Capryloyl glycine and fructose amorphous assembly, and preparation method and application thereof

Abstract

This invention belongs to the fields of biomedicine, beauty, and personal care health technology, and specifically relates to an amorphous assembly of capryloylglycine and tranexamic acid, its preparation method, and its application. The method involves adding capryloylglycine and tranexamic acid to an alcoholic solution, rotary evaporating, and drying to obtain a co-amorphous compound; mixing a cyclodextrin compound solution with the co-amorphous compound, heating to react, and drying to obtain the product. This assembly achieves high drug loading, significantly improves apparent solubility and in vitro dissolution rate, and overcomes application bottlenecks without altering the structure and properties of the active ingredients. This invention achieves multi-pathway targeted oil control and whitening through the synergistic encapsulation of capryloylglycine and tranexamic acid, with effects superior to single components. The cyclodextrin inclusion imparts excellent stability to the system, inhibits recrystallization, and provides both solubilization and controlled release effects; the components are safe and mild, with a near-neutral pH and strong formulation compatibility; its preparation process is mild, simple to operate, has high yield, is environmentally friendly, and easily industrialized.

Description

Technical Field

[0001] This invention belongs to the fields of biomedicine, beauty and personal care health technology, and particularly relates to an amorphous assembly of capryloylglycine tranexamic acid, its preparation method and application. Background Technology

[0002] Acne is a common chronic inflammatory disease of the pilosebaceous unit, and its pathogenesis involves multiple aspects, including excessive sebum secretion, proliferation of Propionibacterium acnes, inflammatory response, and abnormal follicular keratinization. An ideal acne treatment strategy should combine multiple effects such as oil control, antibacterial activity, anti-inflammation, and prevention of pigmentation (acne scars). Capryloyl glycine, as a small-molecule amino acid derivative, has high safety and can target and inhibit 5α-reductase activity to reduce sebum secretion. It can also effectively inhibit the growth of Propionibacterium acnes and has a barrier repair effect, making it valuable in acne prevention and treatment. However, the capryloyl glycine molecule contains both a lipophilic alkyl chain and a hydrophilic carboxylic amide group, resulting in a low hydrophilic-lipophilic balance value and overall hydrophobicity. This leads to poor solubility in aqueous systems, severely limiting its formulation development and bioavailability.

[0003] Current technologies for improving the solubility of capryloylglycine have the following limitations: ① While pH-adjusting salt formation can improve solubility, it introduces strong ionicity, leading to poor formulation compatibility and easy charge neutralization with cationic components, resulting in flocculation; ② The solubilizing effect of organic co-solvents (such as ethanol and propylene glycol) is limited and may increase the risk of skin irritation or systemic toxicity; ③ The use of nano-drug delivery systems such as surfactant micelles and liposomes has problems such as low drug loading, complex preparation processes, and poor long-term physical stability. For example, the existing patent CN116172888B discloses a system that forms mixed micelles by combining glucoside and capryloylglycine. Although this improves its water solubility, the mass ratio of amino acid derivatives to glucoside is as high as 1:5 to 1:10, resulting in low drug loading efficiency and unsuitability for high-dose administration. Another patent, CN119970541A, achieves solubilization by forming a supramolecular structure between capryloyl glycine and the metal ions of antioxidants such as sodium sulfite and sodium metabisulfite. However, the extensive use of such antioxidants poses potential safety risks and does not comply with the regulations on the amount of excipients in cosmetics and pharmaceuticals. Therefore, there is an urgent need in this field to develop a new, efficient, safe, and widely adaptable capryloyl glycine solubilization technology.

[0004] Co-amorphous technology represents a significant breakthrough in drug solid-state research in recent years. However, amorphous states are high-energy states, sensitive to temperature and humidity during storage, and exhibit a strong tendency for spontaneous crystallization. Furthermore, they may gel or rapidly recrystallize upon contact with water during dissolution, leading to a decrease in dissolution. Conventional stabilization strategies often rely on adding polymers such as polyvinylpyrrolidone and hydroxypropyl methylcellulose as inhibitors, but their stabilizing effects are limited and may increase the viscosity of the system. Summary of the Invention

[0005] In order to solve the technical problems existing in the prior art, the purpose of this invention is to provide an amorphous assembly of capryloylglycine tranexamic acid, its preparation method and application, so as to solve the above-mentioned technical problems.

[0006] According to a first aspect of the present invention, the present invention provides a method for preparing an amorphous assembly of capryloylglycine tranexamic acid, comprising the following steps: (1) Add octanoyl glycine and tranexamic acid to an alcohol solution, dissolve them evenly by ultrasonication to obtain a mixture A, evaporate by rotary evaporation and dry to obtain an amorphous product of octanoyl glycine-tranexamic acid. (2) Dissolve the cyclodextrin compound in water to obtain a cyclodextrin compound solution, add the octanoylglycine-tranexamic acid co-amorphous compound, and heat the reaction under stirring to obtain an inclusion solution. Freeze-dry the solution to obtain the octanoylglycine-tranexamic acid amorphous assembly.

[0007] In some embodiments, the mass ratio of capryloylglycine to tranexamic acid in step (1) is (1-6):1.

[0008] In some embodiments, the alcohol solution in step (1) is a mixture of an alcohol compound and water, wherein the volume percentage of the alcohol compound is 50-67%; the alcohol compound is ethanol or methanol; and the mass-volume ratio of the octanoylglycine to the alcohol solution is (0.04-0.09):1 g / mL.

[0009] In some embodiments, the temperature of rotary evaporation in step (1) is 40-60°C; the drying method is vacuum drying, the drying temperature is 40-50°C, and the drying time is 24-48h.

[0010] In some embodiments, the mass-to-volume ratio of the cyclodextrin compound to water in step (2) is 1:30-200 g / mL; the cyclodextrin compound is at least one of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, γ-cyclodextrin, and hydroxypropyl-α-cyclodextrin.

[0011] In some embodiments, the mass ratio of the cyclodextrin compound to the octanoylglycine-tranexamic acid co-amorphous compound in step (2) is 1:(0.5-10).

[0012] In some embodiments, the stirring rate in step (2) is 300-500 rpm, the temperature of the heating reaction is 40-65°C, and the heating reaction time is 2-8 h.

[0013] In some embodiments, the freeze-drying temperature in step (2) is -80°C and the freeze-drying time is 24-48h.

[0014] According to a second aspect of the present invention, the present invention provides an amorphous assembly of octanoylglycine tranexamic acid prepared by the above-described preparation method.

[0015] According to a third aspect of the present invention, the present invention provides the use of an amorphous assembly of capryloylglycine tranexamic acid in the preparation of topical pharmaceuticals or cosmetics.

[0016] The method provided by this invention innovatively introduces cyclodextrin to include the aforementioned capryloylglycine-tranexamic acid co-amorphous compound. The hydrophobic cavity of cyclodextrin can selectively encapsulate hydrophobic segments of drug molecules, while its hydrophilic outer surface enhances the overall water solubility. More importantly, the cyclodextrin molecule acts as a dynamic "physical barrier," effectively isolating the plasticizing effect of water molecules on the amorphous system and inhibiting the collision, migration, and recrystallization processes of drug molecules in an aqueous environment, thereby significantly enhancing the physical stability and dissolution stability of the co-amorphous system at the molecular level.

[0017] The amorphous assembly of caprylyl glycine tranexamic acid provided by this invention can be used in the preparation of acne treatment drugs or cosmetics. The preparation method of this amorphous assembly of caprylyl glycine tranexamic acid overcomes many shortcomings of existing solubilization technologies, providing a novel raw material form and a reliable technical solution for developing efficient, stable, and mild acne and acne scar prevention products.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) High efficiency solubilization and improved bioavailability: The amorphous assembly of caprylyl glycine and tranexamic acid constructed in this invention breaks the crystal structure of caprylyl glycine without changing the molecular structure and properties of the drug, so that it exists in a high-energy disordered state and obtains a high drug loading, thereby significantly improving the apparent solubility and in vitro dissolution rate, providing an innovative solution to the core bottleneck of caprylyl glycine application.

[0019] (2) Synergistic effect, realizing integrated management of oily skin whitening: The preparation method provided by this invention does not simply add up the use of capryloyl glycine and tranexamic acid, but rather produces a synergistic effect based on complementary efficacy. The co-amorphous system enhances pharmacological activity and simultaneously realizes multi-pathway skin care for oily skin anti-acne and whitening, making its efficacy superior to that of a single component, achieving a therapeutic effect of 1+1>2.

[0020] (3) Excellent stability and strong formulation flexibility: In the preparation method provided by the present invention, the inclusion effect of cyclodextrin provides a physical barrier for the co-amorphous material, effectively inhibits water-induced plasticization and recrystallization, ensures the long-term stability of the product, and further improves the drug solubility and dissolution performance, achieving multiple goals such as stability, solubilization and controlled release.

[0021] (4) High safety and good formulation flexibility: The system is a water-soluble powder, and all components (caprylyl glycine, tranexamic acid, cyclodextrin) are generally recognized as safe (GRAS) raw materials. It is mild and non-irritating, with a near-neutral pH and good stability. It is compatible with various cosmetic systems and topical preparation excipients, giving the formulation design a great degree of freedom.

[0022] (5) The preparation process is simple and easy to industrialize: the process conditions of this invention are mild, no complex equipment is required, the yield is high, it meets the requirements of green environmental protection, and it is easy to produce on a large scale. Attached Figure Description

[0023] Figure 1A A comparison chart showing the solubility of octanoylglycine in Test Example 1 and octanoylglycine in the products of Examples 1-3; Figure 1B Comparison of the solubility of caprylyl glycine in the amorphous assemblies of caprylyl glycine and tranexamic acid prepared in Examples 4-8 of Test Example 1, the assemblies prepared in Comparative Example 1, and the assemblies prepared in Comparative Example 2. Figure 2 Polarized light microscope comparison images of octanoylglycine, tranexamic acid, the physical mixture of the two monomers and the co-amorphous material in test example 2; Figure 3 Polarized light microscope comparison photographs of co-amorphous material, cyclodextrin, physical mixture of the two, and co-amorphous assembly in Test Example 2; Figure 4 The dissolution curves of octyl glycine in Example 3 were prepared for the physical mixture of octyl glycine and tranexamic acid, the octyl glycine-tranexamic acid co-amorphous product, and the octyl glycine-tranexamic acid amorphous assembly. Figure 5 XRD comparison spectra of octyl glycine, tranexamic acid, octyl glycine-tranexamic acid co-amorphous compound, cyclodextrin and octyl glycine-tranexamic acid amorphous assembly in Example 4; Figure 6A DLS diagram of the octanoylglycine tranexamic acid amorphous assembly in Example 5; Figure 6B The Tyndall effect results of the octanoylglycine tranexamic acid amorphous assembly in Example 5 are shown in the figure. Figure 7 Transmission electron microscopy comparison of the physically mixed sample prepared in Comparative Example 2 in Test Example 5 and the amorphous assembly of octanoylglycine tranexamic acid prepared in Example 5. Figure 8 A comparison of scanning electron microscopy images of the physically mixed sample prepared in Comparative Example 2 in Test Example 5 and the amorphous assembly of octanoylglycine tranexamic acid prepared in Example 5. Figure 9Infrared comparison images of the physically mixed sample prepared in Comparative Example 2 in Test Example 5 and the amorphous assembly of octanoylglycine tranexamic acid prepared in Example 5. Figure 10 The diagram shows the interaction analysis between octanoylglycine and octanoylglycine tranexamic acid amorphous assemblies and cyclodextrin in Test Example 6. Figure 11 The ESP analysis results of the capryloylglycine and capryloylglycine-tranexamic acid co-amorphous compounds in Example 6 are shown in the figure. Figure 12 The molecular frontier orbital analysis diagram of the capryloylglycine and capryloylglycine-tranexamic acid co-amorphous co-amorphous compound of the present invention in Test Example 6; Figure 13 The figure shows the test results of the inhibitory effect of the octanoylglycine tranexamic acid amorphous assembly on 5α-reductase in Test Example 7; Figure 14 The figure shows the test results of the effect of the octanoylglycine tranexamic acid amorphous assembly on the lipid droplet content of sebaceous gland cells in test example 7; Figure 15 The figure shows the effect of the octanoylglycine tranexamic acid amorphous assembly on the melanin content of cells in test example 8. Detailed Implementation

[0024] To better understand the technical solution of the present invention, the embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the described embodiments are merely some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Example 1 The preparation method of the capryloylglycine-tranexamic acid co-amorphous compound includes the following steps: Accurately weigh 3 g of capryloylglycine and 0.5 g of tranexamic acid, place them in a 100 mL round-bottom flask, add 50 mL of methanol-water solution (methanol to water volume ratio 1:1, v / v), and sonicate at room temperature until clear and transparent to obtain mixture A. Then, remove the solvent by rotary evaporation under reduced pressure at 60 °C to obtain a solid product. Dry the solid product in a vacuum drying oven at 45 °C for 36 h to completely remove residual solvent, thus obtaining the capryloylglycine-tranexamic acid co-amorphous compound.

[0026] Example 2 Accurately weigh 2 g of capryloylglycine and 2 g of tranexamic acid and place them in a 100 mL round-bottom flask. Add 50 mL of an aqueous ethanol solution (ethanol to water volume ratio of 2:1, v / v), and sonicate at room temperature until clear and transparent to obtain mixture A. Then, remove the solvent by rotary evaporation under reduced pressure at 55 °C to obtain a solid product. Place the solid product in a vacuum drying oven at 40 °C for 48 h to completely remove residual solvent, thus obtaining the capryloylglycine-tranexamic acid co-amorphous compound.

[0027] Example 3 Accurately weigh 4.5 g of capryloylglycine and 1.5 g of tranexamic acid and place them in a 100 mL round-bottom flask. Add 50 mL of an aqueous ethanol solution (ethanol to water volume ratio of 1:1, v / v), and sonicate at room temperature until clear and transparent to obtain mixture A. Then, remove the solvent by rotary evaporation under reduced pressure at 40 °C to obtain a solid product. Place the solid product in a vacuum drying oven at 50 °C for 24 h to completely remove residual solvent, thus obtaining the capryloylglycine-tranexamic acid co-amorphous compound.

[0028] Example 4 The preparation method of the amorphous assembly of capryloylglycine tranexamic acid includes the following steps: (1) The preparation method of the octanoylglycine-tranexamic acid co-amorphous compound is the same as in Example 2.

[0029] (2) Weigh 0.25 g of a cyclodextrin compound (γ-cyclodextrin was selected), dissolve it in 50 mL of water, and stir magnetically at 300 rpm until completely dissolved to obtain a cyclodextrin solution; add 2.5 g of the octylglycine-tranexamic acid co-amorphous compound prepared in Example 2 to the solution, maintain the stirring speed at 300 rpm, and continue stirring at 50 °C for 6 h to obtain a clear inclusion solution. After the reaction is completed, transfer the inclusion solution to a freeze dryer and freeze dry at -80 °C for 36 h to finally obtain the octylglycine-tranexamic acid amorphous assembly.

[0030] Example 5 The preparation method of the amorphous assembly of capryloylglycine tranexamic acid includes the following steps: (1) The preparation method of the octanoylglycine-tranexamic acid co-amorphous compound is the same as in Example 2.

[0031] (2) Weigh 1 g of a cyclodextrin compound (hydroxypropyl-α-cyclodextrin was selected), dissolve it in 50 mL of water, and stir magnetically at 300 rpm until completely dissolved to obtain a cyclodextrin solution; add 5 g of the above-prepared octylglycine-tranexamic acid co-amorphous compound to the solution, and increase the stirring speed to 450 rpm, and continue stirring at 55℃ for 4 h to obtain a clear inclusion solution. After the reaction is completed, transfer the inclusion solution to a freeze dryer and freeze dry at -80℃ for 24 h to finally obtain the octylglycine-tranexamic acid amorphous assembly.

[0032] Example 6 The preparation method of the amorphous assembly of capryloylglycine tranexamic acid includes the following steps: (1) The preparation method of the octanoylglycine-tranexamic acid co-amorphous compound is the same as in Example 2.

[0033] (2) Weigh 1.2 g of a cyclodextrin compound (methyl-β-cyclodextrin was selected), dissolve it in 50 mL of water, and stir magnetically at 300 rpm until completely dissolved to obtain a cyclodextrin solution; add 3 g of the above-prepared octylglycine-tranexamic acid co-amorphous compound to the solution, and increase the stirring speed to 400 rpm, and continue stirring at 65℃ for 2 h to obtain a clear inclusion solution. After the reaction is completed, transfer the inclusion solution to a freeze dryer and freeze dry at -80℃ for 28 h to finally obtain the octylglycine-tranexamic acid amorphous assembly.

[0034] Example 7 The preparation method of the amorphous assembly of capryloylglycine tranexamic acid includes the following steps: (1) The preparation method of the octanoylglycine-tranexamic acid co-amorphous compound is the same as in Example 2.

[0035] (2) Weigh 2.6 g of a cyclodextrin compound (hydroxypropyl-β-cyclodextrin was selected), dissolve it in 78 mL of water, and stir magnetically at 300 rpm until completely dissolved to obtain a cyclodextrin solution; add 5 g of the above-prepared octylglycine-tranexamic acid co-amorphous compound to the solution, and increase the stirring speed to 500 rpm, and continue stirring at 60℃ for 3 h to obtain a clear inclusion solution. After the reaction is completed, transfer the inclusion solution to a freeze dryer and freeze dry at -80℃ for 48 h to finally obtain the octylglycine-tranexamic acid amorphous assembly.

[0036] Example 8 The preparation method of the amorphous assembly of capryloylglycine tranexamic acid includes the following steps: (1) The preparation method of the octanoylglycine-tranexamic acid co-amorphous compound is the same as in Example 2.

[0037] (2) Weigh 3 g of a cyclodextrin compound (β-cyclodextrin is selected), dissolve it in 200 mL of water, and stir magnetically at 300 rpm until completely dissolved to obtain a cyclodextrin solution; add 1.5 g of the above-prepared octylglycine-tranexamic acid co-amorphous compound to the solution, and increase the stirring speed to 350 rpm, and continue stirring at 40℃ for 8 h to obtain a clear inclusion solution. After the reaction is completed, transfer the inclusion solution to a freeze dryer and freeze dry at -80℃ for 40 h to finally obtain the octylglycine-tranexamic acid amorphous assembly.

[0038] Comparative Example 1 To investigate the inclusion effect of cyclodextrin on capryloylglycine raw material, Comparative Example 1 provides a method for preparing an assembly. This method is basically the same as that in Example 5, except that the capryloylglycine-tranexamic acid co-amorphous compound added in step (2) of Comparative Example 1 is adjusted to capryloylglycine raw material, and other experimental operations are the same as in Example 5.

[0039] Comparative Example 2 To investigate the inclusion effect of cyclodextrin on the physical mixture of capryloylglycine and tranexamic acid, Comparative Example 2 provides a method for preparing an assembly that is basically the same as that in Example 5, except that the capryloylglycine-tranexamic acid co-amorphous compound added in step (2) of Comparative Example 2 is adjusted to a physical mixture of capryloylglycine and tranexamic acid, and other experimental operations are the same as in Example 5.

[0040] The preparation of a physical mixture of capryloylglycine and tranexamic acid includes: mixing capryloylglycine and tranexamic acid powder evenly to obtain a physical mixture of capryloylglycine and tranexamic acid; wherein the mass ratio of capryloylglycine to tranexamic acid is 1:1.

[0041] Test Example 1: Solubility Test of Caprylyl Glycine Tranexamic Acid Amorphous Assemblies and Caprylyl Glycine-Tranexamic Acid Co-amorphous Compounds Solubility Test 1: 8 g of the products from Examples 1-3 (caprylyl glycine-tranexamic acid co-amorphous compound) and caprylyl glycine raw material were added to 10 mL of pure water, respectively. After equilibration at 25°C and 300 rpm for 24 h, the mixture was filtered, and the equilibrium solubility of caprylyl glycine was determined by HPLC. Three parallel experiments were performed, and the results are as follows: Figure 1A As shown, the amorphous compound of caprylyl glycine and tranexamic acid can significantly improve the solubility of caprylyl glycine. When the mass ratio of caprylyl glycine to tranexamic acid is 1:1 (Example 2), the solubility of caprylyl glycine is increased by the most, which is 9.79 times that of the active pharmaceutical ingredient.

[0042] Solubility Test 2: 8 g of the products from Examples 4-8 (caprylyl glycine tranexamic acid amorphous assembly) were added to 10 mL of pure water, stirred at 300 rpm for 24 h at 25°C, filtered, and the equilibrium solubility of caprylyl glycine was determined by HPLC. The experiment was performed in triplicate, and the results are as follows: Figure 1B As shown. From Figure 1B As can be seen, the inclusion effect of cyclodextrin further improves the solubility of caprylyl glycine, but the effect of different types of cyclodextrin on improving the solubility of caprylyl glycine varies significantly. The solubility of caprylyl glycine in the products of Examples 4-8 is 38.34, 68.19, 81.29, 87.47, and 51.38 times that of the active pharmaceutical ingredient, respectively. Considering the economic benefits of cyclodextrin loading, Example 5 was selected for further study. The solubility of caprylyl glycine in the products of Comparative Examples 1 and 2 is significantly lower than that in Example 5, indicating that the inclusion effect of cyclodextrin on the caprylyl glycine-tranexamic acid co-amorphous compound is better than that of the caprylyl glycine active pharmaceutical ingredient and the physical mixture of caprylyl glycine and tranexamic acid. This may be due to the extremely high instantaneous solubility of the co-amorphous compound, which allows more caprylyl glycine to smoothly enter the cavities of the cyclodextrin.

[0043] Test Example 2: Polarized light microscopy observation of amorphous assemblies of octylglycine and tranexamic acid, and co-amorphous assemblies of octylglycine and tranexamic acid. Experiment 1: Caprylyl glycine, tranexamic acid, a physical mixture of the two monomers (caprylyl glycine and tranexamic acid mixed at a mass ratio of 1:1), and the product of Example 2 (caprylyl glycine-tranexamic acid co-amorphous compound) were observed under a polarizing microscope at a magnification of 40x. The results are as follows: Figure 2 As shown. Figure 2 As shown, the capryloylglycine raw material, tranexamic acid raw material, and their physical mixture all exhibit obvious birefringence, indicating their crystalline structure. In contrast, the product of Example 2 shows a uniformly dark field of view under crossed polarized light, without obvious birefringence, exhibiting optical isotropic characteristics. This result confirms that the product is amorphous, indicating that capryloylglycine and tranexamic acid have successfully formed a co-amorphous compound.

[0044] Experiment 2: The amorphous co-amorphous compound of caprylyl glycine and tranexamic acid prepared in Example 2, cyclodextrin (hydroxypropyl-β-cyclodextrin was selected), a physical mixture of the two (the amorphous co-amorphous compound of caprylyl glycine and tranexamic acid prepared in Example 2 was mixed with hydroxypropyl-β-cyclodextrin at a mass ratio of 1:5 and stirred evenly), and the amorphous assembly of caprylyl glycine and tranexamic acid prepared in Example 5 were observed under a polarizing microscope. The magnification of the polarizing microscope was 40x. The results are as follows: Figure 3As shown, cyclodextrin is mainly dark black, but exhibits a certain degree of birefringence, indicating that it is in a semi-crystalline state; the physical mixing process did not change the semi-crystalline state of cyclodextrin; however, the product of Example 5 (octanoylglycine-tranexamic acid amorphous assembly) is dark in the field of view and is in an amorphous state, indicating that cyclodextrin achieved molecular-level inclusion of the octanoylglycine-tranexamic acid co-amorphous compound, forming a new substance, namely the octanoylglycine-tranexamic acid amorphous assembly.

[0045] Test Example 3: Dissolution Performance Test of Caprylyl Glycine Tranexamic Acid Amorphous Assemblies and Caprylyl Glycine-Tranexamic Acid Co-Amorphous Compounds The amorphous compound of caprylyl glycine and tranexamic acid (product of Example 2), the amorphous assembly of caprylyl glycine and tranexamic acid (product of Example 5), the caprylyl glycine active pharmaceutical ingredient, and the tranexamic acid active pharmaceutical ingredient were ground and then passed through 100-mesh and 200-mesh sieves to control the powder particle size to 75-150 μm, avoiding dissolution differences caused by differences in powder particle size. 100 g of the ground amorphous compound of caprylyl glycine and tranexamic acid (product of Example 2), the amorphous assembly of caprylyl glycine and tranexamic acid (product of Example 5), the caprylyl glycine active pharmaceutical ingredient, and a physical mixture of caprylyl glycine active pharmaceutical ingredient and tranexamic acid active pharmaceutical ingredient (obtained by uniformly mixing caprylyl glycine active pharmaceutical ingredient and tranexamic acid active pharmaceutical ingredient at a mass ratio of 1:1) were added to 100 mL of pure water at a time. The mixture was stirred continuously at 300 rpm at a constant temperature of 25°C. 1 mL samples were taken at 10 min, 20 min, 30 min, 1 h, and 2 h after the addition of the drugs. After filtration, the concentration of caprylyl glycine was determined by HPLC. The experiment was conducted in three parallel trials. The concentration of octanoyl glycine in the solution was calculated at each time point, and the dissolution curves of each sample were plotted.

[0046] Figure 4 Dissolution curves of caprylyl glycine in different forms are presented. It can be seen that the solubility of caprylyl glycine raw material is poor; its concentration increases with time after 30 min, and then remains almost stable, approaching saturation solubility. In the physical mixture (a physical mixture of caprylyl glycine and tranexamic acid raw materials), the dissolution curve of caprylyl glycine is similar to that of caprylyl glycine raw material, approaching saturation after 30 min, but the solubility of caprylyl glycine is improved to some extent. In the caprylyl glycine-tranexamic acid co-amorphous compound, the concentration of caprylyl glycine gradually decreases with time, indicating that it can quickly reach maximum solubility, but then decreases rapidly, exhibiting a typical "spring-parachute" effect. This is consistent with the high-energy state characteristics of co-amorphous compounds. In the caprylyl glycine-tranexamic acid amorphous assembly, the concentration of caprylyl glycine remains close to saturation solubility, indicating that it can dissolve rapidly while remaining stable for a long time. This demonstrates that cyclodextrin inclusion not only further improves the solubility of caprylyl glycine, but also solves the instability of the co-amorphous compound.

[0047] Test Example 4: Observation of the crystal structure of the amorphous assembly of octanoylglycine tranexamic acid The crystal structure of tranexamic acid, capryloyl glycine, capryloyl glycine-tranexamic acid co-amorphous compound (product of Example 2), and capryloyl glycine-tranexamic acid amorphous assembly (product of Example 5) were analyzed by XRD. The results are as follows: Figure 5 As shown in the diagram, both capryloylglycine and tranexamic acid exhibit sharp peaks in their XRD patterns, indicating that they are crystalline. The capryloylglycine-tranexamic acid co-amorphous compound has only one broad peak near 20°, consistent with its amorphous characteristics. Cyclodextrin exhibits broad peaks near 10° and 20°, and small sharp peaks near 35°-45°, 70°, and 80°, indicating the presence of a small amount of crystalline material. The XRD peak positions of the capryloylglycine-tranexamic acid amorphous assembly are similar to those of cyclodextrin, indicating that cyclodextrin effectively encapsulates the capryloylglycine-tranexamic acid co-amorphous compound. Furthermore, compared to cyclodextrin, the broad peak intensity near 10° of the capryloylglycine-tranexamic acid amorphous assembly is weakened, and the other small sharp peaks disappear, indicating that cyclodextrin inclusion does not destroy the structure of the capryloylglycine-tranexamic acid co-amorphous compound, but rather alters its packing pattern at the molecular level, forming the capryloylglycine-tranexamic acid amorphous assembly.

[0048] Test Example 5: Microstructural Characterization of the Amorphous Assembly of Capryloylglycine Tranexamic Acid DLS testing and Tyndall effect observation: 6 g of the product from Example 5 (octanoylglycine tranexamic acid amorphous assembly) was added to 100 mL of deionized water, stirred continuously at 300 rpm for 30 min at 25°C, and then sonicated for 10 min to ensure complete dissolution. Its particle size distribution and Tyndall effect were then tested. Figure 6A and Figure 6B As shown, the solution of the amorphous assembly of capryloylglycine tranexamic acid exhibits a significant Tyndall effect, indicating that it exists in the form of nanoparticles. The particle size distribution shows that the average particle size is approximately 21.39 nm, the PDI (polydispersity index) is 0.23, and the particle size is relatively uniform.

[0049] Transmission electron microscopy (TEM) observation: The amorphous assembly of capryloylglycine tranexamic acid prepared in Example 5 and the physical mixture prepared in Comparative Example 2 (hereinafter referred to as the physical mixture sample) were observed under a transmission electron microscope. The TEM results are as follows: Figure 7 As shown. Figure 7 The left side is a physically mixed sample. Figure 7The right side of the figure shows the amorphous assembly of capryloylglycine tranexamic acid. As shown in the figure, the physically mixed sample exhibits a dispersed, irregular, large particle state, indicating that the two active pharmaceutical ingredients have poor solubility and recrystallization has occurred. In contrast, the amorphous assembly of capryloylglycine tranexamic acid shows aggregated spherical or irregular particles without definite crystal edges or regular shapes; the whole exhibits a continuous, amorphous aggregate state, and the size is significantly reduced to the nanoscale; direct morphological evidence further confirms that the components have achieved molecular-level assembly, forming a new substance.

[0050] Scanning electron microscopy (SEM) analysis: The amorphous assembly of capryloylglycine tranexamic acid was dried and pulverized for convenient storage and transportation. To verify whether this process damaged its microstructure, the morphology of the sample was analyzed using scanning electron microscopy (SEM). Figure 8 SEM images of the physical mixture prepared in Comparative Example 2 (hereinafter referred to as the physical mixture sample) and the amorphous assembly of octanoylglycine tranexamic acid prepared in Example 5, obtained after drying and pulverizing, are shown below. Figure 8 As shown, the physical mixture sample exhibits a typical coexistence of multiple morphologies, with visible dispersed, well-defined plate-like and blocky structures, distinct particle boundaries, and loose packing. In contrast, the amorphous assembly of capryloylglycine tranexamic acid after drying and pulverization still maintains a uniform and continuous morphology, with smooth edges, consistent fusion between regions, and no obvious crystalline features. This morphology indicates that the assembly is still a single amorphous phase, proving that the drying and pulverization process did not destroy its amorphous structure and the inclusion state of cyclodextrin.

[0051] Fourier Transform Infrared Spectroscopy Analysis: The physical mixture prepared in Comparative Example 2 (hereinafter referred to as the physical mixture sample) and the amorphous assembly of capryloylglycine tranexamic acid prepared in Example 5, after drying and pulverizing, were subjected to Fourier transform infrared spectroscopy (FTIR) analysis, respectively. The results are as follows: Figure 9 As shown. Figure 9 As shown, in the spectrum of the physically mixed sample, the characteristic absorption peaks of octanoylglycine and tranexamic acid are clear and independent with sharp peak shapes, indicating that they are simply mixed, with intact crystal structures and no new intermolecular interactions. However, the spectrum of the octanoylglycine-tranexamic acid amorphous assembly shows significant changes, with characteristic peaks becoming noticeably broadened and diffused, and some peaks shifting or disappearing. This change stems from the disruption of the long-range ordered structure of the crystal and strong interactions such as newly formed hydrogen bonds between components, leading to restricted molecular vibrations and a broadened energy level distribution, resulting in a broadened absorption band in the spectrum. This confirms the formation of a homogeneous phase co-amorphous compound at the molecular level.

[0052] Test Example 6: Simulation Test of Amorphous Assemblies of Capryloylglycine Tranexamic Acid To investigate the molecular interaction mechanism in the amorphous assembly of octanoylglycine tranexamic acid, density functional theory (DFT) was used in Gaussian software for computational analysis. Figure 10 The interaction analysis results of the product of Example 5 (caprylyl glycine tranexamic acid amorphous assembly) and the product of Comparative Example 1 are presented. Independent gradient model (IGMH) of Hirshfeld segmentation and atomic topology analysis (AIM) of the molecule show abundant intermolecular interactions between cyclodextrin and both the caprylyl glycine monomer and the co-amorphous compound, indicating that cyclodextrin has a good inclusion effect on both the caprylyl glycine monomer and the co-amorphous compound. The binding energy between the co-amorphous compound and cyclodextrin is -93.8 kcal / mol, significantly lower than the binding energy between the monomer and cyclodextrin (-66.13 kcal / mol). This indicates a stronger intermolecular interaction between the co-amorphous compound and cyclodextrin, resulting in an inclusion complex with higher thermodynamic stability.

[0053] Figure 11 This is a surface electrostatic potential (ESP) analysis diagram of the amorphous co-amorphous compound of capryloylglycine and capryloylglycine-tranexamic acid of the present invention. Figure 11 As shown, octanoylglycine exhibits a typical amphiphilic distribution, with its long alkyl chain region showing a near-neutral potential, while the polar head exhibits a localized high potential difference. In contrast, the octanoylglycine-tranexamic acid amorphous assembly shows a significant difference in charge distribution characteristics: the original defined boundaries are broken, and charges are redistributed and delocalized, reflecting intermolecular charge transfer and reorganization of the overall electron cloud structure. This indicates that the co-amorphous system enhances intermolecular interactions through electrostatic complementarity, thereby affecting its physicochemical properties and stability.

[0054] Figure 12 This paper presents the molecular frontier orbital analysis of the amorphous co-amorphous compound of octanoylglycine and tranexamic acid, as described in this invention. As a core theoretical tool of quantum chemistry, molecular frontier orbital analysis focuses on the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO). By analyzing their energy, spatial distribution, and interactions, it elucidates the electronic structure, reactivity, and pathway selection of molecules, providing a theoretical basis for understanding chemical behavior. Figure 12It is known that the band gap (ΔE) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of capryloylglycine is 4.80 eV, indicating that its electronic excitation requires relatively high energy, reflecting a relatively stable electronic configuration. Meanwhile, the band gap (ΔE) of tranexamic acid is 4.12 eV, while the ΔE of the co-amorphous form significantly decreases to 3.68 eV, indicating a reduced energy barrier for electron transitions from the HOMO to the LUMO, implying enhanced reactivity or charge transfer efficiency. The optimization of electronic structure stems from the orbital energy level reconstruction and spatial expansion caused by molecular assembly during co-amorphous formation, which can potentially affect its physicochemical behavior.

[0055] Test Example 7: Oil-controlling efficacy test of capryloylglycine tranexamic acid amorphous assembly 5α-Reductase Inhibition Rate Test The oil-controlling efficacy of the test samples was evaluated according to the "Biochemical Experimental Method for 5α-Reductase Inhibition Rate". The reagents used were as follows: 5α-reductase (provided by Suzhou Huizhi Heyuan Biotechnology Co., Ltd.), dutasteride (provided by Shanghai Maclean Biochemical Technology Co., Ltd.), testosterone (provided by Beijing Wokai Biotechnology Co., Ltd.), and tetrasodium reductase II (NADPH, provided by Shanghai Maclean Biochemical Technology Co., Ltd.). The test samples were the amorphous assembly of octanoylglycine tranexamic acid prepared in Example 5 and octanoylglycine.

[0056] Referring to Table 1 below, establish sample tubes (T), sample background (T0), blank tubes (C), and blank background (C0). For each sample, each test concentration in the sample tube (T) should be measured in triplicate, and the blank tube (C) should also be measured in triplicate. First, add 440 μL of PBS buffer to all test tubes. Then, add 40 μL of the same concentration of sample solution to each well (T) and sample background (T0), and add 40 μL of PBS buffer to the blank tubes (C) and blank background (C0). Add 40 μL of testosterone solution, 120 μL of reduced coenzyme II solution, and 160 μL of 5α-reductase solution to the sample tubes (T) and blank tubes (C), and add 320 μL of PBS buffer to the sample background (T0) and blank background (C0). Measure the absorbance at 340 nm after sample addition. Record the absorbance A at this point after subtracting the sample background. 样0min And the absorbance A of the blank matrix after subtracting the blank background. 空0min The sample was then incubated at 37°C for 60 minutes, and the absorbance was measured again at 340 nm. The absorbance value A, after subtracting the sample background, was recorded. 样60min And the absorbance A of the blank matrix after subtracting the blank background. 空60min .

[0057] Table 1 Sample Addition Requirements The experiment was performed in triplicate. The inhibition rate of 5α-reductase activity was calculated using the following formula: Inhibition rate (%) = [(A 空0min -A 空60min )-(A 样0min -A 样60min )] / (A empty 0min -A 空60min ) 100% In the formula: A 空0min —The average of three absorbance values ​​obtained from the blank tube at 0 min after subtracting the blank background; A 空60min —The average of three absorbance values ​​obtained from the blank tube after subtracting the blank background, measured over 60 minutes; A 样0min —The absorbance value of the sample tube obtained from the 0-minute measurement, after deducting the sample background, needs to be measured in parallel 3 times; A 样60min —The absorbance value of the sample tube obtained after 60 minutes of measurement, after deducting the sample background, needs to be measured in parallel 3 times.

[0058] The inhibition rate of 5α-reductase activity at a given test concentration is expressed as mean inhibition rate ± standard deviation (SD). P < 0.05 was considered statistically significant, and P < 0.01 was considered highly statistically significant.

[0059] The sample groups included capryloylglycine group 1, capryloylglycine group 2, co-amorphous assembly group 1, and co-amorphous assembly group 2. Specifically, in capryloylglycine group 1, the concentration of capryloylglycine in the sample solution was 0.09 wt%; in capryloylglycine group 2, the concentration of capryloylglycine in the sample solution was 0.15 wt%; in co-amorphous assembly group 1, the concentration of capryloylglycine released from the capryloylglycine-tranexamic acid amorphous assembly in the solution was 0.09 wt%; and in co-amorphous assembly group 2, the concentration of capryloylglycine released from the capryloylglycine-tranexamic acid amorphous assembly in the solution was 0.15 wt%. Figure 13This is a comparison of the inhibitory effects of the capryloylglycine tranexamic acid amorphous assembly and capryloylglycine on 5α-reductase activity at different concentrations. Capryloylglycine 1 represents the test results at a concentration of 0.09 wt% for capryloylglycine, and co-amorphous assembly 1 represents the test results when the capryloylglycine tranexamic acid amorphous assembly releases capryloylglycine at a concentration of 0.09 wt% in the sample solution. Capryloylglycine 2 represents the test results at a concentration of 0.15 wt% for capryloylglycine, and co-amorphous assembly 2 represents the test results when the capryloylglycine tranexamic acid amorphous assembly releases capryloylglycine at a concentration of 0.15 wt% in the sample solution. The results show that at a concentration of 0.09 wt%, the enzyme activity inhibition rate of the co-amorphous assembly is 27% higher than that of the same concentration of capryloylglycine monomer. When the concentration increases to 0.15 wt%, its inhibition rate is further significantly enhanced and is significantly better than that of the monomer at the same concentration, indicating that its inhibitory effect is dose-dependent. These results suggest that, at the same capryloylglycine concentration, the amorphous assembly of capryloylglycine tranexamic acid has better oil control potential than the monomer.

[0060] Sebaceous gland cell lipid droplet content test The oil-control efficacy of the tested sample was evaluated according to the "Standard Operating Procedure for Determination of Lipid Droplet Content in Human Sebaceous Gland Cells in In Vitro" for testing the oil-control efficacy of cosmetic oil-controlling effects. The tested sample consisted of an amorphous assembly of caprylyl glycine and tranexamic acid prepared in Example 5, and caprylyl glycine. The principle is as follows: Sebaceous glands are the source and target tissue of androgens. Dehydroepiandrosterone (DHEA) is produced in sebaceous glands, which is converted into the most active testosterone and 5α-dihydrotestosterone through a series of enzymatic catalysis. These can stimulate lipid synthesis and the proliferation and differentiation of sebaceous gland cells. During this proliferation and differentiation process, undifferentiated immature cells proliferate first, and some daughter cells form lipid droplets and move towards the center of the gland cell, gradually developing and differentiating into mature sebaceous gland cells that can store and secrete lipids. This experiment used Nile Red staining to detect the amount of oil secreted by sebaceous gland cells, thereby determining whether the sample has an oil-controlling effect.

[0061] The sebaceous gland cells used were purchased from Hangzhou Ruixu Kexin Biotechnology Co., Ltd.; the culture medium used was DMEM medium, purchased from Thermo Fisher Scientific (China) Co., Ltd., catalog number C11995500BT.

[0062] 1. Cells were seeded in 12-well plates and incubated at 37°C with 5% CO2 for 24 hours. The experimental groups are shown in Table 2 below.

[0063] Table 2 2. After incubation, remove the culture medium, wash 1-2 times with D-Hanks buffer, replace the normal control group with fresh culture medium, replace the model control group with fresh culture medium containing dihydrotestosterone, and replace the sample group with fresh culture medium containing the sample and dihydrotestosterone. Perform 3 biological replicates and continue incubation at 37°C and 5% CO2 for 24 hours.

[0064] 3. After incubation, remove the culture medium, pre-cool, wash three times with D-Hanks buffer, fix with 4% paraformaldehyde, wash again with D-Hanks buffer, stain with Nile red, take pictures under a fluorescence microscope, and analyze the average fluorescence intensity of each group using ImageJ.

[0065] 4. The oil-controlling effect was calculated using the following formula. P<0.05 was considered statistically significant, and P<0.01 was considered highly statistically significant.

[0066] Oil control efficacy (%) = (A 模型对照组 -A 样品组 ) / A 模型对照组 100% Where: A — average fluorescence intensity The sample groups in Table 2 include an isoconcentration caprylyl glycine group and a co-amorphous assembly group; the drug concentration (the concentration of caprylyl glycine released from the caprylyl glycine tranexamic acid amorphous assembly in the culture medium) in the co-amorphous assembly group was 0.03 wt%, and the corresponding concentration of caprylyl glycine tranexamic acid amorphous assembly in the culture medium was 0.1 wt%; while the drug concentration (the concentration of caprylyl glycine in the culture medium) in the isoconcentration caprylyl glycine group was 0.03 wt%.

[0067] Figure 14 The fluorescence intensity of the amorphous assembly of capryloylglycine tranexamic acid and capryloylglycine on the lipid droplet content of sebaceous gland cells is presented. The mean fluorescence intensity of the model control group was significantly higher than that of the normal control group, indicating that the stimulation condition was effective. Figure 14 The co-amorphous assembly in the text represents the capryloylglycine-tranexamic acid amorphous assembly (releasing 0.03 wt% capryloylglycine in the culture medium). When the capryloylglycine concentration in the culture medium was 0.03 wt%, the fluorescence intensity of the co-amorphous assembly treatment group was significantly reduced by 30% compared to the model control group, indicating that the co-amorphous assembly has good oil-controlling efficacy. Furthermore, the test results of the co-amorphous assembly were not significantly different from those of capryloylglycine, meaning that the co-amorphous technology did not adversely affect the oil-controlling effect of capryloylglycine.

[0068] Test Example 8: Whitening Efficacy Test of Capryloyl Glycine Tranexamic Acid Amorphous Assemblies Ultraviolet (UV) irradiation induces melanin production in melanocytes by damaging cellular DNA and activating a stress response. Tyrosinase, a key enzyme in melanin synthesis, catalyzes the conversion of tyrosine to dopaquinone, which in turn forms melanin; its activity is positively correlated with the rate of melanin production. Using the A375 cell model (purchased from Wuhan Pronosai Life Science Technology Co., Ltd., catalog number CL-0014), the inhibitory effect of the sample on melanin production was evaluated by detecting the melanin expression level after UV irradiation. The sample tested was the amorphous assembly of capryloylglycine tranexamic acid prepared in Example 5, and tranexamic acid; a higher inhibition rate indicates a stronger whitening effect of the sample. The culture medium used was A-375 cell-specific medium (purchased from Wuhan Pronosai Life Science Technology Co., Ltd., catalog number CM-0014).

[0069] The specific experimental steps are as follows: 1. After cell resuscitation, passage twice to expand the culture.

[0070] 2. After digesting, centrifuging, resuspending, and counting the cells from the expanded culture, the cells are seeded into 6-well cell culture plates.

[0071] 3. Experimental Groups: The specific groups are shown in Table 3 below.

[0072] Table 3 4. After the cells have fully adhered, remove the culture medium, add PBS buffer, and irradiate the cells with a combination of UVB and UVA. The NC group was covered with aluminum foil, while the model control group and sample groups were not covered with aluminum foil. After irradiation, add 2000 μl of the corresponding diluted drug (diluted with culture medium) to each of the 6 wells. Detect the cells after 48 hours of incubation.

[0073] 5. After washing the collected cells twice with PBS buffer, they were divided into two equal portions. The protein concentration of one portion was determined using a BCA protein concentration assay kit.

[0074] 6. The other sample was resuspended in 1M NaOH solution containing 10% dimethyl sulfoxide and heated at 80°C for 1 hour. Finally, the absorbance of the extracted melanin was measured at 405 nm using a microplate reader.

[0075] 7. Formula for calculating the relative concentration of melanin Table 3 lists two sample groups: an amorphous assembly group and a tranexamic acid group. In the amorphous assembly group, the added drug was capryloylglycine tranexamic acid amorphous assembly. The concentration of tranexamic acid released by the capryloylglycine tranexamic acid amorphous assembly in the culture medium was 0.02 wt%, corresponding to a concentration of 0.1 wt% in the culture medium. In the tranexamic acid group, the added drug was tranexamic acid, with a concentration of 0.02 wt% in the culture medium. Figure 15 This study demonstrates the effects of capryloylglycine tranexamic acid amorphous assemblies and tranexamic acid on melanin content in melanocytes. Compared to the normal control group, the model control group showed a significant increase, indicating the effectiveness of the stimulation. When the concentration of tranexamic acid released by the capryloylglycine tranexamic acid amorphous assembly in the culture medium was 0.02 wt%, the melanin content of the capryloylglycine tranexamic acid amorphous assembly was significantly reduced by 39.74% compared to the MC group, indicating its whitening effect. Furthermore, compared to the 18.58% decrease in tranexamic acid monomer at the same concentration, the co-amorphous assembly exhibited superior whitening efficacy. This invention not only enhances the pharmacological activity of capryloylglycine but also simultaneously achieves multi-pathway skin care for oily skin, including acne treatment and whitening, making its therapeutic effect superior to that of a single component.

[0076] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A process for the preparation of an octanoyl glycine pantothenic acid amorphous assembly, characterized by, Includes the following steps: (1) Add octanoyl glycine and tranexamic acid to an alcohol solution, dissolve them evenly by ultrasonication to obtain a mixture A, evaporate by rotary evaporation and dry to obtain an amorphous product of octanoyl glycine-tranexamic acid. (2) Dissolve the cyclodextrin compound in water to obtain a cyclodextrin compound solution, add the octanoylglycine-tranexamic acid co-amorphous compound, and heat the reaction under stirring to obtain an inclusion solution. Freeze-dry the solution to obtain the octanoylglycine-tranexamic acid amorphous assembly.

2. The process for the preparation of the suberoyl glycine pteroyl glutamic acid amorphous assembly as claimed in claim 1, wherein, The mass ratio of capryloylglycine to tranexamic acid in step (1) is (1-6):

1.

3. The process for the preparation of suberoyl glycine pteroyl aspartic acid amorphous assembly as claimed in claim 1 wherein, The alcohol solution in step (1) is a mixture of alcohol and water, with the volume percentage of alcohol being 50-67%; the alcohol is ethanol or methanol; the mass-to-volume ratio of octanoylglycine to the alcohol solution is (0.04-0.09):1 g / mL.

4. The process for the preparation of suberoyl glycine pteroyl aspartic acid amorphous assembly as claimed in claim 1 wherein, The temperature of rotary evaporation in step (1) is 40-60℃; the drying method is vacuum drying, the drying temperature is 40-50℃, and the drying time is 24-48h.

5. The process for the preparation of suberoyl glycine pteroyl aspartic acid amorphous assembly as claimed in claim 1 wherein, In step (2), the mass-to-volume ratio of the cyclodextrin compound to water is 1:30-200 g / mL; the cyclodextrin compound is at least one of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, γ-cyclodextrin, and hydroxypropyl-α-cyclodextrin.

6. The process for the preparation of suberoyl glycine pteroyl aspartic acid amorphous assembly as claimed in claim 1 wherein, The mass ratio of the cyclodextrin compound to the octanoyl glycine-tranexamic acid co-amorphous compound in step (2) is 1:(0.5-10).

7. The method for preparing the amorphous assembly of octanoylglycine tranexamic acid according to claim 1, characterized in that, In step (2), the stirring rate under stirring conditions is 300-500 rpm, the heating temperature is 40-65℃, and the heating time is 2-8h.

8. The method for preparing the amorphous assembly of octanoylglycine tranexamic acid according to claim 1, characterized in that, The freeze-drying temperature in step (2) is -80℃, and the freeze-drying time is 24-48h.

9. An amorphous assembly of octanoylglycine tranexamic acid prepared by the preparation method according to any one of claims 1-8.

10. The use of the octanoylglycine tranexamic acid amorphous assembly according to claim 9 in the preparation of topical pharmaceuticals or cosmetics.

Images