A complex combining heterocyclic nitrogen biomolecules and silicic acid, and its applications.

Abstract

This invention provides a novel complex formed from heterocyclic nitrogen biomolecules and silicic acid, a composition containing the same, and its applications. [Solution] A complex is provided comprising a) a heterocyclic nitrogen biomolecule selected from purine nucleic acid bases and / or methylxanthine alkaloid derivatives thereof in free or N-glycosylated form, and b) silicic acid comprising at least one orthosilicic acid and / or its water-soluble oligomer, wherein the complex is preferably formed at the level of at least one nitrogen atom of the heterocyclic nitrogen biomolecule a) via the establishment of at least one weak chemical bond, preferably at least one hydrogen bond, between at least one hydroxyl group of the silicic acid b) and the heterocyclic nitrogen biomolecule a), and the molar ratio of a) to b) is about 0.5 to about 15.

Description

TECHNICAL FIELD

[0001] The present invention relates to a novel complex combining a heterocyclic nitrogen biomolecule and silicic acid, a composition containing the same, and applications thereof. BACKGROUND ART

[0002] Nucleic acids, encompassing two main forms, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are naturally occurring macromolecules found throughout all living organisms. Beyond their widely recognized uniqueness as genetic factors responsible for storing, encoding, and transferring genetic information to other cellular components, nucleic acids also play fundamental roles in humans through their involvement in numerous biological processes within the body, including catalyzing specific biochemical reactions and regulating certain intracellular activities (Wang F. et al., Biosensors, 2022, vol. 12, pp.1-35 and its references). As stated in the online guide to cosmetic ingredients for premium beauty formulations, nucleic acids now represent a group of bioactive molecules and ingredients considered “cutting-edge” because they are innovative, scientifically proven, effective, and most commonly incorporated into high-end skincare products (https: / / inci.guide / nucleic-acids). As a result, in the fields of cosmetics, dermatology, and even aesthetic and regenerative medicine, nucleic acid fragments such as polynucleotides and polydeoxyribonucleotides (linear biopolymers often referred to using the common abbreviations "PN" and "PDRN" respectively for convenience), as well as simple and basic constitutive monomeric units of nucleic acids, have recently gained popularity and potential for use in skin regeneration and bioreconstruction (Zakrewsky M. et al., J. Control Release, 2015, vol. 219, pp. 445-456). Therefore, as the first description of the effects and benefits that the aforementioned "nucleic acids and resulting fragments" have on the skin, a paper published this year reported promising results for the aforementioned PN in terms of its ability to reduce wrinkle depth and improve skin texture, and further concluded that it is an effective and well-tolerated cosmetic treatment (Lampridou S. et al. J. Cosmet. Dermatol., 2025, vol. 24, e16721).A few months ago, another study conducted on these same PNs reported significant improvements in skin elasticity and hydration (Lee KWA et al., Int. J. Mol. Sc., 2024, vol. 25, 8224). As mentioned above, PDRNs are natural fragments of low molecular weight DNA ranging from 50 to 1,500 kDa (Marques C. et al., Biomolecules, 2025, vol. 15, 148), and with the latest technology, they have yielded a wide range of skin effects, from promoting cell activity and collagen synthesis to treating hyperpigmentation, skin regeneration, and angiogenesis (Khan A. et al., Chinese J. Plastic Rec. Sur., 2022, vol. 4, pp. 187-193). Furthermore, the same team of authors chose the suggestive title for their paper: "Polydeoxyribonucleotide: a promising skin anti-aging agent." Based on the findings above, these same PDRNs are also known for their ability to stimulate neocollagenosis in photoaged skin and their potential for skin whitening due to their depigmentation properties (Noh TK et al., Int. J. mol. Sc., 2016, vol. 17, 1448). Furthermore, as a second description, this time we focus on the actions and effects on the skin of the aforementioned "basic constitutive monomeric units of nucleic acids," in other words, the five purine and pyrimidine nitrogen bases, namely adenine, guanine, cytosine, thymine, and uracil. With the latest technology, for example, adenine, a purine nuclear base, has been shown to have the ability to delay the aging of cells located in the dermal papillary layer, that is, the thin region located at the dermal-epidermal junction of the skin (Cheng YF. et al., Exp. Dermatol., 2016, vol. 25, pp. 151-164). The same adenine is N. 6Although functionalized with a compound known as -(4-hydroxybenzyl)adenine riboside, it itself has shown effects against cellular senescence caused by various types of oxidative stress in a mouse model of aging, and therefore shows potential as a potent agent for preventing age-related neurodegeneration and neuroinflammation (Hsu WH et al., Aging, 2020, vol. 12(11), pp.10556-10577). To that extent, and with regard to cosmetic and dermatological applications, guanine, another purine nuclear base, when combined with aldopentoses, is considered a useful active ingredient in maintaining skin homeostasis, particularly in the prevention and / or treatment of dermatitis (French Patent No. 2975595). It should also be noted that a superior form of nucleic acid (DNA) is composed of four of the five nitrogenous bases listed above, and each of these four nucleic acid bases (adenine, guanine, cytosine, and thymine) is listed in the "International Cosmetic Ingredient Dictionary and Handbook" published by the Personal Care Products Council (PCPC) of the American Cosmetic Association, in other words, a reference standard used globally by the cosmetics industry to standardize and define the names of all ingredients present in commercially available skincare product formulations. In any case, and in this stage of the description of the present invention, it should be noted that the list of effects on the skin associated with the use of nucleic acids and derivatives as active and functional ingredients on the skin is now extensive and promising, and that numerous studies on this subject have been published in the last decade. Within the scope of the meaning of this application, the aforementioned "nucleic acids and derivatives" should be understood to use a holistic approach, that is, to include both organic polymers consisting of a series of nucleotides and their constituent monomer units (the latter being free or functionalized by N-glycosidic bonds).However, despite this considerable effort to better understand the skin targets and the mechanisms of action of these nucleic acids and derivatives on the skin, several limitations and obstacles remain to their use, and case-by-case considerations are necessary for optimal utilization in cosmetics and dermacosmetics. In this regard, one challenge that can be mentioned is the stability of these nucleic acids and derivatives when applied topically to the skin, due to environmental factors (UV radiation, heat, humidity), biological factors (nucleases and natural enzymes of the skin), and chemical factors (contamination, pH changes, interactions with other components). All of these factors are likely to cause degradation and, consequently, loss of efficacy (Ingle RG et al., Pharmaceutics, 2023, vol. 15, 1158; Probst J. et al., Genetic Vaccines and Therapy, 2006, vol. 4(4), pp. 1-9). As previously shown, this proves to be particularly problematic with regard to the topical application / administration of these nucleic acids and derivatives to the skin. Indeed, because the stratum corneum of the epidermis acts as a protective barrier, the skin bioavailability and ability of these same nucleic acids and derivatives to penetrate the epidermis to impart targeted effects at the cellular level are likely to be affected, and diffusion may even be extremely limited when the deeper layers of the skin are targeted (Zakrewsky M. et al., J. Control Release, 2015, vol. 219, pp. 445-456 and its references). Similarly, their physicochemical behavior in solution is a “challenge” to overcome in order to optimize the use of these nucleic acids and derivatives in cosmetics and dermacosmetics, particularly in the context of topical application to the skin. In fact, PDRN and PN do not readily dissolve in water and usually require heat treatment, which can degrade their properties and quality (Marques C. et al., Biomolecules, 2025, vol. 15, 148).Regarding the aforementioned nucleic acid bases (sometimes simply called "bases"), their potential for applications is usually hindered by their low solubility in water (Ghoshdastidar D. et al., J. Phys. Chem. B., 2016, vol. 120(3), pp.492-503). Several concepts of general action have been reported regarding strategies to overcome any one of these limitations to the use of nucleic acids and derivatives (Wang F. et al., Biosensors, 2022, vol. 12, pp.1-35 and its references). As an example, we can cite the integration of nucleic acids and derivatives into different types of nanomaterials, such as lipid-based or inorganic nanoparticles, to achieve superior performance in targeted biomedical applications, particularly in the treatment of skin wrinkles (Yeo S. et al., Pharmaceutics, 2021, vol. 13, 33), and even combinations with a group of hydrotropes having amphiphilic molecular structures (U.S. Patent No. 2014107059). Recent technologies have also shown chemical modifications of natural nucleic acids aimed at improving their biological behavior, such as biocompatible chemical reactions (collectively and expressively called "click chemistry"), which "hook" specific bioactive and functional molecules onto them through conjugation, ultimately producing—according to the authors of the paper—"nucleoside hybrids" (Perrone D. et al., Molecules, 2021, vol. 26, 3100). Furthermore, due to its affinity for heteroaromatic compounds, arginine can increase the solubility of all nucleic acid bases being tested, provided that these nucleic acid bases are electrically neutral (Hirano A., Arch. Biochem. Biophys., 2010, vol. 497(1-2), pp. 90-96).Finally, there is also emphasis on less promising approaches aimed at increasing the solubility of substrates known to be poorly soluble in water (first demonstrated in studies with the nucleic acid base "adenine"), which involve the formation and acquisition of "complex" entities resulting from the relationship between the poorly soluble substrate and the selection of appropriate ligands such as water-soluble vitamins and amino acids, along with the determination of the apparent binding constant (Ka) (Chen AX et al., Pharm. Res., 1994, vol. 111(3), pp. 398-401).

[0003] In all cases, it is important to note that despite the availability of various solutions intended to promote the skin application of nucleic acids and derivatives, other studies have reported limited or even no efficacy (Lee KWA et al., Int. J. Mol. Sc., 2024, vol. 25, 8224). At the same time, there is still a need to continue further research aimed at establishing optimal conditions for use and efficacy for the more general applications of nucleic acids and derivatives in cosmetics and dermacosmetics, particularly regarding the aforementioned PDRNs, by evaluating their function and efficacy in a wide range of biological activities / efficacies (Nguyen TH et al., Int. J. Biol. Macromolecules, 2024, vol. 282(3), 137051). Therefore, the present invention fully addresses the need to design and make available (particularly in the market for cosmetic and / or dermacosmetic active ingredients classified as “nucleic acids and derivatives”) novel ingredients that satisfy all or part of the above-mentioned challenges and achieve all or part of the following objectives: i) The aforementioned limitations on the use of nucleic acids and derivatives: addressing stability, bioavailability, and solubility, ii) To maximize the biological potential of nucleic acids and their derivatives, in particular to prevent and / or counteract cosmetic and dermacosmetic abnormalities that may affect both the physiological functions of the body's skin and, more specifically, the physiological functions of the scalp. iii) optionally (but favorably), to indicate additional components to requirements i) and ii), i.e., to indicate complete naturalness for the component, essentially indicating a 100% naturalness index within the meaning of the international standard ISO 16128 (a document aimed at harmonizing and regulating the practices of players in the cosmetics industry regarding what is “natural,” in particular providing guidelines on definitions and criteria applicable to natural and organic cosmetic ingredients and products, and in particular establishing methods for determining “natural,” “naturally derived,” “organic,” and “organic matter derived” indicators applicable to cosmetic ingredients - reference no.: ISO 16128-2:2017(F)).

[0004] Regarding this (optional) requirement iii), its origins lie in the strong trend and demand currently seen among cosmetics developers: fortunately, in a world where concern for environmental issues and sustainability is growing, the cosmetics industry is also evolving, aiming to gradually integrate into more responsible and environmentally friendly practices. As a result, key concepts such as “naturalness,” “circular economy,” “ecodesign,” and “green cosmetics” have emerged in recent years, as reported in the white paper “Circular Economy and the Cosmetics Sector - 120 best practices for cosmetics companies” published by the Federation of Beauty Companies (FEBEA - Federation des Entreprises de la Beaute), a trade association of French cosmetics manufacturers. Essentially, this white paper addresses the challenges and opportunities facing the cosmetics sector in the face of the need to reduce the environmental impact of cosmetics. The white paper encourages waste reduction, resource optimization, and material reuse, while highlighting concrete solutions to ensure that product quality and safety are maintained. Through detailed recommendations, this best practices compilation clearly demonstrates the need to adopt more responsible practices throughout the product lifecycle, from design to end of life. Overall, the white paper urges all players in the cosmetics sector to fundamentally rethink how they manufacture by promoting a circular economy, or so-called “industrial” ecology, with a focus on minimizing waste, maximizing resource utilization, implementing effective recycling systems, and creating sustainable corporate ecosystems, as exemplified by the phrase found online, “Waste for some, raw materials for others.”Due to the growing, and even immediate, need for sustainable, effective, and environmentally and biodiversity-respecting alternatives to conventional fossil-based ingredients, suppliers of cosmetic ingredients, who are at the beginning of the product supply chain, face the challenge of innovation, particularly in the context of the four key concepts mentioned above (Goyal N., et al., Env. Sc. Pollution Res., 2023, vol. 30, pp. 25148-25169). Therefore, the applicant and its inventors also had the ambition to innovate, taking these findings into consideration. [Overview of the project]

[0005] Therefore, the present invention was developed in the context of the ambitious research and specifications described above, with the design and implementation of a set of tests aimed at establishing and developing a biological evaluation model for both skin and hair that can demonstrate the efficacy of the ingredients being tested and clearly show their effects. After extensive research, and contrary to all expectations based on the recognized knowledge that orthosilicate Si(OH)4 (or H4SiO4), a naturally occurring form of silicon absorbable by humans, has the disadvantage of existing at low concentrations in water (less than 2 mM or 56 mg Si / l) due to its extremely strong tendency to self-condense as silicon levels increase, resulting in potentially inactive or biologically inactive polymerized forms that are poorly absorbed or more difficult to absorb by the body (Jurkic LM et al., Nutr. Meta., 2013, vol. 10, pp. 1-12), the applicant has succeeded in designing novel molecular complexes (also known as "supramolecular" complexes) that combine, on the one hand, a limited family of nucleic acid bases and derivatives with, on the other hand, certain (preferably natural) soluble, bioavailable, and biologically absorbable silicon through interactions (supramolecular chemistry) under controlled ratios and conditions. This molecular complex is further advantageously derived from by-products (waste) initially produced by the grain industry [according to the optional requirements mentioned in point iii) above], and in addition, [according to the requirements mentioned in point ii) above] has broad and advantageous general behavior in cosmetics and dermacosmetics. Therefore, the present invention is a) Heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated form, b) Silicic acid comprising at least one orthosilicic acid and / or its water-soluble oligomer A (molecular) complex formed by, Preferably, at the level of at least one nitrogen atom of heterocyclic nitrogen biomolecule a), a weak chemical bond, preferably at least one hydrogen bond, is formed between at least one hydroxyl group of silicate b) and heterocyclic nitrogen biomolecule a), This concerns a complex in which the molar ratio of a) to b) is approximately 0.5 (e.g., 0.5) to approximately 15 (e.g., 15).

[0006] According to one embodiment, the complex according to the present invention is formed by the establishment of a weak bond, preferably a hydrogen bond, between the hydroxyl group of silicate b) and the nitrogen atom of heterocyclic nitrogen biomolecule a).

[0007] Indeed, after conducting numerous tests on both the ratios between the components of the composite and the operating conditions, the applicant has selected such a novel chemical entity and intermolecular bond in the form of a “composite” as defined by the nomenclature of the International Union of Pure and Applied Chemistry (UICPA in French, “Union Internationale de Chimie Pure et Appliquee” in English, “IUPAC”), due to the favorable and promising general behavior exhibited by the composite according to the present invention, namely, the experimental superiority shown by the composite according to the present invention compared to each of the individual components (which should be understood as “not involved in the same composite state”), and the scope of such beneficial technical effects is more precisely shown below: - Its ability to significantly restrict the secretion of lipids (sebum) produced and accumulated in and by sebaceous gland cells [see Test 1 below]. - Its ability to significantly stimulate the proliferation of dermal papilla cells (best known by the abbreviation "HFDPC") in human hair follicles; since the papillae are located at the base of the hair follicle, they play an important role in the hair growth phase (anagen phase) [see Test 2 below]. - Its ability to significantly limit the overgrowth of keratinocytes caused by inflammatory stress suggests a protective effect of the complex according to the present invention on keratinocytes (the constituent cells of the upper layer of skin known as the epidermis, as well as accessory organs such as hair and nails) [see Test 3 below]. -Finally, its ability to significantly improve skin viscoelasticity to skin explants through topical application suggests that the composite according to the present invention has the ability to restore the viscoelastic behavior of aging skin [see Test 4 below].

[0008] In Test 2 below, it is emphasized that the studies conducted and the complex according to the present invention enable the biological behavior of the complex to be demonstrated much more effectively—with broadly superior effects—than by the first component of the complex (adenine functionalized by an N-glycosidic bond, in this case a ribofuranose group via a β-N(9)-glycosidic bond) alone, or by the second component of the complex (silicic acid) alone.

[0009] Furthermore, in Test 2 below, the synergistic effect of such a complex according to the present invention [in this case, shown in the form of a complex formed by adenine functionalized by an N-glycosidic bond, in this case a ribofuranose group via a β-N(9)-glycosidic bond, and silicic acid] is revealed in a completely unexpected way. The synergistic effect of these actions further... -Considering the theoretical instruction given regarding the use of such expressions in the field of chemicals and products, in particular the fact that "there is a synergistic effect when the combined effect of two chemical products is much greater than the sum of the effects of each product taken individually. For example: 2 + 2 >> 4" (as in the original text) [https: / / www.cchst.ca / oshanswers / chemicals / synergism.htm], and -The combination of the two components that constitute the composite according to the present invention produces a much better effect than that obtained for the individual components at equivalent concentrations, in light of the experiments and results obtained in Test 2 below, It is a reasonable assumption.

[0010] It is also reasonable to assume that this particular mode of action, along with the objectified phenomenon of the synergy of this action, allows us to refer to the biological behavior of the aforementioned complex, which has been shown to be "optimal" or "endowed with optimal properties" for hair growth, and thus intended to promote hair growth / regrowth. Finally, it is also reasonable to assume the formation and existence of (molecular) "complex" states, on the one hand, by considering the definitions of "complex" and "hydrogen bond" established by the International Union of Pure and Applied Chemistry (UICPA in French, IUPAC in English), and on the other hand, by considering purine nucleic acid bases and derivatives that are specifically selected and indicated by the presence of non-bonding electron doublets and acidic hydrogen atoms at specific nitrogen atoms that precisely facilitate the establishment of such "hydrogen bond" type interactions by at least one hydroxyl group of silicic acid in their electron-rich regions. To the applicant's knowledge, the aforementioned family of heterocyclic nitrogen biomolecules a) and the aforementioned silicic acid b) (orthosilicic acid and / or at least one of its water-soluble oligomers) have never been combined in the form of molecular complexes for use in cosmetics and / or dermatological cosmetics, or even for abnormalities / changes that may affect both the physiological functions of the body's skin and, more specifically, the physiological functions of the scalp. Furthermore, the phenomenon of synergistic action between the aforementioned family of heterocyclic nitrogen biomolecules a) selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives and the aforementioned silicic acid b) has not been described to date, nor even predicted in the prior art, whether in a "complex" state (simple bonding). In addition, in accordance with the objectives accompanying the technical problems presented by the present invention, the aforementioned complex according to the present invention has the advantage of exhibiting a total naturalness index, i.e., an index of 100% natural origin within the meaning of the international standard ISO 16128, which is an advantage of the favorable embodiment of the present invention.

[0011] According to certain embodiments, the present invention also, a) Heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated form, b) Silicic acid comprising at least one orthosilicic acid and / or its water-soluble oligomer A (molecular) complex formed by, The present invention relates to a complex preferably formed at the level of at least one nitrogen atom of heterocyclic nitrogen biomolecule a) via the establishment of at least one weak chemical bond, preferably at least one hydrogen bond, between at least one hydroxyl group of silicate b) and heterocyclic nitrogen biomolecule a).

[0012] According to one embodiment of the present invention, the heterocyclic nitrogen biomolecule is a free purine nucleic acid base, preferably adenine or guanine, and more preferably adenine.

[0013] According to another embodiment of the present invention, the heterocyclic nitrogen biomolecule is an N-glycosylated purine nucleic acid base, preferably bound to D-ribose.

[0014] Advantageously, the N-glycosylated purine nucleic acid base is selected from 9-β-D-ribofuranosyladenine and / or 9-β-D-ribofuranosylguanine, preferably 9-β-D-ribofuranosyladenine (in IUPAC systematic nomenclature).

[0015] According to another embodiment of the present invention, the heterocyclic nitrogen biomolecule is a methylxanthine alkaloid derived from purine nucleic acid bases, selected from 1,3,7-trimethylxanthine, 1,3-dimethylxanthine, 3,7-dimethylxanthine, and / or 1,3-dimethylxanthine-7-acetic acid, preferably consisting of 1,3,7-trimethylxanthine (in IUPAC systematic nomenclature).

[0016] According to one embodiment of the present invention, silicic acid is orthosilicic acid (H4SiO4).

[0017] According to one embodiment of the present invention, the water-soluble oligomer of orthosilicic acid is disilicic acid (H6Si2O7), linear trisilicic acid (H8Si3O7) 10), and cyclic trisilicic acid (H6Si3O9), preferably disilicic acid (H6Si2O7).

[0018] According to one embodiment of the present invention, the silicic acid consists of orthosilicic acid and optionally at least one water-soluble oligomer thereof.

[0019] According to one embodiment of the present invention, the silicic acid consists of orthosilicic acid and at least one water-soluble oligomer thereof. In this embodiment, the proportion of orthosilicic acid is preferably 70% or more, preferably 90% or more, and advantageously 100%.

[0020] In a preferred embodiment of the present invention, on the one hand, the heterocyclic nitrogen biomolecule a) is adenine or 9-β-D-ribofuranosyladenine, preferably 9-β-D-ribofuranosyladenine, and on the other hand, the silicic acid b) is selected from orthosilicic acid and disilicic acid.

[0021] In a preferred embodiment of the present invention, the silicic acid b) is preferably derived from silicon-containing plant biomass selected from the grass species Oryza sativa (rice), Panicum miliaceum (proso millet), Triticum spp. (wheat), Zea mays (maize), Hordeum vulgare (barley), Avena sativa (oat), Secale cereale (rye), Sorghum bicolor (sorghum), Triticum dicoccum (emmer), Triticum turanicum (khorasan wheat), Eragrostis tef (teff), Digitaria exilis (fonio), and the pseudocereals Chenopodium quinoa (quinoa), Amaranthus spp. (amaranth), Fagopyrum esculentum (buckwheat), in particular selected from the grass species Oryza sativa (rice) and Panicum miliaceum (proso millet), advantageously from the species Oryza sativa (rice).

[0022] Preferably, the silicon-containing plant biomass is a by-product of the grain industry, preferably the husks of Oryza sativa (rice). In this regard, in fact, particularly for the purpose of point iii) above, the applicant examined raw materials derived from recycling (known in English as "upcycling"), in this case, the husks of Oryza sativa (rice), which are merely the outer shells covering the rice grains. There were two reasons for selecting this material first: firstly, it is clearly a natural by-product of rice threshing. Indeed, after the grains have been extracted, these husks are mostly considered agricultural waste and are produced in large quantities due to the activities of the rice industry, which is extremely important to the world's population. Fortunately, for over a decade, these rice husks and large quantities of waste have found numerous applications in various fields, including poultry farming, composting, and combustion, generating heat or electrical energy when used as biomass supplied to fuel reactors (Moraes CAM et al., Waste Management & Research, 2014, vol. 32(11), pp.1034-1048). On the other hand, in the context of the research and specifications described above, the applicant is of interest that these rice husks are also rich in silicon dioxide (SiO2), more commonly known as "rice husk silica," and should be noted as a sustainable alternative to conventional silica sources for environmentally responsible industries (Islam T. et al., Asian J. Chem. Sci., 2024, vol. 14(2), pp. 83-96). Finally, it has been reported that when this rice husk silica is heat-treated, it is converted into amorphous silica, a precursor type, and is a particularly interesting candidate for delivering the aforementioned orthosilicic acid up to its solubility limit (Ali M. et al., Int. J. Cur. Res. Rev., 2021, vol. 13(24), pp.94-99).

[0023] To gain an advantage: i) The molar ratio of heterocyclic nitrogen biomolecule a) to silicate b) is approximately 1 to approximately 7 (e.g., 1 to 7), favorably approximately 2 to approximately 3 (e.g., 2 to 3), and / or ii) The pH of the composition containing the complex (in liquid form, preferably in solution form) is approximately 2.5 to approximately 4.5 (e.g., 2.5 to 4.5), preferably approximately 3 to approximately 3.5 (e.g., 3 to 3.5), preferably approximately 3 (e.g., 3), Preferably, the complex and the liquid composition comprising the complex (preferably in solution form) have features i) and ii) as shown by the preparation process [see Test 5 below].

[0024] The present invention also comprises (or essentially consists of) a composition, preferably in solution form, comprising at least one complex according to the present invention. i) The molar ratio of heterocyclic nitrogen biomolecule a) to silicate b) is about 0.5 to about 15 (e.g., 0.5 to 15), preferably 1 to about 7 (e.g., 1 to 7), and advantageously about 2 to about 3 (e.g., 2 to 3), and / or ii) The pH of the composition containing the complex (in liquid form, preferably in solution form) is about 2.5 to about 4.5 (e.g., 2.5 to 4.5), preferably about 3 to about 3.5 (e.g., 3 to 3.5), and preferably about 3 (e.g., 3). Preferably, the composition relates to a composition having features i) and ii).

[0025] Incidentally, from a semantic perspective, it should be noted that the expression "basically consists of ~" used above has the same meaning as the expression "basically composed of ~," and these two descriptions are interchangeable.

[0026] According to a particular embodiment, the present invention relates to a composition, preferably in the form of a solution, a) A heterocyclic nitrogen biomolecule selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated form (as defined above), b) Silicic acid consisting of at least one of orthosilicic acid and / or its water-soluble oligomers (as defined above) It comprises (or is essentially composed of) at least one complex formed by, Preferably, at the level of at least one nitrogen atom of heterocyclic nitrogen biomolecule a), a weak chemical bond, preferably at least one hydrogen bond, is formed between at least one hydroxyl group of silicate b) and heterocyclic nitrogen biomolecule a), The present invention relates to a composition (in liquid, preferably solution form) whose pH is about 2.5 to about 4.5 (e.g., 2.5 to 4.5), preferably about 3 to about 3.5 (e.g., 3 to 3.5), and preferably about 3 (e.g., 3).

[0027] The present invention also relates to a cosmetic or dermacosmotic composition comprising (or essentially consisting of) at least one complex or composition according to the present invention in combination with at least one cosmetically or dermacosmotically acceptable excipient, preferably the cosmetic or dermacosmotic composition is further in a form suitable for topical administration to the skin, and at least one excipient is further physiologically acceptable to the skin. Advantageously, the amount of the composition according to the present invention in the aforementioned composition is 1% to 10% by weight of the total weight of the composition, preferably 3% to 7% by weight of the total weight of the composition. For example, and without limitation, when the aforementioned composition for cosmetic or dermacosmotic use is suitable for topical administration to the skin, the composition may exist in any form commonly used for such administration. Therefore, advantageously, the composition may be in the form of a solution (e.g., an aqueous solution or an aqueous alcohol solution), which may be liquid, preferably gel-like, which may be a solution, which may be biphasic, which may be a dispersion such as a lotion, which may be oil-in-water or water-in-oil emulsion, which may be a suspension, which may be a lotion, which may be a suspension, which may be a cream, which may be an aqueous gel or an aqueous alcohol gel, and may also be in the form of a (microparticle) powder, foam, serum, paste, suspension, dispersion, or optionally a multiple emulsion which may be a microemulsion or nanoemulsion. From the viewpoint of adjuvants present in the above-mentioned compositions that are physiologically compatible with the skin, we can list compounds selected from oils, waxes, silicone elastomers, surfactants, auxiliary surfactants, solubilizers, auxiliary solubilizers, thickeners and / or gelling agents, humectants, emollients, organic or inorganic sunscreens, light stabilizers, preservatives other than aldehyde-donating preservatives, colorants, abrasive fillers, pearlescent agents, matting agents, tightening agents, scavengers, fragrances, etc., and mixtures thereof.For example, and not exhaustively, such acceptable adjuvants in the application fields covered by the present invention are present in the formulation in an amount of 0.01 to 20% by weight of the total weight of the composition, and preparation and other supplements are described above and, in particular, cited in the "International Cosmetic Ingredient Dictionary and Handbook" published by the "Personal Care Products Council (PCPC)" of the American Cosmetic Association. Finally, these identical compositions described above may, in certain embodiments, contain at least one additional active ingredient, but those skilled in the art will take care to select these possible additional active ingredients and their proportions in such a way that the recognized beneficial properties of these compositions described above do not change, or are substantially changed, by the intended addition. Such additional active ingredients may be selected from, but are not limited to, decolorizing agents, photoprotective agents, barrier function stimulants, moisturizers or water-retaining agents, keratolytic agents, soothing agents, exfoliating agents, agents that stimulate cell proliferation such as fibroblasts and keratinocytes, deglycosylating agents, agents that stimulate collagen or elastin synthesis or prevent their degradation, agents that stimulate glycosaminoglycan or proteoglycan synthesis or prevent their degradation, antioxidants or anti-free radical or anti-pollution agents, lipolysis stimulants, dehydrating agents or detoxifiers, anti-inflammatory agents, penetration enhancers, keratolytic agents, soothing and / or anti-irritant agents, astringents, exfoliating agents, agents that act on microcirculation, etc. Such additional active ingredients are present in the formulation in an amount of 0.0001 to 20% by weight, preferably 0.01 to 5% by weight, relative to the total weight of the composition described above.

[0028] The present invention also relates to non-therapeutic cosmetic or dermacosmetic uses of the complexes or cosmetic or dermacosmetic compositions according to the present invention as defined above, a) To improve non-pathological conditions of excessive sebum secretion of the skin and / or scalp, preferably of the scalp, advantageously, to improve inflammation of the scalp related to non-pathological conditions of excessive sebum secretion of the scalp, and / or b) To promote hair growth or regrowth, and / or c) Preferably selected from skin exhibiting changes in viscoelastic properties and skin exhibiting changes in tissue adhesion, preventing and / or reducing signs of skin aging. Regarding non-therapeutic cosmetic or dermatocosmetic uses.

[0029] As stated above, the aforementioned non-therapeutic cosmetic or dermacosmetic uses target "healthy" skin or "healthy" hair—or areas of healthy skin—rather than "unhealthy" skin or hair—or areas of unhealthy skin—that indicate a pathological condition of the skin or hair.

[0030] In the case of topical application to the skin, this use is performed on one or more areas of “healthy” skin or “healthy” hair, i.e., one or more areas of skin or hair that are not affected by a pathological condition of the skin or hair.

[0031] According to certain embodiments, particularly in the case of administration routes other than topical administration to the skin, the aforementioned non-therapeutic cosmetic or dermacosmotic use is performed on individuals who do not have pathological conditions of the skin or hair. In the context of the present invention, this individual is referred to as a "healthy subject" in contrast to a "sick subject" who has pathological conditions of the skin or hair.

[0032] Another aspect of the present invention, distinct from the "cosmetic" or "dermacosmetic" aspects described above, also relates to a "dermatological" aspect. In this regard, the present invention also, a) Heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated form, b) Silicic acid comprising at least one orthosilicic acid and / or its water-soluble oligomer A complex formed by (or a composition containing or essentially consisting of such a complex), Preferably, at the level of at least one nitrogen atom of heterocyclic nitrogen biomolecule a), a weak chemical bond, preferably at least one hydrogen bond, is formed between at least one hydroxyl group of silicate b) and heterocyclic nitrogen biomolecule a), The molar ratio of a) to b) is approximately 0.5 to 15 (for example, 0.5 to 15). This relates to a complex (or a composition containing such a complex, or essentially consisting of such a complex) for use in the treatment of pathological seborrhea, acne, rosacea, and / or atopic dermatitis.

[0033] The present invention also, i) To promote the bioavailability of heterocyclic nitrogen biomolecules a) as defined above, and / or ii) Increase the solubility of heterocyclic nitrogen biomolecules a) as defined above. This relates to the use of silicate b) as defined above.

[0034] definition General definition "Nucleic acids and derivatives" should be interpreted to mean both organic polymers consisting of a series of nucleotides and their constituent monomer units (the latter may be free or functionalized by N-glycosidic bonds).

[0035] "Orthosilicic acid" should be interpreted as referring to a molecule with a living structure (H4SiO4).

[0036] "At least one of the water-soluble oligomers" should be interpreted as meaning one or more oligomeric forms, such as those described in the paper "Igarashi M. and al, Nature communications, 2017, vol. 8(140), pp.1-8" written by a Japanese team.

[0037] The terms "complex" or "molecular complex" should be interpreted as referring to a molecular entity, or a corresponding chemical species, formed by free bonds between two or more constituent molecular entities (ions or uncharged), and furthermore, the bonds between the constituents are usually weaker than those of covalent bonds (Source: IUPAC, 1994, 66, 1077 - Glossary of terms used in physical organic chemistry - IUPAC - Recommendations 1994 - on page 1098).

[0038] A "hydrogen bond" should be interpreted as the attractive interaction between a hydrogen atom in a molecule or molecular fragment XH (where X is more electronegative than H) and an atom or group of atoms in another molecule. A typical hydrogen bond can be represented as XH···YZ, where the three dots represent the bond, XH represents the hydrogen bond donor, and the acceptor is an electron-rich region such as an unbonded doublet of Y. Evidence for hydrogen bond formation can be experimental, theoretical, or a combination of both (Henry M., Interference International Review of Science, 2015 and its citations).

[0039] The "IUPAC Systematic Nomenclature" should be interpreted as meaning names that conform to a standardization system for compounds, based on the application of the most stringent recommendations established by the International Union of Pure and Applied Chemistry (UICPA in French, "Union Internationale de Chimie Pure et Appliquee" in English, "IUPAC"), which aims to ensure that a given name corresponds to a single molecular structure.

[0040] "Synergism" should be interpreted as meaning that a synergistic effect exists when the combined effect of two chemical products is greater than the sum of the effects of the individual products. For example: 2 + 2 >> 4. [https: / / www.cchst.ca / oshanswers / chemicals / synergism.html]

[0041] "According to controlled ratios and conditions" should be interpreted as meaning that the molar ratio of heterocyclic nitrogen biomolecule a) / silicic acid b) is limited to one of the purine nucleic acid bases or its methylxanthine alkaloid derivatives, established after comparative screening of composite tests aimed at defining the ratio between these two entities, and that this may lead to the identification of the most favorable biological behavior, as well as the operating conditions that enable the simultaneous solubilization of the heterocyclic nitrogen biomolecule a) and silicic acid b) entities, for the composite according to the present invention.

[0042] "Non-pathological hypersebum secretion of the skin and / or scalp" should be interpreted as excessive sebum secretion that results in a greasy, shiny, or even oily appearance of the skin or scalp, without the presence of a dermatological pathological condition.

[0043] As those skilled in the art will understand, "these methylxanthine alkaloid derivatives" refers to compounds that are xanthine-type, methylated, and primarily derived from the secondary metabolism of plants and their purine nucleic acid bases (Monteiro JP et al., Molecules, 2016, vol. 21, 974; Ashihara H. et al., Plant Nucleotide Metabolism - Biosynthesis, Degradation, and Alkaloid Formation, 2020, pp. 213-229). [Modes for carrying out the invention]

[0044] The following detailed description is intended to explain the invention clearly and completely, particularly with reference to examples, but should not be considered to limit the scope of protection to the specific embodiments and examples shown below. [Examples]

[0045] Example 1: Three examples of formulations of compositions according to the present invention for cosmetic or dermacosmetic use are described below, all of which contain the complex according to the invention described above: [Table 1] [Table 2] [Table 3]

[0046] Furthermore, it should be noted that, regarding the aforementioned formulation B, its use in in vivo studies (clinical trials conducted under confidentiality agreements) on humans yielded very favorable preliminary results (compared to placebo) for the scalp in terms of both sebum secretion (decreased sebum production) and its moisturizing (increased) levels.

[0047] Other in vivo studies (clinical trials, conducted under confidentiality agreements) performed on humans using the aforementioned formulation B have also been conducted to illustrate the use of the present invention, specifically focusing on the following parameters (vs. placebo): - Reduced number of hairs that fall out when brushing. - Reduced number of hairs that fall out when pulled. - Increase in density - Increase in hair count during the growth phase - Decrease in hair count during the resting phase.

[0048] Example 2: The present invention is demonstrated, purely for reference purposes, by the following tests (Tests 1-5) described in the description of the present invention. Test 1: Demonstrates the ability of the complex according to the present invention to restrict the secretion of lipids produced and accumulated in sebaceous gland cells, and by sebaceous gland cells. Experimentally, this test is performed on a model of immortalized human sebaceous gland cell line modified to express a functional androgen receptor (see bio-alternative "SEBO66662AR" in Qima Life Sciences Research Report SD230106). Specifically, these "SEBO6662" sebaceous gland cells are seeded in 96-well plates and cultured in medium for 24 hours. Subsequently, this medium is replaced with the test medium containing the reference substance "cerurenin" (a natural inhibitor of fatty acid biosynthesis and steroid metabolism) or the active ingredient to be tested, or (in the case of the control) not containing it. After a further 4-hour incubation, a lipid synthesis stimulant mixture (a mixture of vitamin C, vitamin D3, insulin, calcium, and dihydrotestosterone "DHT") is added, and the cells are incubated again for 7 days. On day 3 (D+3), half of the medium is removed and replaced with the treated substance (containing the lipid synthesis mixture). Non-stimulated control conditions are also performed in parallel. On day 7 (D+7), the cells are rinsed, fixed, and permeabilized. Subsequently, lipid droplets contained in the cells are labeled using a specific fluorescent lipid probe (Bodipy®) and subjected to image analysis using software (INCell Analyzer® 2200 - GE Healthcare). Photographs are taken for each well (20x magnification). Labeling is quantified by measuring the fluorescence intensity normalized to the total number of cells (average %). All experimental conditions are performed in three variations (n=3). The results are specifically expressed as the percentage of accumulated lipids and are summarized in Table 4 below. Results were obtained for the following different configurations: -Case 1, namely: "Control," that is, the version without the addition of the active ingredient. -Case 2, namely: Reference inhibitor (cerurenin), -Case 3, namely: The present invention provides a complex comprising, in a solution [batch number E18127], on the one hand, the compound "9-β-D-ribofuranosyladenine" (heterocyclic nitrogen biomolecule a) and on the other hand, at least one of orthosilicic acid and / or its water-soluble oligomer (silicic acid b), where orthosilicic acid is the initial silicon entity), combined (hydrogen-bonded) with a molar ratio (a / b) of 2.28. [Table 4]

[0049] The results clearly demonstrate that the complex according to the present invention has the ability to significantly inhibit the formation of lipid droplets caused by lipid synthesis mixtures containing androgens, i.e., the ability to reduce lipid synthesis and storage in sebaceous gland cells, and is particularly interesting in that it improves non-pathological excessive sebum secretion conditions of the skin and / or scalp.

[0050] Test 2: Demonstrates the ability of the complex according to the present invention to significantly stimulate cell proliferation in the dermal papilla of human hair follicles. Experimentally, this test will be performed on human dermal papilla cells (abbreviated as "HFDPC" for "Human Follicle Dermal Papilla Cells") obtained from human hair follicles from a temporal facelift of a 66-year-old Caucasian patient (supplied by Promocell: see C-12071-batch 485Z013). The cells will be cultured in medium at 37°C in 5% CO2 ("Human Follicle Dermal Papilla Cell Growth Medium + supplement Mix" - supplied by Promocell: see C-26501). On day 0 (D0), these HFDPCs will be 1.10 4 cells / cm 2The cells are seeded in 24-well plates at a density of [density]. On day 1 (D+1), the HFDPC cells are then treated with 500 μl of "HFDPC Growth Medium" in the presence of the compound to be tested. On day 2 (D+2), the effect of the treatment on cell proliferation is evaluated using a commonly used test for HFDPC cells, namely the "MTT test" or "3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test". The medium is replaced with 500 μL of 0.5 g / L MTT solution. After 3 hours of incubation, the generated formazan is dissolved in 500 μL of DMSO. Subsequently, absorbance is measured at 570 nm using a "Biotech EPOCH2 spectrophotometer (Agilent)". Finally, cell proliferation is compared to the mean DO of the untreated control group. 570nm DO against 570nm It is expressed as a percentage. The average values ​​obtained from three independent experiments are summarized in Table 5 below. The results were obtained for the following different configurations: -Case 1, namely: "Control," that is, the version without the addition of the active ingredient. -Case 2, namely: The compound "9-β-D-ribofuranosyladenine" [batch number E18427] is tested alone. -Case 3, namely: At least one of orthosilicic acid and / or its water-soluble oligomers [batch number E18428], to be tested alone. -Case 4, namely: The present invention provides a complex comprising, in solution [batch number 5148.23], on the one hand, the compound "9-β-D-ribofuranosyladenine" (heterocyclic nitrogen biomolecule a) (Case 3), and on the other hand, at least one of orthosilicic acid and / or its water-soluble oligomer (silicic acid b), where orthosilicic acid is the initial silicon entity (Case 4), combined (hydrogen bonded), with a molar ratio (a / b) of 2.28. [Table 5]

[0051] The results clearly demonstrate that the complex according to the present invention has a significantly superior ability to stimulate cell proliferation in the dermal papilla of human hair follicles, even through a targeted synergistic phenomenon, compared to when its two components are used separately, and is particularly interesting in that it promotes hair growth or regrowth.

[0052] Test 3: Demonstrates the ability of the complex according to the present invention to significantly limit the excessive proliferation of keratinocytes caused by inflammatory stress. Experimentally, this test will be performed on a series of immortalized keratinocytes "HaCaT" (supplier: ATCC) maintained by subculturing in complete "DMEM" medium (containing 1 g / l glucose supplemented with 10% fetal bovine serum) in 5% CO2 at 37°C under a humid atmosphere. On day 0 (D0), HaCaT cells are 2.10 4 cells / cm 2 Cells are seeded in 24-well plates at a density of [density]. On day 1 (D+1) and day 2 (D+2), cells are treated in complete DMEM medium containing 0.5% fetal bovine serum in the presence of inflammatory stress ("LPS stress") induced by an additional (15 ng / ml) bacterial lipopolysaccharide (LPS) containing the compound to be tested, responsible for the hyperproliferative response in keratinocytes. After two 24-hour treatment periods, cells are isolated, harvested, and counted using a Scepter Millipore counting pipette, with the value expressed as the average number of cells. The results, compiled from the mean values ​​obtained from three independent experiments, are shown in Table 6 below. Results were obtained for the following different configurations: -Case 1, namely: "Control," that is, a control group without the addition of active ingredients and without LPS-stress. -Case 2, namely: "LPS control," that is, a control group without the addition of active ingredients and under LPS stress. -Case 3, i.e. (those with LPS stress): In solution [batch number 5120.22], the compounds "methylsilanetriol," "(3-hydroxypropoxy)-(methyl)silanediol," and "9-β-D-ribofuranosyladenine" are combined in a molar ratio of 1, and the compound, such as methylsilanetriol or (3-hydroxypropoxy)-(methyl)silanediol, is a type of "organosilicon" possessed by the applicant, which is known to exhibit significantly superior properties in terms of superior behavior in water, as well as superior assimilation and stability compared to orthosilicic acid. -Case 4, i.e. (those with LPS stress): The present invention provides a complex comprising, in a solution [batch number E18127], on the one hand, compound "9-β-D-ribofuranosyladenine" (heterocyclic nitrogen biomolecule a) and on the other hand, at least one of orthosilicic acid and / or its water-soluble oligomer (silicic acid b), where orthosilicic acid is the initial silicon entity), combined (hydrogen bonded), with a molar ratio (a / b) of 2.28. [Table 6]

[0053] The results clearly demonstrate that the complex according to the present invention has the ability to significantly reduce the excessive proliferation of keratinocytes caused by inflammatory stress.

[0054] Test 4: Demonstrates the ability of the composite according to the present invention to improve the viscoelasticity of the skin. Experimentally, this test is performed on skin explants obtained from abdominal wall reconstruction in 55-year-old (Biomeca reference: 23031PA) and 61-year-old (Reference: 23032PA) patients, preserved in "DMEM-antibiotic" survival medium. Multiple "punches" of the same size (1.20 cm in diameter), i.e., skin sections containing epidermis and dermis, are placed on an insert at the air / liquid interface of the survival medium (Gibco DMEM + antibiotic cocktail, Biomeca reference: 31966021). Subsequently, the skin samples are kept under controlled temperature and humidity conditions (relative humidity: over 93% at 37°C) throughout the experiment.

[0055] The compounds to be tested are applied topically to the entire surface of the punch sample twice a day for 1.5 days, according to a defined protocol (Biomeca research report, ci: DEV-2023-0495) (100 μl is applied to the center of the punch sample). Atomic force microscopy (AFM) acquisition consists of force volume (FV) acquisition at skin level in an atmospheric environment, performed directly on skin explants, using an atomic force microscope (Bioscope Resolve - Bruker) equipped with an epifluorescence microscope (Leica DMi8). This combination also allows for the acquisition of correlated images between mechanical and fluorescence acquisition. Force volume (FV) acquisition corresponds to numerous measurement points, from which viscoelastic properties, expressed as "UA," are ultimately extracted. The combined average results from four independent experiments are summarized in Table 7. Results were obtained for the following different configurations: -Case 1, namely: "Control," that is, the version without the addition of the active ingredient. -Case 2, namely: In solution [batch number 5120], the compounds "methylsilanetriol," "(3-hydroxypropoxy)-(methyl)silanediol," and "9-β-D-ribofuranosyladenine" (Case 2) are combined in a molar ratio of 1, and the compound, such as methylsilanetriol or (3-hydroxypropoxy)-(methyl)silanediol, is a type of "organosilicon" possessed by the applicant, which is known to exhibit significantly superior properties in terms of superior behavior in water, as well as superior assimilation and stability compared to orthosilicic acid. -Case 3, namely: The present invention provides a complex comprising, in a solution [batch number 18127], on the one hand, the compound "9-β-D-ribofuranosyladenine" (heterocyclic nitrogen biomolecule a) and on the other hand, at least one of orthosilicic acid and / or its water-soluble oligomer (silicic acid b), where orthosilicic acid is the initial silicon entity), combined (hydrogen-bonded), with a molar ratio (a / b) of 2.28. [Table 7]

[0056] The results clearly demonstrate that the composite according to the present invention has the ability to significantly improve the viscoelastic properties of the skin, and is particularly useful in improving skin moisturizing and barrier functions, and especially in correcting wrinkle formation and skin laxity.

[0057] Test 5: A process for preparing a complex according to the present invention, which is formed on the one hand as 9-β-D-ribofuranosyladenine (heterocyclic nitrogen biomolecule a) and on the other hand as silicic acid (silicic acid b) consisting of at least one of orthosilicic acid and / or its water-soluble oligomers (orthosilicic acid is the initial silicon entity). To obtain 100 g of the complex according to the present invention, first, 9-β-D-ribofuranosyladenine (8.7 g, 32.5 mmol) is solubilized in a mixture consisting of desalinated water (40 g) and 1,3-dihydroxypropane (50 g). Subsequently, the pH of the solution is acidified to pH 3 with inorganic and / or organic acids. Then, under mechanical stirring at room temperature, 0.44 g (14.2 mmol) of concentrated silicate solution (solution of 90 g / kg silicon) obtained from rice husks (a by-product of the grain industry containing 9% silicon) is added to the aforementioned 9-β-D-ribofuranosyladenine solution, while ensuring that the pH of the mixture is maintained at 3-3.5 (again using inorganic and / or organic acids). After adding desalinated water (appropriate amount until 100) and filtering, a clear, colorless (complex) solution is obtained.

Claims

1. a) Heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated form, b) Silicic acid comprising at least one of orthosilicic acid and / or its water-soluble oligomers A complex formed by, Preferably, at the level of at least one nitrogen atom of the heterocyclic nitrogen biomolecule a), a weak chemical bond, preferably at least one hydrogen bond, is formed between at least one hydroxyl group of the silicate b) and the heterocyclic nitrogen biomolecule a). A complex in which the molar ratio of a) to b) is approximately 0.5 to approximately 15.

2. The complex according to claim 1, wherein the heterocyclic nitrogen biomolecule is a free purine nucleic acid base, preferably adenine or guanine, and more preferably adenine.

3. The complex according to claim 1, wherein the heterocyclic nitrogen biomolecule is an N-glycosylated purine nucleic acid base, preferably bound to D-ribose.

4. The complex according to claim 3, wherein the N-glycosylated purine nucleic acid base is selected from 9-β-D-ribofuranosyladenine and / or 9-β-D-ribofuranosylguanine, preferably 9-β-D-ribofuranosyladenine.

5. The complex according to claim 1, wherein the heterocyclic nitrogen biomolecule is a methylxanthine alkaloid derived from a purine nucleic acid base, and is selected from 1,3,7-trimethylxanthine, 1,3-dimethylxanthine, 3,7-dimethylxanthine, and / or 1,3-dimethylxanthine-7-acetic acid, and preferably consists of 1,3,7-trimethylxanthine.

6. The composite according to any one of claims 1 to 5, wherein the silicic acid is orthosilicic acid.

7. The composite according to any one of claims 1 to 6, wherein the water-soluble oligomer of orthosilicic acid is disilicic acid, linear trisilicic acid, and cyclic trisilicic acid, preferably disilicic acid.

8. The silicic acid b) is derived from silicon-containing plant biomass, preferably from the grass species Oryza sativa (rice), Panicum miliaceum (millet), or Triticum sp. (Wheat), Zea mays (corn), Hordeum vulgare (barley), Avena sativa (wild oats), Sequale cereale (rye), Sorghum bicolor (sorghum), Triticum dicoccum (spelt), Triticum turanicum (cola wheat), Eragrostis tef (teff), Digitaria exilis (fonio), and pseudocereals Chenopodium quinooa (quinoa), Amaranthus sp. (Amaranth), selected from Fagopyrum esculentum (buckwheat), and especially selected from the grass species Oryza sativa (rice) and Panicum miliaceum (millet), favorably the species Oryza sativa (rice), Preferably, the silicon-containing plant biomass is a by-product of the grain industry, preferably the shells of Oryza sativa, according to any one of claims 1 to 7.

9. A composition, preferably in the form of a solution, comprising at least one of the complexes described in any one of claims 1 to 8, i) The molar ratio of the heterocyclic nitrogen biomolecule a) to the silicate b) is about 0.5 to about 15, preferably 1 to about 7, and / or ii) The pH of the composition is about 2.5 to about 4.5, preferably about 3 to about 3.5, and advantageously about 3. A composition having preferably features i) and ii).

10. A cosmetic or dermacosmotic composition comprising, in combination with at least one cosmetically or dermacosmotically acceptable excipient, at least one complex according to any one of claims 1 to 8 or the composition according to claim 9, preferably in the form of a solution. Preferably, the cosmetic or dermacosmetic composition is further in a form suitable for topical administration to the skin, and the at least one excipient is further physiologically acceptable to the skin.

11. The cosmetic or dermacosmetic composition according to claim 10, further comprising at least one additional active ingredient selected from decolorizing agents, photoprotective agents, barrier function stimulating agents, moisturizing or water-retaining agents, keratolytic agents, soothing agents, exfoliating agents, agents that stimulate cell proliferation such as fibroblasts and keratinocytes, deglycosylating agents, agents that stimulate collagen or elastin synthesis or prevent their degradation, agents that stimulate glycosaminoglycan or proteoglycan synthesis or prevent their degradation, antioxidants or anti-free radical or anti-pollution agents, lipolysis stimulating agents, dehydrating agents or detoxifying agents, anti-inflammatory agents, penetration enhancers, keratolytic agents, soothing and / or anti-irritating agents, astringents, agents that act on microcirculation, and mixtures thereof.

12. i) To improve non-pathological conditions of excessive sebum secretion of the skin and / or scalp, preferably of the scalp, advantageously improving inflammation of the scalp associated with non-pathological conditions of excessive sebum secretion of the scalp, and / or ii) To promote hair growth or regrowth, and / or iii) Preferably selected from skin and tissues that exhibit changes in viscoelastic properties and tissue adhesion, to prevent and / or reduce signs of skin aging. Non-therapeutic cosmetic or dermacosmetic use of the complex according to any one of claims 1 to 8 or the composition according to any one of claims 9 to 11.

13. A complex according to any one of claims 1 to 8 or a composition according to claim 9 for use in the treatment of pathological seborrhea, acne, rosacea, and / or atopic dermatitis.

14. i) To promote the bioavailability of heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, in free or N-glycosylated forms, and / or ii) Increase the solubility of heterocyclic nitrogen biomolecules selected from purine nucleic acid bases and / or their methylxanthine alkaloid derivatives, either in free or N-glycosylated form. The use of silicic acid comprising at least one of orthosilicic acid and / or its water-soluble oligomers.

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