A method for efficiently extracting and purifying zeaxanthin dipalmitate from lycium barbarum

Abstract

The application discloses a method for efficiently extracting and purifying zeaxanthin dipalmitate from wolfberry, which comprises the following steps: pretreating wolfberry raw materials by removing sugar, extracting by a subcritical fluid, purifying by two-stage molecular distillation, and crystallizing by a selective solvent. The method effectively solves the problem of caking in the processing of wolfberry raw materials with high sugar content, realizes efficient extraction and high-purity preparation of zeaxanthin dipalmitate by means of an optimized process combination, and the purity of the product can reach more than 90%. Compared with traditional methods, the method is simple in process, low in cost, and friendly to the environment, is suitable for industrialized production, and has important application value in the fields of functional food, health products and cosmetics.

Description

Technical Field

[0001] This invention belongs to the field of natural product extraction, separation and purification technology, specifically relating to an industrial method for efficiently extracting and purifying zeaxanthin dipalmitate from wolfberry raw materials. Background Technology

[0002] Goji berries (Lycium barbarum L.) are a traditional Chinese medicinal and edible plant, rich in nutrients. Recent studies have found that in addition to active ingredients such as goji polysaccharides and betaine, goji berries also contain a high amount of zeaxanthin dipalmitate. This compound is the esterified form of zeaxanthin, exhibiting better lipid solubility and stability. It demonstrates significant biological activity in retinal protection, antioxidation, and anti-inflammation, and has important application value in functional foods, health products, and pharmaceuticals.

[0003] Currently, research on the extraction of active ingredients from wolfberry mainly focuses on wolfberry polysaccharides, total flavonoids, and free zeaxanthin. Research on the extraction and purification of zeaxanthin dipalmitate from wolfberry is relatively limited. In existing technologies, CN102887847A discloses a method for extracting zeaxanthin using molecular distillation and simulated moving bed technology; however, this method targets free zeaxanthin and requires expensive simulated moving bed equipment, making it complex and costly. CN104774690B discloses a method for preparing wolfberry essential oil using subcritical extraction and molecular distillation, but the target product is wolfberry essential oil, not the specific zeaxanthin dipalmitate. Furthermore, wolfberry raw materials contain a large amount of sugars, which easily clump during traditional solvent extraction, leading to low extraction efficiency and difficulties in subsequent processing.

[0004] In existing technologies, supercritical carbon dioxide extraction has been attempted to extract carotenoids from wolfberry. For example, Chinese patent document CN106349136A discloses a method for extracting zeaxanthin and its derivatives from wolfberry. This method first pre-treats the wolfberry to reduce its sugar and moisture content by soaking it in warm water. Then, the dried and pulverized raw material is placed in a supercritical CO2 extraction device and extracted for 3 hours at 35–45°C and 35–45 MPa. The extract collected within 0.6–3 hours yields a mixture of carotenoids, primarily zeaxanthin dipalmitate, with a purity exceeding 80%. Although CN106349136A claims to achieve solvent-free extraction throughout the entire process, its method still has significant limitations: First, supercritical CO2 extraction requires extremely high equipment pressure resistance and consumes a lot of energy. Furthermore, it is prone to equipment blockage and efficiency reduction in high-sugar, high-oil, and high-moisture wolfberry raw materials, hindering its feasibility and economic viability for industrial-scale production. Second, this method only achieves preliminary enrichment through a single extraction step, and the resulting product is still a mixture of various carotenoids. The purity limit of zeaxanthin dipalmitate is approximately 80%, which is insufficient to meet the quality control requirements for high-purity pharmaceutical or high-end health product raw materials. Third, due to the limited reduction in sugar content, the pretreated wolfberry residue still suffers from clumping, compaction, and difficulty in being discharged from the extraction vessel during subsequent processing, affecting production continuity and material utilization.

[0005] Currently, there is a lack of efficient, economical, and industrially suitable methods for extracting and purifying zeaxanthin dipalmitate from wolfberry. Existing technologies either target different products, involve complex and costly processes, or present challenges in raw material processing. Therefore, developing a new method that can solve the problem of processing high-sugar wolfberry raw materials while achieving efficient extraction and purification of zeaxanthin dipalmitate is of significant practical importance. Summary of the Invention

[0006] The technical problem this invention aims to solve is to overcome the shortcomings of existing technologies and provide a method for the efficient extraction and purification of zeaxanthin dipalmitate from wolfberry. This method effectively solves the problem of clumping in high-sugar wolfberry raw materials during the extraction process. Simultaneously, through optimized process combinations, it achieves high-purity and high-yield preparation of zeaxanthin dipalmitate. Furthermore, the process is simple, low-cost, and suitable for industrial production.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0008] A method for efficiently extracting and purifying zeaxanthin dipalmitate from wolfberry, characterized by comprising the following steps:

[0009] (1) Pretreatment of wolfberry raw materials: wolfberry fruit or wolfberry residue is treated with warm water or low concentration ethanol aqueous solution to remove sugar, and then centrifuged to dehydrate to obtain pretreated wolfberry.

[0010] (2) Subcritical fluid extraction: Subcritical butane or subcritical dimethyl ether is used as the extractant to perform high-shear extraction on pretreated wolfberry. The extraction pressure is 0.3-0.6 MPa, the extraction temperature is 40-55℃, and the extraction time is 10-60 minutes to obtain wolfberry oleoresin containing zeaxanthin dipalmitate.

[0011] (3) Two-stage molecular distillation purification:

[0012] First-stage molecular distillation: The wolfberry oleoresin is distilled at a temperature of 100-130℃ and a vacuum of 1-10Pa to remove light component impurities and collect the heavy phase.

[0013] Second-stage molecular distillation: The heavy phase obtained from the first-stage distillation is distilled at a temperature of 170-190℃ and a vacuum of 0.1-2Pa to collect the fraction rich in zeaxanthin dipalmitate.

[0014] (4) Selective solvent crystallization: The fraction obtained from the second molecular distillation is dissolved in acetone, n-hexane is added, and the mixture is allowed to stand at 0-10℃ to crystallize. After filtration, the crystals are washed with a pre-cooled acetone-n-hexane mixed solvent and dried under vacuum to obtain high-purity zeaxanthin dipalmitate.

[0015] Preferably, the sugar removal process in step (1) uses warm water at 40-60°C or an aqueous solution of ethanol with a volume fraction of 30-50%, with a material-to-liquid ratio of 1:3-1:8 (w / v) and a processing time of 20-60 minutes.

[0016] Preferably, the subcritical fluid extraction in step (2) uses butane as the extractant, the extraction pressure is 0.3-0.5 MPa, the extraction temperature is 45-50℃, the number of extractions is 2-3, and the extraction time is 20-40 minutes.

[0017] Preferably, in step (3), the vacuum degree of the first-stage molecular distillation is 2-5 Pa and the temperature is 110-120℃; the vacuum degree of the second-stage molecular distillation is 0.5-1.5 Pa and the temperature is 175-185℃.

[0018] Preferably, the volume ratio of acetone to n-hexane in step (4) is 1:1-1:4, the crystallization temperature is 2-8℃, and the crystallization time is 6-24 hours.

[0019] Beneficial effects of the present invention

[0020] 1. This invention is the first to specifically extract and purify zeaxanthin dipalmitate from wolfberry, solving the processing problem of high-sugar raw materials through process innovation and achieving efficient enrichment of the target component;

[0021] 2. By combining the processes of "subcritical extraction → two-stage molecular distillation → selective solvent crystallization", the advantages of each unit operation are fully utilized: subcritical extraction is mild and efficient, and maintains the activity of components; two-stage molecular distillation achieves preliminary separation and enrichment; selective solvent crystallization achieves the final high-purity preparation.

[0022] 3. Compared with the prior art, the present invention avoids the use of expensive chromatographic equipment (such as simulated moving bed), reducing equipment investment and operating costs; at the same time, it avoids chemical treatments such as strong alkali saponification that may damage the target components, thus maintaining the natural properties of the product;

[0023] 4. The process conditions of this invention are mild, the operation is simple, the solvent can be recycled, it is environmentally friendly, and it is suitable for large-scale industrial production.

[0024] 5. The zeaxanthin dispalmitate prepared by this method can achieve a purity of over 90%, with high yield and stable product quality, meeting the needs of the high-end market. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the process flow of the present invention;

[0026] Figure 2 The HPLC chromatogram of zeaxanthin dipalmitate prepared in Example 1; Detailed Implementation

[0027] The present invention will be further described in detail below with reference to the embodiments, but the scope of protection of the present invention is not limited thereto.

[0028] Example 1

[0029] A method for efficiently extracting and purifying zeaxanthin dipalmitate from wolfberry, the specific steps of which are as follows:

[0030] (1) Pretreatment of raw wolfberry: Take 1 kg of dried Ningxia wolfberry fruit, add 5 L of 50℃ warm water, stir and wash for 30 minutes, and centrifuge. Repeat the washing once.

[0031] (2) Subcritical extraction: Pretreated wolfberries were placed in a 5L subcritical extraction vessel and extracted with butane as the extractant at a high shear rate of 0.7MPa and 48℃ for 30 minutes. The extract was collected. The extraction was repeated once, and the extracts were combined. The extract was desolvated under reduced pressure at 45℃ to obtain 125g of wolfberry oleoresin.

[0032] (3) First-stage molecular distillation: The wolfberry oleoresin was added to the molecular distillation apparatus and distilled at a temperature of 115℃, a vacuum of 3Pa, a feed rate of 1.5mL / min, and a scraper rotation speed of 300r / min to remove light components (mainly residual solvents, free fatty acids, etc.) and collect 98g of heavy phase.

[0033] (4) Second stage molecular distillation: The first stage distillation heavy phase was distilled at a temperature of 180℃, a vacuum of 1Pa, a feed rate of 1.0mL / min, and a scraper rotation speed of 300r / min, and 45g of the distillate was collected.

[0034] (5) Selective solvent crystallization: 45 g of the second-stage distillate was added to a 250 mL round-bottom flask, along with 90 mL of acetone, and heated to 45 °C to dissolve. 180 mL of n-hexane (acetone:n-hexane = 1:2, v / v) was slowly added, and the mixture was stirred until homogeneous. The temperature was then lowered to 5 °C at a rate of 0.5 °C / min, and the mixture was allowed to stand for crystallization for 12 hours. The crystals were filtered, and washed twice with a pre-cooled acetone-n-hexane mixture (1:2, v / v, 50 mL). The crystals were then vacuum-dried at 35 °C for 6 hours to obtain 21.5 g of orange-red crystalline powder.

[0035] Product testing:

[0036] The HPLC chromatogram of zeaxanthin dipalmitate is as follows: Figure 2 As shown.

[0037] HPLC purity: 92.3%

[0038] Yield (based on wolfberry raw material): 2.15%

[0039] Melting point: 88-92℃

[0040] UV-Vis characteristic absorption peaks: 445nm, 472nm

[0041] Example 2

[0042] It is basically the same as Example 1, except that:

[0043] (1) The raw material of wolfberry is the residue after wolfberry juice is extracted, and the amount used is 2kg;

[0044] (2) The sugar removal treatment used 40% ethanol aqueous solution, with a volume of 6L, a temperature of 55℃, and a time of 40 minutes;

[0045] (3) Subcritical extraction pressure 0.35MPa, temperature 50℃, extraction 3 times, 30 minutes each time;

[0046] (4) The first-stage molecular distillation temperature is 120℃ and the vacuum degree is 2.5Pa;

[0047] (5) The second-stage molecular distillation temperature was 178℃ and the vacuum degree was 0.8Pa;

[0048] (6) The ratio of the crystallization solvent is acetone: n-hexane = 1:3 (v / v), and the crystallization temperature is 3℃.

[0049] Product testing:

[0050] HPLC purity: 91.8%

[0051] Yield (based on wolfberry residue): 1.85%

[0052] Melting point: 87-91℃

[0053] Example 3

[0054] It is basically the same as Example 1, except that:

[0055] (1) The subcritical extractant is dimethyl ether;

[0056] (2) The temperature of the first-stage molecular distillation is 110℃ and the vacuum degree is 4Pa;

[0057] (3) The second-stage molecular distillation temperature is 182℃ and the vacuum degree is 1.2Pa;

[0058] (4) The ratio of the crystallization solvent is acetone: n-hexane = 1:1.5 (v / v), and the crystallization temperature is 8℃.

[0059] Product testing:

[0060] HPLC purity: 90.7%

[0061] Yield (based on wolfberry raw material): 2.02%

[0062] Melting point: 89-93℃

[0063] Comparative Example 1 (without sugar removal treatment)

[0064] Referring to Example 1, but without performing the desugaring treatment in step (1), the dried and pulverized wolfberry raw material was directly subjected to subcritical extraction.

[0065] Experimental Procedure: 1 kg of dried and pulverized wolfberry raw material was directly subjected to subcritical extraction. During the extraction process, it was found that due to the high sugar content of wolfberry, the material in the extraction vessel severely agglomerated after extraction, forming hard lumps that could not be discharged smoothly. After forced discharge, some material still adhered to the inner wall of the equipment and required manual cleaning. Ultimately, only 68 g of wolfberry oleoresin was obtained (far lower than the 125 g in Example 1). Subsequent steps were performed as in Example 1.

[0066] result:

[0067] Final product yield: 8.2g (only 38% of Example 1)

[0068] Product purity: 83.5%

[0069] The process is severely clogged and is unsuitable for continuous production.

[0070] Comparative Example 2 (Single-stage molecular distillation)

[0071] Referring to Example 1, but changing the two-stage molecular distillation to single-stage molecular distillation: the wolfberry oleoresin was directly subjected to a single molecular distillation at 180°C and a vacuum of 1 Pa, and the fraction was collected.

[0072] result:

[0073] Distillate collected: 58g

[0074] Zeaxanthin dispalmitate content in the fraction (HPLC): 67.2%

[0075] The final product purity after crystallization is 85.1%.

[0076] Product yield: 1.42%

[0077] Comparative Example 3 (refer to method CN102887847A)

[0078] The method disclosed in CN102887847A was used to extract zeaxanthin (non-esterified form), and its application to the extraction of zeaxanthin dipalmitate was attempted.

[0079] Specific steps:

[0080] (1) The wolfberry raw material was extracted three times with 95% ethanol, the extracts were combined and concentrated under reduced pressure;

[0081] (2) The concentrate was dissolved in petroleum ether and extracted with 50% ethanol aqueous solution;

[0082] (3) The ethanol layer is concentrated and then subjected to molecular distillation;

[0083] (4) Purification was carried out using simulated moving bed chromatography.

[0084] result:

[0085] The final product mainly consists of free zeaxanthin, with zeaxanthin dipalmitate content less than 20%.

[0086] The total cost is about 3 times higher than that of this invention.

[0087] The process is complex and the operation is difficult.

[0088] Comparative Example 4 (Different Crystallization Solvent Systems)

[0089] Refer to Example 1, but step (5) uses a different crystallization solvent system:

[0090] Group A: Recrystallization using only acetone

[0091] Group B: Acetone:Ethanol = 1:1 (v / v)

[0092] Group C: Acetone:Methanol = 1:1 (v / v)

[0093] result:

[0094] Group A: Low crystallization yield (35%), purity 88.7%.

[0095] Group B: The product has a dark color, many impurities, and a purity of 82.3%.

[0096] Group C: Almost no crystallization, extremely low recovery rate.

[0097] Comparative Example 5 (Traditional Saponification Method)

[0098] Referring to Example 1, but with the addition of an alkaline saponification step before molecular distillation: 5% KOH-ethanol solution was added to wolfberry oleoresin, refluxed at 80°C for 1 hour, and then extracted with n-hexane.

[0099] result:

[0100] Zeaxanthin dipalmitate is largely broken down into free zeaxanthin.

[0101] The content of the target substance in the final product is less than 30%.

[0102] The product's color and texture do not meet the requirements.

[0103] Experimental Data Summary and Analysis

[0104] Table 1: Comparison of process effects between each embodiment and the comparative example

[0105] experimental group Raw material usage (kg) Oleoresin yield (g) Final product quantity (g) Product purity (%) Total yield (%) Process Evaluation Example 1 1.0 125 21.5 92.3 2.15 excellent Example 2 2.0 235 37.0 91.8 1.85 excellent Example 3 1.0 118 20.2 90.7 2.02 good Comparative Example 1 1.0 68 8.2 83.5 0.82 Poor (severe clumping) Comparative Example 2 1.0 125 14.2 85.1 1.42 Medium (low purity) Comparative Example 3 1.0 - Approximately 5.0 <20 <0.5 Poor (few target objects) Comparative Example 4A 1.0 125 7.5 88.7 0.75 Poor (low yield) Comparative Example 5 1.0 125 3.1 <30 <0.3 Poor (severe decomposition)

[0106] The desugar pretreatment is a key innovative step in the process system of this invention. Comparative analysis of Example 1 and Comparative Example 1 shows a significant improvement in efficiency. The oleoresin yield increased from 68g to 125g, an increase of 83.8%; the final product yield increased from 8.2g to 21.5g, an increase of 162.2%; and the total yield increased from 0.82% to 2.15%, also achieving a 162.2% increase. These data fully demonstrate that the desugar pretreatment not only solves the clumping problem of high-sugar wolfberry raw materials during extraction, but more importantly, it significantly improves the dissolution efficiency and extractable amount of the target components, laying a high-quality raw material foundation for subsequent purification steps.

[0107] The two-stage molecular distillation design is the core technical feature of this invention, and its separation effect was verified by comparing Example 1 and Comparative Example 2. After adopting two-stage distillation, the final product yield increased from 14.2g to 21.5g, an increase of 51.4%; the product purity increased from 85.1% to 92.3%, an increase of 8.5 percentage points; and the overall yield correspondingly increased from 1.42% to 2.15%, an increase of 51.4%. This optimized design achieves the fractional removal of impurity components and the selective enrichment of the target product, significantly improving the purity and recovery rate of the product, and demonstrating the necessity and superiority of multi-stage separation in the extraction of complex natural products.

[0108] The selection and optimization of the acetone-n-hexane mixed solvent crystallization system is another important technological innovation of this process. Compared with the single acetone solvent system (Comparative Example 4A), the mixed solvent system significantly increased the final product yield from 7.5g to 21.5g, an increase of 186.7%; the product purity increased from 88.7% to 92.3%, an increase of 4.1 percentage points; and the overall yield correspondingly increased from 0.75% to 2.15%, an increase of 186.7%. This result indicates that an appropriate solvent ratio can significantly improve the selective crystallization behavior of the target product, ensuring or even improving product purity while increasing yield.

[0109] A comparison with existing technologies (Comparative Example 3, based on the method in CN102887847A) highlights the specificity and targeted nature of the process in this invention. This invention achieves a high purity of 92.3% for the target product, while the comparative method yields less than 20%. In terms of yield, this invention achieves 2.15%, while the comparative method yields less than 0.5%, a difference of more than four times. This gap profoundly illustrates the irreplaceable necessity of process design targeting a specific product (zeaxanthin dispalmitate rather than free zeaxanthin), as general-purpose methods are insufficient to meet the extraction requirements of specific high-value components.

[0110] A comparison with traditional chemical treatment methods (Comparative Example 5, alkaline saponification) reveals the significant value of gentle physical processes. Alkaline saponification leads to substantial decomposition of the target product, resulting in a final product content of less than 30% of the target compound and a yield of less than 0.3%, far lower than the 2.15% of this invention. This comparison clearly demonstrates that avoiding harsh chemical treatments and employing gentle physical separation methods is crucial for preserving the structural integrity and bioactivity of heat-sensitive and easily decomposed natural active ingredients.

[0111] The subtle differences between the three examples reflect the fineness of the process parameter optimization. Example 1 uses the optimal parameter combination, achieving an ideal balance between purity (92.3%) and yield (2.15%). Examples 2 and 3 make slight adjustments to a few parameters, while maintaining product purity above 90% and yield at a high level. This moderate sensitivity to parameters demonstrates the robustness of the process and provides reasonable room for parameter fine-tuning in industrial production, reflecting the unity of scientific rigor and practicality in process design.

[0112] Table 2: Comparison of Physicochemical Properties of Products

[0113] Testing items Example 1 Example 2 Comparative Example 1 Comparative Example 2 Standard requirements Appearance Orange-red crystalline powder Orange-red crystalline powder orange-red viscous substance Orange-red powder Orange-red to red powder Purity (HPLC) % 92.3 91.8 83.5 85.1 ≥90 Melting point (°C) 88-92 87-91 78-85 80-87 85-95 UV absorption peak (nm) 445,472 445,472 445,472 445,472 445,472 Moisture content (%) 0.8 0.9 2.1 1.5 ≤2.0 Ash content (%) 0.12 0.15 0.35 0.28 ≤0.5 Heavy metals (ppm) <5 <5 <10 <8 ≤20

[0114] The purity level of the products prepared by this invention significantly exceeds industry standards. The HPLC purities of Examples 1-3 reached 92.3%, 91.8%, and 90.7%, respectively, all consistently exceeding the high-purity benchmark of 90%. This data is not only significantly higher than the comparative products' 83.5% and 85.1%, but more importantly, its stability and consistency are outstanding. The stability of purity reflects the effectiveness of precise control of process conditions and optimized formulation, proving that this invention has established a reliable technical guarantee system for core quality indicators.

[0115] The product exhibits a high degree of consistency in key physicochemical indicators, with its melting point concentrated within a narrow range of 87-92℃. This precise melting point control indicates the regularity of the crystal structure and the uniformity of its chemical composition. This contrasts sharply with the comparative product's broad melting point range of 78-87℃, further confirming the effectiveness of the optimized crystallization process achieved by this invention. The standardized physicochemical properties not only improve the product's quality standards but also provide a stable raw material base for downstream applications.

[0116] This invention demonstrates outstanding performance in impurity control, with moisture content maintained at a low level of 0.8-0.9%, ash content at only 0.12-0.15%, and heavy metal residue below 5 ppm. All indicators significantly exceed national standards. Particularly noteworthy is that these impurity indicators not only meet the standards but also allow for ample safety margins. This reflects the comprehensive quality control capabilities throughout the entire process, from raw material processing to final drying, providing dual assurance for product safety and stability.

[0117] Through comparative analysis of data from the various embodiments, the process of this invention exhibits good reproducibility and stability. The three embodiments maintain a high degree of consistency in core quality indicators, with the coefficient of variation controlled within a reasonable range. This stability is not only reflected in laboratory settings but, more importantly, indicates the potential for controllable quality during industrial-scale production. Stable and reliable quality output is a key prerequisite for successful commercialization and a significant manifestation of the technological advancement of this invention.

[0118] Based on a comprehensive analysis of various quality indicators, the product of this invention fully meets the quality requirements for high-end functional raw materials. Its high purity, low impurities, and stable physicochemical properties enable it to meet the stringent standards of health products, pharmaceuticals, and high-end cosmetics. In particular, while maintaining high quality, the product also preserves the structural integrity of its natural active ingredients through a gentle physical process, giving it a unique competitive advantage in the high-end consumer market that values ​​"natural" and "gentle" ingredients.

[0119] In-depth analysis reveals that the fundamental quality advantage of this invention lies in the systematic optimization of its process design. The sugar removal pretreatment controls the introduction of impurities at the source, two-stage molecular distillation achieves precise separation, and selective crystallization completes the final purification. The organic integration of these three key steps constructs a complete quality control chain, ultimately resulting in the product's superior quality performance. This systematic process design approach is precisely the core technological advantage that distinguishes this invention from traditional methods.

[0120] Table 3: Economic Analysis

[0121] project Method of the present invention CN102887847A Method Traditional saponification method Equipment investment medium High (requires simulation of a moving bed) Low Solvent consumption Low (90% recyclable) high medium Energy consumption medium high medium Labor costs Low high medium Product purity >90% Ineffective against the target object <30% Suitable for industrialization Very suitable More difficult Unsuitable

[0122] This invention offers significant economic advantages in terms of equipment investment, falling within the medium investment range. The main equipment includes a subcritical extraction unit, a molecular distillation system, and conventional chemical equipment, all of which are mature industrial equipment with relatively controllable procurement and maintenance costs. In contrast, the CN102887847A method requires an expensive simulated moving bed chromatography system, resulting in high equipment investment; while the traditional saponification method has lower equipment investment, it cannot obtain the target product. The investment strategy of this invention achieves an optimal balance between cost and performance, ensuring both technological advancement and controlled initial investment.

[0123] In terms of operating costs, this invention demonstrates significant cost control advantages. Solvent consumption is low with a recovery rate exceeding 90%, and the main solvents used, acetone and n-hexane, can be efficiently recovered and reused. Energy consumption is moderate, with a reasonable energy ratio between subcritical extraction and molecular distillation, avoiding high-energy-consuming chromatographic separation processes. Labor costs are low, thanks to the continuity of the process and its automation potential, reducing the need for manual intervention. Overall, the operating cost of this invention is significantly lower than control methods requiring complex chromatographic separation, and it also has advantages in solvent recovery and energy consumption compared to traditional methods.

[0124] The product manufactured by this invention possesses outstanding market value, with a purity exceeding 90%, meeting the standards for high-end functional raw materials and having a clear market positioning. Compared to the non-target product (free zeaxanthin) produced by the method in CN102887847A and the low-purity product (<30%) produced by the traditional saponification method, the product of this invention has strong competitiveness in high-end markets such as health products, functional foods, and cosmetics. The high-quality product characteristics support a high market price expectation (5000-8000 RMB / kg), while the moderate production cost (800-1200 RMB / kg) ensures a considerable profit margin, with an expected gross profit margin of 70-80%.

[0125] This invention demonstrates excellent industrialization potential, featuring stable and reliable processes, mature unit operation technologies, and ease of large-scale production. The equipment scaling-up path is clear, with existing industrial equipment fully meeting production requirements and no technical bottlenecks. It boasts superior environmental performance, primarily employing physical methods and a solvent recyclable system, aligning with green manufacturing trends. The process exhibits good continuity, suitable for establishing continuous or semi-continuous production lines, capable of meeting large-scale market demands. These characteristics collectively form a strong foundation for the industrialization of this invention, providing reliable assurance for enterprise investment decisions.

[0126] A comprehensive analysis of various economic indicators demonstrates the invention's superior overall economic performance. In terms of return on investment, the combination of moderate investment and high-value output ensures a short payback period. The cost-effectiveness ratio is significant, with well-controlled unit product costs and high added value. It exhibits strong market adaptability, meeting current market demands while possessing technological flexibility to cope with future market changes. From an investment risk perspective, the high technological maturity, clear market demand, and favorable policy environment ensure overall controllable investment risk. These economic characteristics not only make this invention technologically advanced but also provide a solid foundation for commercial success.

[0127] Experimental data analysis conclusions

[0128] 1. The necessity of desugaring pretreatment: Comparative Example 1 shows that without desugaring treatment, the raw materials will be severely agglomerated, which will not only reduce the extraction efficiency (the yield of oleoresin will be reduced by 45%), but also cause equipment blockage, which will seriously affect continuous production.

[0129] 2. Advantages of two-stage molecular distillation: Comparative Example 2 used single-stage distillation, and the product purity was only 85.1%, significantly lower than 92.3% in Example 1. Two-stage distillation can more effectively separate the target substance from impurities. The first stage removes light components, and the second stage achieves selective distillation of the target substance.

[0130] 3. The key role of selective solvent crystallization: Comparative Example 4 shows that different solvent systems have a significant impact on the crystallization effect. The acetone-n-hexane system preferred in this invention, at an appropriate ratio, can achieve crystallization with high purity and high yield.

[0131] 4. Advantages of avoiding chemical treatment: Comparative Example 5 shows that traditional alkaline saponification treatment leads to the decomposition of zeaxanthin dipalmitate, which is completely unsuitable for the preparation of this target product.

[0132] 5. Overall advantages of the process: Compared with the prior art (Comparative Example 3), the method of the present invention is highly targeted, simple in process, low in cost, and has high product purity, which fully meets the requirements of industrial production.

[0133] Product Application Verification

[0134] To fully verify the product performance and market application potential of the high-purity zeaxanthin dipalmitate obtained in this invention, we conducted systematic formulation research and stability testing in several core application areas.

[0135] 1. Soft capsule formulations (for health food applications)

[0136] Formulation and Process: The zeaxanthin dispalmitate crystals prepared in Example 1 were dissolved in refined soybean oil at a ratio of 1:9 (w / w) in a water bath at 60°C by stirring to prepare a homogeneous oily contents. Using a gelatin-glycerin capsule shell, the contents were filled using a standard soft capsule filling machine to obtain soft capsules with a nominal content of 10 mg of the target ingredient per capsule.

[0137] Stability study: In accordance with the "Guidelines for Stability Testing of Health Foods", the samples were placed under accelerated testing conditions (temperature 40℃±2℃, relative humidity 75%±5%) for 6 months.

[0138] Content retention: Samples were taken monthly, and the content of zeaxanthin dipalmitate in the contents was determined by HPLC. The results showed that the average retention rate reached 96.2% after 6 months, demonstrating its excellent chemical stability in the oil matrix.

[0139] Physical stability: The capsules showed no leakage, adhesion, or deformation, and the contents were uniform without crystallization.

[0140] Peroxide value: The endpoint peroxide value is less than 5.0 mmol / kg, which meets the hygiene standards for edible oils.

[0141] 2. Functional clarified beverages (food additive application)

[0142] Formulation and Process: Given that the target product is fat-soluble, microemulsion technology was employed. First, 0.1g of zeaxanthin dipalmitate was mixed with 2g of emulsifier (a blend of sucrose fatty acid ester and Tween 80) and 2g of glycerol, and after uniform dispersion, it was slowly added to 995.9g of purified water. Through high-speed shearing and homogenization, a stable oil-in-water (O / W) microemulsion system was prepared, with the final product containing 0.01% (w / w) of the target component.

[0143] Stability test: Stored at room temperature under light and at 4°C in the dark for 3 months.

[0144] Color and turbidity: The color difference (HunterLab value) and turbidity (NTU) of the beverage were monitored regularly. The results showed that the product color was bright orange-yellow and stable, with a ΔE value change of <1.5; the turbidity did not increase significantly, and there were no visible sediments or oil rings.

[0145] System stability: No phase separation phenomenon was observed, and the physicochemical properties were stable, verifying its feasibility as a colorant and functional ingredient in water-based foods.

[0146] 3. Eye care cream (cosmetic application)

[0147] Formulation and Process: Design an O / W type eye cream. The oil phase components, including zeaxanthin dipalmitate (0.5%), squalane, and shea butter, were heated to 75°C; the aqueous phase components, including glycerin and sodium hyaluronate, were heated to the same temperature. The aqueous phase was added to the oil phase while stirring, homogenized and emulsified, then cooled. Preservatives were added at 45°C, and stirring continued until room temperature was reached.

[0148] Safety and efficacy stability testing:

[0149] Skin irritation test (human patch test): conducted in accordance with the requirements of the "Cosmetic Safety Technical Specifications", the results of 30 subjects showed that none of them had irritation or allergic reactions, indicating that the product is mild and safe.

[0150] Heat and cold resistance tests: After the paste was cyclically tested three times at (-15℃~-10℃) / 24h and (40℃±1℃) / 24h, there was no oil-water separation, coarse particles, or discoloration, and the paste remained as smooth as before.

[0151] Stability of active ingredients: After being stored at 40℃ for 3 months, HPLC analysis showed that the retention rate of the target ingredient exceeded 92%, confirming its stable presence in the cosmetic matrix.

[0152] Application verification conclusions: The above application studies fully demonstrate that the high-purity zeaxanthin dipalmitate prepared by this invention has excellent stability, good compatibility and safety in use, and can be successfully applied to the development of diversified end products such as health foods, functional beverages and high-end cosmetics, showing broad market transformation prospects.

[0153] Advantages and comprehensive benefits of the invention

[0154] The "method for efficient extraction and purification of zeaxanthin dipalmitate from wolfberry" provided by this invention has the following outstanding substantive features and significant progress compared with the prior art:

[0155] 1. Pioneering Solution with Clear Objectives. This invention is the first to design a complete and specific extraction and purification system for zeaxanthin dipalmitate, a high-value fat-soluble active ingredient in wolfberry. Unlike existing technologies that often focus on wolfberry polysaccharides or free zeaxanthin, this invention precisely targets the esterified form, which has higher stability and bioavailability. This fills a gap in systematic preparation technology in this field, achieving a leap from "general extraction" to "refined preparation."

[0156] 2. Overcoming industry bottlenecks and ensuring continuous production. A novel, gentle desugaring pretreatment step was introduced, fundamentally solving the common industry problem of goji berries easily clumping, sticking to walls, and clogging equipment during extraction due to their high sugar content. Experimental data shows that this step increased the oleoresin yield by 83.8%, clearing obstacles for the continuous, stable, and large-scale operation of subsequent processes, and is a key prerequisite for ensuring the industrial-scale continuous production of the entire process.

[0157] 3. Highly efficient purification and superior product quality. A highly efficient physical purification chain was constructed through the synergistic optimization of "two-stage molecular distillation" and "selective solvent crystallization." This process can stably prepare zeaxanthin dispalmitate crystals with a purity exceeding 90% (92.3% in Example 1). The product exhibits excellent performance in key physicochemical indicators such as melting point, moisture content, ash content, and heavy metals, demonstrating stable and uniform quality that fully meets the stringent raw material standards for functional foods, high-end health products, and cosmetics.

[0158] 4. Controllable costs and strong economic competitiveness. The entire process route eliminates expensive and complex separation equipment such as simulated moving bed chromatography, mainly relying on mature subcritical extraction, molecular distillation, and crystallization unit operations, resulting in moderate equipment investment. The solvent system is simple and has a recovery rate of over 90%, significantly reducing fixed asset investment and material consumption. Combined with a high product yield (2.15% in Example 1), this scheme has a significant advantage in cost control, and the product has extremely high market competitiveness.

[0159] 5. Seamless process, easy to automate and industrialize. From sugar removal, extraction, distillation to crystallization, each step is seamlessly connected, and the process parameters are clearly defined, facilitating automated control using DCS or PLC to improve production efficiency and stability. All steps can be completed in conventional chemical equipment without special devices. The equipment scale-up path is clear, the technical risk is low, and it is extremely easy to carry out technical transformation and large-scale production in existing plants.

[0160] 6. Green and environmentally friendly, in line with the concept of sustainable development. The entire process mainly uses physical and physicochemical methods, avoiding harsh chemical treatments such as strong acids and alkalis, thus protecting the natural structure of the target product to the greatest extent. All organic solvents used are recyclable, and the amount of waste generated is low, which conforms to the modern industrial development concept of green chemistry and clean production.

[0161] 7. The application has been thoroughly validated, and the market prospects are broad. The product has demonstrated excellent stability, good compatibility, and safety in various dosage forms such as soft capsules, functional beverages, and cosmetics (e.g., the 6-month retention rate of soft capsules is >95%), proving that it has great transformation potential and commercial value as a core functional ingredient in many high-growth markets such as health foods, health drinks, and personal care products.

[0162] In summary, this invention not only provides a highly efficient and high-purity method for preparing zeaxanthin dispalmitate, but also forms a systematic technical solution in addressing raw material processing bottlenecks, improving product quality, controlling production costs, and promoting industrialization. This solution combines technological advancement, economic feasibility, and industrial maturity, and has significant practical value and broad application prospects for improving the high-value utilization of wolfberry resources and promoting the development of related industries.

[0163] It should be emphasized that the integrated process concept of "sugar removal pretreatment - subcritical fluid extraction - two-stage molecular distillation - selective solvent crystallization" provided by this invention is a systematic solution to the common industry problems of "high sugar content wolfberry raw materials are prone to clumping and clogging equipment" and "existing processes are difficult to separate zeaxanthin dipalmitate efficiently, with high purity and low cost".

[0164] The core inventive concept of this invention lies in: clearing obstacles to efficient extraction through gentle physical desaccharification pretreatment; utilizing the gentleness and high selectivity of subcritical extraction to obtain oleoresins rich in the target analyte; achieving preliminary purification and enrichment through the fractional separation characteristics of two-stage molecular distillation; and finally obtaining a high-purity product through the precise directional action of solvent crystallization. These four key steps are interconnected and indispensable, together forming a complete, efficient, and economical purification technology system.

[0165] Any technical solution derived from the above-mentioned core process combination and inventive concept through conventional experimental adjustments or parameter optimization (e.g., changing the desaccharification solvent, adjusting the extraction pressure / temperature, optimizing the distillation vacuum and temperature gradient, changing the crystallization solvent ratio or crystallization procedure, etc.), as long as its purpose is to achieve the fundamental objective of "efficiently extracting and purifying high-purity zeaxanthin dipalmitate from wolfberry", should be considered to fall within the protection scope of this invention.

Claims

1. A method for efficiently extracting and purifying zeaxanthin dipalmitate from wolfberry, characterized in that, Includes the following steps: (1) The wolfberry raw material is pretreated by desugaring; (2) Using subcritical fluid as the extractant, pretreated wolfberry was subjected to high-shear extraction to obtain oleoresin containing zeaxanthin dipalmitate. (3) The oleoresin obtained in step (2) is purified by two-stage molecular distillation; (4) Selective solvent crystallization of the fraction obtained by molecular distillation yields high-purity zeaxanthin dipalmitate.

2. The method according to claim 1, characterized in that, The sugar removal pretreatment in step (1) uses warm water or an ethanol aqueous solution with a volume fraction of 30-50%, the treatment temperature is 40-60℃, the treatment time is 20-60 minutes, and then dehydration.

3. The method according to claim 1, characterized in that, The subcritical fluid in step (2) is butane or dimethyl ether, the extraction pressure is 0.3-0.6 MPa, the extraction temperature is 40-55℃, and the extraction time is 10-60 minutes.

4. The method according to claim 1, characterized in that, The two-stage molecular distillation described in step (3) includes: First-stage molecular distillation: temperature 100-130℃, vacuum 1-10Pa; Second-stage molecular distillation: temperature 170-190℃, vacuum degree 0.1-2Pa.

5. The method according to claim 1, characterized in that, The selective solvent crystallization in step (4) uses a mixed solvent of acetone and n-hexane, with a volume ratio of acetone to n-hexane of 1:1-1:4 and a crystallization temperature of 0-10℃.

6. The method according to claim 5, characterized in that, The cooling rate during the crystallization process is 0.3-1℃ / min, and the crystallization time is 6-24 hours.

7. A zeaxanthin dipalmitate prepared by any one of claims 1-6, characterized in that, The purity is not less than 90%.

8. The use of the zeaxanthin dipalmitate according to claim 7 in the preparation of food, health products or cosmetics.

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