is widely used as antiinflammatoric, analgesic, and antipyretic for decades. At topical application in higher concentrations (>5%) acts as keratolytic (removes dead top skin layers) what is used both in medicine and cosmetic (peeling) . In lower concentrations (1-2%), it acts as keratoplastic . Beside this, exhibits topical microbiocidal action. Technical problem of production of improved product with effects of bioavailable silicon based on effective stabilization of ortho- silicic acid (H Si0 ) is solved by the present invention on a new [with salicylic acid (1) ] and significantly better way, as will be demonstrated in detailed description of the invention. **Detailed description of the invention**The present invention represents improved pharmaceutical, cosmetic, veterinary or agrochemical composition which is effective source of highly bioavailable silicon. The formulation is consisting of: (i) ortho-silicic acid (H4Si04), from 0.01-8% w/w; (ii) salicylic acid (1) ,from 1-2 molar equivalents to H Si04; (iii) pharmaceutically acceptable acid, from 0.1-4 molar equivalents to H Si04; or pharmaceutically acceptable base, in amounts of 2 molar equivalents to salicylic acid (1) ; and (iv) diluent, selected from the group consisting of: purified water, 1 , 2-propylene glycol, glycerol, ethanol, or their mixtures, in amounts of up to 100% w/w of the formulation. In the present formulation the following pharmaceutically acceptable acids can be used: hydrochloric (HC1) , sulfuric (H2S04) , nitric (HN03) , phosphoric (H3P04) , methanesulfonic (CH3SO3H) , benzenesulfonic (C6H5S03H) , salicylic ( 1 , 2-C6H4 (OH) COOH) or sulfosalicylic [C6H3(3- COOH) (4-OH)S03H] acid, mixtures of these acids, or other acids which are not of significant toxicity for human, animal, or plant organism. The use of salicylic acid as pharmaceutically acceptable acid represents the special case of the present invention, because then it is in the same time: (i) a stabilizer of ortho-silicic acid at pH values closed to neutral (and physiological) ; (ii) agent for acid-catalyzed hydrolysis of precursor or silicic acid ( PSA) ; and (iii) pH-regulating agent of the present formulation. Pharmaceutically acceptable base is selected from the group comprising sodium hydroxide (NaOH) , potassium hydroxide (KOH) , ammonium hydroxide (NH OH) , tetramethylammonium hydroxide [N(CH3)4OH], tetraethylammonium hydroxide [N (C2H5) 4OH] , mixtures of these bases, or other bases characterized by: (i) negliable toxicity to human, animal or plant organism; and (ii) which do not precipitate insoluble silicates in aqueous medium. Completely unexpectable, it was found that salicylic acid (1) acts as effective stabilizer of ortho-silicic acid (H Si0 ) at pH values closed to neutral. In this manner, it inhibits its polymerization into biologically unavailable polymers of silicic acid. Consequently increases its bioavailability after oral administration of the formulation from the present invention. The effect was found and studied on a model complex 2, disodium salicylate-HSi0 , prepared from sodium silicate (Na2Si03) and salicylic acid at molar ratio of 1:1. Chemically pure sodium silicate was prepared by base-catalyzed hydrolysis of tetraethyl orthosilicate [TEOS; Si(OC2H5)4] with sodium hydroxide (NaOH) . Hydrolysis reaction and formation of the complex 2 with salicylic acid is given in Scheme 2 (at the end of the specification) . Since pH values of solutions of complexes like compound 2 are in basic region, and are between 10-13, these are termed as abasic complexes of salicylic and ortho-silicic acid". The study of stabilizing effect of salicylic acid was carried out in conditions that are known to result in fast polymerization of ortho- silicic acid (H4Si0 ) , and these are at pH values close to neutral. At these conditions, pH= 6-7, relatively fast polymerization of HSi0 takes place with formation of its polymers what is accompanied with generation of opalescent gel. In more concentrated systems, the change from the phase of solution (which is, at the begining, clear and afterwards opalescent) to the moment of formation of (opalescent) gel is relatively fast, and can be used in analytical purpose for determination of gelling (polymerization) rate (time) of ortho-silicic acid (H4Si04) . The test solution was prepared by mixing equal volumes of the solution of compound 2 (sample solution) and 1.5M phosphate buffer pH= 4.5. The time required for conversion of thus prepared clear test solution until the formation of opalescent gel was determined. This time was called gelling or polymerization time (tG) . Longer gelling (tG) time means slower polymerization, this suggests on more stable complex. Beside the complex 2 from the present invention, as control probes, by the same manner the followings are studied: (i) sodium silicate solution (Na2Si03) as standard; (ii) solution of complex with choline chloride [ (CH3) 3N<+> (CH2CH2OH) CI<"> ] ; and (iii) solution of complex with L-serine (HOOCCH (NH2) CH2OH) ; which are described in the prior art as HSi04 stabilizers [S. R. Bronder: Stabilized orthosilicic acid comprising preparation and biological preparation, W095/21124 (1994)]. Results are given in Table 1. Table 1. Basic complexes of salicylic and ortho-silicic acid: Stabilizing effect of salicylic acid (1) on polymerization of ortho- silicic acid (HSi0 ) at pH= 6.5. Image available on "Original document" In all test solutions as diluent was employed distilled water, except otherwise noted. All solutions of complexes contained 6.5 w/w of ethanol which was generated as side-product of hydrolysis of tetraethyl orthosilicate (TEOS) . Stability tests were carried out by mixing 2 mL of each of sample solution or standard with 2 mL of 1.5M phosphate buffer of pH= 4.5; pH values of all solutions after mixing with the buffer were the same (pH= 6.5) . The time from the moment of mixing the sample solution and phosphate buffer (clear solution) until the formation of opalescent gel, expressed in minutes [min] . aRelative stability" is expressed as numerical parameter, coefficient, which describes stability of ortho-silicic acid in the given sample in comparison with the standard [pure solution of sodium silicate (Na2Si03) ] . It shows stabilizing or destabilizing effect on ortho-silicic acid, in other words on its polymerization (gelling) . This was prepared by addition of TEOS (1.2 mL; 1.12 g; 0.0054 mol) to a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 equiv.) in distilled water (6.00 g) with stirring during 6 h, and subsequent dilution with distilled water (7.44 g) up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si]. Samples are prepared by addition of 0.0054 mol of choline chloride (0.75 g) or L-serine (0.57 g) in hydrolyzed solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si]. The solution of the complex was prepared by addition of salicylic acid (0.75 g; 0.0054 mol) in previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS), with subsequent dilution with distilled water up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si]. Solutions are prepared by mixing previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS) and 2.25 g (15% w/w) or 6.00 g (40% w/w) of 1 , 2-propylene glycol with subsequent dilution with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si]. The solution of the complex was prepared by addition of salicylic acid (0.75 g; 0.0054 mol) to previously prepared solution of sodium silicate (6.00 g distilled water + 0.44 g NaOH + 1.2 mL TEOS) . Reaction mixture was stirred at room temperature during 1 h. Then, 1, 2-propilene glycol (2.25 g; 15% w/w) was added, and subsequently diluted with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si] . Solutions like those of the complex 2 are clear and colourless solutions, stable to the occurence of gelling at room temperature (17-25 A degC) , and at temperatures <30 A degC, during minimally 2 years. Alternatively, the formulation from the present invention can be prepared as complex with ortho-silicic acid (HSi04) with salicylic acid salts (like disodium salicylate) in molar ratio of 1:2. Beside basic complexes like compound 2, the formulation from the present invention can be prepared as stabilized solution of ortho- silicic acid (H4Si04) also in acidic medium, by the influence of one or more above-mentioned pharmaceutically acceptable acid (0.1-4 molar equivalents) in the presence of 1-2 molar equivalents of salicylic acid, calculated to H4Si0 . Complex of salicylic acid and ortho-silicic acid, compound 3, was prepared in situ, by phosphoric acid-catalyzed hydrolysis of tetraethyl orthosilicate (TEOS) in the presence of salicylic acid. The reaction is given in Scheme 3 (at the end of the specification) . Since pH values of solutions of the complexes like compound 3 are in acidic region, between 1-2.5, these are called aacidic complexes of salicylic and ortho-silicic acid". The study of stability of acidic complexes of salicylic and ortho- silicic acid (H4Si04) was performed with 1.32M phosphate buffer of pH= 7. As the control, complexes with choline chloride and L-serine, described in the prior art as stabilizers of H Si0 , were used. Results are given in Table 2. Table 2. Acidic complexes of salicylic and ortho-silicic acid: Stabilizing effect of salicylic acid (1) on polymerization of ortho- silicic acid (H4Si04) at pH= 6.5. In all test solutions, as diluent was used distilled water, except otherwise noted. All solutions contained 6.5% w/w of ethanol which was formed as side-product during hydrolysis of tetraethyl orthosilicate (TEOS) . Stability tests were performed by mixing 2 mL of each of sample solution with 2 mL of 1.32M phosphate buffer of pH= 7.0; pH values of all test solutions after mixing with buffer were the same (6.5) . The time from the moment of mixing the given sample solution and phosphate buffer (clear solution) until the formation of opalescent gel, expressed in minutes [min] . c aRelative stability" is expressed as numerical parameter, coefficient, which describes stability of ortho-silicic acid in the given sample in comparison with the standard [pure solution of silicic acid (HSi04) ] . It shows stabilizing or destabilizing effect on ortho-silicic acid, in other words on its polymerization (gelling) . d This was prepared by addition of TEOS (1.2 mL; 1.12 g; 0.0054 mol) to a solution of 85% phosphoric acid (0.2 mL; 0.34 g; 0.289 g H3P04; 0.00295 mol; 0.55 mol. equiv.) in distilled water (13.54 g) with stirring for 6 h [total wight 15.00 g; contains 150 mg (1% w/w) of Si] . e Samples are prepared by addition of 0.0054 mol of choline chloride (0.75 g) or L-serine (0.57 g) to a solution of ortho-silicic acid (H4Si04; 10.00 g destilirana voda + 1.2 mL TEOS + 0.2 mL 85% H3P04; 3 h-stirring / room temperature) with subsequent dilution with distilled water, up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si] . f Samples are prepared by addition of salicylic acid (0.75 g; 0.0054 mol) to a solution of tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) in 1 , 2-propylene glycol (10.00 g) . Distilled water (0.4 mL; 0.022 mol; 4.1 mol. equiv.) was added to the reaction mixture, and stirred at room temperature during 5 h. Then, 1,2- propylene glycol was added to the solution up to the total weight of 15.00 g [contains 150 mg (1% w/w) of Si]. To the solution from the Experiment 5, also 85% phosphoric acid (0.2 mL) was added. From thus obtained results, it was concluded that choline chloride, which is in the literature described as astabilizer" of ortho- silicic acid, actually acts as catalyst of its polymerization under physiological conditions where pH value is close to 7. Solutions which contained choline chloride showed 5-10x faster polymerization process accompanied with formation of silica gel in comparison to the solution of the standard (Experiments 2; Table 1 and 2) . Choline chloride can be obviously considered as astabilizer" of silicic acid in a formulation with very low pH, lower than pH= 3, due to its property of adeep eutectic liquid" in mixture with polyols like glycerol. In fact, it is astabilizer" in technological sense (as excipient) which helps stabilization of final product, solution of H Si0 , providing long term shelf life of the product. However, in contrast to this, under physiological conditions, at pH values close to 7, it destabilizes ortho-silicic acid catalyzing its polymerization, and thus decreases their bioavailability. This finding is in accordance with literature data wherein it was described that bioavailability of choline chloride-stabilized ortho- silicic acid at oral administration is <50% [R. Jugdaohsingh : Silicon and bone health, J. Nutr. Health Aging 11 (2007) 99] . Additionally, amino acid serine, which is also described in the literature as stabilizer of ortho-silicic acid, does exhibit slight stabilizing effect, indeed. However, this effect is almost negliable because observed increase of gelling time was only 8-10% prolonged against that for the standard (Experiments 3; Tables 2 and 3) . In contrast, salicylic acid (1) exhibits significant effect of stabilization of ortho-silicic acid (H4Si04) where observed polymerization time was 2.2x longer (Experiments 4; Tables 2 and 3), what suggest on high stability of the complex H4Si04-salicylic acid (compound 3) . It was found that application of 1 , 2-propylene glycol as humectant which acts as auxiliary stabilizer, in accordance to the literature statements, does increase polymerization time of H Si04, indeed, for approx. 30% (Experiments 5 and 6; Table 1) . Determination of optimal weight percentage of 1 , 2-propylene glycol, where concentrations of 15% w/w (Experiment 5) and 40% w/w (Experiment 6) were studied, showed that the use of higher concentration fail to result in further positive effect on stability of H4Si04. In conclusion, optimal concentration of 1 , 2-propylene glycol in the formulation was 15% w/w. In continuation of the research, it was found a synergistic effect of 1 , 2-propylene glycol (in optimal concentration of 15% w/w) on the basic stabilizing effect of salicylic acid. The formulation of the present invention based on combination of salicylic acid (1 mol . equiv. to H4Si04) and 15% w/w of 1 , 2-propylene glycol showed . lx longer polymerization time than at the standard (Experiment 7; Table 1) . This result represents increase of almost 100% from the result obtained with the use of salicylic acid (Experiment 4; Table 1) as sole stabilizer. These results clearly suggest to those skilled in the art an unexpected additional synergistic effect on stabilization of ortho-silicic acid. By the use of a version of the formulation from the present invention with 1 , 2-propylene glycol as sole diluent, this additional synergistic effect onto basic stabilizing effect of salicylic acid is lost. In this manner, in Experiments 4 and 5 (Table2), obtained gelling times are 2-2.2x longer than at standard, what is also a very good result, but in the same range as with salicylic acid only (Experiment 4; Table 1) . However, such versions of the formulation of the present invention exhibit adequate stability in real time at acidic acomplexes of salicylic and ortho-silicic acid. Except 1, 2-propylene glycol, as humectant can be also used glycerol. Additionally, as alternative diluent, beside purified water, can be employed ethanol, or mixtures of these substances. Solutions of the complex like compound 3 are also clear, colourless and relatively viscous solutions, stable to occurrence of gelling at room temperature (17-25 A degC) , and at temperatures <30 A degC, during minimally 2 years. Explanation of inhibition effect of salicylic acid on polymerization of ortho-silicic acid (HSiQ ) From obtained results, it can be concluded that salicylic acid acts stabilizing to ortho-silicic acid presumably due to formation of relatively stable complexes with it. In the basic medium, as is the case with the complex 2 (Scheme 2) , in solution are present 2 molar equivalents of strong base (e.g. NaOH) which reacts with salicylic acid yielding its disodium salt, disodium salicylate [ 1 , 2-C6H4 (ONa) COONa] . Acidity of ortho-silicic acid [pKa (H4Si04) = 2,2A*10<"10>] is similar to that of hydroxyl group of simple phenol [pKa (C6H5OH) = 1,3A*10<~10>]. However, due to electron- attracting properties of carboxylic group in the ortho-position, acidity of phenolic group of salicylic acid is higher than that of ordinary phenol or ortho-silicic acid (H4Si04) . Because of this, the compound 2 is not correct to name silicate, but it can be rather considered as the complex of disodium salicylate and ortho-silicic acid (H4Si04) . Since in the solution of complex 2 in (predominantly) aqueous medium, due to hydrolysis, is present also significant concentration of hydroxide anions (OH<">) , what is the reason of why the solution is basic, subsequently, certain amounts of ortho-silicic acid is present in the form of ortho-silicate anion Si(OH)30<">, indeed. However, this fact does not have any negative consequences in final use of the formulation from the present invention, because, upon dilution with water at oral administration, it provides ortho- silicic acid exclusively in its monomeric form. This ensures maximal level of bioavailability, what is not the case at choline chloride- stabilized HSi0 where some significant amounts of the same is already polymerized, and thus corresponding product is of lowered bioavailability . In acidic medium salicylic acid also forms complex with ortho- silicic acid, like complex 3 (Scheme 3) . Completely the same (analogous) complex is generated by addition of basic complex like compound 2 into acidic or neutral (physiological) medium. From this follows complete analogy between the complex 2 and complex 3 because : (i) compound 2 in physiological conditions gives the complex 3 (Scheme 4, at the end of specification) ; (ii) whilst the compound 3 exists both in more acidic medium as well as under physiological conditions (at pH values closed to 7) . Finally, stablizing effect of salicylic acid is obviously consequence of its structure, where two functional groups are present, carboxylic (as bidentate ligand) and phenolic hydroxyl group (as monodentate ligand) . Due to their neighbouring, ortho- position, salicylic acid acts as very effective tridentate ligand for ortho-silicic acid (HSi04) . Stability of such complex is significant, what is visible from drastically increased polymerization (gelling) time at pH= 6.5. This actually means that the stability constant of the complex 3 is very high; this result in very low equilibrium concentration of free H4Si0 in the solution of the complex, what consequently leads to drastically slower polymerization process (high values of tG) . Additional synergistic effect of 1 , 2-propylene glycol ( PG) on the basic stabilizing effect of salicylic acid is presumably consequence of additional formation of hydrogen bonds between molecules of PG and the complex 3 . It can be shown by calculation that (roughly) estimated optimal amounts of 1 , 2-propylene glycol of 15% w/w in the formulation corresponds to the value of approx. 5.5 molar equivalents of PG to H4Si04. Probably, minimal molar excess of 4 equivalents of PG to H4Si04 does act positively in a synergistic manner, due to the formation of hydrogen bonds between molecules of PG and the complex 3 . Use of the formulation from the present invention Application of the formulation of the present invention provides all known positive therapeutic effects of silicic acid on human, animal or plant organism, which are known to those skilled in the art. At humans and animals, the present formulation is used in the following medicinal, cosmetic, and veterinary indications: (i) helps in resorption of calcium; takes part in its transport, stimulates osteoblasts, stimulates bone mineralization, accelerates wound healing; in prevention of osteoporosis; (ii) takes part in structure of arterial, vein, and capillary walls, increases elasticity and hardness of blood vessels, decreases its permeability; also takes part in structure of connective tissue and formation of functional tertiary structure of building proteins of soft organs like liver, lung, and brain; (iii) stimulates immune system; thus increases natural ability of organism to fight against microorganisms at infective diseases, and at all diseases and disorders which develop upon weak immune system like various allergic diseases; (iv) antiinflammatory effect of silicon and silicic acid; therapy of various acute and chronic inflammatory diseases, e.g. positively acts at various inflammations of locomotive system such as muscle inflammations, rheumatoid arthritis, etc; skin diseases like psoriasis, seborrheic dermatitis, neurodermitis, eczema, skin irritations, burns, wound healing, at dandruff, and at other skin disorders and diseases; also positively acts at other inflammatory diseases; (v) acts as cross-linking agent for glucosaminoglycans and mucopolysaccharides, and thus helps function of joints, ligaments, and production of synovial fluid; (vi) inhibits resorption of aluminum (Al<3+>) from gastrointestinal tract, thus preventively acts on development of neurodegenerative diseases like Alzheimer or Parkinson diseases ; (vii) stimulates biosynthesis of skin building proteins: collagen and elastin; in treatment of wrinkles and prevention of their development; thus helps in slowing-down skin ageing; (viii) stimulates growth of hair and nails; for strengthening of hair and nails; also hair becomes shinier. Due to the presence of salicylic acid which, beside antiinflammatory action, exhibits also analgesic and antipyretic effects, the formulation from the present invention is used as adjuvant in treatment of pain and decreasing of increased body temperature. This is expecially recommended at indications where basic patological condition is consequence of silicon deficiency. As example, herein is given the treatment of strong pain at bone fractures, joints and/or ligaments. The silicon therapy in these cases is essential for fast mineralization process and healing, and in the same time can provide (due to the content of salicylic acid) : (i) soothing of inflammation process; and (ii) calming pain; which are formed due to given traumatological changes . At topical application (e.g. in cosmetics), the formulation of the present invention, due to the content of salicylic acid, shows: (i) keratoplastic effect, at concentrations of salicylic acid <2% w/w; (ii) keratolytic (peeling) effect, at concentrations of salicylic acid >5% w/w in the final formulation; and (iii) microbiocidal effect. The latter effects of salicylic acid are excellently supplemented with basic actions of silicon, where effects of refreshing of the skin are achieved through combination of wrinkle reducing (biosynthesis of collagen and elastin) , keratolytic/keratoplastic, and microbiocidal effects. Moreover, due to microbiocidal effect of salicylic acid and fungistatic action of ortho-silicic acid, the formulation from the present invention at topical application provides positive effects in conditions like: (i) acne; (ii) problematic skin; (iii) seborrheic dermatitis; and (iv) dandruff. It is known to those skilled in the art that analogous biological effects of silicon (in the form of HSi0) exhibits also at animals, in this manner, the formulation of the present invention is applied in veterinary in all mentioned indications. At plants, the formulation of the present invention provides: (i) increased crop yields (due to stimulation of photosynthesis through better utility of nutrients which are added by common fertilization; silicon effects) ; (ii) resistance to stressful events (e.g. during drought or after hail; silicon effects) ; and (iii) resistance to fungal diseases (effects of silicon and salicylic acid) . The formulation of the present invention intended for medicinal, cosmetic, veterinary, and agrochemical applications is in the dosing form of solution (concentrate) . Before use, the solution is diluted with water and administered orally in a dosage which corresponds to the following daily intakes of silicon (Si) : (i) 5-25 mg of Si at humans; and (ii) 5-250 mg of Si at animals; 5-50 mg at small animals like cats or dogs, 50-250 mg at large ones like horses and cows. In agriculture, the present formulation is also diluted with water up to the final concentration od silicon from 0.005-0.1% w/w, and applied by foliar application by using all common spraying equipments . Lower concentrations (0.005-0.05% w/w of Si) are used preventatively for stimulation of growth and against occurrence of fungal diseases (e.g. at grape), whilst higher concentrations (0.05-0.1% w/w of Si) are applied in urgent conditions of drought or after hail. Dosage rates are from 10-100 g of silicon per hectare (ha) or 1-10 L of the present formulation in concentration of 1% w/w of Si per single tank of 200-400 L of water, applied to the area of 1 ha. Finally, the formulation of the present invention can be used as starting material (intermediate) for production of other pharmaceutical products, cosmetics, then veterinary or agrochemical products with content of silicon (Si) of high bioavailability. For instance, the version of the formulation from the present invention of the composition: acent 3.8% w/w HSi04 [corresponds to 1% w/w of Si] acent 5% w/w salicylic acid; acent 6.5% w/w ethanol; acent ad 100% w/w 1, 2-propylene glycol; in the form of colourless viscous solution, serves as suitable concentrate (intermediate) for production of various oral and topical final dosage forms for human or veterinary use, such as: oral solution, oral suspension, shampoo, lotion, cosmetic mask, cream, ointment, gel, therapeutic patch for human use; or concentrate for solution intended for use in agriculture. Preparation of the formulation from the present invention Basic complexes of ortho-silicic (H4Si04) and salicylic acid are prepared by hydrolysis of precursor of silicic acid ( PSA) tetraethyl orthosilicate (TEOS) : (i) in the presence of 2 molar equivalents of pharmaceutically acceptable base in a diluent, with subsequent addition of salicylic acid; or alternatively, (ii) in previously prepared solution of salt of salicylic acid with pharmaceutically acceptable base in a diluent. Alternatively, the following PSA can be used: (i) sodium or potassium silicate (common composition xM2OySi02; M= Na,K, x:y= 1:1 do 1:3,5); or (ii) silicon tetrachloride (SiCl4) . The use of sodium (Na2Si03) or potassium silicate (K2Si03) as PSA represents a special case of performance of the present invention, because these are in the same time: (i) pharmaceutically acceptable bases, as sources of sodium (NaOH) or potassium (KOH) hydroxide; and (ii) sources of silicic acid ( PSA) . In these cases, no additional pharmaceutically acceptable base is used, since equimolar amounts of these silicates and salicylic acid do directly give salicylate salts like disodium or dipotassium salicylates which, in the same time act as: (i) basic agent for hydrolysis of TEOS; and as (ii) ligand for complexation of in status nascendi formed H4Si04. In the case of the use of SiCl4 as PSA in this synthesis, 6 molar equivalents of pharmaceutically acceptable base (e.g. NaOH) is employed, because, 4 equivalents is spent on neutralization of hydrochloric acid (HC1) generated during hydrolysis of SiCl4, whilst 2 remained equivalents serve for neutralization reaction of salicylic acid yielding salicylate salt (e.g. disodium salicylate) which forms the complex with liberated H4Si04 (complex 2; analogously to Scheme 2) . Acidic complexes of salicylic and ortho-silicic acid, such as compound 3 , are prepared by addition of 0.1-4 molar equivalents of pharmaceutically acceptable acid into previously prepared solution of precursor of silicic acid ( PSA) and salicylic acid in the diluent . In the preparation of the formulation of the present invention, no matter of the kind of either basic or acidic complex of ortho- silicic and salicylic acid, the following molar ratios of salicylic acid and precursor of silicic acid ( PSA; expressed through the molar portion of silicon in the PSA) is used: salicylic acid : Si = 1:1 to 2:1 As the diluent or solvent 1 , 2-propylene glycol, purified water, glycerol, ethanol, or mixtures of these substances can be employed. Reactions are conducted by vigorous stirring at temperatures from - 10 A degC to +40 A degC, preferably from +15 A degC to +30 A degC (conditions of room temperature) during 0,5-6 h. In the case of the use of sodium or potassium silicate or silicon tetrachloride (SiCl ) reaction is very exothermic. At the use of tetraethyl orthosilicate (TEOS) , the reaction is only mildly exothermic, however, with mild cooling; the reaction is conducted without special difficulties. In the case of the use of SiCl4 or sodium/potassium silicate, the reaction is almost instantly finished, whereas the hydrolysis reaction of TEOS tooks 1.5-2 h at room temperature. The use of tetraethyl orthosilicate (TEOS) is preferred because it is neither toxic nor corrosive like SiCl4, and available commercial products are of very high purity due to the fact that TEOS is readily purified by distillation. In this manner, final product of very high purity with the content of unwanted heavy metals (Pb, Cd, Hg, As) far under common limits for pharmaceutical products and food supplements can be produced. In contrast, sodium or potassium silicate are difficult to purify from heavy metals, so, commercial products are not of so high level of chemical purity. In every case, ortho-silicic acid (HSi0 ) , in status nascendi generated in the reaction, forms the complex with: (i) salicylate salt (in basic medium; example is the complex 2, Scheme 2); or wit (ii) salicylic acid (in acidic medium; example is the complex 3, Scheme 3) . In all cases, the formulation of the present invention is clear, colourless, more or less viscous solution. As side-products in reactions of sodium or potassium silicate, equivalent amounts of sodium or potassium salts of pharmaceutically acceptable base are formes, which, after completion of the reaction can be eventually removed by filtration. For instance, at the use of sodium silicate and hydrochloric acid (HC1) , the side-product is sodium chloride (NaCl) which is not soluble in 1 , 2-propylene glycol, and after synthesis is removed by filtration. In the case of the use of tetraethyl orthosilicate (TEOS) , four molar equivalents of ethanol (C2H5OH) are generated. Since ethanol in this concentration is completely harmless and does not influence negatively on the stability of the present solution, it is not removed but kept in the final product as auxiliary solvent or diluent. It is known to those skilled in the art of pharmaceuticaly technology that ethanol is widely used as pharmaceuticaly excipient, diluent. Alternatively, ethanol can be removed from the final solution of the present invention by evaporation under high vacuum at temperatures <40 A degC, without negative effect upon its stability. Finally, the reaction product, the solution, is only diluted with water or 1 , 2-propylene glycol up to the nominal concentration of silicon (Si), filtered, and paked into plastic bottles. The course of the reaction is given in Schemes 2 and 3. **Examples****General remarks**The term room temperature refers to the temperature interval: 20-25 A degC. All percentage (%) portions of ingredients are expressed as weight (w/w) portions. **Example 1**Preparation of standard solutions of sodium silicate and ortho- silicic acid, as well as solution of the control complexes with stabilizers choline chloride and L-serine from the prior art (i) Preparation of standard solution of sodium silicate (Na2Si03) of concentration of 1% w/w of silicon (Si) (Experiment 1; Table 1): To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 mol . equiv.) in distilled water (6.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Then, distilled water (7.44 g) was added up to the total weight of 15.00 g. Silicon content in such prepared standard solution is 150 mg (1% w/w of Si) . Colourless clear solution, pH= 13-14. (ii) Preparation of standard solution of ortho-silicic acid (H4Si04) of 1% w/w concentration of silicon (Si) (Experiment 1; Table 2) : To a solution of 85% phosphoric acid (0.2 mL; 0.34 g; 0.289 g H3P04; 0.00295 mol; 0.55 mol. equiv.) in distilled water (10.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 3 h. Then, destilled water (3.54 g) was added up to the total weight of reaction mixture of 15.00 g. Content of silicon in such prepared standard solution is 150 mg (1% w/w of Si) . Clear colourless solution, pH= 1.5. (iii) Preparation of basic complexes of choline chloride and L- serine with ortho-silicic acid of 1% w/w concentration of silicon (Si) (Experiments 2 and 3; Table 1) . General procedure: To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol 2.05 mol. equiv.) in distilled water (6.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Afterwards, to the reaction mixture that contains sodium silicate in amounts equivalent to 150 mg (0.0054 mol) of silicon (Si), choline chloride (0.75 g; 0.0054 mol) or L-serine (0.57 g; 0.0054 mol) as literature described astabilizers" of ortho-silicic acid was added. Each solution was stirred at room temperature for 30 minutes, and then, in each of them, distilled water was added up to the total weight of 15.00 g. The silicon content in each of solution of complex was 150 mg (1% w/w of Si). pH of solutions was 12.0-12.5. (iv) Preparation of solution of acidic complexes of choline chloride and L-serine with ortho-silicic acid of 1% w/w concentration of silicon (Si) (Experiments 2 and 3; Table 2) . General procedure: To a solution of 85% phosphoric acid (0.2 mL; 0.34 g; 0.289 g H3P04; 0.00295 mol; 0.55 mol. equiv.) in distilled water (10.00 g) : (a) choline chloride (0.75 g; 0.0054 mol; 1 mol. equiv.) was added in one solution; whilst to another, (b) L-serine (0.57 g; 0,0054 mol; 1 mol. equiv.) was added. In each reaction mixture, tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixtures was stirred at room temperature for 3 h. Then, distilled water was added in each solution up to the total weight (of each) of 15.00 g. Silicon content in each of the solution of complex is 150 mg (1% w/w of Si) . **Example 2**Preparation of basic complexes of ortho-silicic and salicylic acid according to the present invention (i) Preparation of the solution of complex 2, disodium salicylate / ortho-silicic acid of 1% w/w concentration of silicon (Experiment 4; Table 1): To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 mol. equiv.) in distilled water (6.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Then, salicylic acid (0.74 g; 0.0054 mol) was added to the reaction mixture in portions during 10 minutes with vigorous stirring. The reaction mixture was stirred at room temperature for 1 h. Afterwards, distilled water (6.70 g) was added up to the total weight of the reaction mixture of 15.00 g. Clear colourless solution; content of silicon in such prepared solution is 150 mg (1% w/w of Si). pH of the solution was 12.0-12.5. (ii) Preparation of control solution of sodium silicate with 15% and 40% concentrations of 1 , 2-propylene glycol of 1% w/w concentration of silicon (Experiments 5 and 6; Table 1) : Two analogous experiments of preparation of sodium silicate from tetraethyl orthosilicate were conducted: To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 mol. equiv.) in distilled water (6.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Then, to the reaction mixtures, 1 , 2-propylene glycol (PG) was added: (a) 2.25 g for the contet of 15% PG; and (b) 6.00 g for the content of 40% PG. Then, distilled water was added up to the total weight of each reaction mixture of 15.00 g. Clear, colourless, and slightly viscous solutions were obtained; the silicon content in such prepared solutions is 150 mg (1% w/w of Si) . (iii) Preparation of complex 2, disodium salicylate and ortho- silicic acid (H4Si04) with 15% 1 , 2-propylene glycol, according to the present invention, of 1% w/w concentration of silicon (Experiment 7; Table 1): To a solution of sodium hydroxide (NaOH; 0.44 g; 0.011 mol; 2.05 mol. equiv.) in distilled water (6.00 g) , tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Then, distilled water (4.45 g) and 1 , 2-propylene glycol (2.25 g) were added to the reaction mixture. Afterwards, salicylic acid (0.74 g; 0.0054 mol) was added in portions during 10 minutes with vigorous stirring. The reaction mixture was stirred at room temperature during 1 h. Then, the product was filtered. Colourless, clear, and slightly viscous solution was obtained; the silicon content was 150 mg (1% w/w of Si). pH value of the solution was 12.0-12.5. The results of stability tests at pH= 6.5 and also the influence of salicylic acid on stability of ortho-silicic acid for basic complexes are given in Table 1. **Example 3**Preparation of acidic complexes of ortho-silicic and salicylic acid according to the present invention (i) Preparation of solution of the complex 3 of ortho-silicic and salicylic acid of 1% w/w concentration of silicon (Experiment 4 ; Table 2): To a solution of salicylic acid (0.74 g; 0.0054 mol) in 1, 2-propylene glycol (10.00 g) , distilled water (0.40 g; 0.022 mol; 4.1 mol. equiv.) followed by tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) were added. The reaction mixture was stirred at room temperature for 5 h. Then, 1 , 2-propylene glycol (2.74 g) was added to the reaction mixture up to the total weight of 15.00 g, and the product is filtered. Colourless, clear, and viscous solution of the following composition was obtained: acent 3.8% w/w HSi04 [or 1% w/w of silicon (Si)]; acent 5% w/w salicylic acid; acent 6.6% w/w ethanol; acent up to 100% w/w 1 , 2-propylene glycol. (ii) Preparation of the complex 3 of ortho-silicic and salicylic acid in the presence of phosphoric acid of 1% w/w concentration of silicon (Experiment 5; Table 2) : To a solution of salicylic acid (0.74 g; 0.0054 mol) in 1 , 2-propylene glycol (10.00 g) , distilled water (0.40 g; 0.022 mol; 4.1 mol. equiv.) and tetraethyl orthosilicate (TEOS; 1.2 mL; 1.12 g; 0.0054 mol) were added. Then, 85% phosphoric acid (0.2 mL; 0.34 g; 0.289 g H3P04; 0.003 mol; 0.55 mol. equiv.) was added and stirred at room temperature for 3 h. To the solution, 1 , 2-propylene glycol (2.40 g) was added up to the total weight of 15.00 g, and the product was filtered. Colourless, clear, and viscous solution of the following composition was obtained: acent 3.8% w/w H4Si0 [or 1% w/w of silicon (Si)]; acent 5% w/w salicylic acid; acent 2% w/w phosphoric acid; acent 6.6% w/w ethanol; acent up to 100% w/w 1 , 2-propylene glycol. The results from stability tests at pH= 6.5, and the effect of the influence of salicylic acid on stability of ortho-silicic acid, for acidic complexes of ortho-silicic acid are presented in Table 2. **Example 4**The study of influence of choline chloride and L-serine on stability of silicic acid (I43I-04) in solution. Influence of salicylic acid on stability of H4Si04 in solution. (i) General procedure for basic complexes: In a test tube, 2 mL of 1.5M phosphate buffer of pH 4.5 and 2 mL of sample solution or solution of standard were mixed. pH values of all resulting test solutions after mixing with the buffer were the same (6.5). To such prepared mixtures (test solutions) , the time from the moment of mixing with phosphate buffer (tc; all solutions in the moment of preparation were clear) to the formation of opalescent (thick) gel was determined. This time interval was termed as agelling (polymerization) time", tG, and expressed in minutes. Obtained results for tG are expressed in comparison with results obtained for the standard solution of sodium silicate (Na2Si03) of the same concentration of 1% w/w of silicon (the standard for basic complexes). The results are given in Table 1. (ii) Preparation of 1.5M phosphate buffer of pH= 4.4 required for the testing of basic complexes: Sodium dihydrogenphosphate (NaH2P04; 18.00 g; 0.15 mol) was quantitatively transferred into a 100 inL measuring flask and dissolved in 80-85 mL of distilled water by shaking at room temperature. Thus obtained solution was diluted with distilled water up to the mark of 100 mL. Colourless clear solution, pH= 4.5. (iii) General procedure for acidic complexes: In a test tube, 2 mL of 1.32M phosphate buffer pH 7 and 2 mL of sample solution or solution of standard were mixed. pH values of all resulting test solutions after mixing with the buffer were the same (6.5). To such prepared mixtures (test solutions) , the time from the moment of mixing with phosphate buffer (tD; all solutions in the moment of preparation were clear) to the formation of opalescent (thick) gel was determined. This time interval was termed as agelling(polymerization) time", tG, and expressed in minutes. Obtained results for tG are expressed in comparison with results obtained for the standard solution of ortho-silicic acid (HSi04) of the same concentration of 1% w/w of silicon (the standard for acidic complexes). The results are given in Table 2. (iv) Preparation of 1.32M phosphate buffer of pH= 7 required for study of acidic complexes: Sodium dihydrogenphosphate (NaH2P04; 16.00 g; 0.132 mol) and sodium hydroxide (NaOH; 3.14 g; 0.0785 mol) were quantitatively transferred into a 100 mL measuring flask and dissolved in about 80 mL of distilled water by shaking at room temperature. Thus obtained solution was diluted with distilled water up to the mark of 100 mL . Colourless clear solution, pH= 7.0. **Example 5**Preparation of the formulation from the present invention in the form of solution of complex of ortho-silicic acid (H4Si04) with dipotassium salicylate of 0.5% w/w concentration of H4Si04 (or 0.15% w/w of Si) To a solution of potassium hydroxide (KOH; 0.31 g; 0.0055 mol; 2.04 mol. equiv.) in distilled water (8.00 g) , 1 , 2-propylene glycol (2.25 g; 15% w/w) was added, followed by salicylic acid (0.37 g; 0.0027 mol; 1 mol. equiv.). The reaction mixture was stirred at room temperature for 1 h. Then, to this clear colourless solution containing dipotassium salicylate, tetraethyl orthosilicate (TEOS; 0.6 mL; 0.56 g; 0.0027 mol) was added. Reaction mixture was stirred at room temperature for 5 h. Then, distilled water (3.51 g) was added up to the total weight of 15.00 g, and the product is filtered. Colourless, clear, and slightly viscous solution was obtained; the silicon content was 0.15% w/w of Si; pH= 12.0-12.5. **Example 6**form of solution of the complex of ortho-silicic acid (H4Si04) with disodium salicylate of Iu !% w/w concentration of HSi04 (or 2.27% w/w of Si) To a solution of sodium hydroxide (NaOH; 1.00 g; 0.025 mol; 2 mol. equiv.) in distilled water (7.00 g) , tetraethyl orthosilicate (TEOS; 2.8 mL; 2.62 g; 0.0126 mol) was added. The reaction mixture was stirred at room temperature for 6 h. Then, salicylic acid (1.74 g; 0.0126 mol; 1 mol. equiv.) was added to the reaction mixture during 30 minutes with vigorous stirring. The reaction mixture was stirred at room temperature for 1 h. Afterwards, 1 , 2-propylene glycol (2.25 g) and distilled water (0.39 g) were added up to the total weight of 15.00 g. Finally, the reaction mixture was filtered. Colourless, clear, and viscous solution was obtained; content 2.27% w/w of Si; pH= 12.0-12.5. **Example 7**Preparation of the formulation from the present invention in the form of 1% w/w solution of ortho-silicic acid (H^SiO^) (or 0.29% w/w of Si) To a solution of salicylic acid (0.43 g; 0.0031 mol; 2 mol. equiv.) in a mixture of 1 , 2-propylene glycol (7.50 g) and glycerol (3.00 g) , tetraethyl orthosilicate (TEOS; 0.35 mL; 0.33 g; 0.00157 mol) was added. The reaction mixture was stirred at room temperature for 5 h. Then, distilled water (3.74 g) was added up to the total weight of 15.00 g. After filtration, colourless, clear, and viscous solution of the following composition was obtained: acent 1% w/w H4Si04 [or 0.29% w/w of silicon (Si)]; acent 2,9% w/w salicylic acid; acent 1.9% w/w ethanol. **Example 8**Preparation of the formulation from the present invention in the form of 2% w/w solution of ortho-silicic acid (HqSiO (or 0.58% w/w of Si) To a solution of salicylic acid (0.43 g; 0.0031 mol; 1 mol. equiv.) in 1, 2-propylene glycol (10.00 g) , distilled water (0.23 g; 0.0128 mol; 4.1 mol. equiv.) and tetraethyl orthosilicate (TEOS; 0.7 mL; 0.65 g; 0.0031 mol) were added. Then, sulfuric acid (0.1 mL; 0.18 g; 0.177 g H2S0 ; 0.0018 mol; 0.58 mol. equiv.) was added dropwise to the reaction mixture, and stirred at room temperature during 3 h. Afterwards, 1 , 2-propylene glycol (3.51 g) was added up to the total weight of 15.00 g. After filtration, colourless, clear, and voscous solution was obtained with the following composition: acent 2% w/w H4Si04 [or 0.58% w/w of silicon (Si)]; acent 2.9% w/w salicylic acid; acent 3.8% w/w ethanol; acent up to 100% w/w 1 , 2-propylene glycol. **Example 9**Preparation of the formulation from the present invention in the form of 6% w/w solution of ortho-silicic acid (H^SiOj) (or 1.75% w/w of Si) To a solution of salicylic acid (1.30 g; 0.0094 mol; 1 mol . equiv.) in 1, 2-propylene glycol (10.00 g) , distilled water (0.70 g; 0.039 mol; 4.1 mol. equiv.) and tetraethyl orthosilicate (TEOS; 2.1 mL; 1.96 g; 0.0094 mol) were added. Then, to the reaction mixture, 85% phosphoric acid (0.16 mL; 0.27 g; 0.23 g H3P04; 0.0024 mol; 0.25 mol. equiv.) was added, and stirred at room temperature during 6 h. Afterwards, 1 , 2-propylene glycol (0.77 g) was added up to the total weight of 15.00 g. After filtration, colourless, clear, viscous solution of the following composition was obtained: acent 6% w/w H4S1O4 [or 1.75% w/w of silicon (Si)]; acent 8.7% w/w salicylic acid; acent 1.5% w/w phosphoric acid; acent 11.5% w/w ethanol; acent up to 100% w/w 1 , 2-propylene glycol. Example 10 Preparation of the formulation from the present invention in the form of solution of the complex of disodium salicylate and ortho- silicic acid (H4Si04) of 2% w/w concentration of H4Si0 (or 0.58% w/w of Si) with the use of sodium silicate as precursor of silicic acid To a solution of sodium silicate (Na2Si03; 0.38 g; 0.0031 mol) in distilled water (10.00 g) , salicylic acid (0.43 g; 0.0031 mol; 1 mol. equiv.) was added in portions during 30 minutes under vigorous stirring. The reaction mixture was stirred at room temperature for 1 h. Then, 1 , 2-propylene glycol (2.25 g) and distilled water (1.94 g) were added up to the total weight of the reaction mixture of 15.00 g. After filtration, colourless, clear solution of the following composition was obtained: acent 2% w/w H4Si04 [or 0.58% w/w of silicon (Si)]; acent 2.9% w/w salicylic acid; acent 15% w/w 1, 2-propylene glycol; acent up to 100% water. **Example 11**Preparation of the formulation from the present invention in the form of 2% w/w solution of ortho-silicic acid (H^SiC (or 0.58% w/w of Si) with the use of silicon tetrachloride as precursor of silicic acid To a solution of salicylic acid (0.43 g; 0.0031 mol; 1 mol. equiv.) and sodium hydroxide (NaOH; 0.46 g; 0.0115 mol; 3.7 mol. equiv.) in mixture of 1 , 2-propylene glycol (12.00 g) and distilled water (2.00 g) cooled to -5 to -10 A degC, under vigorous stirring, silicon tetrachloride (SiCl ; 0.36 mL; 0.53 g; 0.0031 mol) was added dropwise during 15 minutes. The reaction mixture was stirred at this temperature during 1 h, then, for 1 h at temperatures from -5 A degC to room temperature. Afterwards, 1 , 2-propylene glycol (0.25 g) was added to the reaction mixture, and stirring was continued for additional 15 minutes at room temperature. After filtration where a precipitate of sodium chloride (NaCl; approx. 0,67 g) was removed, colourless, clear, and viscous solution of the following composition was obtained: acent 2% w/w H4S1O4 [or 0,58% w/w of silicon (Si)]; acent 2.9% w/w salicylic acid; acent up to 100% w/w 1 , 2-propylene glycol. --- **Process for producing nano-hydroxyapatite bioactive material** **CN101401952** ****[ [PDF](CN101401952A.pdf) ]**** The invention provides a method for preparing a nanometer hydroxyapatite bioactive material, which comprises the following steps: firstly, synthesizing an aqueous dispersion liquid of the nanometer hydroxyapatite by a liquid phase method; secondly, adding an active ortho silicic acid solution into the aqueous dispersion liquid of the nanometer hydroxyapatite; thirdly, controlling the pH value, the temperature and the time of the reaction to condense and gelatinate the active ortho silicic acid solution into silicon dioxide coating the surface of the nanometer hydroxyapatite so as to obtain the nanometer hydroxyapatite coated with the silicon dioxide. The synthesis method provided by the invention improves the reactivity between bone tissues and the nanometer hydroxyapatite which has a core-shell structure and is coated with the silicon dioxide, and improves the shortage that the common nanometer hydroxyapatite is excessively stable. **Technical background**Core/shell composite structure nanoparticles are a novel structure, a nanoscale ordered assembly structure formed by one nanomaterial covering another nanomaterial through chemical bonds or other interactions. It is a higher level Composite nanostructures. In the past decade or so, researchers have mainly focused on core-shell materials with certain functions, such as magnetism, light-to-electricity conversion, and photocatalysis, in their research on nano-core-shell coating technology. The surface of nanoparticles has been coated with shell materials such as polymers, organic substances, inorganic compounds, elemental elements, biological macromolecules, etc., which improves the surface properties of the particles, enhances the stability of the particles, etc., and further broadens the application of nanomaterials. The scope has enabled core-shell materials to be applied in chemistry, biological sciences and materials science. Convenient and effective synthesis methods have become the key to preparing nanocore-shell particles. People use one or several methods to prepare nanocomposites based on the performance requirements of the final product and the properties of the precursors. Among them, the sol-gel method is a commonly used method. The sol-gel method refers to a method in which metal organic or inorganic compounds are solidified through sol or gel, and then heat treated to form oxides or other compound solids. The sol-gel method disperses the required coated particles in the prepared sol, and then completes gelation under certain reaction conditions to form the required coating layer on the surface of the particles. For example, A Imhof et al. On the outside of I+/--Fe2O3 particles, Stober hydrolysis method is used to hydrolyze ethyl orthosilicate (TEOS) in 2-propanol to directly deposit SiO2(A Imhof., Preparation and Characterization of Titania-Coated Polystyrene Spheres and Hollow Titania Shells, Langmuir, 2001, 17: 3579-3585). Liz-Marzan et al. successfully coated gold nanoparticles with a SiO2layer with controllable thickness (Liz-Marzan Luis M, Michael Giersig, Paul Mulvaney, Synthesis of nanosized gold-silica core-shell particles[J], Langmuir, 1996 , 12:4329-4335). The above-mentioned method for preparing core-shell structures has not been reported in nano-inorganic biomaterials. In the field of biomaterials, the remarkable feature of nanohydroxyapatite as a biomaterial is that it is very close to bone apatite in natural bone in terms of composition, crystal size and crystallinity, so it has very good osteoinductivity. , widely used in various bone repair biomaterials. After implantation into the body, under the action of body fluids, the calcium and phosphorus of nanohydroxyapatite will be released from the surface of the material, absorbed by body tissues, and can form chemical bonds with human bone tissue to grow new tissue. Therefore, Nanohydroxyapatite is currently recognized as a material with good biocompatibility and osteoinductivity, that is, bioactive material. However, whether it is nano-hydroxyapatite or ordinary hydroxyapatite, compared with bioactive glass, the disadvantage of implants is that they have lower reactivity with bone and a slower rate of integration with bone. Relatively low, which means patients need longer recovery times. A great advantage of bioactive glass is that in addition to calcium and phosphorus, which are components of bone, it also contains silica. In the body fluid environment, silica can be hydrolyzed to form a gel layer containing calcium and phosphorus on the surface of the material, and induce the formation of bone-like apatite. This gel layer rich in calcium and phosphorus and the formed bone-like phosphorus Limestone can bond well with bone tissue and has higher biological response and surface activity than ordinary calcium phosphate ceramics, such as hydroxyapatite, I2-tricalcium phosphate, etc. However, bioglass requires high-temperature firing and shaping, and multiple high-temperature treatments and changes in composition have a significant impact on biological activity, and bioglass processing and shaping is difficult. In addition, in the application of hydroxyapatite, in order to improve the biological activity of hydroxyapatite, we learn from the characteristics of bioglass with good biological activity due to the silicon element, and add silicon element to improve its clinical performance. Silicon-containing hydroxyapatite is one type of modified material. At present, silicon-containing hydroxyapatite is synthesized by introducing silicon into the crystal lattice of apatite. For example, after synthesizing hydroxyapatite, it is directly coated with ethyl orthosilicate and then calcined, or hydroxyapatite is added in a solid-state reaction. Silicon compounds, calcined together (Arcos D, Rodriguez-Carvajal J, Vallet-Regi M. Neutron scattering for the study of improved bone implants. Physica B, 2004, 350: 607-610); or directly add ethyl orthosilicate in the liquid phase reaction, react together and then calcine, etc. (Gibson I P, Best S M, Bonfield W. Chemical characterize of silicon-substituted hydroxyapatite . J Biomed Mater Res, 1999.4: 422-428), the purpose is to allow silicon elements to enter the crystal lattice of hydroxyapatite, thereby causing defects and disproportionation in the crystal lattice, and improving its reactivity in the implanted organism. However, from the perspective of the entire preparation process, whether it is wet preparation or dry preparation, in order to form a homogeneous doping of silicon element and apatite and perform high-temperature calcination, the purpose is to improve the reaction activity, but the prepared hydroxyphosphorus The agglomeration of limestone powder is serious during the drying and calcining process, and the crystals become thicker and larger, which is far from the weakly crystalline nanobone apatite structure in human bones, reducing biological activity and interfacial reactivity. **Contents of the invention**The present invention combines the synthesis method of nano-hydroxyapatite with the method of preparing silica core-shell structure nanomaterials by the sol-gel method. By adding an orthosilicic acid solution to the aqueous dispersion of nano-hydroxyapatite, the orthosilicic acid solution is passed through the sol-gel method. The sol and gel reaction of acid forms a silica shell layer on the surface of nano-hydroxyapatite. Without high-temperature firing and molding, the core-shell structure of silica-wrapped nano-hydroxyapatite bioactivity can be prepared. Material, the grain size, structure and main components of this material are similar to the bone nanoapatite crystals of natural bone. Therefore, it has the advantages of good biomimetic structure of nanohydroxyapatite and high biological activity of bioglass. Therefore, It is an excellent raw material for preparing medical bone repair materials and bone fillers. The present invention is realized through the following technical solutions: a preparation method of nano-hydroxyapatite bioactive material, which is characterized by going through the following process steps: Step 1. Preparation of nano-hydroxyapatite aqueous dispersion Place the nano-hydroxyapatite indoors for at least 24 hours for aging, wash the aged nano-hydroxyapatite with water, and add water to prepare an aqueous dispersion with a hydroxyapatite mass content of 2.5 to 25% for later use; Step 2. Preparation of nano-hydroxyapatite coated with silica on the surface (1) Preparation of active orthosilicic acid solution Add activated cation exchange resin to a sodium silicate aqueous solution with a silica content of 0.5 to 20% under stirring until the pH value of the solution is 9 to 11, and then filter to remove the cation exchange resin in the solution to obtain active positive ion exchange resin. Silicic acid solution; (2) Preparation of nano-hydroxyapatite surface-coated silica At room temperature and under stirring, add the obtained active orthosilicic acid solution to the nano-hydroxyapatite aqueous dispersion in step 1 and mix. The amount added is based on the mass of silica and hydroxyapatite contained in the orthosilicic acid solution. The ratio is 1:1 to 1000, and then stir for at least 1 hour. When the pH value of the mixed solution is 8 to 11 and the reaction temperature is 25 to 90A degC, continue stirring for 2 to 48 hours, and then wash the reaction product with water for at least Three times, nano-hydroxyapatite with silica coated on the surface was obtained. The nano-hydroxyapatite in step one is prepared by a conventional liquid phase method. The sodium silicate aqueous solution with a silica content of 0.5 to 20% in step two is prepared using conventional methods in the prior art. The activated cation exchange resin in step two is obtained by activating the cation exchange resin using conventional methods in the prior art. Compared with the prior art, the present invention has the following advantages: 1. The present invention prepares nano-hydroxyapatite through a liquid phase method, and uses a sol-gel method to wrap a silica shell on the surface of the nano-hydroxyapatite to prepare a silica-wrapped nano-hydroxyapatite with a core-shell structure. stone, which improves the surface reactivity and interface binding of nano-hydroxyapatite in organisms, as well as the reactivity and integration rate with bone, and overcomes the shortcomings of existing nano-hydroxyapatite being too stable and insufficient in reactivity. 2. The present invention prepares silica-coated nanohydroxyapatite with a core-shell structure through a liquid phase method and a sol-gel method, which avoids the direct agglomeration of nanohydroxyapatite during the drying process of preparation and use, and maintains The original nano-size structure and bone-like apatite characteristics of nano-hydroxyapatite prepared by liquid phase method were obtained. 3. The present invention prepares nano-hydroxyapatite with core-shell structure silica coating through liquid phase method and sol-gel method. The preparation process does not require sintering and maintains the nano-weak crystals of nano-hydroxyapatite synthesized by liquid phase method. structure, overcoming the shortcomings of excessively large crystal size of silicon-modified hydroxyapatite prepared by high-temperature calcination and large differences in crystal size and structure from bone apatite. 4. The nano-hydroxyapatite with core-shell structure silica wrapped prepared by the present invention is more similar to bone apatite in size and composition than the particle crystals of the bioglass phase material with good biosurface reactivity. The close proximity is beneficial to stimulating and inducing the repair and growth of bone tissue, and is also conducive to processing and shaping. 5. The present invention prepares nano-hydroxyapatite with core-shell structure silica wrapped by the sol-gel method of directly adding active orthosilicic acid. There is no need to add catalysts and organic co-solvents during the preparation process. The preparation process is more simplified and reduces the cost. Eliminate the contamination of biological material products by residual organic impurities **Detailed ways**The present invention will be further described below in conjunction with the examples, but the content of the present invention is not limited thereto. **Example 1**Step 1. Preparation of nano-hydroxyapatite aqueous dispersion (1) Use the liquid phase method in the prior art to prepare nano-hydroxyapatite: Prepare analytically pure calcium nitrate solution and diammonium hydrogen phosphate into solutions with a concentration of 0.1 mol/liter respectively. Under stirring conditions, 6 Add 1 liter of diammonium hydrogen phosphate solution dropwise into 10 liters of calcium nitrate solution. During the dropwise addition, adjust the pH of the reaction medium to 10.5 with concentrated ammonia water. The dropping time is 1 hour, and then continue to stir for two hours, and then at room temperature. Aged for 24 hours, centrifuged to remove the supernatant to obtain nano-hydroxyapatite; (2) Use deionized water to centrifugally wash the nano-hydroxyapatite obtained in (1) 3 times, and then add ionized water to prepare 4016g of an aqueous dispersion with a hydroxyapatite content of 2.5%; Step 2. Preparation of nano-hydroxyapatite coated with silica on the surface (1) Preparation of active orthosilicic acid solution Use the ion exchange method in the prior art to prepare active orthosilicic acid solution: Add analytically pure sodium silicate to an appropriate amount of deionized water to prepare a sodium silicate solution, in which the silica content in the solution is 2.5%. Take the aqueous solution 500 grams, under stirring, continuously add strong cation exchange resin activated by hydrochloric acid (produced by Shanghai Resin Factory, and activated by hydrochloric acid using conventional methods of the prior art) until the pH value of the solution is adjusted to 10, and after filtering out the resin, we obtain Silica content is 2.5% active orthosilicic acid solution; (2) Preparation of nano-hydroxyapatite surface-coated silica Using a high-speed disperser commonly used in the laboratory, 4016g of the nano-hydroxyapatite aqueous dispersion obtained in step one (2) was dispersed at a speed of 4000 rpm for 30 minutes, and then the active positive dispersion obtained in step two (1) was dispersed. 4g of silicic acid solution was slowly added dropwise to the hydroxyapatite aqueous dispersion for 10 minutes, and then continued stirring at a speed of 1000 rpm. Afterwards, the reaction temperature was controlled at 25A degC, and the pH value of the reaction solution was adjusted with ammonia water. Adjust to 8, reduce the rotation speed to 200 rpm, continue stirring for 48 hours and then wash with deionized water three times to obtain nano-hydroxyapatite with a core-shell structure and surface-coated silica; add an appropriate amount of deionized water to the reaction product The total solid-liquid content of the product was adjusted to 4017g with water to obtain a silica-coated nanohydroxyapatite dispersion slurry with a solid content of 2.5% and a core-shell structure. The slurry can be directly used as an inorganic component raw material together with water-soluble biopolymers to make organic-inorganic composite bone repair materials. **Example 2**Step 1. Preparation of nano-hydroxyapatite aqueous dispersion (1) Use the liquid phase method in the existing technology to prepare nano-hydroxyapatite: add 0.5 mol of analytically pure calcium hydroxide to one liter of water to prepare a 0.5 mol/l slurry, and use a laboratory high-speed dispersing machine at 2000 rpm/ Disperse at 1000 rpm for 30 minutes, then switch to the mixer at 1000 rpm to continue stirring. Add 0.3 Mol of analytically pure phosphoric acid to 1 liter of water to prepare a 0.3 mol/liter solution. Then add the phosphoric acid solution dropwise to the stirrer at a uniform speed. In the calcium hydroxide slurry, the dropping time is about 2 hours. After the dropping is completed, stirring is continued for 2 hours, and then aged at room temperature for 24 hours. The supernatant is removed by centrifugation to obtain nano-hydroxyapatite; (2) Centrifuge and wash the nano-hydroxyapatite obtained in the above (1) 3 times with deionized water, and then add ionized water to prepare 335g of an aqueous dispersion with a hydroxyapatite content of 15%; Step 2: Preparation of nano-hydroxyapatite with silica coated on the surface: (1) Preparation of active orthosilicic acid solution Use the ion exchange method in the prior art to prepare active orthosilicic acid solution: Add analytically pure sodium silicate to deionized water to prepare a sodium silicate solution, in which the silica content in the solution is 10%. Take 500g of the solution, Continuously add activated strong cation exchange resin (produced by Shanghai Resin Factory, and activated by hydrochloric acid using conventional methods in the prior art) under stirring until the pH value of the solution is adjusted to 9, and then the cation exchange resin in the above solution is Filter and remove to obtain an active orthosilicic acid solution with a silica content of 10%; (2) Preparation of nano-hydroxyapatite surface-coated silica Use a high-speed disperser commonly used in laboratories to disperse 335g of the nano-hydroxyapatite aqueous dispersion obtained in step one (2) at a speed of 2000 rpm for 30 minutes. 125g of the acid solution was slowly added dropwise to the stirring hydroxyapatite slurry for 30 minutes. During the dropping process, the stirrer speed was 1000 rpm and the stirring time was 1 hour. Afterwards, the pH value of the reaction solution was adjusted with ammonia water. Control it at 9, adjust the reaction temperature to 60A degC, reduce the stirrer speed to 250 rpm and continue stirring the reaction for 24 hours, and then wash it with deionized water 3 times to obtain a surface-coated silica nanometer with a core-shell structure. Hydroxyapatite; then the product is washed three times with absolute ethanol, and finally the reaction product is dried using existing freeze-drying technology to obtain nano-hydroxyapatite wrapped with silica with a core-shell structure. This product can be directly used to fill and repair local bone defects, or it can be combined with biopolymers to form a massive organic-inorganic composite material, which can be used to repair bone defects or as a scaffold material for in vitro bone cell culture. **Example 3**Step 1. Preparation of nano-hydroxyapatite aqueous dispersion (1) Use the liquid phase method in the prior art to prepare nano-hydroxyapatite: 0.5 mol of analytically pure calcium nitrate is prepared into a 1 liter solution, 0.3 mol liter of analytically pure sodium phosphate is prepared into a 1 liter solution, and phosphoric acid is prepared into a 1 liter solution. The sodium solution is heated to 70A degC, and then the above-mentioned calcium nitrate solution is added dropwise to the above-mentioned sodium phosphate solution in a stirring state. The dropping time is 2 hours. After the dropwise addition is completed, the pH of the reaction product is adjusted to 10 with sodium hydroxide solution. , continue stirring for 2 hours, then age at room temperature for 24 hours, filter the supernatant to obtain nano-hydroxyapatite; (2) Centrifuge and wash the nano-hydroxyapatite obtained in (1) above 3 times with deionized water, and then add ionized water to prepare 201g of aqueous dispersion with a hydroxyapatite content of 25%; Step 2. Preparation of nano-hydroxyapatite coated with silica on the surface (1) Use the ion exchange method in the prior art to prepare active orthosilicic acid solution: Prepare the sodium silicate solution into an aqueous solution with a silica mass concentration of 20%, then take 500g, and continuously add activated strong silicic acid solution under stirring. Cation exchange resin (produced by Shanghai Resin Factory, and activated by hydrochloric acid using conventional methods in the prior art), adjust the pH value of the solution to 11, and then filter and remove the cation exchange resin in the above solution to obtain a silica content of 20%. Active orthosilicic acid solution; (2) Use a high-speed disperser commonly used in laboratories to disperse 201g of the nano-hydroxyapatite aqueous dispersion obtained in step one (2) at a speed of 2000 rpm for 30 minutes. Slowly add 251g of orthosilicic acid dropwise into the stirring aqueous dispersion of hydroxyapatite for 1 hour, then use a stirrer to continue stirring at a speed of 1000 rpm for 1 hour, and then use ammonia to adjust the pH of the reaction solution. The value is controlled at 11, the reaction temperature is controlled at 90A degC, reduce the stirrer speed to 200 rpm and continue stirring for 4 hours, then the reaction product is centrifuged and washed three times with deionized water, and then washed three times with absolute ethanol, and finally After vacuum drying at 100A degC for 48 hours, nanometer hydroxyapatite wrapped with core-shell structure silica was obtained. This product can be directly used to fill and repair local bone defects, or it can be combined with biopolymers to form a massive organic-inorganic composite material, which can be used to repair bone defects or as a scaffold material for in vitro bone cell culture. **Example 4**Step 1. Preparation of nano-hydroxyapatite aqueous dispersion (1) Use the liquid phase method in the prior art to prepare nanohydroxyapatite: prepare analytically pure calcium nitrate into a 0.1mol/liter solution, and dissolve 0.06mol analytically pure triethyl phosphate in 150 ml of In absolute ethanol, add 1 liter of the prepared calcium nitrate solution to the triethyl phosphate ethanol solution at a stirring speed of 1000 rpm, then adjust the pH of the above solution to 11 with ammonia water, and place it at a temperature of In a water bath at 50A degC, heat and stir for 4 hours. After the reaction is completed, age at room temperature for 24 hours. Centrifuge to remove the supernatant to obtain nano-hydroxyapatite; (2) Centrifuge and wash the nano-hydroxyapatite obtained in (1) above 3 times with deionized water, and then add ionized water to prepare 201g of aqueous dispersion with a hydroxyapatite content of 5%; Step 2. Preparation of nano-hydroxyapatite coated with silica on the surface (1) Use the ion exchange method in the prior art to prepare active orthosilicic acid solution: Prepare the sodium silicate solution into an aqueous solution with a silica mass concentration of 0.5%, then take 500g, and continuously add activated orthosilicic acid solution under stirring. Strong cation exchange resin (produced by Shanghai Resin Factory, and activated by hydrochloric acid using conventional methods in the prior art), adjust the pH value of the solution to 9, and then filter and remove the cation exchange resin in the above solution to obtain a silica content of 0.5% Active orthosilicic acid solution; (2) Stir 201g of the nano-hydroxyapatite slurry obtained in step one (2) using an electric stirrer at 1000 rpm for 30 minutes, and slowly add all 500g of the active orthosilicate solution obtained in step two (1) dropwise into the stirred hydroxyapatite slurry, the dropping time is 2 hours, and then use an electric stirrer to continue stirring at a speed of 1000 rpm for 1 hour, and then use ammonia water to control the pH value of the reaction solution at 11, and the reaction temperature at 60A degC, reduce the speed to 200 rpm and continue stirring for 48 hours. Afterwards, the reaction product is centrifuged and washed with deionized water 3 times, and then an appropriate amount of deionized water is added to make the total amount of solid and water 62.5g, that is, the mass content is obtained It is an aqueous dispersion of nano-hydroxyapatite wrapped with 20% core-shell structured silica. This product can be directly used to fill and repair local bone defects, or it can be combined with biopolymers to form a massive organic-inorganic composite material, which can be used to repair bone defects or as a scaffold material for in vitro bone cell culture. --- **Stabilized orthosilicic acid comprising preparation and biological preparation** **US5922360** ****[ [PDF](US5922360A.pdf) ]**** A preparation comprising ortho silicic acid which is stabilized with a stabilizing agent and is substantially free of organic silicon compounds, preferably a nitrogen-containing stabilizing agent such as choline, to a method for preparing such a preparation, comprising: i) providing a solution containing a stabilizing agent; ii) dissolving an inorganic silicon compound in the solution containing the stabilizing agent; and iii) hydrolyzing the silicon compound to ortho silicic acid, and to the obtained biological preparation. Silicon is an essential trace element for plants, animals and humans. In a watery environment silicon is initially present as ortho silicic acid which is quickly converted by polycondensation to polysilicic acid, which transposes into a colloidal solution and gels. Ultimately, insoluble silicates are formed. In the same way as carbonic acid for compounds comprising carbon, ortho silicic acid is the most important metabolite for organic silicon compounds. Water glass (sodium ortho silicate) is the usual source of ortho silicic acid, which however hydrolyses after oral administration to mammals and forms insoluble and non-absorbable gels through polycondensation. Organic silicon compounds such as alcohol esters, such as ethyl ortho silicate and glycol ortho silicate, cannot be used in biological systems because of the poor solubility and the low resistance to hydrolysis, but above all because of the unacceptable toxicity. There therefore exists a need for a silicon-comprising preparation not possessing the above stated drawbacks, because silicon has a positive biological effect on nails, hair, skin, teeth, collagen, connective tissue, bones, encourages cell generation, stimulates the immune system against infections and toxins and inhibits degenerative (ageing)-processes. The present invention is based on the insight that if ortho silicic acid is formed in the presence of a stabilizing agent, polycondensation is inhibited and even avoided and, furthermore organic silicon compounds substantially do not occur. A first aspect of the present invention therefore relates to a preparation comprising ortho silicic acid which is stabilized with a stabilizing agent and is substantially free of organic silicon compounds. A second aspect of the present invention relates to a method for preparing a preparation as according to claims 1-7, which comprises of: i) providing a solution containing a stabilizing agent; ii) dissolving an inorganic silicon compound in the solution containing the stabilizing agent; and iii) hydrolyzing the silicon compound to ortho silicic acid. A third aspect of the present invention relates to a biological preparation containing a preparation according to claims 1-7, and/or a preparation prepared according to claims 8-13, and a pharmacologically acceptable diluent. The biological preparation according to the invention is can be used for: chronic infections with destruction of the mucous membranes: forms of sinusitis and ulcers. problems with connective tissues, arteriosclerosis, bone and tendon problems, gynaecology (fibroids, polycystic adenopathy); and the growth of children: children with recurrent infections with overload of the lymphatic system. The stabilization using a stabilizing agent preferably takes place with stabilizing agents containing a nitrogen atom with a free electron pair which forms a complex with the silanol groups of the ortho silicic acid. Quaternary ammonium compounds are preferably used, for instance tetra-alkyl compounds, wherein each alkyl group contains for instance 1-5 carbon atoms, in particular methyl and ethyl groups. Very highly recommended are trialkylhydroxyalkyl compounds, wherein the hydroxy group is preferably methanol or ethanol. Choline has been found very suitable, which is further recommended in that it provides the option of the stabilizing agent also forming the solution for the ortho silicic acid, and an inert solvent can therefore be omitted. Another or additional type of stabilizing agent is an amino acid, such as proline and serine. Serine enhances uptake in the stomach and gives additional stability. Starting point for the preparation of the ortho silicic acid-comprising preparation is a solution containing the stabilizing agent, wherein an inert solvent can be used. Incorporated in -This solution is an inorganic silicon compound which hydrolysis under the influence of water to ortho silicic acid, which is immediately stabilized by the stabilizing agent that is present. The solution containing the stabilizing agent can initiate the hydrolysis immediately after addition of the inorganic silicon compound. Usually recommended is a solution containing a stabilizing agent in which no hydrolysis can take place until after the addition of a hydrolyzing agent, such as water. If choline is used as stabilizing agent it can be converted to choline hydrochloride using dry hydrochloric acid. In this liquid stabilizing agent can be incorporated the inorganic silicon compound, such as a silicon halogenide, particularly silicon tetrachloride. Simultaneously with the addition of the inorganic silicon compound, or following the addition of the hydrolyzing agent, the hydrolysis of the inorganic silicon compound to ortho silicic acid takes place. The silicic acid formed in situ is subsequently stabilized by forming a complex with the stabilizing agent. It is of great importance herein that the stabilizing agent only forms a complex and does not enter into a reaction, particularly an esterifying reaction, with the ortho silicic acid. Then achieved is that no organic silicon compounds are created which have an inherent toxicity, are absorbed in the stomach and enter the blood circulation. After forming a complex the ortho silicic acid-comprising solution can if desired be partially neutralized by adding a base, such as a lye, particularly sodium hydroxide. Neutralization can take place to a pH smaller than 4, in particular smaller than 3, in general to a pH lying in the range of 1-3, whereby any polycondensation of ortho silicic acid is substantially avoided. If desired, a further purification of the preparation can take place, for instance through absorption of contaminants on active carbon, optionally followed by filtration. If desired, the content of hydrolyzing agent, particularly water, can be reduced by removing the hydrolyzing agent, for instance through distillation, whereby a constant viscosity is achieved if use is made of choline as the stabilizer. Preparations then result with a silicon content generally of 1% by weight, preferably of about 4% by weight, such as 8% by weight. A very acceptable preparation contains 3-5% by weight of silicon, 70s by weight of choline hydrochloride and the rest water. The pH of this preparation lies within the range 1-3. Biological preparations can be-manufactured from this prepared preparation for the purpose of administering ortho silicic acid to plants, animals and humans, whereby the bio-availability of silicon is greatly improved. The above prepared solution can be administered as biological preparation as such, for instance as nail tincture. A usage of 0.5 ml of a 2% Si-solution per day for three weeks caused a fungal infection to disappear (3 patients), where treatment with ketonazols did not render any improvement. If for instance an edible acid, such as malic acid, is added a preparation results which is very suitable for administering to horses. If a solid carrier is added, for instance cattle feed, cattle feed pellets can be pressed therefrom which contain ortho silicic acid in stabilized form for administering silicon to cattle. If sugar/maltose is used as solid carrier, tablets and gels can be formed therefrom. Through use of a glucuronic acid buffer a preparation on a cream basis can be formed wherein the pH is less than 4, which creams are suitable for local cutaneous application. It will be apparent that all kinds of diluents can be used in order to obtain a preparation for biological application. Such diluents contain lower alkanols, such as ethanol, dichloromethane, ethyl acetate, glycerine and polyalcohols. PREPARATION EXAMPLE Choline hydrochloride (UCB) is dried under vacuum (100 DEG C./6 hours). The choline hydrochloride is treated with dry hydrochloric acid. Silicon hydrochloride (1 mol per mol) is added to the formed choline solution at a temperature which is kept below 40 DEG C. For hydrolysis, water (ice/ice water) is added to the solution while cooling, wherein the temperature is held within the range of -20 DEG C. to -30 DEG C. The solution containing the ortho silicic acid is subsequently neutralized by adding sodium hydroxide wherein cooling takes place to a temperature below 0 DEG C. The pH neutralization amounts to about 1.3. A purification over active carbon is then performed, followed by filtering off the formed precipitate and the active carbon. After distillation under vacuum a preparation is obtained which contains 3% by weight of silicon, 70% by weight choline hydrochloride and the rest water. FAB/MS with glycerol as liquid matrix provides a spectrum with a molecular cation at M/Z 104 (C@+) and an MC@+ adduction at M/Z243/245, typical for chloride isotropy. This spectrum is the same as the spectrum for choline. NMR-SPECTRUM OF THE PREPARATION SHOWING CHOLINE/ALCOHOL GROUPS Element analysis produces 24.A+/-.2% by weight chlorine and 9.A+/-.1% by weight N. This points to a ratio of chloride to nitrogen of 1:1. Neutralization is subsequently carried out to a pH of 2.7-3.0. The preparation is stable for more than two years when stored at room temperature. FORMULATION EXAMPLES Formulation Example A The biological preparation contains 3% by weight silicon in the form of ortho silicic acid, 70% by weight choline hydrochloride, the rest water and a pH of 2.7-3.0. This liquid is suitable for oral and cutaneous administering. Formulation Example B The biological preparation as prepared above is mixed with cattle feed which ultimately contains silicon as ortho silicic acid in a concentration of 0.001-0.005% by weight. This mixture can be pressed to pellets which are administered to cattle. Formulation Example C The preparation A is mixed with sugar and/or maltose which is pressed to tablets containing silicon in the form of ortho silicic acid at a content of 0.1-0.2% Si by weight. Formulation Example D A silicon-comprising cream is prepared as follows. A fat phase containing Imwitor 960 (Huls) 7%, Miglyol 812 10%, Softigon 701 (Huls) 2%, Marlowet TA 25 (Huls) 2%, Lanette N (Henkel) 4%, Isopropylmyristate 3%, a water phase containing Inositol 0.2%, Gluconate buffer 0.05 M, pH 3.8 ad 100, Glycerol 10% and the preparation A, as well as a perfume. The fat phase is melted at 80 DEG C., whereafter the water phase, also heated to 80 DEG C., is admixed, followed by cooling. Shortly before solidifying, the preparation A and perfume (4 drops) are added. The cream eventually contains 0.01-0.05% by weight silicon as ortho silicic acid. Flavourings can be added if desired, for instance by dilution (1:30) in a 0.01 M citrate buffer (pH 3.5-3.8) and by adding a flavouring (raspberry and the like). ---