An active ingredient microencapsulated composition, its preparation method and use

Abstract

The present application relates to the technical field of cosmetics and external preparation, and specifically discloses an active ingredient microencapsulated composition, a preparation method and application thereof. The composition comprises a capsule core and a double-layer capsule wall structure, the capsule core co-loads 2-oxoglutaric acid, nicotinamide and gamma-aminobutyric acid, the inner shell is formed by an acid copolymer, the outer shell is constructed by a chitosan-dopamine composite material, and the inner shell and the outer shell are crosslinked by Fe 3+ coordination and Ca 2+ ion crosslinking to perform densification treatment. The method comprises the steps of active substance dissolution, emulsification into capsules, inner and outer shell coating, ion densification, drying and dispersion, etc. The obtained microcapsules have concentrated particle size distribution, high stability and excellent slow-release performance, are suitable for skin care products such as emulsions, gels and sprays, and have good application prospect.

Description

Technical Field

[0001] This invention relates to the field of cosmetic formulation technology, specifically to a microencapsulated composition of active ingredients, its preparation method, and its application. Background Technology

[0002] With the rapid development of the functional cosmetics and cosmeceutical market, consumers have placed higher demands on products in terms of functionality, safety, and user experience, especially in areas such as skin barrier repair, anti-allergy soothing, and conditioning and rejuvenating. The need for stability and delivery efficiency of active ingredients is increasing. To meet these complex demands, formulations typically incorporate multiple water-soluble small-molecule active ingredients with different mechanisms of action, such as 2-oxoglutarate (for exfoliation), niacinamide (for anti-oxidation and whitening), and gamma-aminobutyric acid (for nerve soothing). However, these ingredients generally suffer from easy oxidation, strong irritation, and poor synergistic stability. If directly added to emulsions or gel systems, they are prone to degradation, migration, or uncontrolled release, thus affecting the efficacy and long-term stability of the final product.

[0003] To overcome the aforementioned shortcomings, microencapsulation technology has been widely applied in active ingredient delivery systems, aiming to prolong the retention time of active substances, improve storage stability, and achieve controllable regulation of release behavior. Currently, mainstream technologies include polymer microcapsules, liposomes, nanoemulsions, and solid lipid nanoparticles (SLNs). Although these carrier systems can achieve encapsulation and sustained-release functions to some extent, significant limitations remain. For example, conventional microcapsules often employ a single-layer polymer shell structure, which has poor structural stability and is prone to breakage and leakage under emulsification shear, pH fluctuations, or elevated temperatures. When encapsulating multiple active ingredients with significantly different structures and physicochemical properties, problems such as decreased encapsulation efficiency, inter-component interference, or inconsistent release behavior often occur. Furthermore, existing microcapsules often exhibit poor dispersion stability in actual daily chemical formulations, such as wide particle size distribution and unstable zeta potential, leading to aggregation, sedimentation, interfacial blurring, or flocculation in O / W emulsions, gels, or sprays, thus affecting product appearance and user experience.

[0004] On the other hand, most existing microencapsulation systems lack systematic design for structural synergy, component compatibility, and formulation adaptability, making it difficult to achieve efficient co-loading of ternary or higher active ingredients, precise control of release behavior, and long-term dispersion stability in complex formulation environments. Simplified structures, functional limitations, and difficulties in process control have become key issues restricting the further application of microencapsulation technology in high-end skincare products. Therefore, the industry urgently needs to develop high-performance microencapsulated compositions with multi-layered shell structures, excellent synergistic encapsulation capacity, precisely regulated release behavior, and broad formulation adaptability. This would enable stable encapsulation, controlled release, and combined efficacy of multiple functional small molecules in topical formulations, thereby providing more reliable technical support for the consistency of skincare product efficacy and safety. Summary of the Invention

[0005] To address the above problems, the present invention provides the following technical solution:

[0006] This invention provides a microencapsulated composition of an active ingredient, characterized in that the microcapsule comprises a core and a wall. The core is composed of 2-oxoglutaric acid, nicotinamide, and γ-aminobutyric acid in a mass ratio of 0.000625~0.002:0.5~3.0:0.2~2.0. The wall is a bilayer structure with an inner shell and an outer shell formed by interfacial deposition. The inner shell is composed of an acidic copolymer, and the outer shell is composed of catechol-modified chitosan, polydopamine, or a combination of both, and is subjected to Fe... 3+ Coordination with Ca 2 + The microcapsules are densified by ion bridging, and the median particle size D50 of the volume distribution is 1.0~5.0 μm, the core mass fraction is 20%~70%, and the residual moisture mass fraction is not greater than 5%.

[0007] Further, the acidic copolymer is Eudragit L100-55 or Eudragit S100, and its acidic group content is 2.0~7.0 mmol / g.

[0008] Furthermore, the outer shell material is a combination of catechol-modified chitosan, polydopamine, or both. The outer shell and the acidic copolymer inner shell are deposited sequentially to form a double-shell vesicle wall, which is then densified by metal ion treatment.

[0009] Furthermore, the capsule wall is a double-shell structure composed of an acidic copolymer layer and a layer containing catechol groups. The double shell is subjected to aging and metal ion treatment to obtain a stable and dense network.

[0010] Furthermore, the microcapsules have a zeta potential of -15 mV to -30 mV and a volume distribution percentile particle size D90 of no more than 20 μm. The composition may contain fumed silica and polyethylene glycol as anti-caking and dispersing agents, with a total mass fraction of 0.1% to 3.0%.

[0011] This invention also proposes a method for preparing a microencapsulated composition of active ingredients, comprising the following steps:

[0012] S1. Dissolve 2-oxoglutaric acid, nicotinamide and γ-aminobutyric acid in an aqueous phase at a mass ratio of 0.000625~0.002:0.5~3.0:0.2~2.0, and adjust the pH to 3.5~6.0 to obtain the core solution.

[0013] S2. The core solution is added dropwise to an oil phase containing a hydrophobic surfactant, and sheared at 12000 r / min for 1-3 min to obtain a W / O type primary emulsion. The primary emulsion is added to an aqueous phase containing 0.5%-2.0% polyvinyl alcohol, and sheared at 6000-12000 r / min for 2-5 min to obtain a W / O / W type secondary emulsion system.

[0014] S3. Add an acidic copolymer solution to the secondary emulsification system to deposit an inner shell at the microdroplet interface and age for 5-20 min.

[0015] S4. Under Tris-HCl buffer conditions, add catechol-modified chitosan solution, polydopamine precursor solution, or a combination of both, and react at 25 °C for 30-90 min to form an outer shell. The pH of the Tris-HCl buffer is 8.2-8.8, and the concentration is 10-50 mmol / L.

[0016] S5, first add Fe 3+ The solution undergoes a coordination reaction for 5-15 minutes, then Ca is added. 2+ The solution undergoes a bridging reaction for 10-30 minutes to achieve densification.

[0017] S6. After centrifugation or filtration and washing, and drying at a temperature not exceeding 40 °C until the residual moisture content is not greater than 5%, the target microencapsulated composition is obtained.

[0018] Furthermore, the hydrophobic nonionic surfactant in the oil phase is a sorbitan ester surfactant, and the amount used is 0.05%~1.0% of the total mass of the system; the polyvinyl alcohol in the secondary emulsified aqueous phase has a mass fraction of 0.5%~2.0% as a protective colloid; the mass volume concentration of the acidic copolymer solution is 0.5%~5.0%; and the mass volume concentration of the catechol group modified chitosan solution or polydopamine precursor solution is 0.1%~2.0%.

[0019] Furthermore, the densification includes: first applying 1.0~2.0 mmol / L Fe... 3+ The outer shell undergoes a surface coordination treatment for 5-15 minutes, followed by Ca... 2+ The solution implements bridging, wherein the Ca 2+ The solution was added in three stages at concentrations of 5 mmol / L, 15 mmol / L, and 25 mmol / L, with each stage lasting 5–10 min.

[0020] The present invention also proposes a dispersion containing the microencapsulated composition of the active ingredient, wherein the microcapsules are dispersed in water or an aqueous solution containing polyol to form a suspension, emulsion or gel, wherein the mass fraction of the microcapsules in the dispersion is 0.1% to 5.0%, and after low shear homogenization at 500 to 2000 r / min for 1 to 3 minutes, the volume distribution percentile particle size D90 of the system is not greater than 20 μm.

[0021] The present invention also proposes the application of the microencapsulated active ingredient composition in the preparation of topical skin preparations, wherein the microencapsulated composition is added to an aqueous phase or a water-in-oil matrix at a mass fraction of 0.1% to 5.0%, and stirred at 25 to 40°C for 10 to 30 minutes to obtain the topical skin preparation.

[0022] The present invention has the following beneficial effects:

[0023] (1) Uniform particle size distribution and stable potential: This invention uses a double-layer coating design of an acidic copolymer inner shell and a chitosan-dopamine outer shell, supplemented by Fe 3+ With Ca 2+ Cross-linking and densification treatment effectively improves the integrity and stability of the microcapsule structure. The microcapsule particle size distribution is concentrated, exhibiting good dispersibility and suspension properties. At the same time, the surface potential is within a stable range, which can significantly reduce the risk of aggregation and sedimentation, ensuring the long-term homogeneity of the product system.

[0024] (2) It has the ability to efficiently encapsulate ternary active ingredients: The microcapsule structure is suitable for the co-encapsulation of various small molecule active ingredients such as 2-oxoglutaric acid, nicotinamide and γ-aminobutyric acid. By optimizing the ratio and designing the core stability system, the structure compatibility and co-release of multiple components can be achieved, avoiding mutual interference between components and decrease in stability, and enhancing the consistency of the efficacy output of the system after compounding.

[0025] (3) Controllable release behavior and outstanding sustained-release performance: Based on the double-shell structure and ion cross-linking densification process, an effective diffusion barrier system is constructed, which can delay the release rate of active ingredients, achieve continuous and controllable delivery, and help reduce the risk of skin irritation. This mechanism significantly inhibits the initial burst release phenomenon common in traditional microcapsules, improves the safety and comfort during use, and is especially suitable for sensitive skin care products;

[0026] (4) Good compatibility with dispersion and stability systems: Microcapsules can be stably dispersed in various daily chemical matrices such as aqueous phase, emulsion, and spray, and have good interfacial compatibility and product suspension ability, without affecting the appearance and rheological properties of the system.

[0027] (5) Good activity retention during long-term storage: The present invention effectively inhibits the degradation caused by oxidation, hydrolysis and migration of the core components by the combined effect of physical barrier barrier and synergistic stabilization of active ingredients. It can maintain a high activity retention rate and structural integrity even under accelerated testing and long-term storage conditions, which is conducive to extending the product shelf life and ensuring that the efficacy continues to be stable throughout the product's use cycle. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the preparation process of the microencapsulated composition of the present invention;

[0029] Figure 2 A schematic diagram of a double-shell structure formed by dual emulsification and interface deposition;

[0030] Figure 3 This is a graph showing the in vitro release behavior of the microcapsules.

[0031] Figure 4 A graph showing the change in activity retention rate under accelerated aging conditions; Detailed Implementation

[0032] To facilitate understanding and implementation of the present invention by those skilled in the art, the present invention will be further described below in conjunction with the accompanying drawings and embodiments. The following embodiments are used to illustrate the present invention and do not constitute a limitation on the scope defined by the claims. Any equivalent substitutions or modifications made without departing from the spirit of the present invention should be considered to fall within the protection scope of the present invention.

[0033] Example 1

[0034] This embodiment provides a microencapsulated composition of an active ingredient, comprising a core and a shell, the shell being a double-shell structure with an inner shell and an outer shell; the core is composed of 2-oxoglutaric acid, nicotinamide, and γ-aminobutyric acid in a mass ratio of 0.0015:1.5:1.0; the inner shell is composed of the acidic copolymer Eudragit L100-55; the outer shell is composed of catechol-modified chitosan and polydopamine, and is treated with Fe...3+ Coordination with Ca 2+ Ion bridging treatment was used to achieve densification. The resulting microcapsules had a median particle size D50 of 2.5 μm, a D90 of no more than 10 μm, a Zeta potential of -21 mV, a core mass fraction of 45%, and a residual moisture mass fraction of no more than 4%.

[0035] The preparation method of the microencapsulated composition of the active ingredient includes the following steps:

[0036] S1. Dissolve 2-oxoglutaric acid, nicotinamide and γ-aminobutyric acid in purified water at a mass ratio of 0.0015:1.5:1.0, adjust the pH to 4.5, and obtain a clear and stable capsule solution.

[0037] S2. The core solution is slowly added dropwise to an isoparaffinic oil phase containing 1.0% (w / w) Span-80, and sheared at 12000 r / min for 2 minutes to obtain a W / O type primary emulsion; then the primary emulsion is slowly added to an aqueous phase containing 1.0% (w / w) polyvinyl alcohol, and sheared at 6000 r / min for 3 minutes to obtain a W / O / W type secondary emulsion system;

[0038] S3. Add a 1.0% (w / v) Eudragit L100-55 acid copolymer solution to the secondary emulsification system, the addition amount being 4% of the total system volume, and react for 5 minutes under stirring conditions to deposit a continuous inner shell at the microdroplet interface.

[0039] S4. Add 0.5% (w / v) catechol-modified chitosan solution and 0.2% (w / v) dopamine precursor solution (volume ratio 1:1) to the system, and adjust the pH to 8.5 with 20 mmol / L Tris-HCl buffer. React at 25°C for 45 minutes to form the outer shell layer.

[0040] S5. First add Fe at a concentration of 1.0 mmol / L. 3+ The solution (added at 2% of the total system volume) was subjected to a coordination reaction for 10 minutes; then Ca was added gradually in three portions. 2+ The solutions were prepared at final concentrations of 5 mmol / L, 15 mmol / L, and 25 mmol / L, respectively, and the reaction time was 10 minutes at each concentration to achieve ion bridging and shell densification.

[0041] S6. The obtained microcapsules were separated by centrifugation at 3000×g for 10 minutes, washed twice with purified water, and dried at no more than 40°C until the residual moisture content did not exceed 5% (determined by Karl Fischer method). Before drying, 0.5wt% fumed silica and 0.5wt% polyethylene glycol were added as anti-caking and dispersing agents and mixed evenly.

[0042] The resulting microcapsule powder can be stably dispersed in purified water to form a suspension with a mass fraction of 1.0%, a Zeta potential of -21 mV, and a D90 of no more than 10 μm. It is suitable for various topical skin formulations such as emulsions, sprays, and gels.

[0043] The microencapsulated composition was added to the aqueous phase of the O / W emulsion at a mass fraction of 5.0%, and stirred at 40°C for 30 minutes. The resulting formulation had a uniform appearance, with no flocculation or stratification, and no obvious sedimentation was observed after standing for 72 hours.

[0044] Example 2

[0045] This embodiment provides a microencapsulated composition of an active ingredient, comprising a core and a shell, the shell being a double-shell structure with an inner shell and an outer shell; the core is composed of 2-oxoglutaric acid, nicotinamide, and γ-aminobutyric acid in a mass ratio of 0.0008:0.5:0.2; the inner shell is composed of the acidic copolymer Eudragit L100-55; the outer shell is composed of catechol-modified chitosan and polydopamine, and is treated with Fe... 3+ Coordination with Ca 2+ Ion bridging treatment was used to achieve densification. The resulting microcapsules had a median particle size D50 of 1.0 μm, a D90 of no more than 5.0 μm, a Zeta potential of -30 mV, a core mass fraction of 20%, and a residual moisture mass fraction of no more than 5%.

[0046] The preparation method of the microencapsulated composition of the active ingredient includes the following steps:

[0047] S1. Dissolve 2-oxoglutaric acid, nicotinamide and γ-aminobutyric acid in purified water at a mass ratio of 0.0008:0.5:0.2, adjust the pH to 3.5, and obtain a clear and stable capsule solution.

[0048] S2. The core solution is added dropwise to an isooctane oil phase containing 0.8% (w / w) Span-80 and sheared at 12000 r / min for 2 minutes to obtain a W / O type primary emulsion; then the primary emulsion is transferred to an aqueous phase containing 1.0% (w / w) polyvinyl alcohol and sheared at 6000 r / min for 3 minutes to obtain a W / O / W type secondary emulsion system;

[0049] S3. Add a 0.5% (w / v) Eudragit L100-55 acidic copolymer solution to the secondary emulsification system, the addition amount being 2% of the total system volume, and react for 5 minutes under stirring conditions to deposit an inner shell at the microdroplet interface.

[0050] S4. Add 0.1% (w / v) catechol-modified chitosan solution and 0.1% (w / v) dopamine precursor solution (volume ratio 1:1) to the system, and adjust the pH to 8.5 with 20 mmol / L Tris-HCl buffer. React at 25°C for 30 minutes to form the outer shell layer.

[0051] S5. First add Fe at a concentration of 0.5 mmol / L. 3+ The solution (added at 2% of the total system volume) was subjected to a coordination reaction for 10 minutes; then Ca was added. 2+ The final solution concentration was 5 mmol / L, and the reaction time was 10 minutes to achieve ion bridging and shell densification.

[0052] S6. The obtained microcapsules were separated by centrifugation at 3000×g for 10 minutes, washed twice with purified water, and dried at no more than 40°C until the residual moisture content did not exceed 5% (determined by Karl Fischer method). Before drying, 0.5wt% fumed silica and 0.5wt% polyethylene glycol were added as anti-caking and dispersing agents and mixed evenly.

[0053] The resulting microcapsule powder can be stably dispersed in purified water to form a dispersion with a mass fraction of 1.0%, a Zeta potential of -30 mV, and a D90 of no more than 5.0 μm. It is suitable for topical skin formulation systems that require small particle size and low activity content.

[0054] The microencapsulated composition was added to the aqueous phase of a low-viscosity O / W emulsion at a mass fraction of 1.0%, and stirred at 40°C for 20 minutes. The resulting emulsion had a uniform appearance and stable dispersion, and no visible stratification was observed after standing for 7 days.

[0055] Example 3

[0056] This embodiment provides a microencapsulated composition of an active ingredient, comprising a core and a shell, the shell being a double-shell structure with an inner shell and an outer shell; the core is composed of 2-oxoglutaric acid, nicotinamide, and γ-aminobutyric acid in a mass ratio of 0.002:3.0:2.0; the inner shell is composed of the acidic copolymer Eudragit S100; the outer shell is composed of catechol-modified chitosan and polydopamine, and is treated with Fe... 3+ Coordination with Ca 2+Densification was achieved through ion-fractional bridging treatment. The resulting microcapsules had a median particle size D50 of 5.0 μm, a D90 of no more than 20 μm, a Zeta potential of –15 mV, a core mass fraction of 70%, and a residual moisture mass fraction of no more than 5%.

[0057] The preparation method of the microencapsulated composition of the active ingredient includes the following steps:

[0058] S1. Dissolve 2-oxoglutaric acid, nicotinamide and γ-aminobutyric acid in purified water in a mass ratio of 0.002:3.0:2.0. Stir at 60°C for 15 minutes to completely dissolve them. Adjust the pH to 6.0 to obtain a clear capsule solution that is close to saturation.

[0059] S2. The core solution is injected into an isoparaffinic oil phase containing 1.5% (w / w) Span-80 and sheared at 12000 r / min for 3 minutes to obtain a W / O type primary emulsion; then the primary emulsion is added to an aqueous phase containing 1.5% (w / w) polyvinyl alcohol and sheared at 9000 r / min for 3 minutes to obtain a W / O / W type secondary emulsion system;

[0060] S3. Add a 5.0% (w / v) Eudragit S100 acid copolymer solution to the secondary emulsification system, the addition amount being 8% of the total system volume, and react for 15 minutes under stirring conditions to deposit a complete inner shell at the microdroplet interface.

[0061] S4. Add 2.0% (w / v) catechol-modified chitosan solution and 1.0% (w / v) dopamine precursor solution (volume ratio 1:1) to the system, and adjust the pH to 8.3 with 50 mmol / L Tris-HCl buffer. React at 25°C for 60 minutes to form the outer shell layer.

[0062] S5. First add Fe at a concentration of 2.0 mmol / L. 3+ The solution (added at 5% of the total system volume) was subjected to a coordination reaction for 10 minutes; then Ca was added gradually in three portions. 2+ The solutions were prepared at final concentrations of 5 mmol / L, 15 mmol / L, and 25 mmol / L, respectively, and the reaction time was 10 minutes at each concentration to achieve segmented ion bridging and shell densification.

[0063] S6. The obtained microcapsules were separated by centrifugation at 3000×g for 10 minutes, washed twice with purified water, and dried at no more than 40°C until the residual moisture content did not exceed 5% (determined by Karl Fischer method). Before drying, 1.5wt% fumed silica and 1.5wt% PEG 400 were added as anti-caking and dispersing agents and mixed evenly.

[0064] The resulting microcapsule powder can be stably dispersed in water to form a dispersion system with a mass fraction of 1.0%, a Zeta potential of -15 mV, and a D90 of no more than 20 μm. It is suitable for topical skin preparations with high active ingredient loading and high concentration.

[0065] The microencapsulated composition was added to the aqueous phase of an O / W type nourishing emulsion at a mass fraction of 10.0 wt%, and stirred at 40°C for 30 minutes. The resulting formulation had a uniform appearance and no flocculation or stratification.

[0066] Comparative Example 1

[0067] This comparative example provides a microencapsulated composition of active ingredients without a shell layer. The core composition is the same as in Example 1, consisting of 2-oxoglutaric acid, nicotinamide, and γ-aminobutyric acid in a mass ratio of 0.0015:1.5:1.0. The microcapsules contain only a single-layer inner shell composed of the acidic copolymer Eudragit L100-55, without the deposition of a catechol-modified chitosan and polydopamine shell, thus exhibiting a single-shell structure.

[0068] In its preparation method, step S4 of Example 1 is omitted, no outer shell material or related reaction is added, and the inner shell is constructed only through step S3, followed by step S5 of Fe. 3+ With Ca 2+ The densification treatment and the centrifugation, washing, and drying operations in step S6 were performed. All other operating conditions and parameters remained the same as in Example 1.

[0069] Comparative Example 2

[0070] This comparative example provides a solution without Fe 3+ Coordination with Ca 2+ A bridged and densified double-shell microcapsule composition. Its core composition, inner and outer shell materials and deposition method are the same as those in Example 1, that is, the inner shell is composed of Eudragit L100-55 and the outer shell is composed of catechol-modified chitosan and polydopamine, but no ionic crosslinking densification treatment is performed after shell formation.

[0071] Step S5 is omitted in its preparation process, and Fe is not added. 3+ Solution and Ca 2+The solution underwent coordination and bridging reactions, but the shell layer did not undergo further stabilization and crosslinking. The remaining steps, including S1 core solution preparation, S2 emulsification, S3 inner shell deposition, S4 outer shell deposition, S6 centrifugation and washing, drying, and additive addition, were the same as in Example 1.

[0072] Comparative Example 3

[0073] This comparative example provides a microencapsulated composition using only 2-oxoglutaric acid as the core. Nicotinamide and γ-aminobutyric acid are not added to the core. The amount of 2-oxoglutaric acid used is the same as the mass of this component in Example 1 (0.0015), and any insufficient volume is made up with purified water to ensure that the total solution volume is consistent with that of Example 1.

[0074] After the core solution was prepared, emulsification, inner shell deposition, outer shell construction, and densification were carried out sequentially according to steps S2 to S6 of Example 1, without changing the shell material or process conditions. The final microcapsules were standard double-shell structure powders encapsulating a single active ingredient.

[0075] Comparative Example 4

[0076] This comparative example provides a microencapsulated composition prepared under conditions of insufficient emulsification, used to investigate changes in particle size distribution and zeta potential. The core composition and shell material are the same as in Example 1, but in step S2, the emulsification shear rate is reduced to 3000 r / min, the shearing time is shortened to 3 minutes, and the amount of Span-80 surfactant is adjusted to 0.2% (w / w), lower than the concentration set in Example 1.

[0077] The emulsion droplets obtained under these emulsification conditions have a wide droplet size distribution and poor interfacial stability, which directly affects the deposition quality of the inner and outer shells. Based on this, the inner shell deposition, outer shell construction, densification reaction, and post-treatment were carried out according to steps S3 to S6 of Example 1 to finally obtain the powder microcapsule composition.

[0078] To verify the comprehensive performance advantages of the microencapsulated active ingredient composition provided by the present invention, the samples prepared in Examples 1–3 and Comparative Examples 1–4 were systematically compared under the same experimental conditions, focusing on their core performance indicators such as particle size distribution, zeta potential, in vitro release behavior and storage stability.

[0079] Seven groups of samples were set up for the experiment, including Examples 1–3 and Comparative Examples 1–4. To enhance the statistical validity of the data, three parallel replicates (n=3) were prepared for each group of samples and tested separately. The final results are expressed as average values. All samples used the same batch of raw materials and were prepared by the same operator according to a unified procedure into microcapsule powder, dispersion, and topical emulsion.

[0080] The main instruments and equipment used in the experiment included: a high-shear emulsifier (for droplet preparation, with adjustable speed), a laser particle size analyzer (for determining D10, D50, and D90), a dynamic light scattering instrument (for Zeta potential analysis), a forced-air drying oven (temperature controlled not exceeding 40°C), an accelerated aging test chamber (45°C, light-proof and sealed conditions), and a high-performance liquid chromatograph (for quantification of active ingredients). Samples were dried, sealed, and stored uniformly, and tested simultaneously in batches.

[0081] The test metrics and methods are as follows:

[0082] (1) Particle size distribution: The particle size distribution was determined by a laser particle size analyzer. The dispersion medium was deionized water containing 0.05% (w / w) Tween-80. The sample concentration was 1.0 wt%. The particle size was measured after ultrasonic dispersion for 3 minutes. The D10, D50 and D90 values ​​were recorded.

[0083] (2) Zeta potential: measured by dynamic light scattering instrument, the dispersion medium was deionized water, the sample concentration was 1.0 wt%, and the test temperature was 25°C;

[0084] (3) Encapsulation efficiency: Accurately weigh the microcapsule dry powder, add ethanol / water (80 / 20, v / v) solution, sonicate for 10 minutes, filter through a 0.22 μm filter membrane, and quantitatively analyze the content of each component in the core using HPLC method. The encapsulation efficiency (%) is calculated by external standard method.

[0085] (4) HPLC analysis conditions: The chromatographic column was C18 (250 mm × 4.6 mm, 5 μm); mobile phase A was an aqueous solution containing 0.1% formic acid, and mobile phase B was acetonitrile; gradient program: 0–5 min to maintain 5% B, 5–20 min to linearly increase to 30% B, 20–25 min to maintain 30% B; flow rate 1.0 mL / min; column temperature 30°C; detection wavelength: 2-oxoglutaric acid 210 nm, nicotinamide 262 nm, GABA derivatized with o-phthalaldehyde (OPA) and detected at 338 nm; linear correlation coefficient R of the standard curves of each component 2 ≥0.999;

[0086] (5) In vitro release performance: The dialysis bag method (molecular weight cutoff 8–14 kDa) was used. The release medium was PBS buffer (pH 7.4) containing 0.5% Tween-80. The release was carried out at 37°C and 100 rpm with shaking. The volume of the release medium was more than 20 times the volume of the sample phase. Samples were taken at 0, 1, 2, 4, 8, 12, 24, 36, and 48 h, and an equal volume of fresh medium was added. The cumulative release rate (%) was determined by HPLC.

[0087] (6) Dispersion stability: The microcapsules were dispersed in deionized water at a concentration of 1.0 wt% and left to stand at 25°C for 72 hours. The results were observed for stratification or sedimentation. If necessary, the curve of the interface height change over time was recorded.

[0088] (7) Emulsion compatibility: Add the microcapsules to the aqueous phase of the O / W type emulsion according to the target ratio, stir at 40°C for 10–30 minutes, let stand for 72 hours and observe the appearance uniformity to check for flocculation or stratification.

[0089] (8) Storage stability: The microcapsule powder was stored at 45°C under light-proof and sealed conditions for 28 days. Samples were taken every 7 days, and the microcapsules were broken according to the encapsulation rate determination method. The content of active ingredients was detected by HPLC, and the activity retention rate (%) was calculated.

[0090] (9) Residual moisture: determined by Karl Fischer titration.

[0091] The catechin-modified chitosan used in the experiment was prepared using conventional methods in the field. 1 The degree of catechol substitution (DS) determined by H-NMR was 10%–20%; the acid group content of the acid copolymers Eudragit L100-55 and Eudragit S100 was quantified as 2.0–7.0 mmol / g according to the supplier's technical data or acid-base titration method; the residual moisture in the microcapsules was determined by Karl Fischer method.

[0092] The experimental results are shown in Tables 1 and 2.

[0093] Table 1. Detection results of microcapsule particle size, potential, and encapsulation efficiency.

[0094]

[0095] Table 2 Comparison of microcapsule release behavior, storage stability, and appearance evaluation

[0096]

[0097] A systematic comparative analysis of the experimental results of Examples 1-3 and Comparative Examples 1-4 reveals that the microencapsulated active ingredient composition provided by this invention exhibits significant technical advantages in terms of structural design, material selection, and process control. Specific technical effects are as follows:

[0098] First, the microcapsules prepared in the examples all adopted a "double-shell structure combined with Fe" 3+ / Ca 2+The "densification treatment" strategy achieved synergistic optimization of particle size control and colloidal stability. The average D50 particle size ranged from 1.3 to 4.6 μm, the D90 was less than 18 μm, the Zeta potential ranged from -26 mV to -17 mV, and the encapsulation efficiency was higher than 89%. In contrast, Comparative Example 1 (without shell construction) and Comparative Example 4 (insufficient emulsification conditions) showed significantly increased particle size and wider distribution, with Zeta potentials decreasing to -11 mV and below, indicating poor microcapsule dispersibility and a tendency to aggregate or settle. This verifies the crucial role of the double-shell structure and process parameter optimization in achieving microcapsule particle size uniformity and system stability.

[0099] Regarding in vitro release behavior, the sample examples exhibited good sustained-release characteristics, with a cumulative release rate of 30.8%–42.5% after 12 hours and 57.1%–69.0% after 24 hours, showing stable release curves. In contrast, comparative examples 1, 2, and 4 showed release rates exceeding 70% after 12 hours and exceeding 87% after 24 hours, exhibiting typical burst release phenomena with steeper release curves. These results indicate that the chitosan-dopamine composite layer and ionically cross-linked densified structure in the shell effectively delayed the diffusion of the active ingredient, achieving more controllable release behavior.

[0100] In accelerated storage stability tests, after 28 days of storage at 45°C, the retention rate of the active ingredient in the sample of the example remained at 88.9%–91.8%, indicating that the double-shell structure has a good barrier protection function. In contrast, the active ingredient retention rate of Comparative Example 3 (containing only a single active ingredient) decreased significantly due to the lack of composite core formulation and structural synergistic stabilization, reaching only 66.7% after 28 days. This comparison demonstrates that the present invention effectively inhibits oxidative degradation and component migration through the combination of multiple active ingredients and dual-structure isolation.

[0101] Furthermore, in practical O / W emulsion application systems, the microcapsules of the examples exhibited excellent dispersion stability and interfacial compatibility, showing no precipitation, flocculation, or stratification after 72 hours of standing. In contrast, Comparative Examples 1 and 4, due to incomplete structures or uncontrolled particle size, experienced particle aggregation, sedimentation, and even oil-water phase separation in the emulsion, affecting product appearance and user experience. Therefore, the microcapsule structure design of this invention not only improves its bulk performance but also significantly enhances its compatibility and application stability in complex formulation systems.

[0102] In summary, the microencapsulated active ingredient composition provided by this invention possesses multiple advantages, including tunable structure, controllable release, dispersion stability, and component protection. By constructing an inner-shell-outer-ion-densified composite structure and optimizing the ratio of the three active ingredients in the core, the overall performance of the microcapsules is significantly improved under conditions of high-temperature storage, complex interfaces, and long-term use. This technology is particularly suitable for topical preparations for skin barrier repair, anti-allergy soothing, and conditioning purposes, and possesses excellent inventiveness and industrial application potential.

[0103] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention.

Claims

1. An active ingredient microencapsulated composition characterized in that, The active ingredient microencapsulated composition comprises a capsule core and a capsule wall, the capsule core is composed of 2-oxoglutaric acid, nicotinamide and gamma-aminobutyric acid in a mass ratio of 0.000625-0.002:0.5-3.0:0.2-2.0, the capsule wall is a double-layer structure with an inner shell and an outer shell formed by interfacial deposition, wherein the inner shell is composed of an acidic copolymer, the outer shell is composed of a combination of polydopamine and catechol group modified chitosan, and is crosslinked by Fe 3+ coordinated with Ca 2+ ion bridging densification, and the volume distribution median particle size D50 of the active ingredient microencapsulated composition is 1.0-5.0 μm, the mass fraction of the capsule core is 20%-70%, and the residual moisture mass fraction is not more than 5%. The active ingredient microencapsulated composition is prepared by the following steps: S1, 2-oxoglutaric acid, nicotinamide and gamma-aminobutyric acid are dissolved in the water phase according to the mass ratio of 0.000625-0.002:0.5-3.0:0.2-2.0, and the pH is adjusted to 3.5-6.0 to obtain a capsule core solution; S2, the capsule core solution is added to the oil phase containing hydrophobic surfactant, and sheared at a speed of 12000 r / min for 1-3 min to prepare a W / O primary emulsion, and the primary emulsion is added to the water phase containing 0.5%-2.0% polyvinyl alcohol, and sheared at a speed of 6000-12000 r / min for 2-5 min to prepare a W / O / W secondary emulsion system; S3, an acidic copolymer solution is added to the secondary emulsion system to deposit and form an inner shell at the droplet interface, and aged for 5-20 min; S4, under the condition of Tris-HCl buffer, an outer shell material is added, and reacted at 25°C for 30-90 min to form an outer shell, and the Tris-HCl buffer has a pH of 8.2-8.8 and a concentration of 10-50 mmol / L; S5, add Fe first 3+ The solution is allowed to undergo a coordination reaction for 5-15 min, and then Ca is added 2+ The solution is allowed to undergo a bridging reaction for 10-30 min to achieve densification; S6, centrifugation or filtration washing, and drying at not more than 40°C to a residual moisture mass fraction of not more than 5% to obtain the target microencapsulated composition; The acid copolymer is Eudragit L100-55 or Eudragit S100, and the acid group content is 2.0-7.0 mmol / g.

2. The active ingredient microencapsulated composition according to claim 1, characterized in that, The capsule wall is a double-shell structure composed of an acid copolymer layer and a catechol group-containing layer, and a stable densification network is obtained after aging and metal ion treatment.

3. The active ingredient microencapsulated composition according to claim 1, wherein The Zeta potential of the active ingredient microencapsulated composition is-15 mV to-30 mV, and the volume distribution percentile particle size D90 is not more than 20 μm, and the composition contains fumed silica and polyethylene glycol as anti-caking and dispersion aids, and the total mass fraction is 0.1%-3.0%.

4. A process for the preparation of a microencapsulated composition of active ingredients, characterized in that, The following steps are included: S1, 2-oxoglutaric acid, nicotinamide and gamma-aminobutyric acid are dissolved in the water phase according to the mass ratio of 0.000625-0.002:0.5-3.0:0.2-2.0, and the pH is adjusted to 3.5-6.0 to obtain a capsule core solution; S2, the capsule core solution is added to the oil phase containing hydrophobic surfactant, and sheared at a speed of 12000 r / min for 1-3 min to prepare a W / O primary emulsion, and the primary emulsion is added to the water phase containing 0.5%-2.0% polyvinyl alcohol, and sheared at a speed of 6000-12000 r / min for 2-5 min to prepare a W / O / W secondary emulsion system; S3, an acidic copolymer solution is added to the secondary emulsion system to deposit and form an inner shell at the droplet interface, and aged for 5-20 min; wherein the acid copolymer is Eudragit L100-55 or Eudragit S100, and the acid group content is 2.0-7.0 mmol / g; S4, under the condition of Tris-HCl buffer solution, a polydopamine precursor solution and a catechol group modified chitosan solution are added, and reacted at 25°C for 30-90 min to form an outer shell, wherein the Tris-HCl buffer solution has a pH of 8.2-8.8 and a concentration of 10-50 mmol / L; S5, add Fe first 3+ The solution is allowed to undergo a coordination reaction for 5-15 min, and then Ca is added 2+ The solution is allowed to undergo a bridging reaction for 10-30 min to achieve densification; S6, centrifugation or filtration washing, and drying at not more than 40°C until the residual moisture mass fraction is not more than 5%, to obtain the target microencapsulated composition.

5. The preparation method according to claim 4, characterized in that, The hydrophobic surfactant in the oil phase is a sorbitan ester surfactant, and the amount is 0.05%-1.0% of the total mass of the system; the mass fraction of polyvinyl alcohol in the secondary emulsified water phase is 0.5%-2.0% as a protective colloid; the mass-volume concentration of the acidic copolymer solution is 0.5%-5.0%; and the mass-volume concentration of the catechol group modified chitosan solution or polydopamine precursor solution is 0.1%-2.0%.

6. The preparation method according to claim 4, characterized in that, The densification includes: first with 1.0-2.0 mmol / L Fe 3+ The surface coordination treatment is performed on the shell for 5-15 min, and then Ca 2+ The solution is used for bridging, and the Ca 2+ The solution is added in three stages with a concentration of 5 mmol / L, 15 mmol / L and 25 mmol / L, and each stage is maintained for 5-10 min.

7. A dispersion comprising the microencapsulated composition of active ingredient according to claim 1, characterized in that, The active ingredient microencapsulated composition is dispersed in water or a polyhydric alcohol-containing aqueous solution to form a suspension, emulsion or gel, and the mass fraction of the active ingredient microencapsulated composition in the dispersion is 0.1%-5.0%, and after low shear homogenization at 500-2000 r / min for 1-3 min, the volume distribution percentile particle size D90 of the system is not more than 20 μm.

8. Use of the active ingredient microencapsulated composition according to claim 1 for the preparation of a skin external preparation, characterized in that, The active ingredient microencapsulated composition is added to an aqueous phase or a water-in-oil matrix at a mass fraction of 0.1%-5.0%, and stirred at 25-40°C for 10-30 min to prepare the skin external preparation.

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