A highly stable lutein-zeaxanthin soft capsule and its preparation process

Abstract

This invention relates to a highly stable lutein-zeaxanthin soft capsule and its preparation process, belonging to the field of health product technology. The soft capsule comprises a shell and contents. The contents include core-shell structured composite coated particles and a plant oil carrier. The particles have a core-shell structure: the core is a microcapsule formed by emulsifying lutein and zeaxanthin with sodium octenyl succinate starch; the outer shell is a coating layer formed by in-situ deposition of zein on the surface of the core microcapsule using an antisolvent precipitation method. Natural antioxidants are dissolved in the plant oil carrier, spontaneously enriching in the oil phase region between the inner wall of the shell and the composite coated particles to form an interfacial antioxidant protective layer. The preparation process is carried out at low temperature, under nitrogen protection, and protected from light throughout. The gradient core-shell structure achieves stable protection in the stomach and targeted release into the intestine. Combined with interfacial antioxidant protection and comprehensive process protection, it improves the storage stability and bioavailability of the active ingredients. The product has no solvent residue and is safe for industrial production.

Description

Technical Field

[0001] This invention relates to the field of health product technology, and more particularly to a highly stable lutein-zeaxanthin soft capsule and its preparation process. Background Technology

[0002] Lutein and zeaxanthin are both natural fat-soluble carotenoids that protect the retina and relieve eye fatigue, and are widely used in the health food industry. However, their molecular structure contains multiple conjugated double bonds, making them chemically unstable and sensitive to light, heat, and oxygen. They are easily oxidized and degraded during processing and storage, leading to the loss of active ingredients. Furthermore, they are easily inactivated and decomposed in the acidic environment of the stomach, resulting in low intestinal absorption efficiency and making it difficult to fully exert their health benefits.

[0003] Existing technologies often employ simple mixtures or single coating materials to treat lutein and zeaxanthin, lacking a gradient protective structure. This results in poor oxygen and light barrier effects, easy detachment of the coating layer, and an inability to achieve gastric stability and targeted intestinal release. Furthermore, existing formulations often neglect the oxidation risks at the interface between the capsule and contents, and some products contain artificial synthetic pigments, posing safety hazards. The preparation process lacks a comprehensive low-temperature, low-oxygen, and light-protection system, leading to significant losses of active ingredients during processing and solvent residue issues, thus failing to meet the safety requirements for health food products.

[0004] In summary, existing technologies cannot simultaneously solve the technical challenges of poor stability, low bioavailability, and insufficient safety of lutein and zeaxanthin. Therefore, developing a lutein and zeaxanthin soft capsule with natural raw materials, high stability, and targeted intestinal release has significant practical importance and market value. Summary of the Invention

[0005] To address the aforementioned problems in the prior art, this invention provides a highly stable lutein-zeaxanthin soft capsule and its preparation process, solving issues such as easy oxidation of the active ingredient, instability in the stomach, interfacial oxidation, low bioavailability, and solvent residue.

[0006] The objective of this invention can be achieved through the following technical solutions: In one aspect, a highly stable lutein-zeaxanthin soft capsule is provided, comprising a capsule shell and contents filling the capsule shell. The contents comprise core-shell structured composite coated particles and a vegetable oil carrier; The core-shell structured composite coated particles include a core and an outer shell. The core is a core microcapsule formed by emulsifying sodium octenyl succinate starch with lutein and zeaxanthin. The outer shell is a coating layer formed by zein deposited on the surface of the core microcapsule. The plant oil carrier contains dissolved natural antioxidants.

[0007] Furthermore, the capsule shell is made from the following raw materials in parts by weight: 30-50 parts gelatin, 10-20 parts glycerin, 30-50 parts deionized water, and 0.1-1.0 parts titanium dioxide.

[0008] Furthermore, the mass ratio of lutein to zeaxanthin is 5~10:1.

[0009] Furthermore, in the core-shell structured composite coated particles, the total mass percentage of lutein and zeaxanthin is 10% to 20%, sodium octenyl succinate starch accounts for 45% to 55%, and zein accounts for 30% to 35%.

[0010] Furthermore, the vegetable oil carrier is selected from one or more of flaxseed oil, olive oil, sunflower seed oil, or wheat germ oil.

[0011] Furthermore, the natural antioxidant is selected from one or more of rosemary extract and tocopherol, and the amount added is 0.01% to 0.5% of the total mass of the contents.

[0012] Secondly, a method for preparing the soft capsules of the first aspect is provided, comprising the following steps: (1) Lutein, zeaxanthin and sodium octenyl succinate starch were added to deionized water and homogenized by high-speed shearing under nitrogen protection to form an emulsion; (2) Slowly add a zein solution prepared with 70%~80% (v / v) ethanol to the emulsion obtained in step (1), control the dropping rate and stirring speed, so that the zein is deposited on the surface of the core microcapsule to form a coating layer, and then remove the ethanol by vacuum distillation to obtain core-shell structure composite coated particles. (3) Disperse the core-shell structure composite coated particles obtained in step (2) in a vegetable oil carrier pre-dissolved with natural antioxidants, stir evenly, and obtain the contents oil phase; (4) Mix gelatin, glycerin and deionized water, heat to dissolve, cool and add titanium dioxide, stir evenly and degas to obtain capsule shell solution; (5) Under conditions of nitrogen protection and light protection, the oil phase of the contents and the capsule shell are granulated, shaped, and dried at low temperature to obtain high-stability lutein zeaxanthin soft capsules.

[0013] Furthermore, in step (1), the homogenization speed is 2000~3000 r / min, the emulsification time is 10~15 min, and the emulsification temperature is 25℃~35℃.

[0014] Furthermore, in step (2), the dropping rate is 3~5 mL / min, the stirring speed is 200~300 r / min, and the concentration of the zein solution is 5%~10% w / v.

[0015] Furthermore, the core-shell structure composite coated particles are prepared by low-temperature spray drying, wherein the inlet air temperature of the low-temperature spray drying is 60~80℃, the outlet air temperature is 40~50℃, and the moisture content of the resulting particles is ≤5%.

[0016] The beneficial effects of this invention are as follows: (1) The inner layer of sodium octenyl succinate starch of the present invention is amphiphilic, which can stabilize the emulsified lutein and zeaxanthin to form a uniformly dispersed core microcapsule and prevent aggregation and precipitation; the outer layer of zein is processed with ethanol. In an aqueous system, antisolvent precipitation forms a dense, hydrophobic barrier layer in situ. The outer zein layer forms a stable physical barrier in the acidic environment of gastric juice, effectively preventing gastric acid from contacting the inner core microcapsules. The inner sodium octenyl succinate maintains the stability of its emulsion structure in an acidic environment. Together, they ensure a high retention rate of the active ingredients in the stomach. Upon entering the alkaline environment of the intestine, the outer zein layer gradually dissolves and disintegrates, while the inner core microcapsules release lutein and zeaxanthin. The active ingredients form mixed micelles under the action of bile salts, promoting absorption and improving bioavailability.

[0017] (2) In this invention, natural antioxidants are dissolved in a vegetable oil carrier. Due to their lipid solubility and concentration diffusion equilibrium, antioxidant molecules will spontaneously migrate to the capsule. The contents are enriched at the interface, forming an antioxidant protective layer in the oil phase region between the inner wall of the capsule and the core-shell structure composite coated particles. This precisely blocks oxygen penetration at the interface, inhibits interface oxidation and degradation of active ingredients, and significantly improves storage stability. Titanium dioxide is added to the capsule shell to provide physical light shielding, forming a dual protection system with the interface antioxidant system. The formula does not use artificial synthetic pigments, making it natural and safe, meeting the needs of health food consumers.

[0018] (3) In view of the heat-sensitive, oxygen-sensitive and photosensitizing properties of lutein and zeaxanthin, the present invention adopts low-temperature emulsification, pelleting and drying throughout the process to reduce the thermal degradation rate. Nitrogen protection is used in key processes such as emulsification, pelleting and drying to inhibit oxidation from the source and avoid loss of active ingredients during processing. The entire process is protected from light and combined with a light-shielding shell to further reduce the risk of photodegradation and achieve stable protection throughout the entire processing process.

[0019] (4) The gradient core-shell structure, the interface antioxidant system, and the low-temperature nitrogen protection and light-shielding process of this invention work together to construct a full life-cycle protection system from processing and storage to release in vivo. The gradient structure is responsible for gastric protection, intestinal release, and long-term oxygen barrier; the interface antioxidant is responsible for inhibiting interface oxidation; and the process protection is responsible for reducing processing losses, together achieving the simultaneous improvement of product stability, bioavailability, and food safety. Detailed Implementation

[0020] To further illustrate the technical means and effects of the present invention in achieving the intended purpose, the following detailed description of the specific implementation methods, structures, features and effects of the present invention, in conjunction with preferred embodiments, is provided below.

[0021] Example 1 Contents formulation: (1) Core-shell structure composite coated particles: 4.5 parts lutein, 0.5 parts zeaxanthin; 15 parts sodium octenyl succinate starch, 10.5 parts zein.

[0022] (2) Vegetable oil carrier: 20 parts olive oil; 0.05 parts rosemary extract.

[0023] Capsule formulation: 40 parts gelatin, 15 parts glycerin, 40 parts deionized water, 0.5 parts titanium dioxide.

[0024] Preparation process (1) Under nitrogen protection, lutein, zeaxanthin and sodium octenyl succinate starch were added to an appropriate amount of deionized water and homogenized by high-speed shearing at 2500 r / min. The emulsification temperature was 30℃ and the emulsification time was 12 min to form a uniform emulsion.

[0025] (2) Dissolve zein in 75% (v / v) ethanol to prepare a zein solution with a concentration of 7.5% (w / v); add it slowly dropwise to the emulsion obtained in step (1) at a stirring speed of 250 r / min at a speed of 4 mL / min, so that zein is deposited on the surface of the core microcapsule to form a coating layer. Then, remove the ethanol by vacuum distillation, spray dry at low temperature, control the inlet air temperature to 70℃ and the outlet air temperature to 45℃, and obtain core-shell structure composite coated particles with a moisture content of ≤5%.

[0026] (3) Disperse the core-shell structured composite coated particles obtained in step (2) in olive oil containing rosemary extract and stir evenly to obtain the contents oil phase.

[0027] (4) Mix gelatin, glycerin and deionized water, heat to 60°C to form a sol, cool to 45°C and add titanium dioxide, stir evenly and degas under vacuum for 10 minutes to obtain a uniform capsule shell solution without bubbles.

[0028] (5) Under the conditions of nitrogen protection and light protection at 30°C, the oil phase of the contents and the capsule shell were granulated; the mixture was fixed at 20°C for 4 hours and dried at 22°C for 10 hours to obtain high-stability lutein zeaxanthin soft capsules.

[0029] Example 2 Contents formulation: (1) Core-shell structure composite coated particles: 3 parts lutein, 0.3 parts zeaxanthin; 16.5 parts sodium octenyl succinate starch and 10.5 parts zein.

[0030] (2) Plant oil carrier: 15 parts flaxseed oil and 0.012 parts rosemary extract.

[0031] Capsule formulation: 30 parts gelatin, 10 parts glycerin, 30 parts deionized water, 0.1 parts titanium dioxide.

[0032] Preparation process (1) Add lutein, zeaxanthin and sodium octenyl succinate starch to an appropriate amount of deionized water, and homogenize by high-speed shearing at 2000 r / min under nitrogen protection. The emulsification temperature is 25℃ and the emulsification time is 10 min to form a uniform emulsion.

[0033] (2) Dissolve zein in 70% (v / v) ethanol to prepare a zein solution with a concentration of 5% (w / v); add it slowly dropwise to the emulsion obtained in step (1) at a stirring speed of 200 r / min at a speed of 3 mL / min, so that zein is deposited on the surface of the core microcapsule to form a coating layer. Then, remove the ethanol by vacuum distillation, spray dry at low temperature, control the inlet air temperature to 62℃ and the outlet air temperature to 41℃, and obtain core-shell structure composite coated particles with a moisture content of ≤5%.

[0034] (3) Disperse the core-shell structured composite coated particles obtained in step (2) in flaxseed oil containing rosemary extract, stir evenly, and obtain the contents oil phase.

[0035] (4) Mix gelatin, glycerin and deionized water, heat to 60°C to sol, cool to 40°C and add titanium dioxide, stir evenly and degas under vacuum for 8 minutes to obtain capsule shell solution.

[0036] (5) Under nitrogen protection and light protection at 20°C, the oil phase of the contents and the capsule shell are granulated together; the mixture is set at 18°C ​​for 3 hours and dried at 20°C for 8 hours to obtain the finished product.

[0037] Example 3 Contents formulation: (1) Core-shell structure composite coated particles: 6 parts lutein, 0.6 parts zeaxanthin, 15 parts sodium octenyl succinate starch, and 9 parts zein.

[0038] (2) Vegetable oil carrier: 25 parts wheat germ oil and 0.175 parts tocopherol.

[0039] Capsule formulation: 50 parts gelatin, 20 parts glycerin, 50 parts deionized water, 1.0 part titanium dioxide.

[0040] Preparation process (1) Add lutein, zeaxanthin and sodium octenyl succinate starch to an appropriate amount of deionized water, and homogenize by high-speed shearing at 3000 r / min under nitrogen protection. The emulsification temperature is 35℃ and the emulsification time is 15 min to form a uniform emulsion.

[0041] (2) Dissolve zein in 80% (v / v) ethanol to prepare a 10% (w / v) zein solution; add it slowly dropwise to the emulsion obtained in step (1) at a stirring speed of 300 r / min at a speed of 5 mL / min, so that zein is deposited on the surface of the core microcapsule to form a coating layer. Then, remove the ethanol by vacuum distillation, spray dry at low temperature, control the inlet air temperature to 79℃ and the outlet air temperature to 50℃, and obtain core-shell structure composite coated particles with a moisture content of ≤5%.

[0042] (3) Disperse the core-shell structured composite coated particles obtained in step (2) in wheat germ oil containing tocopherol, stir evenly, and obtain the contents oil phase.

[0043] (4) Mix gelatin, glycerin and deionized water, heat to 60°C to form a sol, cool to 50°C and add titanium dioxide, stir evenly and degas under vacuum for 12 minutes to obtain capsule shell solution.

[0044] (5) Under nitrogen protection and light protection at 35°C, the oil phase of the contents and the capsule shell are granulated together; the mixture is set at 22°C for 5 hours and dried at 25°C for 12 hours to obtain the finished product.

[0045] Comparative Example 1 Based on Example 1, no sodium octenyl succinate starch, zein, or natural antioxidants were added; the preparation process involved no low-temperature control, no nitrogen protection, and no light-protection operation; lutein, zeaxanthin, and oil phase were directly mixed as the contents and then pressed with capsule shell gelatin to obtain soft capsules.

[0046] Comparative Example 2 Based on Example 1, no coating treatment was performed, and the surfaces of lutein and zeaxanthin were not coated with sodium octenyl succinate starch and zein. Other conditions were the same as in Example 1.

[0047] Comparative Example 3 Based on Example 1, only sodium octenyl succinate starch was coated on the surface of lutein and zeaxanthin, without coating zein, and no gradient bilayer structure was formed. Other conditions were the same as in Example 1.

[0048] Comparative Example 4 Based on Example 1, only zeaxanthin was coated on the surface of lutein and zeaxanthin, without coating sodium octenyl succinate starch, and no gradient bilayer structure was formed. Other conditions were the same as in Example 1.

[0049] Comparative Example 5 Based on Example 1, no natural antioxidants were added to the vegetable oil carrier, and all other conditions were the same as in Example 1.

[0050] Comparative Example 6 Based on Example 1, the preparation process was carried out without low temperature control, nitrogen protection, or light protection, while other conditions were the same as in Example 1.

[0051] Comparative Example 7 Based on Example 1, the low-temperature control was eliminated throughout the preparation process, while other conditions remained the same as in Example 1.

[0052] Comparative Example 8 Based on Example 1, the preparation process was carried out without nitrogen protection, and other conditions were the same as in Example 1.

[0053] Comparative Example 9 Based on Example 1, the entire preparation process was carried out without light protection, and other conditions were the same as in Example 1.

[0054] Effect verification For the finished products of the above embodiments and comparative examples, the core indicators were tested, and the testing methods for each indicator are as follows. Zeaxanthin and lutein have similar structures and stability, and their test results show a consistent trend with lutein; therefore, lutein was used as a representative for testing. Simulated lutein retention rate in gastric juice The determination of dissolution and release was performed according to Method II of General Chapter 0931, Part IV, of the 2020 edition of the Chinese Pharmacopoeia, and in conjunction with an international in vitro food digestion model: 0.5 g of sample contents were added to 500 mL of simulated gastric juice (pH 1.2) and incubated at 37°C for 2 h; the supernatant was discarded by centrifugation, and the precipitate was used to extract lutein, which was then determined by HPLC. Retention rate = lutein content in precipitate / initial lutein content × 100%.

[0055] Simulated intestinal fluid lutein release rate The precipitate obtained after incubation with gastric juice and centrifugation was transferred to 500 mL of simulated intestinal fluid (pH 7.4) and incubated at 37°C for 2 h. The supernatant was then centrifuged and the lutein content was determined. Release rate = lutein content in supernatant / initial lutein content × 100%.

[0056] Lutein retention rate According to GB 5009.83-2016 standard, each sample was placed in a constant temperature and humidity chamber with a set temperature of 40±1℃ and relative humidity of 75±5% and stored for 3 months. The lutein content in the samples before and after storage was measured. Lutein retention rate = (lutein content after storage / initial lutein content before storage) × 100%.

[0057] The test for ethanol residue was conducted in accordance with GB 5009.225-2016 standard, and the ethanol content was determined by headspace gas chromatography.

[0058] Table 1. Test results of performance indicators for the examples and comparative examples.

[0059] The results showed that Examples 1-3 exhibited superior overall performance, with significantly better lutein retention rates in simulated gastric juice, lutein release rates in simulated intestinal juice, and lutein preservation rates compared to the comparative examples. This indicates that the gradient core-shell structure, the interfacial antioxidant system, and the continuous low-temperature nitrogen protection and light-shielding process synergistically improved the gastric stability, intestinal release efficiency, and storage stability of lutein. Furthermore, ethanol was only used as a dissolving agent for zein and evaporated after the entire low-temperature drying process. Compared to the examples, Comparative Examples 2-4 demonstrate that the double-layer gradient coating structure is an important condition for achieving stable protection in the stomach and efficient release in the intestine; Comparative Example 5 shows that natural antioxidants can inhibit interfacial oxidation and improve storage stability without significantly affecting gastrointestinal release behavior; Comparative Examples 6-9 demonstrate that the absence of any one of the conditions of low temperature, low oxygen, or light protection will cause degradation of the active ingredient, and the synergistic protective effect of the three is better than that of any single measure.

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A highly stable lutein-zeaxanthin soft capsule, comprising a capsule shell and contents filled within the capsule shell, characterized in that: The contents comprise core-shell structured composite coated particles and a vegetable oil carrier; The core-shell structured composite coated particles include a core and an outer shell. The core is a core microcapsule formed by emulsifying sodium octenyl succinate starch with lutein and zeaxanthin. The outer shell is a coating layer formed by zein deposited on the surface of the core microcapsule. The plant oil carrier contains dissolved natural antioxidants.

2. The soft capsule according to claim 1, characterized in that, The capsule shell is made from the following raw materials in parts by weight: 30-50 parts gelatin, 10-20 parts glycerin, 30-50 parts deionized water, and 0.1-1.0 parts titanium dioxide.

3. The soft capsule according to claim 1, characterized in that, The mass ratio of lutein to zeaxanthin is 5~10:

1.

4. The soft capsule according to claim 1, characterized in that, In the core-shell structured composite coated particles, the total mass percentage of lutein and zeaxanthin is 10% to 20%, sodium octenyl succinate starch accounts for 45% to 55%, and zein accounts for 30% to 35%.

5. The soft capsule according to claim 1, characterized in that, The vegetable oil carrier is selected from one or more of flaxseed oil, olive oil, sunflower seed oil, or wheat germ oil.

6. The soft capsule according to claim 1, characterized in that, The natural antioxidant is selected from one or more of rosemary extract and tocopherol, and the amount added is 0.01% to 0.5% of the total mass of the contents.

7. A method for preparing the soft capsules according to any one of claims 1 to 6, characterized in that, Includes the following steps: (1) Lutein, zeaxanthin and sodium octenyl succinate starch were added to deionized water and homogenized by high-speed shearing under nitrogen protection to form an emulsion; (2) Slowly add a zein solution prepared with 70%~80% (v / v) ethanol to the emulsion obtained in step (1), control the dropping rate and stirring speed, so that the zein is deposited on the surface of the core microcapsule to form a coating layer, and then remove the ethanol by vacuum distillation to obtain core-shell structure composite coated particles. (3) Disperse the core-shell structure composite coated particles obtained in step (2) in a vegetable oil carrier pre-dissolved with natural antioxidants, stir evenly, and obtain the contents oil phase; (4) Mix gelatin, glycerin and deionized water, heat to dissolve, cool and add titanium dioxide, stir evenly and degas to obtain capsule shell solution; (5) Under conditions of nitrogen protection and light protection, the oil phase of the contents and the capsule shell are granulated, shaped, and dried at low temperature to obtain high-stability lutein zeaxanthin soft capsules.

8. The preparation method according to claim 7, characterized in that, In step (1), the homogenization speed is 2000~3000 r / min, the emulsification time is 10~15 min, and the emulsification temperature is 25℃~35℃.

9. The preparation method according to claim 7, characterized in that, In step (2), the dropping rate is 3~5 mL / min, the stirring speed is 200~300 r / min, and the concentration of the zein solution is 5%~10% w / v.

10. The preparation method according to claim 7, characterized in that, The core-shell structured composite coated particles are prepared by low-temperature spray drying. The inlet air temperature of the low-temperature spray drying is 60~80℃, the outlet air temperature is 40~50℃, and the moisture content of the resulting particles is ≤5%.

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