A cosmetic composite material for removing acne marks and a method for preparing the same

Abstract

The present application relates to the technical field of cosmetic raw materials, and particularly relates to a cosmetic composite raw material for removing acne spots and a preparation method thereof. The preparation method of the cosmetic composite raw material for removing acne spots comprises the following steps: preparation of betulinic acid-ostruthin co-assembled nanoparticles, double modification of mannose, preparation of retinol slow-release particles, and preparation of the cosmetic composite raw material. The present application realizes efficient acne spot removal through the synergy of multiple components. The core components, such as betulinic acid, have multiple anti-inflammatory and antibacterial effects, ostruthin inhibits melanin production, glutathione lightens old pigments, retinol and salicylic acid accelerate keratin metabolism, the co-assembly of betulinic acid-ostruthin nanoparticles improves bioavailability, modified mannose / epsilon-polylysine layer-by-layer embedding realizes retinol slow-release synergism, the synergy among the components enhances the effects of spot lightening and anti-inflammation, and the modified mannose can also repair the skin barrier, so that the effect of targeted treatment and barrier repair for removing acne spots is finally realized.

Description

Technical Field

[0001] This invention relates to the field of cosmetic raw material technology, specifically to a cosmetic compound raw material for removing acne spots and its preparation method. Background Technology

[0002] Acne is a common chronic inflammatory skin disease of the pilosebaceous unit, prevalent among adolescents and people with oily skin. Its pathogenesis is related to multiple factors, including the proliferation of Propionibacterium acnes, abnormal keratinization of the pilosebaceous duct, inflammatory response, and excessive sebum secretion. After the inflammation subsides, acne scars often remain on the skin, mainly manifesting as pigmentation spots (acne marks). The formation mechanism is complex. On the one hand, during the acne inflammation process, inflammatory factors stimulate excessive activation of melanocytes, leading to abnormal melanin synthesis and deposition. On the other hand, after acne heals, the metabolism of the stratum corneum is disordered, and the shedding of melanin-containing keratinocytes is slow, further aggravating pigment retention. Acne scars are mostly distributed on exposed areas such as the face and chest, seriously affecting the patient's skin appearance and mental health.

[0003] The main methods for improving acne spots fall into two categories: medical treatment and daily care. Medical treatments, such as chemical peels (glycolic acid and salicylic acid peels), intense pulsed light (IPL), pulsed dye lasers, and Q-switched lasers, while relatively effective, have limitations including long treatment cycles, high costs, potential risks of pain, redness, swelling, and abnormal pigmentation, and the need for professional operation, making them inconvenient for long-term daily use. Therefore, developing safe, effective, and easy-to-use cosmetic products has become an important way to meet the market demand for improving acne spots.

[0004] Currently, cosmetic ingredients used to remove acne spots are mainly divided into two categories: chemically synthesized ingredients and natural plant extracts. Among them, chemically synthesized ingredients such as hydroquinone, retinoids, salicylic acid, and azelaic acid are traditional active ingredients for removing spots. Hydroquinone blocks melanin synthesis by inhibiting tyrosinase activity and has a relatively fast effect, but long-term use may cause side effects such as skin irritation, allergies, and even skin darkening, and its safety is highly controversial. Although retinoids can promote keratin metabolism and accelerate the shedding of pigment cells, they are highly irritating and can easily lead to dry skin and redness. The concentration needs to be strictly controlled, and user tolerance varies greatly. Although salicylic acid has both anti-inflammatory and keratolytic effects, concentrations exceeding 2% need to be managed as drugs, and the effect of a single ingredient on removing deep pigmentation is limited.

[0005] Natural plant extracts, due to their relatively high safety profile, have gradually become a research hotspot. Extracts such as licorice extract, aloe vera extract, arbutin, and tea tree oil have all been proven to have certain anti-inflammatory, whitening, and spot-removing effects. However, single plant extracts suffer from limitations such as limited target efficacy and slow onset of action, making it difficult to meet consumers' demands for rapid spot removal. Furthermore, some active ingredients themselves have poor stability and are easily deactivated; or, due to limitations in molecular structure and the skin barrier, they are difficult to effectively penetrate to the target area, affecting their bioavailability.

[0006] Therefore, this application aims to develop a cosmetic composite raw material for removing acne spots that has excellent anti-inflammatory repair and barrier maintenance functions, and is mild, low-irritant, stable, and highly transdermal absorbed. Summary of the Invention

[0007] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a cosmetic compound raw material for removing acne spots and its preparation method.

[0008] This invention provides a method for preparing a cosmetic compound raw material for removing acne spots, comprising:

[0009] S1: Preparation of betulinic acid-osthol co-assembled nanoparticles;

[0010] Betulinic acid and osthol were dissolved in an ethyl acetate-methanol mixed solvent, and then added dropwise to a polyvinyl alcohol aqueous solution for ultrasonic emulsification. After magnetic stirring, depressurization to remove organic solvent, centrifugation and washing, and freeze drying, betulinic acid-osthol co-assembled nanoparticles were obtained.

[0011] S2: Dual modification of mannan;

[0012] First, mannan is enzymatically hydrolyzed, enzyme-inactivated, precipitated and dried to obtain enzymatically hydrolyzed mannan. Then, sodium hydroxide-isopropanol blend and chloroacetic acid-sodium hydroxide-isopropanol blend are prepared and reacted with enzymatically hydrolyzed mannan step by step. After pH adjustment, concentration, ethanol precipitation and centrifugation, modified mannan is obtained.

[0013] S3: Preparation of retinol sustained-release particles;

[0014] Modified mannan and ε-polylysine were prepared into modified mannan aqueous solution and ε-polylysine aqueous solution, respectively. Retinol was dissolved in ethanol and injected into the modified mannan aqueous solution in the dark and nitrogen-purified environment. Then, ε-polylysine aqueous solution was added dropwise to react. After ultrafiltration, centrifugation and freeze drying, retinol sustained-release particles were obtained.

[0015] S4: Preparation of cosmetic compound raw materials;

[0016] 3-5 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles, 3-5 parts by weight of retinol sustained-release particles, 3-5 parts by weight of glutathione, 2-5 parts by weight of white willow bark extract, 2-5 parts by weight of glycyrrhizin, 6-10 parts by weight of 1,2-pentanediol, 3-5 parts by weight of catechin, and 5-8 parts by weight of 1,2-propylene glycol were mixed, and deionized water was added to bring the total to 100 parts by weight to obtain a cosmetic compound raw material.

[0017] As a preferred aspect, S1: the preparation of betulinic acid-osthol co-assembled nanoparticles specifically includes the following steps:

[0018] S1.1: Add 8-10 parts by weight of betulinic acid and 8-10 parts by weight of osthol to 80-100 parts by weight of ethyl acetate, then add 1-2 parts by weight of methanol, and stir and mix at 300-500 rpm for 20-30 min to obtain a mixed solution.

[0019] S1.2: Add the mixed solution dropwise to 30-50 parts by weight of 2.5wt% polyvinyl alcohol aqueous solution at a dropwise rate of 1-2 mL / min, then shake for 10-20 min, and then place it in a probe-type ultrasonic instrument for ultrasonic emulsification under ice-water bath conditions for 10-20 min to obtain a mixed emulsion;

[0020] S1.3: Add the mixed emulsion to 80-100 parts by weight of 0.3wt% polyvinyl alcohol aqueous solution, then stir magnetically at room temperature for 10-12 hours, then remove the organic solvent by vacuum distillation, then centrifuge at 10000-12000 rpm for 20-30 minutes using a low-temperature refrigerated centrifuge, then wash the precipitate with deionized water 3-5 times, and finally freeze-dry to obtain betulinic acid-osthol co-assembled nanoparticles.

[0021] As a preferred aspect, S2: dual modification of mannan specifically includes the following steps:

[0022] S2.1: Add 2-4 parts by weight of mannan to 100-120 parts by weight of phosphate buffer with pH 5.0, then add β-mannanase, and then enzymatically hydrolyze at 50-60℃ for 2-3 hours. After the enzymatic hydrolysis is completed, heat the hydrolysate at 100℃ for 10-12 minutes to inactivate the enzyme, then precipitate with 3 volumes of ethanol, collect the solid by centrifugation, and vacuum dry at 40-50℃ to obtain enzymatically hydrolyzed mannan.

[0023] S2.2: Mix 5-8 parts by weight of 20wt% sodium hydroxide solution and 12-15 parts by weight of isopropanol to obtain a sodium hydroxide-isopropanol blend; mix 2.3-2.5 parts by weight of chloroacetic acid, 5-8 parts by weight of 20wt% sodium hydroxide solution and 12-15 parts by weight of isopropanol to obtain a chloroacetic acid-sodium hydroxide-isopropanol blend.

[0024] S2.3: Under ice bath conditions, add the above sodium hydroxide-isopropanol blend to 1-2 parts by weight of enzymatically hydrolyzed mannan, then stir and mix under ice bath conditions for 2-3 hours, then add the above chloroacetic acid-sodium hydroxide-isopropanol blend, react at room temperature for 2-3 hours, then react at 60-70℃ for 1.2-1.4 hours, then adjust the pH to neutral, then concentrate, precipitate with ethanol at low temperature, and centrifuge to obtain modified mannan.

[0025] As a preferred aspect, the amount of β-mannanase added in S2.1 is 200-300 U / g.

[0026] As a preferred aspect, S3: the preparation of retinol sustained-release particles specifically includes the following steps:

[0027] S3.1: Dissolve 1-2 parts by weight of modified mannan in deionized water, disperse it at 300-500 rpm for 20-30 min with a magnetic stirrer to prepare an aqueous solution of 2-4 mg / mL, adjust the pH to 6.0-6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 2-4 mg / mL modified mannan.

[0028] S3.2: Dissolve 1-1.5 parts by weight of ε-polylysine in deionized water, stir and disperse for 20-30 min to prepare an aqueous solution of 1-2 mg / mL, adjust the pH to 6.0-6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 1-2 mg / mL of ε-polylysine.

[0029] S3.3: Dissolve 2-3 parts by weight of retinol in 10-15 parts by weight of anhydrous ethanol, vortex until completely dissolved, to obtain a retinol ethanol solution. Under light protection and continuous nitrogen purging, slowly inject the retinol ethanol solution into the modified mannan aqueous solution at a rate of 0.5-1 mL / min, while continuously stirring at 500-800 rpm. After the addition is complete, continue stirring for 2-3 hours under light protection and inert gas protection to obtain a suspension containing retinol nanocores.

[0030] S3.4: Under light-protected and inert gas protection, slowly add ε-polylysine aqueous solution at a rate of 1-2 mL / min to the suspension containing retinol nanonuclei at 300-400 rpm. After the addition is complete, continue stirring and mixing for 1-2 h. Then transfer to an ultrafiltration centrifuge tube with a molecular weight cutoff of 10 kDa and centrifuge at 4-6℃ and 5000-8000 rpm for 15-20 min. After that, freeze dry to obtain retinol sustained-release particles.

[0031] As a preferred aspect, the volume ratio of retinol ethanol solution to modified mannan aqueous solution in step S3.3 is 1:5-6.

[0032] As a preferred aspect, in step S3.4, the volume ratio of the ε-polylysine aqueous solution to the suspension containing retinol nanonuclei is 1-2:5.

[0033] As a preferred aspect, S4: the preparation of cosmetic compound raw materials specifically includes the following steps:

[0034] S4.1: Add 3-5 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles and 3-5 parts by weight of retinol sustained-release particles to 10-15 parts by weight of deionized water, and sonicate for 10-15 minutes under light-proof, 40-45℃ water bath and 300-500rpm stirring to obtain mixed system I.

[0035] S4.2: Under stirring at 300-400 rpm, add 3-5 parts by weight of glutathione and 2-5 parts by weight of white willow bark extract to 20-22 parts by weight of deionized water, and stir for 20-30 minutes to obtain mixed system II.

[0036] S4.3: Under light-protected conditions, add 2-5 parts by weight of glycyrrhizin to 6-10 parts by weight of 1,2-pentanediol, and stir in a water bath at 40-45°C until completely dissolved to form mixed system III. Add 3-5 parts by weight of catechin to 10-12 parts by weight of deionized water, stir and mix to obtain an aqueous solution of catechin.

[0037] S4.4: Under light-proof conditions and with inert gas continuously introduced, at 200-300 rpm, add the above-mentioned mixture III to mixture II, then add mixture I, and stir and mix at 400-500 rpm for 20-30 min. Then add catechin aqueous solution and 5-8 parts by weight of 1,2-propylene glycol, and mix at 200-300 rpm for 10-20 min. Finally, add deionized water to 100 parts by weight to obtain the cosmetic compound raw material.

[0038] As a preferred aspect, the inert gas in step S4.4 is nitrogen.

[0039] The present invention also provides a cosmetic compound raw material for removing acne spots, which is prepared by any of the preparation methods of the cosmetic compound raw material for removing acne spots described in any one of the present invention.

[0040] The present invention has the following advantages:

[0041] 1. In this invention, betulinic acid can directly inhibit the proliferation of Propionibacterium acnes and block the release of inflammatory factors; osthol and catechin exert antioxidant and anti-inflammatory effects, clearing free radicals generated by inflammatory reactions and reducing the damage of inflammation to skin cells; white willow bark extract and glycyrrhizin further enhance the anti-inflammatory and soothing effects, inhibiting multiple inflammatory signaling pathways. Furthermore, osthol and glycyrrhizin are key steps in inhibiting tyrosinase activity and blocking melanin synthesis, reducing the formation of new melanin. Glutathione, as a reducing agent, can reduce the already generated oxidized melanin to colorless form. The melanin precursor lightens existing acne pigmentation. Retinol in the retinol slow-release particles promotes the renewal of stratum corneum cells and accelerates the shedding of melanin-containing keratinocytes. Salicylic acid, metabolized from white willow bark extract, further softens the stratum corneum, unclogs pores, and enhances melanin metabolism efficiency, achieving a dual effect of lightening acne spots by reducing new pigmentation at the root and fading old pigmentation on the surface. Furthermore, modified mannan has excellent moisturizing and film-forming properties, forming a protective film on the skin surface to reduce moisture loss. Through formula optimization, the treatment achieves targeted therapy and barrier repair for acne spot removal.

[0042] 2. This invention incorporates betulinic acid-osthol co-assembled nanoparticles into cosmetic composite raw materials. Utilizing co-assembly nanotechnology, betulinic acid and osthol are co-assembled at the molecular level. Betulinic acid possesses significant anti-inflammatory, antibacterial, and sebum-regulating activities, directly inhibiting the proliferation of Propionibacterium acnes and reducing inflammatory responses in pilosebaceous follicles. Osthol not only enhances the antibacterial and anti-inflammatory effects but also inhibits tyrosinase activity to reduce melanin production. When co-assembled, the two components form a synergistic system with significantly superior anti-acne activity compared to single-component or simple physical mixtures. Co-assembly greatly enhances their apparent solubility and dispersion stability in aqueous systems, preventing sedimentation and aggregation during storage. Furthermore, the nanoscale particles have a large specific surface area, significantly increasing the contact area with the skin and allowing them to more easily penetrate the gaps in the stratum corneum. This enables the active ingredients to be efficiently delivered to the deep epidermis and even the pilosebaceous unit, thereby effectively improving bioavailability and skin permeability. This achieves the dual effects of "anti-inflammatory and antibacterial - sebum regulation," addressing acne problems at their root.

[0043] 3. This invention constructs a physical and chemical "protective chamber" for retinol molecules through layer-by-layer encapsulation of modified mannan / ε-polylysine. These micro- and nano-sized particles effectively isolate the external environment, ensuring that retinol maintains high activity during formulation storage, transportation, and until use. Furthermore, the retinol sustained-release particles have a dense core-shell structure, with the core encapsulating the active retinol ingredient and the outer shell formed by cross-linking of modified mannan and ε-polylysine through intermolecular forces. In the application of this composite material to the skin, a uniform release of retinol is achieved, avoiding the "burst release effect" caused by the traditional direct addition of retinol. Simultaneously, the nanoscale particle size of the sustained-release particles allows them to penetrate to the target sites in the stratum corneum and superficial dermis, prolonging the retention time of retinol in the skin and significantly improving its bioavailability. This allows it to continuously promote keratin metabolism and lighten pigmentation. Furthermore, using double-modified mannan as the wall material, the increased active sites from enzymatic hydrolysis, in synergy with carboxymethyl groups, can tightly cross-link with ε-polylysine through electrostatic attraction and hydrogen bonding, forming a core-shell structure with controllable porosity. This significantly improves the encapsulation rate of lipid-soluble retinol. The double modification, through a stepwise process of enzymatic hydrolysis followed by carboxymethylation, further enhances the retinol's effectiveness. The enzymatic hydrolysis process degrades long mannan chains into short, uniformly sized fragments, reducing molecular rigidity and increasing surface active sites. This provides more binding sites for subsequent carboxymethylation modification, allowing carboxymethyl groups to be more evenly grafted onto the mannan molecular chain. Simultaneously, the short fragments generated by enzymatic hydrolysis increase molecular fluidity and permeability. The introduction of carboxymethyl groups significantly enhances water solubility and skin affinity. The sustained-release particles formed by cross-linking with ε-polylysine can easily pass through the stratum corneum intercellular spaces. Furthermore, the modified mannan short fragments can interact hydrophobically with lipids in the stratum corneum, opening intercellular channels and promoting retinol penetration into the superficial dermis. This significantly improves transdermal absorption, thereby effectively enhancing the efficacy of retinol in fading acne spots.

[0044] 4. The core active ingredient of the white willow bark extract in this invention is salicin, which can be converted into salicylic acid after entering the skin. On the one hand, it can dissolve keratin and unclog pores, improving the problem of keratin buildup and enlarged pores left after acne healing; on the other hand, it can accelerate the metabolism of the stratum corneum and promote the shedding of keratinocytes containing melanin, achieving physical fading of spots. At the same time, salicylic acid has anti-inflammatory and soothing effects, which can relieve residual inflammation in acne spots and prevent the recurrence of inflammation from aggravating pigmentation. The salicylic acid produced by the metabolism of salicin in the white willow bark extract has the effect of a penetration enhancer, which can soften the intercellular lipids of the stratum corneum and increase the permeability of the stratum corneum. This process further promotes the skin penetration of betulinic acid-osthol co-assembled nanoparticles, significantly enhancing the bioavailability of the two core ingredients. This allows the betulinic acid-osthol co-assembled nanoparticles to exhibit tyrosinase inhibitory activity, which, in conjunction with the keratin metabolism effect of white willow bark extract, significantly improves the efficiency of melanin removal from acne spots, resulting in a longer-lasting spot-fading effect with less rebound. Furthermore, the anti-inflammatory activity of betulinic acid and the anti-inflammatory effect of white willow bark extract are combined to quickly relieve redness, swelling, and sensitivity in acne-prone areas, preventing recurrence of inflammation-mediated pigmentation and reducing the risk of skin irritation when using high concentrations of a single ingredient. Attached Figure Description

[0045] Figure 1 This is a flowchart illustrating the preparation method of the cosmetic composite raw material for removing acne spots used in an embodiment of the present invention. Detailed Implementation

[0046] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of this invention.

[0047] The white willow bark extract in this example was prepared by using 80% ethanol aqueous solution as the extraction solvent. White willow bark was extracted for 2 hours at a power of 200W, a temperature of 50℃, and a material-to-liquid ratio of 1:12. The extract was centrifuged at 8000rpm to remove residues. The supernatant was adsorbed through HPD-100 macroporous resin and then eluted with 80% ethanol to obtain a purified solution. Finally, the purified solution was concentrated under vacuum and spray-dried to obtain the white willow bark extract.

[0048] Example 1: A method for preparing a cosmetic compound raw material for removing acne spots, referring to... Figure 1 ,include:

[0049] S1: Preparation of betulinic acid-osthol co-assembled nanoparticles

[0050] S1.1: Add 8 parts by weight of betulinic acid and 8 parts by weight of osthol to 80 parts by weight of ethyl acetate, then add 1 part by weight of methanol, and stir at 300 rpm for 20 min to obtain a mixed solution;

[0051] S1.2: Add the mixed solution dropwise to 30 parts by weight of 2.5wt% polyvinyl alcohol aqueous solution at a dropwise rate of 1mL / min, then shake for 10min, and then place it in a probe-type ultrasonic instrument for ultrasonic emulsification under ice-water bath conditions for 10min to obtain a mixed emulsion;

[0052] S1.3: The mixed emulsion was added to 80 parts by weight of 0.3wt% polyvinyl alcohol aqueous solution, and then magnetically stirred at room temperature for 10 h. After that, the organic solvent was removed by vacuum distillation, and then centrifuged at 10000 rpm for 20 min using a low-temperature refrigerated centrifuge. The precipitate was then washed three times with deionized water and finally freeze-dried to obtain betulinic acid-osthol co-assembled nanoparticles.

[0053] S2: Dual modification of mannan

[0054] S2.1: Add 2 parts by weight of mannan to 100 parts by weight of phosphate buffer with pH 5.0, then add 200 U / g β-mannanase, and then enzymatically hydrolyze at 50℃ for 2 h. After the enzymatic hydrolysis is completed, heat the hydrolysate at 100℃ for 10 min to inactivate the enzyme, then precipitate with 3 volumes of ethanol, collect the solid by centrifugation, and vacuum dry at 40℃ to obtain enzymatically hydrolyzed mannan.

[0055] S2.2: Mix 5 parts by weight of 20 wt% sodium hydroxide solution and 12 parts by weight of isopropanol to obtain a sodium hydroxide-isopropanol blend; mix 2.3 parts by weight of chloroacetic acid, 5 parts by weight of 20 wt% sodium hydroxide solution and 12 parts by weight of isopropanol to obtain a chloroacetic acid-sodium hydroxide-isopropanol blend.

[0056] S2.3: Under ice bath conditions, the above sodium hydroxide-isopropanol blend was added to 1 part by weight of enzymatically hydrolyzed mannan, and then stirred and mixed under ice bath conditions for 2 hours. Then, the above chloroacetic acid-sodium hydroxide-isopropanol blend was added, and the mixture was reacted at room temperature for 2 hours. Then, it was reacted at 60°C for 1.2 hours. Then, the pH was adjusted to neutral, and then the mixture was concentrated, precipitated with ethanol at low temperature, and centrifuged to obtain modified mannan.

[0057] S3: Preparation of retinol sustained-release particles

[0058] S3.1: Dissolve 1 part by weight of modified mannan in deionized water, disperse it at 300 rpm for 20 min with a magnetic stirrer to prepare an aqueous solution of 2 mg / mL, adjust the pH to 6.0, filter it through a 0.45 μm filter membrane to obtain an aqueous solution of 2 mg / mL modified mannan.

[0059] S3.2: Dissolve 1 part by weight of ε-polylysine in deionized water, stir and disperse for 20 min to prepare an aqueous solution of 1 mg / mL, adjust the pH to 6.0, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 1 mg / mL ε-polylysine.

[0060] S3.3: Dissolve 0.5 parts by weight of retinol in 10 parts by weight of anhydrous ethanol, vortex until completely dissolved, to obtain a retinol ethanol solution. Under light protection and continuous nitrogen purging, slowly inject the retinol ethanol solution into the modified mannan aqueous solution at a rate of 0.5 mL / min. The volume ratio of the retinol ethanol solution to the modified mannan aqueous solution is 1:5. Stir continuously at 500 rpm during the process. After the addition is complete, continue stirring for 2 hours under light protection and inert gas protection to obtain a suspension containing retinol nanocores.

[0061] S3.4: Under light-protected and inert gas protection, at 300 rpm, the above ε-polylysine aqueous solution was slowly added dropwise at a rate of 1 mL / min to the suspension containing retinol nanonuclei. The volume ratio of the ε-polylysine aqueous solution to the suspension containing retinol nanonuclei was 1:5. After the addition was completed, the mixture was stirred and mixed for 1 h. Then, it was transferred to an ultrafiltration centrifuge tube with a molecular weight cutoff of 10 kDa and centrifuged at 4 °C and 5000 rpm for 15 min. After that, it was freeze-dried to obtain retinol sustained-release particles.

[0062] S4: Preparation of Cosmetic Compound Raw Materials

[0063] S4.1: Add 3 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles and 3 parts by weight of retinol sustained-release particles to 10 parts by weight of deionized water, and sonicate for 10 min under light protection, 40℃ water bath and 300rpm stirring to obtain mixed system I.

[0064] S4.2: Under stirring at 300 rpm, add 3 parts by weight of glutathione and 2 parts by weight of white willow bark extract to 20 parts by weight of deionized water, stir and mix for 20 min to obtain mixed system II;

[0065] S4.3: Under light-protected conditions, add 2 parts by weight of glycyrrhizin to 6 parts by weight of 1,2-pentanediol and stir in a 40°C water bath until completely dissolved to form mixed system III. Add 3 parts by weight of catechin to 10 parts by weight of deionized water and stir to obtain an aqueous solution of catechin.

[0066] S4.4: Under light-proof conditions and with continuous nitrogen purging, add the above-mentioned mixture III to mixture II at 200 rpm, then add mixture I, and stir at 400 rpm for 20 min. Then add catechin aqueous solution and 5 parts by weight of 1,2-propylene glycol, and mix at 200 rpm for 10 min. Finally, add deionized water to 100 parts by weight to obtain the cosmetic compound raw material.

[0067] Example 2: A method for preparing a cosmetic compound raw material for removing acne spots, see [link to example]. Figure 1 ,include:

[0068] S1: Preparation of betulinic acid-osthol co-assembled nanoparticles

[0069] S1.1: Add 10 parts by weight of betulinic acid and 10 parts by weight of osthol to 100 parts by weight of ethyl acetate, then add 2 parts by weight of methanol, and stir at 500 rpm for 30 min to obtain a mixed solution;

[0070] S1.2: Add the mixed solution dropwise to 50 parts by weight of 2.5 wt% polyvinyl alcohol aqueous solution at a dropwise rate of 2 mL / min, then shake for 20 min, and then place it in a probe-type ultrasonic instrument for ultrasonic emulsification under ice-water bath conditions for 20 min to obtain a mixed emulsion;

[0071] S1.3: The mixed emulsion was added to 100 parts by weight of 0.3wt% polyvinyl alcohol aqueous solution, and then magnetically stirred at room temperature for 12h. After that, the organic solvent was removed by vacuum distillation, and then centrifuged at 12000rpm for 30min using a low-temperature refrigerated centrifuge. The precipitate was then washed 5 times with deionized water and finally freeze-dried to obtain betulinic acid-osthol co-assembled nanoparticles.

[0072] S2: Dual modification of mannan

[0073] S2.1: Add 4 parts by weight of mannan to 120 parts by weight of phosphate buffer with pH 5.0, then add 300 U / g β-mannanase, and then enzymatically hydrolyze at 60℃ for 3 h. After the enzymatic hydrolysis is completed, heat the hydrolysate at 100℃ for 12 min to inactivate the enzyme, then precipitate with 3 volumes of ethanol, collect the solid by centrifugation, and vacuum dry at 50℃ to obtain enzymatically hydrolyzed mannan.

[0074] S2.2: Mix 8 parts by weight of 20 wt% sodium hydroxide solution and 15 parts by weight of isopropanol to obtain a sodium hydroxide-isopropanol blend; mix 2.5 parts by weight of chloroacetic acid, 8 parts by weight of 20 wt% sodium hydroxide solution and 15 parts by weight of isopropanol to obtain a chloroacetic acid-sodium hydroxide-isopropanol blend.

[0075] S2.3: Under ice bath conditions, the above sodium hydroxide-isopropanol blend was added to 2 parts by weight of enzymatically hydrolyzed mannan, and then stirred and mixed under ice bath conditions for 3 hours. Then, the above chloroacetic acid-sodium hydroxide-isopropanol blend was added, and the mixture was reacted at room temperature for 3 hours. Then, it was reacted at 70°C for 1.4 hours. Then, the pH was adjusted to neutral, and then the mixture was concentrated, precipitated with ethanol at low temperature, and centrifuged to obtain modified mannan.

[0076] S3: Preparation of retinol sustained-release particles

[0077] S3.1: Dissolve 2 parts by weight of modified mannan in deionized water, disperse it at 500 rpm for 30 min with a magnetic stirrer to prepare an aqueous solution of 4 mg / mL, adjust the pH to 6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 4 mg / mL modified mannan.

[0078] S3.2: Dissolve 1.5 parts by weight of ε-polylysine in deionized water, stir and disperse for 30 min to prepare an aqueous solution of 2 mg / mL, adjust the pH to 6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of ε-polylysine of 2 mg / mL;

[0079] S3.3: Dissolve 3 parts by weight of retinol in 15 parts by weight of anhydrous ethanol, vortex until completely dissolved, to obtain a retinol ethanol solution. Under light protection and continuous nitrogen purging, slowly inject the retinol ethanol solution into the modified mannan aqueous solution at a rate of 1 mL / min. The volume ratio of the retinol ethanol solution to the modified mannan aqueous solution is 1:6. Stir continuously at 800 rpm during the process. After the addition is completed, continue stirring for 3 hours under light protection and inert gas protection to obtain a suspension containing retinol nanonuclei.

[0080] S3.4: Under light-protected and inert gas protection, at 400 rpm, the above ε-polylysine aqueous solution was slowly added dropwise at a rate of 2 mL / min to the suspension containing retinol nanonuclei. The volume ratio of the ε-polylysine aqueous solution to the suspension containing retinol nanonuclei was 2:5. After the addition was completed, the mixture was stirred and mixed for 2 h. Then, it was transferred to an ultrafiltration centrifuge tube with a molecular weight cutoff of 10 kDa and centrifuged at 6 °C and 8000 rpm for 20 min. After that, it was freeze-dried to obtain retinol sustained-release particles.

[0081] S4: Preparation of Cosmetic Compound Raw Materials

[0082] S4.1: Add 5 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles and 5 parts by weight of retinol sustained-release particles to 15 parts by weight of deionized water, and sonicate for 15 min under light-protected conditions, 45℃ water bath and 500rpm stirring to obtain mixed system I.

[0083] S4.2: Under stirring at 400 rpm, add 5 parts by weight of glutathione and 5 parts by weight of white willow bark extract to 22 parts by weight of deionized water, and stir for 30 min to obtain mixed system II;

[0084] S4.3: Under light-protected conditions, add 5 parts by weight of glycyrrhizin to 10 parts by weight of 1,2-pentanediol and stir in a 45°C water bath until completely dissolved to form mixed system III. Add 5 parts by weight of catechin to 12 parts by weight of deionized water and stir to obtain an aqueous solution of catechin.

[0085] S4.4: Under light-protected conditions and with continuous nitrogen purging, add the above-mentioned mixture III to mixture II at 300 rpm, then add mixture I, and stir at 500 rpm for 30 min. Then add catechin aqueous solution and 8 parts by weight of 1,2-propylene glycol, and mix at 300 rpm for 20 min. Finally, add deionized water to 100 parts by weight to obtain the cosmetic compound raw material.

[0086] Example 3: A method for preparing a cosmetic compound raw material for removing acne spots, see [link to example]. Figure 1 ,include:

[0087] S1: Preparation of betulinic acid-osthol co-assembled nanoparticles

[0088] S1.1: Add 9 parts by weight of betulinic acid and 9 parts by weight of osthol to 90 parts by weight of ethyl acetate, then add 1.5 parts by weight of methanol, and stir at 400 rpm for 25 min to obtain a mixed solution;

[0089] S1.2: Add the mixed solution dropwise to 40 parts by weight of 2.5 wt% polyvinyl alcohol aqueous solution at a dropwise rate of 1.5 mL / min, then shake for 15 min, and then place it in a probe-type ultrasonic instrument for ultrasonic emulsification under ice-water bath conditions for 15 min to obtain a mixed emulsion;

[0090] S1.3: The mixed emulsion was added to 90 parts by weight of 0.3wt% polyvinyl alcohol aqueous solution, and then magnetically stirred at room temperature for 11 h. After that, the organic solvent was removed by vacuum distillation, and then centrifuged at 11000 rpm for 25 min using a low-temperature refrigerated centrifuge. The precipitate was then washed 4 times with deionized water and finally freeze-dried to obtain betulinic acid-ostrichin co-assembled nanoparticles.

[0091] S2: Dual modification of mannan

[0092] S2.1: Add 3 parts by weight of mannan to 110 parts by weight of phosphate buffer with pH 5.0, then add 250 U / g β-mannanase, and then enzymatically hydrolyze at 55℃ for 2.5 h. After the enzymatic hydrolysis is completed, heat the hydrolysate at 100℃ for 11 min to inactivate the enzyme, then precipitate with 3 volumes of ethanol, collect the solid by centrifugation, and vacuum dry at 45℃ to obtain enzymatically hydrolyzed mannan.

[0093] S2.2: Mix 6.5 parts by weight of 20 wt% sodium hydroxide solution and 13.5 parts by weight of isopropanol to obtain a sodium hydroxide-isopropanol blend; mix 2.4 parts by weight of chloroacetic acid, 6.5 parts by weight of 20 wt% sodium hydroxide solution and 13.5 parts by weight of isopropanol to obtain a chloroacetic acid-sodium hydroxide-isopropanol blend.

[0094] S2.3: Under ice bath conditions, the above sodium hydroxide-isopropanol blend was added to 1.5 parts by weight of enzymatically hydrolyzed mannan, and then stirred and mixed under ice bath conditions for 2.5 h. Then, the above chloroacetic acid-sodium hydroxide-isopropanol blend was added, and the mixture was reacted at room temperature for 2.5 h, and then reacted at 65 °C for 1.3 h. The pH was then adjusted to neutral, and the mixture was concentrated, precipitated with ethanol at low temperature, and centrifuged to obtain modified mannan.

[0095] S3: Preparation of retinol sustained-release particles

[0096] S3.1: Dissolve 1.5 parts by weight of modified mannan in deionized water, disperse it at 400 rpm for 25 min with a magnetic stirrer to prepare an aqueous solution of 3 mg / mL, adjust the pH to 6.25, filter it through a 0.45 μm filter membrane to obtain an aqueous solution of 3 mg / mL modified mannan.

[0097] S3.2: Dissolve 1.25 parts by weight of ε-polylysine in deionized water, stir and disperse for 25 min to prepare an aqueous solution of 1.5 mg / mL, adjust the pH to 6.25, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 1.5 mg / mL ε-polylysine.

[0098] S3.3: Dissolve 2.5 parts by weight of retinol in 12.5 parts by weight of anhydrous ethanol, vortex until completely dissolved, to obtain a retinol ethanol solution. Under light protection and continuous nitrogen purging, slowly inject the retinol ethanol solution into the modified mannan aqueous solution at a rate of 0.75 mL / min. The volume ratio of the retinol ethanol solution to the modified mannan aqueous solution is 1:5.5. Stir continuously at 650 rpm during the process. After the addition is complete, continue stirring for 2.5 h under light protection and inert gas protection to obtain a suspension containing retinol nanocores.

[0099] S3.4: Under light-protected and inert gas protection, the above ε-polylysine aqueous solution was slowly added dropwise at a rate of 1.5 mL / min to the suspension containing retinol nanonuclei at 350 rpm. The volume ratio of the ε-polylysine aqueous solution to the suspension containing retinol nanonuclei was 1.5:5. After the addition was completed, the mixture was stirred and mixed for 1.5 h. Then, it was transferred to an ultrafiltration centrifuge tube with a molecular weight cutoff of 10 kDa and centrifuged at 5 °C and 6500 rpm for 17.5 min. After that, it was freeze-dried to obtain retinol sustained-release particles.

[0100] S4: Preparation of Cosmetic Compound Raw Materials

[0101] S4.1: Add 4 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles and 4 parts by weight of retinol sustained-release particles to 12.5 parts by weight of deionized water, and sonicate for 12.5 min under light-protected conditions, in a water bath at 42.5℃ and with stirring at 400 rpm to obtain mixed system I.

[0102] S4.2: Under stirring at 450 rpm, add 4 parts by weight of glutathione and 3.5 parts by weight of white willow bark extract to 21 parts by weight of deionized water, stir and mix for 25 min to obtain mixed system II;

[0103] S4.3: Under light-protected conditions, 3.5 parts by weight of glycyrrhizin were added to 8 parts by weight of 1,2-pentanediol and stirred in a water bath at 42.5°C until completely dissolved to form mixed system III. 4 parts by weight of catechin were added to 11 parts by weight of deionized water and stirred to obtain an aqueous solution of catechin.

[0104] S4.4: Under light-proof conditions and with continuous nitrogen purging, add the above-mentioned mixture III to mixture II at 250 rpm, then add mixture I, and stir at 450 rpm for 25 min. Then add catechin aqueous solution and 6.5 parts by weight of 1,2-propylene glycol, and mix at 250 rpm for 15 min. Finally, add deionized water to 100 parts by weight to obtain the cosmetic compound raw material.

[0105] Comparative Example 1 differs from Example 1 in that steps S2-S3 are removed, and the retinol sustained-release particles in step S4.1 are replaced with 2 parts by weight of retinol, while the remaining steps remain unchanged in the preparation of the cosmetic composite raw material. This is referred to as Comparative Example 1.

[0106] Comparative Example 2 differs from Example 1 in that step S2.1 is removed, and the enzymatic hydrolysis of mannan in step S2.3 is replaced with an equal amount of mannan, while the remaining steps remain unchanged in the preparation of the cosmetic composite raw material. This is referred to as Comparative Example 2.

[0107] Comparative Example 3 differs from Example 1 in that step S1 is removed, and the betulinic acid-ostrichin co-assembled nanoparticles in step S4.1 are replaced with an equal amount of white willow bark extract, while the remaining steps remain unchanged to prepare the cosmetic composite raw material. This is referred to as Comparative Example 3.

[0108] Comparative Example 4 differs from Example 1 in that the white willow bark extract in step S4.2 is replaced with an equal amount of betulinic acid-ostrichin co-assembled nanoparticles, while the remaining steps remain unchanged to prepare the cosmetic composite raw material. This is referred to as Comparative Example 4.

[0109] Comparative Example 5 differs from Example 1 in that step S1 is removed, and the betulinic acid-ostrichin co-assembled nanoparticles in step S4.1 are replaced with a physical mixture of betulinic acid and ostrichin with a mass ratio of 1:1. The remaining steps are unchanged to prepare the cosmetic composite raw material, which is referred to as Comparative Example 5.

[0110] Comparative Example 6 differs from Example 1 in that step S1 is removed, and the betulinic acid-ostrichin co-assembled nanoparticles in step S4.1 are replaced with an equal amount of betulinic acid, while the remaining steps remain unchanged to prepare the cosmetic composite raw material. This is referred to as Comparative Example 6.

[0111] Comparative Example 7 differs from Example 1 in that step S1 is removed, and the betulinic acid-ostrichin co-assembled nanoparticles in step S4.1 are replaced with an equal amount of ostrichin, while the remaining steps remain unchanged to prepare the cosmetic composite raw material. This is referred to as Comparative Example 7.

[0112] Preparation of cream:

[0113] 8.0% caprylic / capric triglyceride, 5.0% shea butter, 3.0% squalane, and 2.0% cetearyl glucoside were added to a beaker, heated and stirred until homogeneous, and kept at 80°C to form the oil phase. 5.0% glycerin and 2.0% panthenol were mixed and added to deionized water, stirred and mixed, and kept at 80°C to form the aqueous phase. 3.0% oleostearate, 0.5% xanthan gum, and 0.1% disodium EDTA were added to the oil phase, mixed, and then slowly added to the aqueous phase. The mixture was emulsified for 5 minutes and homogenized for 8 minutes. Finally, 0.2% sodium hyaluronate and 4% cosmetic compound raw materials were added and stirred until homogeneous to obtain the cream.

[0114] Creams were prepared using cosmetic composite raw materials prepared in Examples 1-3 and Comparative Examples 1-7, and experiments were conducted using the creams prepared in each group.

[0115] Seven-week-old specific pathogen-free (SPF) grade male C57BL / 6 mice were used for modeling. After one week of acclimatization, 2cm × 2cm of hair was removed from the back area of ​​the mice. Except for the normal control group, all other groups of mice were injected intradermally with 50μL of P. acnes (2×10⁷ CFU) on their backs. Immediately after injection, 20μL of artificial sebum was applied, and injections were repeated for 2 consecutive days. The normal control group was injected with an equal volume of phosphate-buffered saline. After successful modeling, the mice were divided into a model control group, Example 1-3 groups, and Comparative Example 1-7 groups, with 10 mice in each group. On the third day, the medication was applied to the modeling site. The normal control group and the model control group were applied with petroleum jelly, while the other groups were applied with the corresponding cream. The medication was administered twice daily, morning and evening, at a dose of 50mg each time.

[0116] Seven days later, the condition of the mice's backs was observed. The mice were scored according to the following three clinical indicators: diameter of acne (0: 0-1.9 mm, 1: 2-3.9 mm, 2: 4-5.9 mm, 3: 6-8 mm), height (0: flat, 1: small, 2: large), and degree of crusting (0: none, 1: mild, 2: obvious). The sum of the three scores was the disease score of acne. The score was the average of 10 mice. The lower the score, the better the effect. The specific results are shown in Table 1.

[0117] Table 1. Disease score results of acne in Examples 1-3 and Comparative Examples 1-7

[0118]

[0119] As can be seen from the data in Table 1, the cosmetic composite raw material prepared by this invention can effectively improve acne problems. Comparative Example 1 shows that layer-by-layer encapsulation of retinol using modified mannan / ε-polylysine is more effective in improving acne than direct addition of retinol. Comparative Example 2 shows that mannan treated with enzymatic hydrolysis followed by carboxymethyl modification is more effective in improving acne than directly carboxymethyl modified mannan. This is because using double-modified mannan as a wall material significantly increases the encapsulation rate of lipid-soluble retinol, thus allowing for a longer-lasting effect. Furthermore, the short-chain fragments of double-modified mannan can interact hydrophobically with lipids in the stratum corneum, opening intercellular channels and promoting retinol penetration into the superficial dermis, thus resulting in a better effect in improving acne.

[0120] The data from Comparative Examples 3-4 show that the co-assembled nanoparticles of white willow bark extract and betulinic acid-osthol can exert a synergistic effect compared to the addition of a single component, thus promoting the improvement of acne problems.

[0121] The data from Comparative Examples 5-7 show that when betulinic acid and osthol are co-assembled at the molecular level using co-assembly nanotechnology, their anti-acne activity is significantly increased compared to single-component or simple physical mixture systems, thus effectively improving acne problems.

[0122] Mice from the normal control group, model control group, Examples 1-3, and Comparative Examples 3-7 were euthanized with an overdose of isoflurane. Skin tissue from the inflammatory nodules on the back was then harvested for pathological examination. Samples were fixed in 4% paraformaldehyde, then dehydrated using a gradient method, and embedded in paraffin. Hematoxylin-eosin staining was then performed, and pathological changes were observed and scored under a microscope.

[0123] The inflammation score of the back tissue was as follows: 0 points, normal; 1 point, a few cells infiltrating (5-20%); 2 points, moderate infiltration (21-40%); 3 points, severe infiltration (41-60%); 4 points, extensive infiltration (>60%). The score was the average of 10 mice. For specific scores, please refer to Table 2. The lower the score, the better the anti-inflammatory effect.

[0124] Table 2. Inflammation scores of back tissues in Examples 1-3 and Comparative Examples 3-7

[0125]

[0126] As can be seen from the data in Table 2, the cosmetic composite raw material prepared by this invention has a good anti-inflammatory effect. As can be seen from the data in Comparative Examples 3-4, the anti-inflammatory effects of betulinic acid-ostrichin co-assembled nanoparticles and white willow bark extract are superimposed, which can quickly relieve inflammatory response and avoid the aggravation of pigmentation caused by repeated inflammation. As can be seen from the data in Comparative Examples 4-6, the betulinic acid-ostrichin co-assembled nanoparticles prepared by molecular-level co-assembly of betulinic acid and ostrichin have better antibacterial and anti-inflammatory effects than single-component or simple physical mixture systems.

[0127] Retinol was used as the detection substance, and the transdermal release was determined using a Franz diffusion cell experiment: the transdermal release was measured using isolated pig skin, and the cumulative transdermal release of the creams prepared in Examples 1-3 and Comparative Example 2 was measured over 24 hours. The measurements were taken three times, and the average value was taken. The results are shown in Table 3.

[0128] Table 3. Results of transdermal release assays in Examples 1-3 and Comparative Example 2

[0129]

[0130] As can be seen from the data in Table 3, using double-modified mannan as a wall material to encapsulate fat-soluble retinol can promote the penetration of retinol into the superficial dermis, and its transdermal absorption rate is significantly improved.

[0131] Osthol was used as the detection substance, and the transdermal release was determined using a Franz diffusion cell experiment: the transdermal release was measured using isolated pig skin, and the cumulative transdermal release of the creams prepared in Examples 1-3 and Comparative Examples 4-5 was measured over 24 hours. The measurements were taken three times, and the average value was taken. The results are shown in Table 4.

[0132] Table 4. Results of transdermal release assays for Examples 1-3 and Comparative Examples 4-5

[0133]

[0134] As shown in Table 4, and specifically in Comparative Example 4, the added white willow bark extract acts as a penetration enhancer, promoting the skin penetration of betulinic acid-osthol co-assembled nanoparticles. The data from Comparative Example 5 demonstrate that the betulinic acid-osthol co-assembled nanoparticles can more easily penetrate the gaps in the stratum corneum, efficiently delivering active ingredients to the deep epidermis and even the pilosebaceous unit, thereby effectively improving bioavailability and skin permeability.

[0135] Skin irritation experiments were conducted on the creams prepared in Examples 1-3: Hair was removed from the backs of mice, and the skin was divided into 1cm × 1cm sections. Each group received a dose of 1g of the preparation per mouse via transdermal application to the backs of the mice. The application area was covered with cellophane and gauze, and then sealed with medical tape. After 12 hours, residual preparation on the skin of each group of animals was washed off with 0.9% sodium chloride injection. Skin condition was observed after another 12 hours for erythema, edema, etc. The results are shown in Table 5.

[0136] The DPPH scavenging rate and tyrosinase inhibition rate of the creams prepared in Examples 1-3 were also measured, and the results are shown in Table 5.

[0137] Table 5. Results of Basic Performance Measurements in Examples 1-3

[0138]

[0139] As can be seen from the data in Table 5, the cosmetic composite raw material prepared by this invention is mild and non-irritating, and has good antioxidant capacity and tyrosinase inhibition capacity, which can effectively inhibit melanin production and promote the removal of acne spots.

[0140] It should be understood that those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims. Parts not described in detail in this specification are prior art known to those skilled in the art.

Claims

1. A method for preparing a cosmetic compound raw material for removing acne spots, characterized in that, include: S1: Preparation of betulinic acid-osthol co-assembled nanoparticles; S1.1: Add 8-10 parts by weight of betulinic acid and 8-10 parts by weight of osthol to 80-100 parts by weight of ethyl acetate, then add 1-2 parts by weight of methanol, and stir and mix at 300-500 rpm for 20-30 min to obtain a mixed solution. S1.2: Add the mixed solution dropwise to 30-50 parts by weight of 2.5wt% polyvinyl alcohol aqueous solution at a dropwise rate of 1-2 mL / min, then shake for 10-20 min, and then place it in a probe-type ultrasonic instrument for ultrasonic emulsification under ice-water bath conditions for 10-20 min to obtain a mixed emulsion; S1.3: Add the mixed emulsion to 80-100 parts by weight of 0.3wt% polyvinyl alcohol aqueous solution, then stir magnetically at room temperature for 10-12 hours, then remove the organic solvent by vacuum distillation, then centrifuge at 10000-12000 rpm for 20-30 minutes using a low-temperature refrigerated centrifuge, then wash the precipitate with deionized water 3-5 times, and finally freeze-dry to obtain betulinic acid-osthol co-assembled nanoparticles; S2: Dual modification of mannan; S2.1: Add 2-4 parts by weight of mannan to 100-120 parts by weight of phosphate buffer with pH 5.0, then add β-mannanase, and then enzymatically hydrolyze at 50-60℃ for 2-3 hours. After the enzymatic hydrolysis is completed, heat the hydrolysate at 100℃ for 10-12 minutes to inactivate the enzyme, then precipitate with 3 volumes of ethanol, collect the solid by centrifugation, and vacuum dry at 40-50℃ to obtain enzymatically hydrolyzed mannan. S2.2: Mix 5-8 parts by weight of 20wt% sodium hydroxide solution and 12-15 parts by weight of isopropanol to obtain a sodium hydroxide-isopropanol blend; mix 2.3-2.5 parts by weight of chloroacetic acid, 5-8 parts by weight of 20wt% sodium hydroxide solution and 12-15 parts by weight of isopropanol to obtain a chloroacetic acid-sodium hydroxide-isopropanol blend. S2.3: Under ice bath conditions, add the above sodium hydroxide-isopropanol blend to 1-2 parts by weight of enzymatically hydrolyzed mannan, then stir and mix under ice bath conditions for 2-3 hours, then add the above chloroacetic acid-sodium hydroxide-isopropanol blend, react at room temperature for 2-3 hours, then react at 60-70℃ for 1.2-1.4 hours, then adjust the pH to neutral, then concentrate, precipitate with ethanol at low temperature, and centrifuge to obtain modified mannan; S3: Preparation of retinol sustained-release particles; S3.1: Dissolve 1-2 parts by weight of modified mannan in deionized water, disperse it at 300-500 rpm for 20-30 min with a magnetic stirrer to prepare an aqueous solution of 2-4 mg / mL, adjust the pH to 6.0-6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 2-4 mg / mL modified mannan. S3.2: Dissolve 1-1.5 parts by weight of ε-polylysine in deionized water, stir and disperse for 20-30 min to prepare an aqueous solution of 1-2 mg / mL, adjust the pH to 6.0-6.5, filter through a 0.45 μm filter membrane to obtain an aqueous solution of 1-2 mg / mL of ε-polylysine. S3.3: Dissolve 2-3 parts by weight of retinol in 10-15 parts by weight of anhydrous ethanol, vortex until completely dissolved, to obtain a retinol ethanol solution. Under light protection and continuous nitrogen purging, slowly inject the retinol ethanol solution into the modified mannan aqueous solution at a rate of 0.5-1 mL / min, while continuously stirring at 500-800 rpm. After the addition is complete, continue stirring for 2-3 hours under light protection and inert gas protection to obtain a suspension containing retinol nanocores. S3.4: Under light-protected and inert gas protection, slowly add ε-polylysine aqueous solution at a rate of 1-2 mL / min to the suspension containing retinol nanonuclei at 300-400 rpm. After the addition is complete, continue stirring and mixing for 1-2 h. Then transfer to an ultrafiltration centrifuge tube with a molecular weight cutoff of 10 kDa and centrifuge at 4-6℃ and 5000-8000 rpm for 15-20 min. After that, freeze dry to obtain retinol sustained-release particles. S4: Preparation of cosmetic compound raw materials; 3-5 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles, 3-5 parts by weight of retinol sustained-release particles, 3-5 parts by weight of glutathione, 2-5 parts by weight of white willow bark extract, 2-5 parts by weight of glycyrrhizin, 6-10 parts by weight of 1,2-pentanediol, 3-5 parts by weight of catechin, and 5-8 parts by weight of 1,2-propylene glycol were mixed, and deionized water was added to bring the total to 100 parts by weight to obtain a cosmetic compound raw material.

2. The method for preparing a cosmetic composite raw material for removing acne spots according to claim 1, characterized in that, The amount of β-mannanase added in S2.1 is 200-300 U / g.

3. The method for preparing a cosmetic composite raw material for removing acne spots according to claim 1, characterized in that, In step S3.3, the volume ratio of retinol ethanol solution to modified mannan aqueous solution is 1:5-6.

4. The method for preparing a cosmetic composite raw material for removing acne spots according to claim 1, characterized in that, In step S3.4, the volume ratio of the ε-polylysine aqueous solution to the suspension containing retinol nanonuclei is 1-2:

5.

5. The method for preparing a cosmetic composite raw material for removing acne spots according to claim 1, characterized in that, S4: The preparation of cosmetic compound raw materials specifically includes the following steps: S4.1: Add 3-5 parts by weight of betulinic acid-ostrichin co-assembled nanoparticles and 3-5 parts by weight of retinol sustained-release particles to 10-15 parts by weight of deionized water, and sonicate for 10-15 minutes under light-proof, 40-45℃ water bath and 300-500rpm stirring to obtain mixed system I. S4.2: Under stirring at 300-400 rpm, add 3-5 parts by weight of glutathione and 2-5 parts by weight of white willow bark extract to 20-22 parts by weight of deionized water, and stir for 20-30 minutes to obtain mixed system II. S4.3: Under light-protected conditions, add 2-5 parts by weight of glycyrrhizin to 6-10 parts by weight of 1,2-pentanediol, and stir in a water bath at 40-45°C until completely dissolved to form mixed system III. Add 3-5 parts by weight of catechin to 10-12 parts by weight of deionized water, stir and mix to obtain an aqueous solution of catechin. S4.4: Under light-proof conditions and with inert gas continuously introduced, at 200-300 rpm, add the above-mentioned mixture III to mixture II, then add mixture I, and stir and mix at 400-500 rpm for 20-30 min. Then add catechin aqueous solution and 5-8 parts by weight of 1,2-propylene glycol, and mix at 200-300 rpm for 10-20 min. Finally, add deionized water to 100 parts by weight to obtain the cosmetic compound raw material.

6. The method for preparing a cosmetic composite raw material for removing acne spots according to claim 5, characterized in that, The inert gas in step S4.4 is nitrogen.

7. A cosmetic compound ingredient for removing acne spots, characterized in that, It is prepared by the method for preparing a cosmetic composite raw material for removing acne spots as described in any one of claims 1-6.

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