A dual-targeting oil control peptide co-amorphous assembly, and a preparation method and application thereof

Abstract

This invention belongs to the fields of biomedicine, beauty, and personal care health technology, and discloses a dual-target oil-controlling peptide co-amorphous assembly, its preparation method, and its application. The method involves adding capryloylglycine and acetyl tetrapeptide-5 to an alcohol solution, heating to dissolve, rotary evaporating, and drying to obtain a co-amorphous compound. This compound is then mixed with a cyclodextrin compound and water, rotary evaporating, and drying to obtain the dual-target oil-controlling peptide co-amorphous assembly. This invention employs a co-amorphous combination with cyclodextrin inclusion to assemble acetyl tetrapeptide-5 and capryloylglycine, solving the problem of their large solubility differences and difficulty in coexistence, and significantly improving the solubility of capryloylglycine. This assembly enables simultaneous transdermal delivery of the two active components through nano-assembly, helping to enhance the stability of acetyl tetrapeptide-5 and reduce its oxidative degradation. The two components synergistically control oil through a dual pathway of inhibiting 5α-reductase and targeting the MC5R receptor, respectively, exhibiting superior bioavailability and efficacy compared to a single component.

Description

Technical Field

[0001] This invention belongs to the fields of biomedicine, beauty and personal care health technology, and particularly relates to a dual-target oil-controlling peptide co-amorphous assembly, its preparation method and application. Background Technology

[0002] With the rapid development of biotechnology, peptide drugs, due to their structural diversity, target specificity, and excellent biological activity, have become an important research direction in the fields of medicine, cosmetics, and functional foods. Acetyltetrapeptide-5 is a short peptide composed of four amino acids, with the structure acetyl-Gly-His-Lys-Pro (glycine-histidine-lysine-proline), and a molecular weight of approximately 492.5 Da. It is mainly used as a cosmetic ingredient, especially in eye care products (such as eye creams and serums), where it reduces eye bags, dark circles, and fine lines by inhibiting collagen glycation, improving microcirculation, and having anti-edema effects, while also enhancing skin elasticity and smoothness.

[0003] Existing patent CN119656057A discloses a novel application of acetyl tetrapeptide-5 in the preparation of skin oil-controlling products, and cell experiments have confirmed that it can reduce lipid content in human sebaceous gland cells. Molecular docking results show that acetyl tetrapeptide-5 can act on the MC5R receptor, thereby regulating sebaceous gland cell differentiation and reducing sebum secretion. This is significantly different from the mechanism of action of traditional oil-controlling ingredients (such as salicylic acid and retinol), exhibiting higher targeting and safety.

[0004] Despite its potent efficacy, acetyl tetrapeptide-5 faces several limitations in practical application. Firstly, its high water solubility results in insufficient lipid solubility, and its relatively large molecular weight restricts its transdermal efficiency, making it difficult to reach the dermis in sufficient quantities to exert its effects. Secondly, as a peptide, acetyl tetrapeptide-5 is susceptible to enzymatic hydrolysis and oxidation, exhibiting poor stability and requiring refrigerated storage, further limiting its application scenarios. Existing oil-controlling ingredients (such as salicylic acid and retinol) are fast-acting but highly irritating and can damage the skin barrier. Therefore, to achieve the gentle oil-controlling effects of acetyl tetrapeptide-5, its delivery efficiency needs to be addressed.

[0005] Capryloyl glycine is an amphiphilic small molecule composed of an octyl group (C8) and glycine, possessing both a lipophilic alkyl chain and a hydrophilic amide group. Studies have shown that capryloyl glycine can reduce dihydrotestosterone-mediated lipid secretion by inhibiting 5α-reductase activity, and its antibacterial activity (such as inhibition of Propionibacterium acnes) can further enhance its oil-controlling effect. However, the lipophilic nature of capryloyl glycine results in poor solubility in water-based formulations, requiring the use of solubilizers or specific processes, increasing the complexity of formulation. Furthermore, although capryloyl glycine has a high safety profile, its effectiveness is limited when used alone, necessitating combination with other active ingredients to enhance overall efficacy, which somewhat limits its applicability in simplified formulations.

[0006] Combining capryloylglycine with acetyl tetrapeptide-5 can achieve a dual-target oil-control effect. However, significant differences in solubility prevent them from coexisting in the same system. Co-amorphous solids are single-phase amorphous solids formed by the homogeneous mixing of two or more different chemical molecules at the molecular level, stabilized through various non-covalent interactions such as hydrogen bonds and van der Waals forces. Their core advantage lies in significantly improving the solubility and dissolution rate of poorly soluble drugs, thereby greatly enhancing bioavailability. They also support synergistic delivery of two drugs and inhibit recrystallization through molecular interlocking mechanisms, exhibiting better physical stability compared to pure amorphous forms. However, this system is essentially still in a metastable state. Long-term storage or adverse environmental conditions such as high temperature and humidity pose a risk of phase separation or spontaneous crystallization, which may lead to the loss of its enhanced solubility and other properties. Therefore, strengthening stability control is a key challenge for its practical application. Summary of the Invention

[0007] In order to solve the technical problems existing in the prior art, the purpose of this invention is to provide a dual-targeted oil-controlling peptide co-amorphous assembly, its preparation method and application, so as to solve the above-mentioned technical problems.

[0008] According to a first aspect of the present invention, the present invention provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, comprising the following steps: (1) Add octanoyl glycine and acetyl tetrapeptide-5 to an alcohol solution, heat to dissolve, and obtain mixture A. Rotary evaporate and dry to obtain octanoyl glycine-acetyl tetrapeptide-5 co-amorphous product. (2) Mix the cyclodextrin compound, the octanoylglycine-acetyl tetrapeptide-5 co-amorphous compound from step (1) with water, mix well to obtain mixture B, rotary evaporate, and dry to obtain the dual-targeted oil-controlling peptide co-amorphous assembly.

[0009] In some embodiments, the mass ratio of capryloylglycine to acetyl tetrapeptide-5 in step (1) is 1:(0.3-2).

[0010] In some embodiments, the mass-to-volume ratio of octanoylglycine to alcohol solution in step (1) is 0.01-0.05:1 g / ml.

[0011] 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 60-80%; the alcohol compound is ethanol or isopropanol.

[0012] In some embodiments, the heating and dissolving temperature in step (1) is 40-60°C; the rotary evaporation temperature is 40-60°C, and the rotary evaporation is stopped when a gel appears in the mixture.

[0013] In some embodiments, the drying temperature in step (1) is 30-50°C and the drying time is 24-72h.

[0014] In some embodiments, the mass-to-volume ratio of the cyclodextrin compound to water in step (2) is 1:40-60 g / mL; the cyclodextrin compound is at least one of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, γ-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and hydroxypropyl-α-cyclodextrin.

[0015] In some embodiments, the mass ratio of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound to the cyclodextrin compound in step (2) is 1:(0.5-2).

[0016] In some embodiments, the rotary evaporation temperature in step (2) is 60-70°C, and the evaporation is stopped when gel appears in the mixture B; the drying temperature is 40-60°C, and the drying time is 24-72 hours.

[0017] According to a second aspect of the present invention, the present invention provides a dual-targeting oil-controlling peptide co-amorphous assembly prepared by the above-described preparation method.

[0018] According to a third aspect of the present invention, the present invention provides the application of a dual-targeting oil-controlling peptide co-amorphous assembly in the preparation of topical pharmaceuticals or cosmetics.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) Significantly improves the solubility of active ingredients: Acetyl tetrapeptide-5 has good water solubility but insufficient liposolurity, while capryloyl glycine has strong lipophilicity, resulting in poor solubility in water-based formulations. The two cannot coexist due to their difference in solubility. However, the preparation method provided by this invention achieves uniform mixing at the molecular level by forming a co-amorphous compound and further encapsulating it with cyclodextrin, which greatly improves the solubility of capryloyl glycine.

[0020] (2) Enhance the physical stability and long-term storage of the system: The preparation method provided by the present invention forms a stable supramolecular structure through the inclusion effect of cyclodextrin and through non-covalent interactions such as hydrogen bonds and van der Waals forces, which is beneficial to isolate external degradation factors such as oxygen, light and moisture, and significantly reduce the oxidation or hydrolysis of active substances.

[0021] (3) Optimize transdermal absorption efficiency and bioavailability: The preparation method provided by this invention achieves the simultaneous delivery of acetyl tetrapeptide-5 and capryloyl glycine through co-amorphous technology and nano-level assembly. The transdermal amount is significantly higher than that of the monomer, thereby improving the targeted accumulation in the dermis and enhancing the oil control effect.

[0022] (4) Achieving dual-target synergistic oil control with better effect than single component: In the preparation method provided by the present invention, the selected capryloylglycine can reduce lipid secretion by inhibiting 5α-reductase, while acetyl tetrapeptide-5 targets melanocortin receptor 5 (MC5R) to downregulate lipid synthesis pathway; the present invention encapsulates the two in a synergistic manner to achieve multi-pathway targeted oil control, and experimental data also corroborate the improvement in efficacy of co-amorphous assembly. Attached Figure Description

[0023] Figure 1A This is a comparison chart of the solubility of octanoylglycine, the raw material in Test Example 1 of the present invention, and the product of step (1) in Examples 1-3; Figure 1B This is a comparison chart of the solubility of octanoyl glycine in the product of step (2) of Example 1 in Test Example 1 of the present invention and the product of step (2) of Examples 4-8; Figure 2 The polarized light microscope images are of the physical mixture of octanoylglycine, acetyl tetrapeptide-5, and two monomers in Test Example 1 of the present invention and the product of step (1) of Example 1. Figure 3 These are polarized light microscope comparison photographs of the co-amorphous material, cyclodextrin, physical mixture of the two, and co-amorphous assembly formed by the two in Example 1 of Test Example 1 of the present invention. Figure 4 The XRD patterns of the amorphous assemblies of acetyl tetrapeptide-5, capryloyl glycine, capryloyl glycine-acetyl tetrapeptide-5, cyclodextrin, and dual-targeted oil-controlling peptide in Test Example 2 of this invention are shown below. Figure 5 The dissolution curves are shown for the physical mixture of capryloylglycine, capryloylglycine and acetyl tetrapeptide-5, their co-amorphous products, and the co-amorphous assembly of the dual-targeting oil-controlling peptide in Test Example 3 of this invention. Figure 6A This is a DLS particle size distribution of the dual-targeting oil-controlling peptide co-amorphous assembly in Test Example 4 of this invention. Figure 6BThis is a Tyndall effect diagram of the dual-targeted oil-controlling peptide co-amorphous assembly in Test Example 4 of the present invention; Figure 7 This is a transmission electron microscope comparison image of the physical mixture in Test Example 4 of the present invention and the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1; Figure 8 This is a comparison of scanning electron microscope images of the physical mixture in Test Example 4 of the present invention and the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1; Figure 9 The Fourier transform infrared spectrum analysis results are shown for the physical mixture in Test Example 4 and the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1 of this invention. Figure 10 The diagram shows the interaction results of octanoyl glycine and cyclodextrin in the product prepared in Comparative Example 1 in Test Example 5 of this invention, and the interaction results of amorphous material and cyclodextrin in the co-amorphous assembly of dual-targeted oil-controlling peptide prepared in Example 1. Figure 11 The ESP analysis diagram of the acetyl tetrapeptide-5 monomer, the octyl glycine monomer, and the octyl glycine-acetyl tetrapeptide-5 co-amorphous compound prepared in step (1) of Example 1 of the present invention is shown in Test Example 5 of the present invention. Figure 12 The diagram shows the molecular frontier orbital analysis of the amorphous compound of octanoyl glycine-acetyl tetrapeptide-5 and acetyl tetrapeptide-5 and octanoyl glycine prepared in Example 1 of Test Example 5 of this invention. Figure 13 This is a comparison of the inhibitory effects of the dual-targeting oil-controlling peptide co-amorphous assembly and capryloylglycine on 5α-reductase activity at different concentrations in Test Example 6 of the present invention. Figure 14 This is a comparison of the fluorescence intensity of the dual-targeting oil-controlling peptide co-amorphous assembly and capryloylglycine during the determination of lipid droplet content in sebaceous gland cells in Test Example 7 of this invention. Figure 15 This is a fluorescent labeling image of the transdermal absorption of acetyl tetrapeptide-5, capryloyl glycine-acetyl tetrapeptide-5 co-amorphous compound, and dual-targeting oil-controlling peptide co-amorphous assembly on pig skin in Test Example 7 of the present invention. Figure 16 The images show Raman permeation images of the amorphous assembly of the dual-targeting oil-controlling peptide and the monomeric capryloylglycine in isolated porcine skin in Test Example 7 of this invention. 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 A method for preparing a dual-targeting oil-controlling peptide co-amorphous assembly includes the following steps: (1) 3 g of capryloylglycine and 0.9 g of acetyl tetrapeptide-5 were added to 300 mL of 70% ethanol aqueous solution (v:v) and heated to dissolve at 40 °C to obtain mixture A. Mixture A was placed in a rotary evaporator and evaporated under reduced pressure at 50 °C until a viscous gel appeared in mixture A. It was then transferred to a vacuum drying oven and dried at 50 °C for 72 h to obtain capryloylglycine-acetyl tetrapeptide-5 co-amorphous product. (2) Mix 2 g of cyclodextrin compound (hydroxypropyl-β-cyclodextrin) and 4 g of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous material described in step (1) with 80 ml of deionized water, mix well to obtain mixture B, place mixture B in a rotary evaporator, and rotary evaporate under reduced pressure at 70°C until a viscous gel appears in mixture B, then quickly transfer it to a vacuum drying oven and dry at 50°C for 48 h to obtain the dual-targeted oil-controlling peptide co-amorphous assembly.

[0026] Example 2 A method for preparing a dual-targeting oil-controlling peptide co-amorphous assembly includes the following steps: (1) Add 3 g of capryloylglycine and 3 g of acetyl tetrapeptide-5 to 60 mL of 70% ethanol aqueous solution (v:v) and heat at 60 °C to dissolve to obtain mixture A. Place mixture A in a rotary evaporator and evaporate under reduced pressure at 60 °C until a viscous gel appears in mixture A. Transfer to a vacuum drying oven and dry at 30 °C for 60 h to obtain capryloylglycine-acetyl tetrapeptide-5 co-amorphous product; (2) Mix 2 g of cyclodextrin compound (hydroxypropyl-β-cyclodextrin) and 1 g of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous material described in step (1) with 120 ml of deionized water, mix well to obtain mixture B, place mixture B in a rotary evaporator, and rotary evaporate under reduced pressure at 60°C until a viscous gel appears in mixture B, then transfer it to a vacuum drying oven and dry at 60°C for 72 h to obtain the dual-targeted oil-controlling peptide co-amorphous assembly.

[0027] Example 3 A method for preparing a dual-targeting oil-controlling peptide co-amorphous assembly includes the following steps: (1) 3 g of capryloylglycine and 6 g of acetyl tetrapeptide-5 were added to 100 mL of 70% ethanol aqueous solution (v:v) and heated to dissolve at 50 °C to obtain mixture A. Mixture A was placed in a rotary evaporator and evaporated under reduced pressure at 40 °C until a viscous gel appeared in mixture A. It was then quickly transferred to a vacuum drying oven and dried at 45 °C for 24 h to obtain capryloylglycine-acetyl tetrapeptide-5 co-amorphous product. (2) Mix 3 g of cyclodextrin compound (hydroxypropyl-β-cyclodextrin) and 4 g of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous material described in step (1) with 150 ml of deionized water, mix well to obtain mixture B, place mixture B in a rotary evaporator, and rotary evaporate under reduced pressure at 65°C until a viscous gel appears in mixture B, then transfer it to a vacuum drying oven and dry at 40°C for 24 h to obtain the dual-targeted oil-controlling peptide co-amorphous assembly.

[0028] Example 4 Example 4 also provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, which is basically the same as that in Example 1, except that: in step (2) of this example, the amount of cyclodextrin compound (β-cyclodextrin is used in this example) is 2.5 g, the amount of capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound is 1.5 g, and the amount of deionized water is 140 mL; other experimental operations are the same as in Example 1.

[0029] Example 5 Example 5 also provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, which is basically the same as Example 1, except that: in step (2) of this example, the amount of cyclodextrin compound (methyl-β-cyclodextrin is used in this example) is 3 g, the amount of capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound is 3 g, and the amount of deionized water is 120 mL; other experimental operations are the same as in Example 1.

[0030] Example 6 Example 6 also provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, which is basically the same as that in Example 1, except that: in step (2) of this example, the amount of cyclodextrin compound (γ-cyclodextrin is used in this example) is 1.5 g, the amount of capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound is 3 g, and the amount of deionized water is 90 mL; other experimental operations are the same as in Example 1.

[0031] Example 7 Example 7 also provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, which is basically the same as that in Example 1, except that: in this example, the alcohol solution used in step (1) is an isopropanol solution with a volume percentage concentration of 60%; at the same time, in step (2), the amount of cyclodextrin compound (selected as sulfobutyl ether-β-cyclodextrin) is 2.5 g, while the amount of capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound is 1.875 g, and the amount of deionized water is 125 mL; other experimental operations are the same as in Example 1.

[0032] Example 8 Example 8 also provides a method for preparing a dual-targeted oil-controlling peptide co-amorphous assembly, which is basically the same as Example 1, except that: in this example, the alcohol solution used in step (1) is an isopropanol solution with a volume percentage concentration of 60%; at the same time, in step (2), the amount of cyclodextrin compound (hydroxypropyl-α-cyclodextrin) is 3.5 g, while the amount of capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound is 4.375 g, and the amount of deionized water is 154 mL; other experimental operations are the same as in Example 1.

[0033] Comparative Example 1 To investigate the inclusion effect of cyclodextrin on octanoylglycine, Comparative Example 1 provides a method for preparing an assembly. This method is basically the same as that in Example 1, except that the octanoylglycine-acetyl tetrapeptide-5 co-amorphous compound added in step (2) is changed to octanoylglycine. Other experimental operations are the same as in Example 1.

[0034] Comparative Example 2 To investigate the inclusion effect of cyclodextrin on the physical mixture of octylglycine and acetyl tetrapeptide-5, Comparative Example 2 provides a method for preparing an assembly. This method is basically the same as that in Example 1, except that the octylglycine-acetyl tetrapeptide-5 co-amorphous compound added in step (2) is adjusted to a physical mixture of octylglycine and acetyl tetrapeptide-5. Other experimental operations are the same as in Example 1. The preparation of the physical mixture of capryloylglycine and acetyl tetrapeptide-5 includes: mixing capryloylglycine and acetyl tetrapeptide-5, stirring evenly to obtain the physical mixture of capryloylglycine raw material and acetyl tetrapeptide-5 raw material; the mass ratio of capryloylglycine to acetyl tetrapeptide-5 is 1:0.3.

[0035] Test Example 1: Solubility test and observation under polarized light microscope of the dual-targeted oil-controlling peptide co-amorphous assembly Solubility test: 10 g of the product (octanoylglycine-acetyl tetrapeptide-5 co-amorphous compound) from step (1) of Examples 1-3 and octanoylglycine were added to 10 mL of pure water respectively. The mixture was stirred at 300 rpm for 24 h at 25°C until equilibrium was reached. The filtrate was then filtered, and the equilibrium solubility of octanoylglycine was determined by HPLC. Three parallel experiments were performed, and the results are as follows: Figure 1A As shown. It can be seen that co-amorphizing acetyl tetrapeptide-5 with capryloyl glycine can significantly improve the solubility of capryloyl glycine. When the mass ratio of capryloyl glycine to acetyl tetrapeptide-5 is 1:0.3 (Example 1), the solubility of capryloyl glycine is increased the most, which is 20 times that of capryloyl glycine raw material. Further, the solubility of the product (dual-targeted oil-controlling peptide co-amorphous assembly) from step (2) of Examples 1-3 was compared with that of capryloyl glycine raw material, and it was found that Example 1 still had the best effect. The dual-targeted oil-controlling peptide co-amorphous assembly from step (2) of Example 1 can increase the solubility of capryloyl glycine from about 1.557 mg / ml to about 130 mg / ml (refer to Figure 1B As shown), the concentration increased by approximately 83.49 times (approximately 75 mg / ml in Example 2 and approximately 104 mg / ml in Example 3). Therefore, Example 1 was selected for further study.

[0036] To investigate the effects of different cyclodextrin compounds on the co-amorphous process, solubility tests were conducted on the co-amorphous assemblies of the dual-targeted oil-controlling peptides from Examples 4-8, based on Example 1. Specifically, the equilibrium solubility of octanoyl glycine in the co-amorphous assemblies of the dual-targeted oil-controlling peptides prepared in these examples was determined using the methods described above. The results are as follows: Figure 1B As shown, different types of cyclodextrins have significant differences in the formation of the dual-targeted oil-controlling peptide co-amorphous assembly. The hydroxypropyl-β-cyclodextrin used in Example 1 has the best effect on improving the solubility of capryloylglycine. Therefore, all subsequent test examples used the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1 for testing.

[0037] Experiment 1: Octylglycine, acetyl tetrapeptide-5, a physical mixture of the two monomers (octylglycine and acetyl tetrapeptide-5 mixed at a mass ratio of 1:0.3), and the product of step (1) in Example 1 (octylglycine-acetyl tetrapeptide-5 co-amorphous compound) were observed under a polarizing microscope at a magnification of 40x. The results are as follows: Figure 2 As shown. From Figure 2 As can be seen, the capryloylglycine raw material, acetyl tetrapeptide-5 raw material and their physical mixture all exhibit birefringence and are crystalline; while the product of step (1) in Example 1 has a dark field of view and is amorphous, indicating that capryloylglycine and acetyl tetrapeptide-5 form a co-amorphous compound.

[0038] Experiment 2: The amorphous co-amorphous compound of octanoylglycine-acetyl tetrapeptide-5 prepared in step (1) of Example 1, cyclodextrin (hydroxypropyl-β-cyclodextrin was selected), and a physical mixture of the two (the amorphous co-amorphous compound of octanoylglycine-acetyl tetrapeptide-5 prepared in step (1) of Example 1 and hydroxypropyl-β-cyclodextrin were mixed in a mass ratio of 2:1 and stirred evenly), and the amorphous assembly of the dual-targeted oil-controlling peptide obtained in step (2) of Example 1 were observed under a polarizing microscope. The magnification of the polarizing microscope was 40 times. The results are as follows. Figure 3 As shown. From Figure 3 It can be observed that the dual-targeting oil-controlling peptide co-amorphous assemblies are uniformly distributed, exhibiting relatively small and well-dispersed black dot-like structures with a more ordered overall arrangement. This reflects a stable assembly state formed by intermolecular inclusion complexation, which usually indicates a more stable physical state, better drug solubility, or higher bioavailability.

[0039] Test Example 2: Crystal Structure Testing of Dual-Targeted Oil-Controlling Peptide Co-Amorphous Assemblies The crystal structure of acetyl tetrapeptide-5, capryloyl glycine, the capryloyl glycine-acetyl tetrapeptide-5 co-amorphous compound prepared in Example 1, the hydroxypropyl-β-cyclodextrin used in Example 1, and the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1 were analyzed by XRD. The results are as follows: Figure 4 As shown, the XRD patterns of both capryloylglycine and acetyl tetrapeptide-5 show sharp peaks, indicating that they are crystalline. The capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound has only one broad peak near 20°, consistent with its amorphous characteristics. Hydroxypropyl-β-cyclodextrin has broad peaks near 10° and 20°, and small sharp peaks near 70° and 80°, indicating the presence of a small amount of crystalline form. The XRD peak positions of the dual-targeting oil-controlling peptide co-amorphous assembly are the same as those of cyclodextrin, indicating that cyclodextrin has a good inclusion effect on the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound. Meanwhile, compared with cyclodextrin, the broad peak intensity near 10° of the dual-targeted oil-controlling peptide co-amorphous assembly was weakened, and the small sharp peak disappeared, indicating that the inclusion of cyclodextrin did not destroy the structure of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound. At the same time, the inclusion of cyclodextrin in the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound changed the stacking mode of cyclodextrin at the molecular level, forming the capryloylglycine-acetyl tetrapeptide-5-cyclodextrin co-amorphous assembly (i.e., the dual-targeted oil-controlling peptide co-amorphous assembly).

[0040] Test Example 3: Dissolution Performance Test of Dual-Targeted Oil-Controlling Peptide Co-Amorphous Assemblies The products from step (1) of Example 1 (caprylyl glycine-acetyl tetrapeptide-5 co-amorphous compound), the product from step (2) of Example 1 (dual-targeted oil-controlling peptide co-amorphous assembly), caprylyl glycine, and acetyl tetrapeptide-5 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 caprylyl glycine-acetyl tetrapeptide-5 co-amorphous compound, dual-targeted oil-controlling peptide co-amorphous assembly, caprylyl glycine, and a physical mixture of caprylyl glycine and acetyl tetrapeptide-5 (a mixture obtained by mixing caprylyl glycine and acetyl tetrapeptide-5 at a mass ratio of 1:0.3 and stirring until homogeneous) 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 triplicate. The concentration of octanoyl glycine in the solution was calculated at each time point, and the dissolution curves of each sample were plotted. Figure 5 As shown.

[0041] Figure 5 Dissolution curves of caprylyl glycine in different forms are presented. It can be seen that caprylyl glycine has poor solubility, quickly approaching saturation and remaining stable. In the physical mixture of caprylyl glycine and acetyl tetrapeptide-5, the dissolution curve of caprylyl glycine is similar to that of the monomer, but its solubility is improved to some extent. In the caprylyl glycine-acetyl tetrapeptide-5 co-amorphous compound, although caprylyl glycine can quickly reach maximum solubility, its solubility gradually decreases over time due to the instability caused by the high-energy state of the co-amorphous compound. In the dual-targeted oil-controlling peptide co-amorphous assembly of Example 1, the concentration of caprylyl glycine remains close to saturation solubility, indicating that it can dissolve rapidly and remain 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.

[0042] Test Example 4: Microstructure Test of Dual-Targeted Oil-Controlling Peptide Co-Amorphous Assemblies DLS testing and Tyndall effect observation: 3g of the product from Example 1 (amorphous assembly of dual-targeted oil-controlling peptides) was added to 100mL of deionized water, stirred continuously at 300rpm for 30min at 25°C, and then sonicated for 10min to ensure complete dissolution. The particle size distribution was tested by DLS, and the Tyndall effect was also tested. The results are as follows: Figure 6A and Figure 6B As shown. From Figure 6B As can be seen above, the solution of the capryloylglycine-acetyl tetrapeptide-5-cyclodextrin co-amorphous assembly exhibits a significant Tyndall effect, indicating that it exists in the form of nanoparticles. From... Figure 6AThe particle size distribution shows an average particle size of approximately 209 nm and a PDI (polydispersity index) of 0.1764, demonstrating that the dual-targeting oil-controlling peptide co-amorphous assembly possesses nanoscale particle size. This nanoscale assembly can effectively isolate water, oxygen, light, and enzymes, significantly improving the structural stability of acetyl tetrapeptide-5 during storage and transdermal delivery through spatial shielding.

[0043] Transmission electron microscopy observation: The dual-targeting oil-controlling peptide co-amorphous assembly prepared in Example 1 and the physical mixture of capryloylglycine and acetyl tetrapeptide-5 prepared in Comparative Example 2 (hereinafter referred to as the physical mixture) were observed under a transmission electron microscope. Figure 7 These are TEM images of the samples prepared in Example 1 and Comparative Example 2 of this invention. Figure 7 The left side is a physical mixture. Figure 7 The right side is a co-amorphous assembly of dual-targeted oil-controlling peptides. For example... Figure 7 As shown, during physical mixing, each component is independent at the microscale, with irregular morphology and wide size distribution. For the dual-targeted oil-controlling peptide co-amorphous assembly, multiple active ingredients form near-spherical nanoparticles with uniform size and good dispersion through intermolecular interactions such as hydrogen bonds at the molecular level, proving the formation of new substances.

[0044] Scanning electron microscopy (SEM) observation and analysis: The amorphous assembly of the dual-targeted oil-controlling peptides was dried and pulverized for convenient storage and transportation. To verify that the drying and pulverization process did not damage the microstructure of the amorphous assembly of the dual-targeted oil-controlling peptides, the amorphous assembly of the dual-targeted oil-controlling peptides prepared in Example 1 and the physical mixture of capryloylglycine and acetyl tetrapeptide-5 prepared in Comparative Example 2 (hereinafter referred to as the physical mixture) were dried and pulverized, passed through an 80-mesh sieve, and then observed and analyzed under a scanning electron microscope. The SEM results are as follows: Figure 8 As shown, Figure 8 The left side shows the results of the physical mixture. Figure 8 The image on the right shows the results of the amorphous assembly of the dual-targeting oil-controlling peptides. The physical mixture consists of irregular sheet-like or blocky particles, with relatively independent physical packing between particles and obvious gaps. In contrast, the amorphous assembly of the dual-targeting oil-controlling peptides after drying and pulverization exhibits a uniform amorphous morphology, consistent texture, and smooth edges. This result indicates that the drying and pulverization process did not disrupt the inclusion state of the cyclodextrin.

[0045] Fourier Transform Infrared Spectroscopy Analysis: The dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1 (hereinafter referred to as the co-amorphous assembly) and the physical mixture of capryloylglycine and acetyl tetrapeptide-5 prepared in Comparative Example 2 (hereinafter referred to as the physical mixture) were dried and pulverized, passed through an 80-mesh sieve, and then subjected to Fourier Transform Infrared Spectroscopy (FTIR) analysis. The results are as follows: Figure 9As shown. Fourier transform infrared spectroscopy analysis indicates that the spectrum of the physical mixture is merely a superposition of the characteristic peaks of each component, suggesting that no strong intermolecular interactions have formed. In contrast, the co-amorphous assemblies exhibit peaks at 3000–3500 cm⁻¹. -1 The O–H / N–H stretching vibration peak at this point is significantly broadened and enhanced, indicating the formation of a stronger hydrogen bond network; its carbonyl C=O stretching vibration peak (approximately 1600 cm⁻¹) is also significantly enhanced. -1 The electron cloud density undergoes shift and broadening, indicating that it is affected by intermolecular interactions; in the low-frequency region (500–1500 cm⁻¹), the electron cloud density is affected by intermolecular interactions. -1 The presence of peak fusion and shift further confirms the change in molecular packing and vibrational coupling. These characteristics collectively demonstrate that co-amorphous assemblies are single-phase, homogeneous, and thermodynamically stable supramolecular structures formed based on strong non-covalent interactions, which are fundamentally different from multiphase coexisting physical mixtures.

[0046] Test Example 5: Simulated testing of dual-targeted oil-controlling peptide co-amorphous assembly and capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound. Based on density functional theory, the interaction between the amorphous material and cyclodextrin in the dual-targeted oil-controlling peptide co-amorphous assembly prepared in Example 1 of this invention was analyzed using Gauss software. Figure 10 (Right side), and at the same time, the interaction between octanoyl glycine and cyclodextrin in the product prepared in Comparative Example 1 of this invention was analyzed using Gauss software. Figure 10 (Left side), the result is as follows Figure 10 As shown, the independent gradient model (IGMH) of Hirshfeld segmentation and the atomic topology analysis (AIM) method reveal a richer intermolecular interaction between the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound and cyclodextrin. Furthermore, the absolute value of its binding energy (-110.52 kcal / mol) is significantly greater than that of the monomer (-66.13 kcal / mol), indicating stronger intermolecular forces and a more stable complex. Simultaneously, a large hydrogen bond network forms between the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound and cyclodextrin, reducing the exposure of the active sites of acetyl tetrapeptide-5 through conformational confinement, thus enhancing its environmental stability.

[0047] Figure 11This is a comparison of the surface electrostatic potential (ESP) analysis before and after in this invention. The left side shows the ESP analysis results of the capryloylglycine monomer and the acetyl tetrapeptide-5 monomer, while the right side shows the ESP analysis results of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound prepared in step (1) of Example 1. The numbers in the figure represent the electrostatic potential energy values ​​at specific positions on the molecular surface, with units of kcal / mol. ESP analysis shows that the molecular polarity index (MPI) of capryloylglycine-acetyl tetrapeptide-5 increased significantly from 0.70 eV of the capryloylglycine monomer to 1.20 eV, and the proportion of polar (ESP>10 kcal / mol) surface area also increased from 53.27% of the monomer to 72.22%, indicating an improvement in the water solubility of capryloylglycine. At the same time, the extreme value of the positive potential of acetyl tetrapeptide-5 increased significantly (from 77.87 to 84.48), indicating an increase in its positive charge density. This change helps enhance the electrostatic attraction between molecules and the skin surface, making it easier for them to penetrate the stratum corneum, thereby improving skin permeability.

[0048] Figure 12 This paper presents a comparative analysis of the molecular frontier orbitals of the amorphous octanoic acid-acetyl tetrapeptide-5 co-amorphous compound and its monomer prepared in step (1) of Example 1 of this invention. Molecular frontier orbital theory, as a core tool of quantum chemistry, can deeply reveal the relationship between molecular electronic structure and chemical reactivity by analyzing the energy distribution and spatial characteristics of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Figure 12 As shown, the HOMO level of the co-amorphous compound shifted significantly upward, while the LUMO level shifted downward, resulting in a reduction in its orbital gap (ΔE) from 4.80 eV in the monomer to 4.23 eV. This narrowing of the gap directly confirms the enhanced bioactivity of capryloylglycine. Simultaneously, the overall HOMO and LUMO of the co-amorphous compound remained primarily localized within the acetyl tetrapeptide-5 molecular backbone, indicating that its active site was preserved. Compared to acetyl tetrapeptide-5, the HOMO level of the co-amorphous compound decreased significantly, indicating a reduced electron-losing ability and enhanced antioxidant stability. In summary, the formation of the co-amorphous compound not only enhanced the bioactivity of capryloylglycine but also significantly improved the molecular stability of acetyl tetrapeptide-5.

[0049] Test Example 6: Biochemical Experiment of Dual-Targeted Oil-Controlling Peptide Co-Amorphous Assembly The amorphous assembly of the dual-targeting oil-controlling peptide and capryloylglycine were used as samples. The oil-controlling efficacy of the 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.).

[0050] Referring to Table 1 below, set up 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 of the sample wells (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 of the sample 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 .

[0051] Table 1 Sample Addition Requirements Calculate the inhibition rate of 5α-reductase activity using the following formula, and plot the average value after three parallel experiments: 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 absorbance of the blank tube obtained at 0 min after subtracting the blank background; A 空60min —The absorbance of the blank tube after subtracting the blank background, measured over 60 minutes; A样0min —The absorbance of the sample tube measured at 0 min after subtracting the sample background; A 样60min —The absorbance of the sample tube measured over 60 minutes, minus the sample background.

[0052] 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 dual-targeting oil-controlling peptide co-amorphous assembly in the solution was 0.09 wt%; and in co-amorphous assembly group 2, the concentration of capryloylglycine released from the dual-targeting oil-controlling peptide co-amorphous assembly in the solution was 0.15 wt%. Figure 13 This is a comparison of the inhibitory effects of the dual-targeting oil-controlling peptide co-amorphous assembly and capryloylglycine on 5α-reductase activity at different concentrations. In the figure, capryloylglycine 1 represents the test results when capryloylglycine concentration is 0.09 wt%, co-amorphous assembly 1 represents the test results when the concentration of capryloylglycine released from the dual-targeting oil-controlling peptide co-amorphous assembly in the sample solution is 0.09 wt%, capryloylglycine 2 represents the test results when the concentration of capryloylglycine released from the dual-targeting oil-controlling peptide co-amorphous assembly in the sample solution is 0.15 wt%, and co-amorphous assembly 2 represents the test results when the concentration of capryloylglycine released from the dual-targeting oil-controlling peptide co-amorphous assembly in the sample solution is 0.15 wt%. The dual-targeting oil-controlling peptide co-amorphous assembly was prepared according to the method described in Example 1.

[0053] like Figure 13 As shown, for both systems, the inhibition rate of 5α-reductase activity increased with increasing caprylyl glycine concentration, indicating that the oil-controlling effect of caprylyl glycine is dose-dependent; the higher the concentration, the better the oil-controlling effect. At the same concentrations of caprylyl glycine in the sample solutions (0.09 wt% and 0.15 wt%), the 5α-reductase activity inhibition rate of the dual-targeting oil-controlling peptide co-amorphous assembly was superior to that of the caprylyl glycine monomer at the same concentration. This may be due to the poor solubility of the caprylyl glycine monomer, which affects its oil-controlling efficacy.

[0054] Test Example 7: In vitro cell assay of dual-targeted oil-controlling peptide co-amorphous assemblies Cellular Test 1: The test was conducted according to the "Standard Operating Procedure for Determining the Lipid Droplet Content of Human Sebaceous Gland Cells in In Vitro" to evaluate the oil-controlling efficacy of the sample. The sample in Test Example 7 consisted of a dual-target oil-controlling peptide co-amorphous assembly and capryloyl glycine. The principle is as follows: Sebaceous glands are the source and target tissue of androgens. Dehydroepiandrosterone (DHEA) is produced in sebaceous glands, which, through a series of enzymatic catalysis, is converted into the most active testosterone and 5α-dihydrotestosterone. These 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, which migrate towards the center of the gland cell, gradually developing and differentiating into mature sebaceous gland cells capable of storing and secreting lipids. This experiment uses Nile Red staining to detect the amount of oil secreted by sebaceous gland cells, thereby determining whether the sample has oil-controlling efficacy. 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.

[0055] 1. Human sebaceous gland 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.

[0056] Table 2 2. After incubation, remove the culture medium and wash 1-2 times with D-Hanks buffer. Replace the normal control group with fresh culture medium, the model control group with fresh culture medium containing dihydrotestosterone, and 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.

[0057] 3. After incubation, remove the culture medium, pre-cool to 4°C, wash three times with D-Hanks buffer, fix with 4% paraformaldehyde, wash 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.

[0058] 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.

[0059] Oil control efficacy (%) = (A 模型对照组 -A 样品组 ) / A 模型对照组 100% In the formula: 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 by the dual-targeting oil-controlling peptide co-amorphous assembly in the culture medium) in the co-amorphous assembly group is 0.03 wt%, and the corresponding concentration of the dual-targeting oil-controlling peptide co-amorphous assembly in the culture medium is 0.1 wt%; while the drug concentration (the concentration of caprylyl glycine in the culture medium) in the isoconcentration caprylyl glycine group is 0.03 wt%.

[0060] Figure 14 This is a comparison of the fluorescence intensity of the dual-targeting oil-controlling peptide co-amorphous assembly and capryloyl glycine in the determination of lipid droplet content in sebaceous gland cells. The co-amorphous assembly represents the result when the dual-targeting oil-controlling peptide co-amorphous assembly is released into the culture medium at a capryloyl glycine concentration of 0.03 wt%. The isoconcentration capryloyl glycine represents the result when the sample has a capryloyl glycine concentration of 0.03 wt%. Based on the test results (… Figure 14 The average fluorescence intensity of the model control group was significantly enhanced compared to the normal control group, indicating that the stimulation conditions in this test were effective. The average fluorescence intensity of the co-amorphous assembly was significantly reduced by 39% at an octylglycine concentration of 0.03 wt% compared to the model control group, revealing that the co-amorphous assembly has oil-controlling efficacy. Furthermore, compared to the 35% decrease in the group with the same concentration of octylglycine, the co-amorphous assembly showed superior efficacy. The preparation method of the dual-target oil-controlling peptide co-amorphous assembly was carried out according to the method described in Example 1.

[0061] Test 2: Referring to the group standard T / ZGKSL010-2023 "Method for Determination of Transdermal Absorption of Recombinant Collagen", acetyl tetrapeptide-5 was labeled with FITC. Then, using the FITC-labeled acetyl tetrapeptide-5, amorphous assemblies of capryloylglycine-acetyl tetrapeptide-5 and dual-targeting oil-controlling peptides were prepared according to the method described in Example 1. The obtained FITC-labeled acetyl tetrapeptide-5, capryloylglycine-acetyl tetrapeptide-5 amorphous assemblies, and dual-targeting oil-controlling peptide amorphous assemblies were subsequently tested to evaluate the transdermal absorption capacity of acetyl tetrapeptide-5 in porcine skin. The fluorescence labeling results are shown below. Figure 15 As shown. By Figure 15 It can be seen that after the formation of the co-amorphous compound, the permeability of acetyl tetrapeptide-5 was improved by 131%, proving the improvement effect of the co-amorphous technology; after further forming the dual-targeted oil-controlling peptide co-amorphous assembly, its permeability was improved by 408%, proving the permeation-promoting effect of cyclodextrin inclusion on the co-amorphous compound.

[0062] Test 3: The dual-targeted oil-controlling peptide co-amorphous assembly and the monomer capryloyl glycine prepared according to the preparation method described in Example 1 were used as test samples. The test was carried out according to the method described in T / SHRH064-2024 "Transdermal Permeation Test of Cosmetic Ingredients - In Vivo Raman Spectroscopy" to obtain Raman permeation images of the two on isolated pig skin.

[0063] Figure 16 This is a Raman permeation image of isolated porcine skin containing the amorphous assembly of the dual-targeting oil-controlling peptide and the monomeric capryloylglycine. (See image for details.) Figure 16 As shown, compared to the monomeric capryloylglycine, the co-amorphous assembly of the dual-targeted oil-controlling peptide showed a 5.32-fold increase in permeability after 4 hours; the maximum penetration depth also increased from 60 μm to 120 μm; simultaneously, it reached the active epidermis within 4 hours, significantly improving bioavailability. The increased permeability, penetration depth, and penetration rate of capryloylglycine all corroborate the improved effect of the co-amorphous technology.

[0064] Depend on Figure 15 and 16 It is known that the dual-targeting oil-controlling peptide co-amorphous assembly can simultaneously improve the transdermal delivery performance of capryloylglycine and acetyl tetrapeptide-5, thereby enhancing drug bioavailability and therapeutic efficacy.

[0065] 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 method of preparing a dual targeting oil control peptide co-amorphous assembly, characterized in that, Includes the following steps: (1) Add octanoyl glycine and acetyl tetrapeptide-5 to an alcohol solution, heat to dissolve, and obtain mixture A. Rotary evaporate and dry to obtain octanoyl glycine-acetyl tetrapeptide-5 co-amorphous product. (2) The cyclodextrin compound, the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound, and water were mixed evenly to obtain mixture B. The mixture was then evaporated by rotary evaporation and dried to obtain the dual-targeted oil-controlling peptide co-amorphous assembly.

2. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, The mass ratio of capryloylglycine to acetyl tetrapeptide-5 in step (1) is 1:(0.3-2); the mass-volume ratio of capryloylglycine to alcohol solution in step (1) is 0.01-0.05:1g / ml.

3. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, The alcohol solution in step (1) is a mixture of alcohol and water, with the volume percentage of the alcohol being 60-80%; the alcohol is ethanol or isopropanol.

4. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, The heating and dissolving temperature in step (1) is 40-60℃; the rotary evaporation temperature is 40-60℃, and the evaporation is stopped when a gel appears in the mixture.

5. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, The drying temperature in step (1) is 30-50℃, and the drying time is 24-72h.

6. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, In step (2), the mass-to-volume ratio of the cyclodextrin compound to water is 1:40-60 g / mL; the cyclodextrin compound is at least one of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, γ-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and hydroxypropyl-α-cyclodextrin.

7. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, In step (2), the mass ratio of the capryloylglycine-acetyl tetrapeptide-5 co-amorphous compound to the cyclodextrin compound is 1:(0.5-2).

8. The method for preparing the dual-targeted oil-controlling peptide co-amorphous assembly according to claim 1, characterized in that, The rotary evaporation temperature in step (2) is 60-70℃, and the evaporation is stopped when gel appears in the mixture B; the drying temperature is 40-60℃, and the drying time is 24-72h.

9. A dual-targeting oil-controlling peptide co-amorphous assembly prepared by the preparation method according to any one of claims 1-8.

10. The application of the dual-targeting oil-controlling peptide co-amorphous assembly according to claim 9 in the preparation of topical pharmaceuticals or cosmetics.

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