A drug delivery composition containing a telomerase activator and nanoparticles, and a composition containing the same for preventing, improving, or treating hair loss.

Abstract

The present invention relates to a drug delivery composition comprising a telomerase activator and nanoparticles, and a composition for preventing, improving, or treating hair loss comprising the same. More specifically, the present invention relates to a nanoliposome, nanosilica particle, or nanobubble composition encapsulating drugs such as the plant extract component TA-65 and its derivatives that increase telomerase activity, the telomerase activating compound GPC and its derivatives, and having the efficacy of promoting the regeneration and growth of hair follicles.

Description

Technical Field

[0001] The present invention relates to a drug delivery composition containing a telomerase activator and nanoparticles, and a composition for preventing, improving or treating hair loss containing the same. More specifically, it relates to a nano-liposome, nano-silica particle, or nano-bubble composition encapsulating drugs such as a plant extract component TA-65 that increases telomerase activity and its derivatives, a telomerase activation compound GPC and its derivatives, etc., and has the efficacy of promoting the regeneration and growth of pores.

Background Art

[0002] Generally, hair loss means the loss of thick and black hair on the scalp. The causes of hair loss are diverse, but genetic factors and the male hormone androgen are considered important factors. Among them, male pattern baldness, which accounts for 60 - 70%, is caused by testosterone being converted to dihydrotestosterone (DHT) by 5α-reductase (5-alpha reductase, SRD5A), and the excessively produced dihydrotestosterone binds to the androgen receptor (AR) of dermal papilla cells (DPC) to induce apoptosis, leading to hair loss through hair follicle shrinkage. Among 5α-reductases, men with high expression of type 2 5α-reductase (5-alpha reductase type 2, SRD5A2), which is mainly distributed in the hair papilla and outer root sheath of hair follicles, or those with high activity of type 2 5α-reductase have a relatively higher amount of dihydrotestosterone than ordinary men, so the possibility of hair loss is increased. Therefore, the core of the treatment of male pattern baldness is to reduce the amount or activity of type 2 5α-reductase to prevent the conversion of testosterone to dihydrotestosterone.

[0003] Telomeres are DNA structures found at the ends of chromosomes, consisting of repeating DNA hexamer (TTAGGG) sequences. They are known to stabilize the structure and function of chromosomes. Telomere length shortens as cells repeatedly replicate chromosomal DNA. When telomere length shortens below a certain length, the cell enters an aging state where it can no longer grow. Cellular telomere length can be used as an indicator of the degree of cellular aging. Telomere length shortens as living organisms age, and is also shortened by stress, smoking, pollution, lack of exercise, and obesity. It is also known that the shorter the telomere length, the higher the incidence of various age-related diseases, including cardiovascular disease. Cellular aging can be seen as inducing the aging of human tissues and organs.

[0004] Telomerase is an enzyme protein that catalyzes the addition of telomere repeat sequences to the 3' end of telomeres, playing a role in repairing telomeres that are shortened by DNA replication and various extracellular stresses. After the discovery of telomerase, many scientists focused their attention on its role in cancer research. Since cancer cells need telomerase to continue proliferating, it was thought that telomerase expression could induce cancer. However, recent studies using genetically modified mice with telomerase have shown that high levels of telomerase expression do not cause cancer, but rather restore (regenerate) human bodily functions associated with aging.

[0005] Gene-knockout mice lacking the telomerase gene lost their reproductive capacity and exhibited age-related symptoms such as osteoporosis, diabetes, and nerve damage, demonstrating faster aging than normal mice. On the other hand, in genetically modified mice that expressed telomerase only when orally administered doxycycline, administering doxycycline after aging had progressed to induce high levels of telomerase expression restored weakened brain function, reproductive capacity, and the function of organs such as the spleen, liver, and intestines. Furthermore, it was confirmed that hair follicle growth and regeneration were induced, resulting in the regeneration of hair. These results indicate that telomerase activation induces the growth and regeneration of hair follicle stem cells that induce hair follicle growth, thereby causing changes that regenerate aged hair follicles.

[0006] However, research using genetically modified animals (gene-engineered animals) showing that telomerase activity can reverse various aging processes has spurred the search for telomerase activators that can be directly used in humans, resulting in the discovery of various telomerase activators.

[0007] Telomerase activators can be classified into two types based on their origin. The first type consists of plant extracts and their derivatives that possess telomerase-activating properties, and the second type consists of compounds.

[0008] Cycloastragenol and its derivatives, which are components of plants; cycloastragenol (abbreviated as CAG, chemical formula C), which is a component of plants of the genus Astragalus. 30 H 50O5) is also known as TAT2 or GRN665. TA-65 is a telomerase activator containing cycloastragenol extracted and purified by TA Science, Inc. in the United States from Astragalus plants using a patented method. Other plant-derived telomerase activators include genistein from soybeans, Centella asiatica extract, and maslinic acid from olive pomace oil.

[0009] Among the substances discovered to activate telomerase, GRN510 (Le Saux et al., 2013) and C3-(L)-valyl-cycloastragenol (US 9,913,852 B2) are derivatives of cycloastragenol.

[0010] On the other hand, N-propyl-5-(2-thienyl)isoxazole-3-carboxamide (US 2009 / 0143451 Al) and various derivatives have been reported as compounds that increase telomerase expression. Guanidinopentyl phenylisoxazolecarboxamide (chemical formula; C), one of the derivatives of N-propyl-5-(2-thienyl)isoxazole-3-carboxamide, is a compound that increases telomerase expression. 16 H 21 N5O2 (abbreviated as GPC) is a well-known telomerase-activating compound.

[0011] Other compounds include AGS499 and AGS500, whose telomerase activity has been reported by Shi et al (2020).

[0012] While there are papers and patents reporting that the aforementioned telomerase activators can restore weakened brain function, reproductive capacity, and the function of organs such as the spleen, liver, and intestines, as well as improve biological functions such as immune activation, there have been no reports of these substances being delivered to hair follicles to activate hair follicle cells and improve hair loss and promote hair growth. The applicant of the present invention conducted research and development on whether or not telomerase activators have efficacy in preventing hair loss. [Overview of the project] [Problems that the invention aims to solve]

[0013] The object of the present invention is to provide a drug delivery composition using nanobubbles, nanoliposomes, nanoparticles, etc., or a method for producing the same, and a composition for preventing, improving, or treating hair loss containing the same as an active ingredient, which uses a telomerase activator to induce the regrowth of aging hair follicles that have entered a complete resting phase due to aging and have interrupted hair growth, thereby restarting hair growth.

[0014] The present invention aims to provide nanoparticles containing a telomerase-activating substance and a composition for improving or treating hair loss containing the same, as a drug for treating hair loss.

[0015] More specifically, the object of the present invention is to provide a composition in which a drug such as the plant extract component TA-65 that increases telomerase activity and its derivatives, or the telomerase activating compound GPC and its derivatives is encapsulated, and which has the efficacy of promoting the regeneration and growth of pores. [Means for solving the problem]

[0016] The present invention relates to a nanoliposome conjugate, a mesoporous silica nanoparticle conjugate, or a nanobubble conjugate containing a telomerase activator.

[0017] The telomerase activating substance is a telomerase activating substance that increases telomerase expression in cells or increases telomere synthase activity, and comprises one or more substances selected from the group consisting of TA-65, a plant-derived extract component, and GPC, among other compounds, for improving or treating hair loss.

[0018] In this invention, nanobubbles, nanoliposomes, and nanosilica solutions can be prepared using TA-65 and GPC at concentrations of 0.2 mg / L to 2 g / L, respectively.

[0019] Furthermore, the aforementioned pore regeneration promoting drug may have the efficacy of increasing telomerase expression or enzyme activity.

[0020] The nanoliposomes may contain lecithin, cholesterol, and cationic, anionic, or amphoteric phospholipids.

[0021] The aforementioned nanobubbles are bubbles ranging in size from 50 nm to 500 nm, generated by various methods such as electricity, ultrasound, and pressure. They are preferably large enough to penetrate pores, but may also include larger ones.

[0022] The silica nanoparticles are mesoporous silica nanospheres (MSNs) having empty porous structures ranging in size from 2 nm to 50 nm. Among M41S-type silica nanoparticles with uniform pore size and volume, the composition and structure of hexagonal MCM-41 (Mobile Crystalline Material-41) and silica nanoparticles can vary. In this invention, 100 nm MCM-41 nanoparticles purchased from Sigma-Aldrich, Inc. in the United States were used as silica nanoparticles.

[0023] The present invention can provide a composition for improving or treating hair loss that contains nanoliposomes, nanobubbles, or mesoporous silica nanoparticle conjugates containing a telomerase activating substance.

Advantages of the Invention

[0024] The present invention relates to nanoliposomes or mesoporous silica particles encapsulated with a substance that activates telomerase as a component or compound of a plant extract such as TA-65 or GPC, or nanobubbles bound to these substances, and a composition for improving or treating hair loss containing the same.

[0025] As a result of applying a solution in which a telomerase activating substance was dissolved in a standard lotion to aging animals, there was no improvement in hair loss or hair growth effect. This result explains the reason why there have been no papers or patents reporting the hair loss improvement effect of telomerase activating substances so far.

[0026] However, activation of telomerase induces regeneration of aged pores and activation of pore stem cells. This has been proven by experiments using genetically modified mice. Specifically, when the telomerase gene is expressed in telomerase animals by an artificial method after the pores of mice are aged due to aging and hair growth is interrupted, the regrowth of pore stem cells, the regrowth of pores, and hair growth resume.

[0027] However, the reason why there is no report that telomerase activating substances induce the regrowth of pore stem cells and hair growth is considered to be that even when telomerase activating substances are applied to the scalp, these substances cannot reach the inside of the pores to activate telomerase, and therefore cannot induce pore regeneration and exert the effect of restarting hair growth.

[0028] Therefore, it is important to utilize drug delivery systems to enhance the transmission efficiency of telomerase activating substances into the pores. When using the nanobubbles, nanoliposomes, mesoporous silica nanoparticles, etc. of the present invention, it is shown that telomerase activating substances have the efficacy as a drug for improving and treating hair loss. It is possible to very effectively treat hair loss caused by pore aging due to aging and hair growth interruption.

[0029] While nanoliposomes, mesoporous silica nanoparticles, and nanobubbles have attracted attention as drug delivery methods, they have never been used to deliver telomerase-activating substances to aging pores.

[0030] In this invention, nanobubbles, nanoliposomes, and mesoporous silica nanoparticles containing telomerase-activating substances each showed a certain degree of hair growth and pore regeneration efficacy. Therefore, mixtures of drugs and carriers, although varying in degree depending on the composition, demonstrate efficacy as agents for improving and treating hair loss. [Brief explanation of the drawing]

[0031] [Figure 1] Standard lotion and a solution containing TA-65 (100 ng / ml) or GPC (100 ng / ml) were applied to the skin of 20-month-old C57 / BL6 mice for 8 weeks after depilation, following confirmation that no hair regrowth occurred for 4 weeks. Hair growth was then observed after 8 weeks. The mice were not limited to 20 months of age. However, aged mice that did not regrow after depilation were selected for the experiment. [Figure 2] A solution (A) in which nanobubbles were generated in triple-distilled water, and a solution (B) in triple-distilled water containing TA-65 or GPC (C) were applied to the skin of 20-month-old C57 / BL6 mice after depilation of their body hair, and after confirming that no hair regrowth occurred for 4 weeks, the solution was applied to the skin three times a week for 8 weeks, and the hair growth status was checked after 8 weeks. [Figure 3] Nanoliposome solutions containing nanoliposomes (A), TA-65 (B), or GPC (C) were applied to the skin of 20-month-old C57 / BL6 mice after depilation of body hair, and after confirming that no hair regrowth occurred for 4 weeks, the solution was applied to the skin for 8 weeks (5 times a week). After 8 weeks, the hair growth status was checked. [Figure 4]A solution containing nanosilica particles (A), TA-65 (B), or GPC (C) was applied to the skin of 20-month-old C57 / BL6 mice after depilation of body hair, and after confirming that no hair regrowth occurred for 4 weeks, the solution was applied to the skin for 8 weeks (5 times a week), and the hair growth status was checked after 8 weeks. [Figure 5] Figures 2, 3, and 4 show the distribution and condition of hair follicles after biopsy and subsequent H&E staining of mouse skin. In Figure 5C, the types of hair follicles are shown as inactive hair follicles (black arrows), and active hair follicles as primary hair follicles (red arrows) and secondary hair follicles (yellow arrows). The images show a solution with generated nanobubble solution (A), nanobubble-TA-65 (B) or nanobubble-GPC (C), nanoliposomes (D), nanoliposome-TA-65 (E), nanoliposome-GPC (F), nanosilica particles (G), nano-silica-TA-65 (H), and nanosilica-GPC (I). [Figure 6] This shows an increase in active pores due to telomerase activating substances. The diagram shows the distribution of active pores (primary pores + secondary pores), excluding inactive pores, in H&E-stained skin tissue, with a unit area of ​​1 square millimeter. [Figure 7] As shown in Figures 2, 3, and 4, the skin of mice coated with a nanobubble solution, nanoliposomes, or nanosilica solution containing GPC was biopsied, and the tissue solidified with paraffin was then cut laterally. Subsequently, H&E staining was performed to observe the depth of the hair follicles. [Figure 8] This shows the pore depth induced by the telomerase-activating substance GPC. Pore depth was measured using a unit area of ​​20 square millimeters. Skin treated with GPC solutions contained in nanobubbles and nanosilica showed similar pore depths, while nanoliposomes showed approximately 50% of that of nanobubbles and nanosilica. In the case of standard lotion, hardly any activated pores were observed, making it impossible to calculate statistical values. [Examples]

[0032] The present invention will be described in more detail below with reference to the following examples. However, these examples are merely illustrative of the present invention, and the scope of the present invention is not limited by these examples.

[0033] The present invention will be described in detail below through preferred embodiments and comparative examples.

[0034] [Comparative Example 1] Solutions were prepared by dissolving TA-65 (100 ng / ml) at a concentration of 100 mg / L in each of the following standard lotion toners (99.5% Ethanol, 1% Carbomer solution, Reverse Osmosis water, 1,2-Hexanediol).

[0035] [Comparative Example 2] Solutions were prepared by dissolving GPC (100 ng / ml) at a concentration of 100 mg / L in each of the following standard lotion toners (99.5% Ethanol, 1% Carbomer solution, Reverse Osmosis water, 1,2-Hexanediol).

[0036] [Experimental Example 1] Hair growth efficacy of TA-65 and GPC dissolved in standard lotion To prepare animals in which hair growth has ceased due to aging of the hair follicles, C57 / BL6 mice are first depilated when they reach approximately 20 months of age (not limited to 20-month-old mice). After depilation, mice that do not show hair growth for 4 weeks are selected, as these are considered to have entered a complete resting phase (a state in which hair production has ceased) due to aging of the hair follicles.

[0037] Solutions from Comparative Examples 1 and 2 were applied five times a week for eight weeks to the depilated skin of aging animals that had not shown hair growth for four weeks after depilation, respectively. Hair growth was observed from eight weeks to sixteen weeks. Referring to Figure 1, (A) shows the application of the standard lotion, (B) shows the application of the solution from Comparative Example 1, and (C) shows the application of the solution from Comparative Example 2. TA-65 and GPC dissolved in the standard lotion did not induce hair growth in the aging animals.

[0038] The hair growth efficacy of TA-65 and GPC using nanobubbles was confirmed in Example 1 below.

[0039] [Example 1] - Generation of nanobubble solution in which TA-65 is collected

[0040] A solution was prepared in which nanobubbles containing TA-65 were generated by dissolving TA-65 in triple-distilled water at a concentration of 100 mg / L, then injecting the solution into a nanobubble housing, and applying approximately 200 watts of electricity for 20 minutes.

[0041] [Example 2] -GPC capture and nanobubble generation

[0042] GPC was dissolved in triple-distilled water at a concentration of 100 mg / L. This solution was then injected into a nanobubble housing, and approximately 200 watts of electricity were applied for 20 minutes to prepare a solution in which nanobubbles containing the captured GPC were generated.

[0043] As a control group, a solution was prepared in which nanobubbles were generated using triple-distilled water that did not contain either TA-65 or GPC.

[0044] [Experimental Example 2] 1. Experiments on solutions in which nanobubbles are generated

[0045] As shown in Figure 2(A), mice treated with a solution containing nanobubbles in triple-distilled water showed no significant skin lesions even after 16 weeks. Furthermore, when the nanobubble-containing solution was applied five times a week for eight weeks to the depilated skin of aging animals that had not shown hair regrowth for four weeks after depilation, the hair regrowth status was observed after eight weeks, but no hair regrowth was confirmed even after a total of 16 weeks.

[0046] To examine the pore condition of animal skin, a 4mm biopsy was taken from the lower dorsal skin of C57 / BL6 mice. The skin biopsy was stored in a 10% formalin solution for 16 hours, and then solidified using paraffin as an embedding material. The tissue was horizontally sectioned using a microtome, the paraffin was removed with xylene, and then stained with hematoxylin-eosin (H&E) stain to observe the morphology (degenerated pores, primary pores, secondary pores) and number of pores. Vertical sections were also prepared simultaneously with the horizontal sections to observe the depth (length) of the pores. No abnormalities were found with H&E staining, but there was almost no increase in pores, and degenerated pores were observed (Figure 5A).

[0047] 2. Experiments with the solutions of Examples 1 and 2

[0048] When the nanobubble solution of Example 1 containing TA-65 and the nanobubble solution of Example 2 containing GPC were applied for 8 weeks, hair regrowth progressed in almost the entire area of ​​the depilated skin after 16 weeks (Figure 2B, C).

[0049] Therefore, skin biopsies were taken from these mice and the hair follicles were observed (Figure 5B, C), and the number of hair follicles increased significantly compared to Figure 5(A). However, the hair follicles in Figure 5(C) are larger and more densely packed compared to those in Figure 5(B).

[0050] [Example 3] - Generation of a nanoliposome solution containing captured TA-65

[0051] The composition of the cationic liposomes used in the present invention is as follows: dimyristoylphosphatidylcholine, N-(2,3-dioleoyloxy-1-propyl)trimethylammonium methyl sulfate, and cholesterol (50:10:40 mol%).

[0052] -The method for manufacturing liposomes is as follows:

[0053] First, the lipids are dissolved in a chloroform / methanol (3:1) solution, and then dried under vacuum in an evaporator.

[0054] Prepare a drug solution by dissolving TA-65 at a concentration of 100 mM in a 10 mM N-(2-hydroxyethyl)piperazine-NO-[2-ethanesulfonic acid] + 150 mM NaCl (pH=7.5, readjusted with sodium hydroxide after drug dissolution).

[0055] Lipid solids are placed in 2 ml of drug solution at 60°C to prepare a solution with a lipid concentration of 50 mM. After repeating the freezing and thawing process three times, the solution is extruded through polycarbonate filters with a pore size of 400 nm to prepare a nanoliposome solution in which TA-65 is collected.

[0056] [Example 4] - Generation of a nanoliposome solution containing GPC

[0057] A nanoliposome solution containing GPC was prepared in the same manner as in Example 1 above, except that GPC was used instead of TA-65 in the process of producing the nanoliposome solution in which TA-65 was collected.

[0058] Then, as a control group, a nanoliposome solution containing neither TA-65 nor GPC was prepared.

[0059] To confirm the hair growth efficacy of TA-65 or GPC captured in nanoliposomes, the following Experiment Example 3 was performed.

[0060] [Experimental Example 3] 1. Experiments with nanoliposome solutions

[0061] The solution containing nanoliposomes did not cause any significant skin lesions after 16 weeks (Figure 3A). H&E staining also showed no abnormalities, but very few hair follicles were found, and only vestigial-looking hair follicles were observed (Figure 5D).

[0062] Furthermore, when mice that did not show hair regrowth for 4 weeks after hair removal were selected, no hair regrowth was observed even 16 weeks later (Figure 3A).

[0063] 2. Solutions containing nanoliposomes containing TA-65 or GPC from Examples 3 and 4 were applied five times a week for eight weeks to the depilated skin of aging animals in which no hair growth was observed four weeks after depilation, and the state of hair growth was observed after eight weeks.

[0064] However, the nanoliposome solutions containing TA-65 or GPC at a concentration of 60 mg / L in Examples 3 and 4, after 8 weeks of application, promoted hair growth in almost the entire area of ​​the depilated skin after 16 weeks (Figure 3B, C). Consequently, when skin biopsies were taken from these mice and the hair follicles were observed (Figure 5E, F), the number of hair follicles increased significantly compared to Figure 5(D). However, the hair follicles in Figure 5(F) were larger and more densely packed than those in Figure 5(E).

[0065] [Example 5] TA-65 was reacted with the above-mentioned MCM-41 under constant stirring speed for 48 hours to prepare a silica nanoparticle solution (300 mg / L, TA-65 60 mg / L + MCM-41 240 mg / L) in which TA-65 was collected.

[0066] [Example 6] GPC was reacted with MCM-41 at a constant stirring rate for 48 hours to prepare a silica nanoparticle solution (300 mg / L, GPC 60 mg / L + MCM-41 240 mg / L) in which the GPC was collected.

[0067] Then, as a control group, a nanosilica solution containing neither TA-65 nor GPC was prepared.

[0068] To confirm the hair growth efficacy of TA-65 and GPC captured in nanosilica, the following Experiment Example 4 was conducted.

[0069] [Experimental Example 4] 1. Mice treated with a solution containing mesoporous silica nanoparticles showed no significant skin lesions after 16 weeks (Figure 4A). H&E staining also revealed no abnormalities, but very few hair follicles were found, and only degenerated hair follicles were observed (Figure 5G). Furthermore, when mice that showed no hair regrowth after 4 weeks of depilation were selected, these mice showed no hair regrowth even after 16 weeks (Figure 4A).

[0070] 2. However, the nanoliposome solution containing TA-65 or GPC at a concentration of 60 mg / L in Examples 5 and 6, when applied for 8 weeks, resulted in hair regrowth progressing in almost the entire area of ​​the depilated skin after 16 weeks (Figure 4B, C). Therefore, when skin biopsies were taken from these mice and the hair follicles were observed (Figure 5H, I), the number of hair follicles had increased significantly compared to Figure 5(G), but the hair follicles in Figure 5(I) were larger and more densely packed than those in Figure 5(H).

[0071] On the other hand, Figure 6 shows the increase in active pores due to telomerase activating substances. It is a distribution map of the number of active pores (primary pores + secondary pores) excluding inactive pores, with a unit area of ​​1 square millimeter in H&E-stained skin tissue. In Figure 5(C), representative pores are shown as inactive pores, primary pores, and secondary pores, respectively, indicated by black, red, and yellow arrows. Active pores were difficult to detect in the skin of aging animals to which telomerase activating substances (TA-65 and GPC) dissolved in lotion were applied.

[0072] However, when telomerase-activating substances bound to or captured in nanobubbles, nanoliposomes, or mesoporous silica nanoparticles were applied, the number of active pores in animal skin clearly increased.

[0073] Figure 7 shows the depth of hair follicles observed after biopsy of mouse skin coated with a nanobubble solution (B) containing GPC, a nanoliposome (C) solution (D), or a nanosilica (D) solution, as shown in Figures 2, 3, and 4. The tissue was then solidified with paraffin, cut laterally, and stained with H&E. Figure 8 shows the depth of hair follicles measured using the telomerase-activating substance GPC, with a unit area of ​​20 square millimeters. As can be seen in Figures 7 and 8, the pore depth was greater with the nanobubble solution (B), nanoliposome (C), or nanosilica (D) solution containing GPC compared to the standard lotion (A). The nanoliposome solution (C) containing GPC showed approximately 50% of the pore depth of the nanobubble solution (B) and nanosilica (D) solutions containing GPC. For the standard lotion, almost no activated pores were observed, making it impossible to calculate statistical values.

[0074] In the examples described above, nanobubbles, nanoliposomes, and nanosilica solutions were prepared using TA-65 and GPC at concentrations of 60 to 100 mg / L, respectively. However, the examples are not limited to these concentrations, and preferably, concentrations of 0.2 mg / L to 2 g / L can be used.

[0075] The present invention described herein is merely illustrative, and it will be obvious to any person with ordinary skill in the art to which the invention pertains that various modifications and equivalent other embodiments are possible therefrom. Therefore, it should be understood that the present invention is not limited to the forms mentioned in the detailed description above. Accordingly, the true scope of technical protection of the present invention should be determined by the technical idea of ​​the appended claims. Furthermore, the present invention should be understood to encompass the spirit of the invention as defined by the appended claims and all modifications, equivalents, and substitutes within that scope. [Industrial applicability]

[0076] A drug delivery composition containing a telomerase activator and nanoparticles, and a composition for preventing, improving, or treating hair loss containing the same, have industrial applicability.

Claims

1. Telomerase activators; and nanoparticles; A composition for preventing, improving, or treating hair loss, characterized by containing the following:

2. The composition for preventing, improving, or treating hair loss according to claim 1, characterized in that the telomerase activator is at least one of cycloastragenol, guanidinopentyl isoxazole carboxamide, GRN510, AGS-500, genistein, Centella asiatica extract, or maslinic acid.

3. The aforementioned nanoparticles are at least one of nanobubbles, nanoliposomes, and nanosilica. The composition for preventing, improving, or treating hair loss according to claim 1, characterized in that the telomerase activator is in a conjugated structure encapsulated or captured within the nanoparticles.

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