An adenosyl-based supramolecular composition, and a method of preparing and using the same

Abstract

The application provides an adenosine-based supramolecular composition, a preparation method and application thereof, and belongs to the technical field of daily chemical products, and the composition comprises the following chemical components in mass fraction: adenosine: 0.2-8%, adenosine acid derivative: 0.2-15%, antifreeze agent: 0.5-35%, pH regulator: 0.05-3.0%, and water: 60-98%; wherein the antifreeze agent comprises at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerol, sodium iodide and guanidine hydrochloride. The composition solves the problem of low solubility of adenosine in weak acid or neutral aqueous solution, and can maintain the stability of the solution under long-term storage, repeated freezing and thawing conditions or high-temperature conditions.

Description

Technical Field

[0001] This invention belongs to the field of daily chemical products technology, and specifically relates to an adenosine-based supramolecular composition, its preparation method, and its application. Background Technology

[0002] The most common types of hair loss currently fall into the following categories: The first is androgenetic alopecia (AGA), which accounts for approximately 90% of male pattern baldness. Besides genetic factors, AGA is mainly caused by the following factors: excessively high activity of 5α-reductase, increased expression of androgen receptors, fungal and bacterial infections and skin inflammation, and oxidation of hair follicles, leading to non-scarring progressive miniaturization of hair follicles, accompanied by a shortened growth cycle. The second common type of hair loss is telogen effluvium, whose main pathogenic mechanisms include: physiological (postpartum, seasonal hair loss), disease-related (fever and infection), stress-related (severe trauma, significant psychological stress, strenuous exercise), nutritional (malnutrition, fast-acting diets), and local factors (hair transplantation, contact dermatitis, scalp inflammation, scalp infection), ultimately manifesting as premature arrest and shortening of the growth phase and premature cell apoptosis.

[0003] Hair loss is primarily caused by impaired hair follicle cell activity, altering the hair follicle growth cycle and prematurely entering the regression phase. Common measures to combat hair loss include preventing damage to hair follicle cell activity and preventing shortened hair follicle growth cycles: such as blocking androgen stimulation of hair follicles (inhibiting 5α-reductase activity and androgen receptor activity), enhancing hair follicle resistance to androgens (activating cell metabolism, helping to synthesize more keratin or key components in the extracellular matrix, increasing hair follicle volume), and inhibiting micro-inflammatory stimulation of hair follicle cells. Common treatments include finasteride, spironolactone, minoxidil, and hair transplantation. Among these, commonly used chemical hair-reducing agents for treating androgenetic alopecia include minoxidil and finasteride. Finasteride is a potent 5α-reductase inhibitor that inhibits the conversion of serum testosterone to dihydrotestosterone, lowering dihydrotestosterone levels in the body to prevent hair follicle damage caused by androgen-induced hair loss. Minoxidil, by mediating the opening of potassium channels, enhances blood circulation in the epidermal region, thereby stimulating vascular endothelial growth factor and promoting hair growth in the dermal papilla. However, finasteride or minoxidil can easily cause negative reactions such as shedding phase, mood swings, insomnia, or skin inflammation. To address these issues, current methods often employ combinations of endogenous metabolites and / or natural extracts to improve hair regeneration quality while reducing side effects.

[0004] Among commonly used endogenous metabolites, adenosine has anti-aging and skin-whitening effects, while also promoting the regeneration of bone and skin tissues and possessing strong immunomodulatory effects. Furthermore, small-molecule adenosine has been proven in clinical and numerous basic studies to significantly promote hair regeneration. Adenosine is an active substance with nucleosides and purines as its basic structure. It is a nucleoside formed by adenine binding to D-ribose via a β-glycosidic bond. It is an intermediate product of metabolism, playing a crucial role in cellular energy metabolism by participating in the synthesis and degradation of ATP (adenosine triphosphate) and ADP (adenosine diphosphate), and is an important energy carrier in biochemical reactions. Adenosine can inhibit inflammatory responses and the activation of immune cells, helping to maintain homeostasis in the body. Simultaneously, adenosine can dilate blood vessels and promote blood circulation. When hair follicles shrink or are in the resting phase, adenosine can activate adenosine receptors, stimulating anti-hair loss factors and reducing hair loss. Therefore, anti-hair loss and hair regrowth promotion compositions with adenosine as their core are gradually becoming a hot topic in the scalp care field.

[0005] Chinese patent CN 117598920 A, "A Hair Loss Prevention and Hair Growth Composition and Its Preparation Method and Application," discloses that adenosine achieves its hair loss prevention and hair growth effect by promoting the secretion of FGF-7 factor and the growth rate of hair. Chinese patent CN117257667 A, "Hair Growth Liquid for Hair Loss Prevention and Strengthening and Its Preparation Method," discloses that adenosine's main effect on hair is to promote the proliferation and differentiation of hair follicle cells, thereby increasing the quantity and quality of hair; adenosine can also inhibit the activity of 5α-reductase, reducing androgen damage to hair follicles and preventing hair loss. Chinese patent CN 118370806 A, "A Compound Hair Growth Combination for Treating Hair Loss or Baldness," reports a formulation combining adenosine and other ingredients that can significantly promote the growth of new hair follicles. However, adenosine has poor solubility, is only slightly soluble in water, making it difficult to add large quantities to conventional formulations of hair loss prevention and hair growth liquids, and is almost insoluble in ethanol, making it impossible to solubilize with alcohol, thus limiting its application.

[0006] To address the poor solubility of adenosine, co-crystallization is commonly used to improve its solubility in aqueous solutions. Chinese patent CN119633104A, "A Method for Preparing Recombinant Type XVII Collagen and Adenosine Co-crystallization and Its Application," discloses a method for preparing recombinant type XVII collagen and adenosine co-crystallization and its application. The synergistic effect of the two substances improves the solubility and skin permeability of the co-crystallization, with adenosine solubility around 1%. Chinese patent CN117143164A, "An Adenosine Co-crystallization, Its Preparation Method and Application," discloses an adenosine co-crystallization formed by adenosine and ectoine or nicotinamide in a molar ratio of 1:0.2-16.9. Compared to adenosine, this co-crystallization exhibits higher solubility, with the resulting adenosine co-crystallization generally having a water solubility of around 1.5%. Chinese Patent CN 118047823 A, entitled "An Adenosine-Citrate-Betaine Ternary Cocrystal and Its Preparation Method and Application in the Cosmetic Field," discloses an adenosine-citric acid-betaine ternary cocrystal and its preparation method to improve the solubility of adenosine and its efficacy in cosmetics. Using adenosine as a hydrogen bond donor and citric acid and betaine as hydrogen bond acceptors, the ternary cocrystal prepared by a cooling crystallization method achieves an adenosine solubility of 2.184%. While effectively solving the crystallization problem of adenosine in cosmetics, the ternary cocrystal combines the keratin-softening effects of citric acid and the moisturizing and irritation-reducing effects of betaine, resulting in excellent moisturizing and anti-wrinkle effects.

[0007] Chinese Patent CN 119350416 A, "A Dihydroxysuccinate-Adenosine Cocrystal and Its Preparation Method and Application," discloses a method for preparing a dihydroxysuccinate-adenosine cocrystal. This method combines dihydroxysuccinate with adenosine to improve the water solubility of adenosine, preparing the poorly soluble adenosine into a water-soluble dihydroxysuccinate-adenosine cocrystal. The water solubility of the dihydroxysuccinate-adenosine cocrystal reaches 4%. This method not only preserves the efficacy of both dihydroxysuccinate and adenosine monomers but also enhances their synergistic effect, resulting in better efficacy than monomers or simple mixtures in antibacterial, antioxidant, anti-aging, and hair care / anti-hair loss aspects.

[0008] Existing methods can significantly improve the solubility of adenosine in aqueous solutions, but these involve multiple processes, increasing preparation costs. More importantly, increased adenosine solubility in aqueous solutions is often accompanied by a gradual decrease in pH value. Achieving a solubility exceeding 2% under weakly acidic or neutral conditions is difficult, and low pH results in highly irritating products. Furthermore, although adenosine may exhibit high short-term solubility in aqueous solutions, significant amounts precipitate out with prolonged storage or repeated freeze-thaw cycles, limiting the lifespan and application scope of adenosine-based hair growth products. Finally, for applications involving hair loss prevention and hair regrowth promotion, the functions of adenosine cocrystals in energy metabolism, immune regulation, and tissue regeneration need further enhancement. Therefore, there is an urgent need to develop a green, mild, soluble, easily prepared, and significantly effective compound adenosine product for preventing hair loss and promoting hair regrowth. Summary of the Invention

[0009] To address the problem of low solubility and unstable solubility of adenosine in weakly acidic or neutral aqueous solutions, this invention provides an adenosine-based supramolecular composition that solves the problem of low solubility of adenosine in weakly acidic or neutral aqueous solutions and maintains the stability of the solution under long-term storage, repeated freeze-thaw conditions, or high-temperature conditions.

[0010] The present invention also provides a method for preparing an adenosine-based supramolecular composition and its application.

[0011] This invention is achieved through the following technical solution:

[0012] This invention provides an adenosine-based supramolecular composition, which, by mass fraction, comprises the following chemical components:

[0013] Adenosine: 0.2–8%, adenosine derivatives: 0.2–15%, antifreeze: 0.5–35%, pH adjuster: 0.05–3.0%, water: 60–98%;

[0014] The adenosine derivatives include at least one of adenosine-5'-monophosphate (adenosine), sodium adenosine-5'-monophosphate, disodium adenosine-5'-monophosphate, 2′-deoxyadenosine-5′-monophosphate, adenosine 5'-diphosphate, sodium adenosine-5′-diphosphate, disodium adenosine-5′-diphosphate, potassium adenosine 5′-diphosphate, adenosine-5′-triphosphate (adenosine triphosphate, ATP), disodium adenosine-5′-triphosphate (adenosine triphosphate disodium), adenosine-5′-triphosphate dipotassium, sodium 2′-deoxyadenosine-5′-triphosphate, disodium 2′-deoxyadenosine-5′-triphosphate, and cyclic adenosine monophosphate.

[0015] The antifreeze includes at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerin, sodium iodide, and guanidine hydrochloride.

[0016] Furthermore, the pH adjuster includes at least one of trisodium citrate, sodium hydroxide, sodium carbonate, disodium hydrogen phosphate, sesquicarbonate, bicarbonate, silicate, bisulfate, phosphate, citrate, and pyrophosphate.

[0017] Optionally, the phosphate includes at least one of potassium dihydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, pentapotassium tripolyphosphate, and phosphoric acid.

[0018] The citrate includes citric acid and / or trisodium dehydrated citrate.

[0019] Optionally, the bicarbonate includes sodium bicarbonate;

[0020] The pyrophosphate includes tetrapotassium pyrophosphate or tetrasodium pyrophosphate.

[0021] Based on the same inventive concept, the present invention provides a method for preparing an adenosine-based supramolecular composition, the method comprising: dissolving an adenosine derivative and an antifreeze agent together in water, then adding adenosine at 50-80°C, and homogenizing the mixture to obtain a mixed solution;

[0022] The pH of the mixed solution was adjusted to 4.5–8.0 using a pH adjuster to obtain an adenosine-based supramolecular composition;

[0023] The mass ratio of adenosine, adenosine derivative, antifreeze and water is (0.2-8): (0.2-15): (0.5-35%): (60-98).

[0024] Furthermore, the adenosine derivative includes at least one of adenosine-5'-monophosphate, sodium adenosine-5'-monophosphate, disodium adenosine-5'-monophosphate, 2′-deoxyadenosine-5′-monophosphate, adenosine 5'-diphosphate, sodium adenosine-5′-diphosphate, disodium adenosine-5′-diphosphate, potassium adenosine-5′-diphosphate, adenosine-5′-triphosphate, disodium adenosine-5′-triphosphate, dipotassium adenosine-5′-triphosphate, sodium 2′-deoxyadenosine-5′-triphosphate, disodium 2′-deoxyadenosine-5′-triphosphate, and cyclic adenosine monophosphate.

[0025] The antifreeze includes at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerin, sodium iodide, and guanidine hydrochloride.

[0026] The pH adjuster includes at least one of trisodium citrate, sodium hydroxide, sodium carbonate, disodium hydrogen phosphate, sesquicarbonate, bicarbonate, silicate, bisulfate, phosphate, citrate, and pyrophosphate.

[0027] Furthermore, the step of dissolving the adenosine derivative and the antifreeze agent together in water, then adding adenosine at 50–80°C, and homogenizing to obtain a mixed solution specifically includes:

[0028] Adenosine derivatives and antifreeze agents are dissolved together in water, homogenized, and then adenosine is added at 50–80°C. The mixture is then mechanically stirred or ultrasonically homogenized for 0.5–4 hours to obtain a mixed solution.

[0029] Preferably, the power of the ultrasonic homogenizer is 200–1200 W, and the ultrasonic frequency is 20–60 kHz.

[0030] Based on the same inventive concept, this invention provides the application of an adenosine-based supramolecular composition in the preparation of anti-hair loss reagents, hair growth reagents, or skin care products.

[0031] Based on the same inventive concept, the present invention also provides a product for preventing and / or treating hair loss, wherein the active ingredient of the product comprises the above-mentioned adenosine supramolecular composition.

[0032] Furthermore, the dosage form of the product includes any one of cream, gel, patch, soluble microneedle, spray, ointment, plaster, emulsion, liniment, paste and mud dressing;

[0033] The products include any one of the following: conditioner, hair serum, shampoo, hair cream, hair mask, hair soap, hair cleanser, hair oil, hair dyeing aid, and hairspray.

[0034] Alternatively, the present invention provides a product for preventing and / or treating hair loss, wherein the product comprises the following ingredients by mass fraction:

[0035] Adenosine supramolecular composition: 79.35%, betaine: 6%, arginine: 2%, glycine: 3%, valine: 0.4%, lactic acid: 3%, sodium citrate: 2%, hexanediol: 2%, polylysine: 0.05%, lysozyme: 1%, NaOH: 1.2%;

[0036] The adenosine supramolecular composition is one of the above-mentioned adenosine supramolecular compositions.

[0037] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0038] 1. This invention discloses an adenosine-based supramolecular composition comprising adenosine, adenosine derivatives, an antifreeze agent, and water. The adenosine / adenosine derivative / antifreeze agent supramolecular system has the following advantages in terms of physicochemical properties: First, it can effectively improve the solubility stability of adenosine under near-physiological environmental conditions, greatly improving the solubility of adenosine. Even under repeated freeze-thaw conditions, adenosine can be stably dissolved in aqueous solution, greatly enhancing the therapeutic effects of adenosine in tissue regeneration, whitening, moisturizing, and anti-aging. Second, the active ingredients have complementary effects and can be applied to the field of hair loss prevention and hair growth promotion. The active ingredients for hair loss prevention and hair growth promotion (adenosine and adenosine derivatives) have a synergistic effect in promoting hair growth, with complementary functions, which can quickly stimulate the activity of hair follicle stem cells and promote hair growth in a short time.

[0039] 2. The present invention provides an adenosine-based supramolecular composition, which is obtained by screening and optimizing adenosine, adenosine derivatives and antifreeze supramolecular compositions from a variety of supramolecular raw materials. This composition can improve the solubility and skin permeability of adenosine in a weakly acidic to neutral pH environment without skin irritation. Even in a low temperature environment, adenosine does not precipitate, the solution is stable and uniform, and it can maintain the long-term stability of adenosine-based supramolecular composition under harsh conditions (e.g., high temperature, high pressure, etc.).

[0040] 3. This invention provides a method for preparing an adenosine-based supramolecular composition. This method is simple, easy to operate, green, safe, and can be mass-produced. It has good economic efficiency and sustainability. The selected components are mainly endogenous metabolites of the human body, which are easily absorbed and metabolized. It is mild and non-irritating, with no side effects. When the product obtained by this method is applied to the field of hair growth promotion, the adenosine-based supramolecular composition can be effectively enhanced by combining with other natural small molecule systems such as betaine, arginine, and glycine to improve the penetration effect of the anti-hair loss and hair growth promotion active ingredients (adenosine, adenosine derivatives), thereby improving the efficacy of anti-hair loss and hair growth promotion. Attached Figure Description

[0041] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0042] Figure 1 Stability observations of Examples 1, 2, and 3 at room temperature (left) and freeze-thaw (right);

[0043] Figure 2 For the stability observation of Comparative Examples 8, 9, 12 and 13 at room temperature (left) and freeze-thaw (right);

[0044] Figure 3Near-infrared spectral analysis for Example 1;

[0045] Figure 4 Analysis of thermal difference results for Example 1;

[0046] Figure 5 Thermogravimetric analysis for Example 1;

[0047] Figure 6 Evaluation of the therapeutic effect of adenosine-based ternary supramolecular molecules on a mouse AGA model;

[0048] Figure 7 Stability photos of application example 1 after 3 months of placement under different conditions;

[0049] Figure 8 To analyze the inhibition zone experiment of Malassezia furfur in Example 1;

[0050] Figure 9 To evaluate the effect of Example 1 in a human hair growth promotion experiment. Detailed Implementation

[0051] The present invention will be described in detail below with reference to specific embodiments and examples, thereby making the advantages and various effects of the present invention more clearly apparent. Those skilled in the art should understand that these specific embodiments and examples are for illustrative purposes only and are not intended to limit the present invention.

[0052] Throughout this specification, unless otherwise specified, the terminology used herein should be understood as having the meaning commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the event of any conflict, this specification shall prevail.

[0053] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0054] The technical principle of this invention is as follows:

[0055] To address the problem of low and unstable solubility of adenosine in weakly acidic or neutral aqueous solutions, this invention aims to construct a green, safe, and economical adenosine-based supramolecular composition. A supramolecular composition is a novel form in which active ingredients and excipients are combined through hydrogen bonds or other non-covalent bonds. Supramolecular technology can improve the physicochemical properties of active ingredients, such as stability, solubility, hygroscopicity, permeability, dissolution rate, and bioavailability. In the cosmetics field, supramolecular technology can not only improve the compatibility of poorly soluble raw materials but also increase their skin permeability, thereby enhancing their efficacy. For example, in the development and application of cosmetic raw materials, different raw materials can be self-assembled and spontaneously arranged into novel, structurally stable supramolecular composition raw materials through calculation, simulation, and design using intermolecular forces such as hydrogen bonds, electrostatic attraction, and van der Waals forces. Such supramolecular composition raw materials simultaneously possess the effects of two or more active ingredients and co-crystal formations, complementing each other and synergistically enhancing the effect. In addition, the active ingredients and eutectic formations used in the preparation of supramolecular composition raw materials are all taken from the cosmetic raw material reserve list, with high purity and few impurities. After self-assembly, they can promote the absorption of cosmetic efficacy ingredients, reduce irritation, and increase the water solubility and compatibility stability of efficacy ingredients.

[0056] To address the issues of poor adenosine solubility, low pH, and low permeability when applied to the scalp, this invention screens and optimizes various supramolecular raw materials to obtain a supramolecular composition of adenosine, adenosine derivatives, and antifreeze. This improves the solubility and skin permeability of adenosine in weakly acidic to neutral pH conditions without skin irritation. Even at low temperatures, adenosine does not precipitate, the solution is stable and homogeneous, and the adenosine-based supramolecular composition maintains long-term stability under harsh conditions (e.g., high temperature, high pressure, etc.). This completes the preparation route of the adenosine-based supramolecular composition of this invention.

[0057] Specifically, the present invention provides an adenosine-based supramolecular composition, wherein the composition comprises the following chemical components by mass fraction:

[0058] Adenosine: 0.2–8%, adenosine derivatives: 0.2–15%, antifreeze: 0.5–35%, pH adjuster: 0.05–3.0%, water: 60–98%;

[0059] The adenosine derivatives include at least one of adenosine-5'-monophosphate, sodium adenosine-5'-monophosphate, disodium adenosine-5'-monophosphate, 2′-deoxyadenosine-5′-monophosphate, adenosine 5'-diphosphate, sodium adenosine-5′-diphosphate, disodium adenosine-5′-diphosphate, potassium adenosine-5′-diphosphate, adenosine-5′-triphosphate, disodium adenosine-5′-triphosphate, dipotassium adenosine-5′-triphosphate, sodium 2′-deoxyadenosine-5′-triphosphate, disodium 2′-deoxyadenosine-5′-triphosphate, and cyclic adenosine monophosphate.

[0060] The antifreeze includes at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerin, sodium iodide, and guanidine hydrochloride.

[0061] In this invention, the adenosine derivative small molecules can not only directly stimulate the proliferation and differentiation of hair follicle epithelial cells, but also provide them with energy and nutrition, restore the metabolic balance of hair papilla cells, promote hair papilla cell proliferation, and inhibit cell apoptosis. Adenosine derivatives also improve metabolism, participate in the metabolism of fats, proteins, sugars, nucleic acids, and nucleotides in the body, and are also a source of energy.

[0062] The adenosine-based supramolecular structure of this invention achieves excellent exfoliation under weakly acidic to neutral conditions, exhibits minimal irritation and excellent low-temperature safety, and maintains its exfoliation effect even under harsh conditions. The inventors, through systematic screening of numerous natural small molecules, unexpectedly discovered that adenosine derivatives can improve the water solubility of adenosine under weakly acidic or neutral conditions. However, the supramolecular composition formed by the adenosine derivative and adenosine is unstable at low temperatures after dissolving in water. When placed in a low-temperature environment and then thawed after a period of time, a large amount of adenosine precipitates out, affecting the product's applicability.

[0063] In this invention, antifreeze agents enhance the low-temperature stability of supramolecular compositions. The inventors unexpectedly discovered that adding antifreeze agents to supramolecular compositions of adenosine and its derivatives effectively improves the stability of adenosine at low temperatures; even after repeated freeze-thaw cycles at -20°C, no adenosine precipitation occurs. Urea, in particular, is an important component of natural moisturizing factors. It effectively absorbs moisture from the air, forming a protective film on the skin surface and reducing moisture loss. Its moisturizing ability is especially suitable for dry, flaky skin, significantly improving roughness and dryness. Urea can also dissolve keratin, soften the stratum corneum, and promote the shedding of old keratinocytes. This property makes it commonly used in hand creams, foot creams, and other products to help improve keratosis pilaris or localized thickened keratin. Urea can enhance the skin barrier function, promote epidermal cell regeneration, and accelerate wound healing. For minor skin injuries or dermatitis, urea-containing skincare products can aid in repair. Urea can improve the skin's absorption efficiency of other active ingredients (such as anti-inflammatory agents and moisturizers) and enhance the transdermal absorption effect of adenosine supramolecular molecules. Therefore, urea is preferred as the antifreeze agent in this invention.

[0064] In the supramolecular composition of this invention, the adenosine content is 0.2-8%. If the concentration is too low, the hair growth effect will not be observed; if the concentration is too high, the system stability cannot be maintained. The adenosine derivative content is 0.2-15%. If the concentration is too low, adenosine will easily precipitate; if the concentration is too high, the irritation of the system will increase significantly. The antifreeze content is 0.5-35%. If the antifreeze content is too low, adenosine will gradually precipitate during freezing; if the content is too high, the irritation of the system will increase.

[0065] In the supramolecular composition of the present invention, the water content is 60-98%. If the water content is less than 60%, the system will be particularly viscous, and adenosine will precipitate out after prolonged standing. If the water content is higher than 98%, the active ingredients in the system are too low, which weakens the therapeutic effect.

[0066] Furthermore, the pH adjuster includes at least one of trisodium citrate, sodium hydroxide, sodium carbonate, disodium hydrogen phosphate, sesquicarbonate, bicarbonate, silicate, bisulfate, phosphate, citrate, and pyrophosphate.

[0067] Optionally, the phosphate includes at least one of potassium dihydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, pentapotassium tripolyphosphate, and phosphoric acid.

[0068] The citrate includes citric acid and / or trisodium dehydrated citrate.

[0069] The present invention also provides a method for preparing an adenosine-based supramolecular composition, the method comprising: dissolving an adenosine derivative and an antifreeze agent together in water, then adding adenosine at 50-80°C, and homogenizing the mixture to obtain a mixed solution;

[0070] The pH of the mixed solution was adjusted to 4.5–8.0 using a pH adjuster to obtain an adenosine-based supramolecular composition;

[0071] The mass ratio of adenosine, adenosine derivative, antifreeze and water is (0.2-8): (0.2-15): (0.5-35%): (60-98).

[0072] The following will provide a detailed description of an adenosine-based supramolecular composition, its preparation method, and its application, in conjunction with examples and experimental data.

[0073] The adenosine and adenosine derivatives used in the various embodiments of the present invention were purchased from Jiangsu Suryu Biotechnology Co., Ltd., and other chemical reagents were purchased from Shanghai Maclean Biotechnology Co., Ltd.

[0074] Example 1

[0075] The preparation of a supramolecular mixture of adenosine / disodium adenosine triphosphate / urea includes the following steps:

[0076] S1. Weigh 3 parts by weight of disodium adenosine triphosphate and 5 parts by weight of urea and dissolve them in 85 parts by weight of purified water. Stir at room temperature (200 r / min) for 2 h to obtain an aqueous solution of disodium adenosine triphosphate and urea.

[0077] S2. Heat the above mixed solution system to 50°C, weigh 1.5 parts by weight of adenosine and slowly add it to the system, maintain the system temperature and stir magnetically (200 r / min) for 2 h.

[0078] S3. Adjust the pH of the above solution to 5.7 with NaOH, and titrate with purified water to 100 parts by weight to prepare an adenosine supramolecular complex solution. The stability of the complex solution was observed by placing it at room temperature (20℃), high temperature (60℃), and -20℃ for different times.

[0079] A DSC 214 differential scanning calorimeter (NETZSCH, Germany) was used to measure the calorimeter temperature at 10 °C·min. -1 The thermodynamic behavior of the supramolecular composition was analyzed by heating rate. A TG209F1 Libra thermogravimetric analyzer (NETZSCH, Germany) was used in a nitrogen atmosphere at a rate of 10 °C·min. -1 Thermogravimetric analysis (TGA) and differential thermogravimetric analysis (DTG) were performed at the specified rates. A Spectrum Two spectrometer (PerkinElmer, USA) was used at 4000–400 cm⁻¹. -1 Within a range of 4 cm -1 Fourier transform infrared (FTIR) spectra were acquired with high spectral resolution.

[0080] Example 2

[0081] The preparation of a supramolecular mixture of adenosine / disodium adenosine triphosphate / urea includes the following steps:

[0082] S1. Weigh 6 parts by weight of disodium adenosine triphosphate and 30 parts by weight of urea and dissolve them in 50 parts by weight of purified water. Stir at room temperature (400 r / min) for 2 h to obtain an aqueous solution of disodium adenosine triphosphate and urea.

[0083] S2. Heat the above mixed solution system to 60°C, weigh 5 parts by weight of adenosine and slowly add it to the system, maintain the system temperature and stir magnetically (400 r / min) for 2 h.

[0084] S3. Adjust the pH of the above solution to 5.8 with NaOH, and titrate with purified water to 100 parts by weight to prepare an adenosine supramolecular complex solution. The stability of the complex solution was observed by placing it at room temperature (20℃), high temperature (60℃), and -20℃ for different times.

[0085] Example 3

[0086] Preparation of adenosine / adenosine-5'-monophosphate (adenosine acid) / urea supramolecular mixture: The preparation of the adenosine supramolecular mixture includes the following steps:

[0087] S1. Weigh 0.5 parts by weight of adenosine and 3 parts by weight of urea and dissolve them in 95 parts by weight of purified water. Stir at room temperature (800 r / min) for 2 h to obtain an aqueous solution of adenosine and urea.

[0088] S2. Heat the above mixed solution system to 65°C, weigh 1 part by weight of adenosine and slowly add it to the system, maintain the system temperature and stir magnetically (600 r / min) for 2 h.

[0089] S3. Adjust the pH of the above solution to 5.5 with NaOH, and titrate with purified water to 100 parts by weight to prepare the adenosine / adenosine acid / urea supramolecular structure. The stability of the composite solution was observed by placing it at room temperature (20℃), high temperature (60℃), and -20℃ for different times.

[0090] The stirring rate, time, and reaction temperature of Examples 4-9 were the same as those of Example 3 (the preparation method was the same), and the components and their weight parts are shown in Table 1.

[0091] Table 1. Composition description of adenosine supramolecular molecules in Examples 1-9 at different pH values.

[0092]

[0093] Table 2. Stability analysis of the adenosine supramolecular molecules in Examples 1-9 at room temperature (20°C), refrigeration (-20°C), repeated freeze-thaw cycles 20 times, and high temperature (60°C) for 3 months.

[0094]

[0095] Evaluation of in vivo hair regeneration experiments:

[0096] After a one-week acclimatization period, seven-week-old healthy male mice were anesthetized, and a 2 cm × 2 cm area on their backs was treated with an electric shaver, followed by application of depilatory cream for 3 minutes. Mice were randomly assigned to groups. During the 21-day experimental period, except for the control group, all other groups received daily topical application of 200 µL of testosterone solution (0.5%, v / v) to induce androgenetic alopecia (AGA). Fifty minutes after application, the treatment groups received 200 µL of the corresponding formulation (minoxidil, or adenosine supramolecular formulation as described in Example 3). Histological and immunofluorescence analysis: On day 21, mice were sacrificed, and full-thickness skin samples were collected from the backs and fixed in 4% paraformaldehyde (PFA) for 24 hours. The fixed tissues were processed, embedded in paraffin, and sectioned to a thickness of 3–5 µm. For histological analysis, the sections were dewaxed, hydrated, and stained with hematoxylin and eosin (H&E). For immunofluorescence staining, dewaxed sections were incubated overnight at 4°C with primary antibodies (anti-Sox9 antibody, Huaan Biotechnology; anti-8-OHdG antibody, Bio-Sens) followed by incubation at room temperature with the corresponding fluorescent secondary antibody (Jackson). Cell nuclei were counterstained with DAPI (Beyotime). Cell proliferation was detected by the EdU incorporation assay using the Click-it EdU Alexa Fluor 488 imaging kit (Thermo Fisher Scientific, C10337). Images of all stained sections were acquired using a laser confocal microscope (FV3000RS, Olympus, Japan) and a fluorescence microscope (DMi8, Leica, Germany). Positive staining areas for each marker were quantitatively analyzed using ImageJ software.

[0097] Comparative Example 1

[0098] This comparative example provides an adenosine complex solution, prepared by the following method:

[0099] S1. Weigh 98 parts by weight of purified water and heat it to 50°C;

[0100] S2. Weigh 1.5 parts by weight of adenosine, slowly add it to the above solution, stir at 50°C (400 r / min) for 2 hours, and add citric acid to adjust the pH of the solution to 5.2.

[0101] The stability of the composite solution was observed by placing it at room temperature (20℃), refrigeration (-20℃), high temperature (60℃) and repeated freeze-thaw conditions for different periods of time. It was observed that adenosine was rapidly precipitated under all three conditions: room temperature, refrigeration and repeated freeze-thaw conditions, indicating that the formulation was unstable.

[0102] Comparative Example 2

[0103] This comparative example provides an adenosine complex solution, prepared by the following method:

[0104] S1. Weigh 30 parts by weight of urea and dissolve it in 65 parts by weight of purified aqueous solution, then stir and mix at room temperature.

[0105] S2. Slowly raise the temperature of the above solution to 50°C, weigh 2 parts by weight of adenosine, slowly add it to the above solution, stir at 50°C (400 r / min) for 2 h, add NaOH to adjust the pH of the solution, and titrate with purified water to 100 parts by weight.

[0106] The stability of the composite solution was observed by placing it in different environments at room temperature, refrigeration, high temperature (60℃), and repeated freeze-thaw cycles for different periods of time. It was observed that adenosine precipitated rapidly under all three conditions: room temperature, refrigeration, and repeated freeze-thaw cycles, indicating that the formulation was unstable.

[0107] Comparative Example 3

[0108] This comparative example provides an adenosine complex solution, prepared by the following method:

[0109] S1. Weigh 0.5 parts by weight of adenosine and dissolve it in 95 parts by weight of purified water. Stir at room temperature (800 r / min) for 2 h to obtain an aqueous solution of adenosine.

[0110] S2. Heat the above mixed solution system to 65°C, weigh 1 part by weight of adenosine and slowly add it to the system, maintain the system temperature and stir magnetically (600 r / min) for 2 h.

[0111] S3. Adjust the pH of the above solution with NaOH, and titrate with purified water to 100 parts by weight to prepare an adenosine / urea mixed solution. Observe the stability of this composite solution by placing it at room temperature, high temperature (60℃), and -20℃ for different times.

[0112] Comparative Example 4

[0113] This comparative example provides an adenosine complex solution, prepared by the following method:

[0114] S1. Weigh 5 parts by weight of disodium adenosine triphosphate and dissolve it in 90 parts by weight of purified water. Stir at room temperature (200 r / min) for 2 h to obtain a mixed aqueous solution.

[0115] S2. Heat the above mixed solution system to 50°C, weigh 2 parts by weight of adenosine and slowly add it to the above system, maintain the system temperature and stir magnetically (200 r / min) for 2 h.

[0116] S3. Adjust the pH of the above solution with citric acid, and titrate with purified water to 100 parts by weight to prepare a mixed solution of adenosine / adenosine triphosphate disodium. Observe the stability of the composite solution by placing it at room temperature, high temperature (60℃), and -20℃ for different times.

[0117] The reaction temperature, stirring rate, and time in the preparation process of Comparative Examples 5-13 were kept the same as those in Comparative Example 4, and their specific components and weight parts are shown in Table 3.

[0118] Table 3. Description of the composition and weight fractions of the adenosine complex solutions in Comparative Examples 1-13 at different pH values.

[0119]

[0120] Table 4. Stability analysis of samples from Comparative Examples 1-13 at room temperature (20℃), refrigerated (-20℃), after 20 freeze-thaw cycles, and after 3 months at high temperature (60℃).

[0121]

[0122] Application Example 1

[0123] Preparation of a scalp serum containing adenosine supramolecular molecules and its application in promoting hair regeneration. The preparation process of the serum is as follows:

[0124] The specific steps are as follows: Prepare a supramolecular system of adenosine / adenosine acid / urea / pure water according to Example 3. Stir magnetically at 50°C, then slowly add 6 parts by weight of betaine, 2 parts by weight of arginine, 3 parts by weight of glycine, 0.4 parts by weight of valine, 3 parts by weight of lactic acid, and 2 parts by weight of sodium citrate. Then, lower the solution temperature to room temperature, add 2 parts by weight of hexanediol, 0.05 parts by weight of polylysine, and 1 part by weight of lysozyme, and continue homogenization for 2 hours. Finally, add 1.2 parts by weight of NaOH to adjust the pH of the system to approximately 6.0 to obtain the adenosine-based supramolecular scalp essence.

[0125] Malassezia antibacterial test: This test was conducted according to the laboratory method (LC-WI-HZ-192 Dandruff Efficacy Evaluation Experiment (Antibacterial Ring Method) Operating Instructions). Malassezia is a lipophilic fungus that resides on the surface of human skin and feeds on sebum secreted by the scalp. Abnormal activity of Malassezia is generally considered the main cause of dandruff formation. Excessive proliferation of Malassezia severely weakens the scalp's protective barrier, causing large clusters of epidermal cells to detach, resulting in recurring dandruff. In this experiment, a dry paper strip soaked in the sample was placed on a contaminated plate, and the growth of bacteria around the paper strip was observed. The presence of bacterial colonies around the paper strip indicated no antibacterial effect, while the absence of bacterial colonies and the formation of an inhibited area indicated an antibacterial effect. This was used to determine the product's dandruff-reducing efficacy. The test sample was dropped onto sterile filter paper and allowed to dry naturally. The test sample was placed on a stained agar plate, and the plate was placed in an incubator and incubated at 30°C for 5 days. The diameter of the inhibition zone against Malassezia furfur was calculated. If the diameter of the inhibition zone against Malassezia furfur is greater than 7 mm, the test sample can be considered to have a certain dandruff-removing effect.

[0126] Clinical observation experiment: 202 participants (120 males and 82 females) aged 25-68 years were randomly selected.

[0127] 1) Before using application example 1, take a photo to record the area where hair growth is needed;

[0128] 2) Apply to the entire scalp or areas with severe hair loss in the morning and evening, massaging until absorbed. (Note: Wash your hair as usual.)

[0129] 3) Photo standards for severe hair loss: Photos should be taken from the top, back, left, and right sides of the head, as well as the areas with severe hair loss.

[0130] 4) Standard for photographing localized hair loss (hairline): localized sparse hair loss, with areas where products have been used.

[0131] 5) Criteria for fine and sparse hair: The photo should be taken from the top, back, left, or right side of the head;

[0132] 6) Take photos every two weeks to document the process. Continue until three months have passed;

[0133] 6) Safety and management of adverse reactions: For the first three days of use, subjects should be asked daily if they experience any adverse reactions, such as itching or stinging. Simultaneously, observe whether the subject's scalp shows redness, rashes, or other adverse symptoms. Are there any suggestions for improvement regarding the user experience?

[0134] 7) All adverse reactions should be recorded, including subjective adverse reactions, objective adverse manifestations, the time of occurrence, and their relationship to the trial content.

[0135] Table 5. Explanation of component content and weight parts in Application Example 1

[0136]

[0137] To achieve the above objectives, this invention uses adenosine supramolecular molecules as the basic active ingredient of the anti-hair loss and hair growth promoting liquid, and employs natural amino acids and their derivatives, organic acids and other natural molecules to improve the absorption efficiency of adenosine active drugs through the skin and cell membrane and the effect of promoting hair regeneration.

[0138] In the formulation of Application Example 1, betaine (also known as trimethylglycine) has attracted widespread attention due to its wide availability, good biocompatibility, economic benefits, and rich biological functions. The applicant's comparative study found that, compared to betaine, it can reshape the aging microenvironment homeostasis by reducing reactive oxygen species levels, alleviating inflammation, improving DNA / RNA methylation, regulating mitochondrial function, reducing homocysteine ​​concentration, promoting angiogenesis, and regulating cell osmotic pressure, thereby delaying the aging process.

[0139] In addition, arginine, an amino acid naturally present in the human body, is a common nutritional supplement in cosmetics. Recent studies have confirmed that arginine has free radical scavenging capabilities, can promote macrophage polarization from M1 to M2, and can synthesize nitric oxide (NO) signaling molecules in the body. L-arginine promotes the shift from glycolysis to oxidative phosphorylation in inflammatory cells, thereby increasing ATP production, promoting purine metabolism, and increasing inosine and hypoxanthine levels. Arginine can also act on potassium ion channels in cells, dilating blood vessels and thus improving blood flow to hair follicles. Simultaneously, arginine is an important precursor for NO synthesis, and NO has the potential to stimulate hair follicle regeneration and prevent hair loss. Furthermore, amino acids such as glycine and valine also have certain moisturizing functions, enhancing the comfort of serums.

[0140] Finally, lactic acid in the system plays a key role in promoting keratin exfoliation and drug penetration, and a large number of studies have reported that lactic acid can improve hair regeneration to a certain extent.

[0141] In Application Example 1, relatively safe and environmentally friendly preservatives were used, including polylysine, hexanediol, and nisin. More importantly, the preservatives in the system play a positive role in regulating the scalp's microbial microenvironment.

[0142] Results Analysis

[0143] The adenosine supramolecular molecules in Examples 1-9 remained stable for more than 3 months under various conditions, including room temperature, refrigeration, repeated freeze-thaw cycles at -20°C (10 times), and 60°C, without precipitation or color change (Table 2). Figure 1 ).

[0144] The adenosine mixtures in Comparative Examples 1-13 all precipitated after repeated freeze-thaw cycles at room temperature, especially at -20°C, indicating instability and affecting the subsequent use of adenosine (Table 4). Figure 2 ).

[0145] The Fourier transform infrared spectroscopy analysis results in Example 1 are as follows ( Figure 3 ): 3100-3500 cm -1 The broad and strong absorption band in the region is due to the superposition of vibrations of the ribohydroxyl (OH) of ATP, the amino (NH) of adenosine, and the amide (NH) of urea. The significant red shift and broadening of the peak position proves the formation of multiple intermolecular hydrogen bonds between the components. (1600-1700 cm⁻¹) -1 The interval corresponds to the C=O stretching vibration of urea (amide I band) and the skeletal vibration of adenine bases. The shift of the urea carbonyl peak to lower wavenumbers indicates that its oxygen atom acts as a hydrogen bond acceptor, interacting strongly with ATP or adenosine. (1000-1250 cm⁻¹) -1 The region is mainly attributed to the phosphate groups of ATP (P=O, PO). - The asymmetric stretching vibrations and the peak splitting and shifting of the ternary molecule in this region reflect the "anchoring" effect of urea molecules on the phosphate backbone. This environmental difference confirms the unique charge-assisted hydrogen bonding effect in the supramolecular system.

[0146] The thermal difference test results in Example 1 show that ( Figure 4 The sharp endothermic peak at 133℃, due to the melting of pure urea crystals, the disappearance of this characteristic peak in the ternary system, and the appearance of new endothermic events at lower temperatures (approximately 100-120℃) demonstrate that the urea lattice was disrupted and a new eutectic or eutectic phase was formed. The peak near 230℃ corresponds to the melting of adenosine and the thermal decomposition of ATP; the peak fusion and broadening of the ternary system at this point reflect the collapse of the supramolecular structure and complex phase transitions at high temperatures. The absence of characteristic melting points of individual components and the appearance of new phase transition peaks in the overall heat flow curve, from a thermodynamic perspective, confirm that the components achieved supramolecular assembly driven by hydrogen bonds at the molecular level, rather than macroscopic physical mixing.

[0147] The thermogravimetric test results of Example 1 show that ( Figure 5The main weight loss steps in the 130-200℃ range correspond to the thermal decomposition of urea and the loss of ATP-bound water. The lag in the initial decomposition temperature of urea in the ternary system demonstrates that the supramolecular lattice restricts the escape of urea molecules and the release of ammonia. The 200-400℃ range involves the condensation of the ATP phosphate backbone and the degradation of the adenosine organic portion. The rate of thermal weight loss slows down in this range, reflecting that strong interactions between components increase the pyrolysis activation energy. The abnormally high char residue in the high-temperature range is due to the ATP phosphate groups catalyzing the cross-linking of urea degradation products into carbon. This synergistic effect indicates that the three components are not simply physically mixed, but rather form a supramolecular whole with higher thermal stability.

[0148] To evaluate the in vivo germinal effect of the adenosine supramolecular molecules in Example 3, we treated AGA model mice with minoxidil (Example 3 and the positive control group). Figure 6 From day 13, the Example 3 group and the minoxidil group showed the most significant hair growth effects, with the hair regrowth promotion effect of the Example 3 group being comparable to that of minoxidil. In summary, these results indicate that the Example 3 group effectively promoted hair growth in terms of both hair coverage and diameter.

[0149] The sample in Application Example 1 was relatively stable under repeated freeze-thaw cycles, refrigeration, and storage at room temperature and high temperature. The solution was transparent, with no adenosine precipitation or bacterial contamination, indicating that the system has long-term stability and preservative effect. Figure 7 At the same time, such as Figure 8 As shown, the inhibition zone diameter of Malassezia furfur in Application Example 1 was greater than 7 mm, indicating a significant antibacterial effect against Malassezia furfur, thus confirming the sample's anti-dandruff efficacy. More importantly, clinical observation revealed that among 202 patients using the scalp serum product in Application Example 1 of this invention, 68% experienced significant anti-hair loss effects after two weeks of use, particularly showing good oil control for oily scalps. 56% of patients showed a significant increase in dandruff on the forehead and crown after 6 weeks of use of the scalp serum in Example 1, with female patients experiencing increased fine hair growth on their parting and forehead, and no allergic reactions were observed (e.g., ...). Figure 9 (Example).

[0150] In summary, this invention, using adenosine supramolecular molecules as its core, can effectively improve the solubility and stability of adenosine in weakly acidic or neutral aqueous solutions, thereby enhancing the therapeutic effects of adenosine in tissue regeneration, whitening and moisturizing, and tissue regeneration. In particular, for the field of hair regeneration, this invention further enhances the transdermal efficiency and drug activity of adenosine supramolecular mixtures by combining them with natural small molecules, achieving the effect of stimulating hair regrowth through a simple topical application method.

[0151] Finally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0152] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0153] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. An adenosine-based supramolecular composition, characterized in that, The composition comprises the following chemical components by mass fraction: Adenosine: 1.5–5%, adenosine acid or adenosine acid derivatives: 0.5–6%, antifreeze: 1.8–30%, pH adjuster: 0.3–1.6%, water: 57.4–95.2%; The adenosine derivatives include at least one of the following: sodium adenosine-5'-monophosphate, disodium adenosine-5'-monophosphate, 2′-deoxyadenosine-5′-monophosphate, adenosine 5'-bisphosphate, sodium adenosine-5′-bisphosphate, disodium adenosine-5′-bisphosphate, potassium adenosine-5′-bisphosphate, adenosine-5′-triphosphate, disodium adenosine-5′-triphosphate, potassium adenosine-5′-triphosphate, sodium 2′-deoxyadenosine-5′-triphosphate, disodium 2′-deoxyadenosine-5′-triphosphate, and cyclic adenosine monophosphate. The antifreeze includes at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerin, sodium iodide, and guanidine hydrochloride.

2. The adenosine-based supramolecular composition according to claim 1, characterized in that, The pH adjuster includes at least one of trisodium citrate, sodium hydroxide, sodium carbonate, phosphoric acid, citric acid, sesquicarbonate, bicarbonate, silicate, bisulfate, phosphate, and pyrophosphate.

3. The adenosine-based supramolecular composition according to claim 2, characterized in that, The phosphate includes at least one of potassium dihydrogen phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, and pentapotassium tripolyphosphate.

4. A method for preparing an adenosine-based supramolecular composition according to any one of claims 1-3, characterized in that, The preparation method includes: dissolving adenosine or adenosine derivative together with an antifreeze agent in water, then adding adenosine at 50-80°C, and homogenizing to obtain a mixed solution; The pH of the mixed solution was adjusted to 4.5–8.0 using a pH adjuster to obtain an adenosine-based supramolecular composition; The mass ratio of adenosine, adenosine acid or adenosine acid derivative, antifreeze and water is (1.5-5): (0.5-6): (1.8-30): (57.4-95.2).

5. The method for preparing an adenosine-based supramolecular composition according to claim 4, characterized in that, The adenosine derivatives include at least one of the following: sodium adenosine-5'-monophosphate, disodium adenosine-5'-monophosphate, 2′-deoxyadenosine-5′-monophosphate, adenosine 5'-bisphosphate, sodium adenosine-5′-bisphosphate, disodium adenosine-5′-bisphosphate, potassium adenosine-5′-bisphosphate, adenosine-5′-triphosphate, disodium adenosine-5′-triphosphate, dipotassium adenosine-5′-triphosphate, sodium 2′-deoxyadenosine-5′-triphosphate, disodium 2′-deoxyadenosine-5′-triphosphate, and cyclic adenosine monophosphate. The antifreeze includes at least one of urea, mannitol, 1,2-hexanediol, propylene glycol, glycerin, sodium iodide, and guanidine hydrochloride. The pH adjuster includes at least one of trisodium citrate, sodium hydroxide, sodium carbonate, phosphoric acid, citric acid, sesquicarbonate, bicarbonate, silicate, bisulfate, phosphate, and pyrophosphate.

6. The method for preparing an adenosine-based supramolecular composition according to claim 4, characterized in that, The process of dissolving adenosine or adenosine derivatives together with an antifreeze agent in water, then adding adenosine at 50–80°C, and homogenizing the solution to obtain a mixed solution specifically includes: Adenosine or adenosine derivatives are dissolved together with an antifreeze agent in water, homogenized, and then adenosine is added at 50–80°C. The mixture is then mechanically stirred or ultrasonically homogenized for 0.5–4 hours to obtain a mixed solution.

7. The use of an adenosine supramolecular composition as described in any one of claims 1-3 in the preparation of anti-hair loss agents, hair growth agents, or skin care products.

8. A product for preventing and / or treating hair loss, characterized in that, The active ingredient of the product comprises an adenosine-based supramolecular composition as described in any one of claims 1-3.

9. A product for preventing and / or treating hair loss according to claim 8, characterized in that, The dosage forms of the product include any one of creams, gels, patches, soluble microneedles, sprays, ointments, plasters, emulsions, liniments, pastes, and mud dressings; The products include any one of the following: conditioner, hair serum, shampoo, hair cream, hair mask, hair soap, hair cleanser, hair oil, hair dyeing aid, and hairspray.

10. A product for preventing and / or treating hair loss, characterized in that, The product comprises the following components by mass fraction: Adenosine supramolecular composition: 79.35%, betaine: 6%, arginine: 2%, glycine: 3%, valine: 0.4%, lactic acid: 3%, sodium citrate: 2%, hexanediol: 2%, polylysine: 0.05%, lysozyme: 1%, NaOH: 1.2%; The adenosine supramolecular composition is one of the adenosine supramolecular compositions according to any one of claims 1-3.

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