A curcumin / anthocyanin oral formulation containing a self-microemulsifying coconut oil

Abstract

The application discloses a curcumin / anthocyanin oral preparation containing a self-microemulsion of coconut oil and a preparation method thereof, and belongs to the technical field of health foods. The preparation is prepared by solidifying a liquid self-microemulsion precursor composed of curcumin, anthocyanin, refined coconut oil, a specific food-grade surfactant and a co-surfactant, and a porous starch and microcrystalline cellulose compound carrier. The application realizes stable co-loading of two active ingredients with relatively large differences in physicochemical properties by relying on a full food-grade formula and a narrow window spray drying process, plays a synergistic role, and solves the problems of poor stability and low bioavailability of traditional preparations. The finished powder has good flowability, a rapid self-emulsification reaction and stable long-term storage quality, can be processed into a solid beverage or a soft capsule dosage form, the production process is mature and controllable, the product safety meets the specification requirements, and is suitable for health food filing and industrialized batch production.

Description

Technical Field

[0001] This invention belongs to the field of health food formulation technology, specifically relating to an oral formulation based on a whole food-grade coconut oil-based solid self-microemulsion (S-SMEDDS) system, co-loaded with curcumin and anthocyanin dual active ingredients, its preparation method, and its application in antioxidant health foods. Background Technology

[0002] Curcumin and anthocyanins are recognized as highly active natural antioxidants. However, curcumin is a strongly hydrophobic molecule with extremely poor water solubility and low oral bioavailability; anthocyanins are water-soluble polyphenols that are highly sensitive to light, heat, and pH, and have poor stability. When the two are combined, their contrasting physicochemical properties easily interfere with each other, leading to accelerated degradation of active ingredients and difficulty in simultaneously improving bioavailability. Self-microemulsion drug delivery systems (SMEDDS) can spontaneously form nanoscale microemulsions, significantly improving the dispersion and absorption of poorly soluble components. However, traditional liquid SMEDDS suffers from poor flowability and easy layering. Their solidification modification often employs synthetic ester oil phases and chemical excipients such as silica, which limits food safety and fails to meet the compliance and safety requirements of health food products for "natural, food-grade" raw materials and excipients. Furthermore, existing technologies lack coconut oil-based self-microemulsion systems constructed with food-grade carriers, and there is no specific formulation and process adaptation for co-loading curcumin and anthocyanins. When coconut oil is used as the oil phase, it is prone to wall adhesion, oil seepage, and damage to heat-sensitive components during conventional spray drying. There is an urgent need to develop precise narrow-window drying processes to simultaneously achieve excellent powder properties and high activity retention. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide an oral formulation of curcumin / anthocyanin containing coconut oil self-microemulsion, which has food-grade raw materials, stable co-loading of dual active ingredients, high oral bioavailability and excellent formulation performance. To solve the above problems, the present invention adopts the following technical solution: 1. Core Formulation Composition This formulation is formed by solidifying a drug-loaded liquid self-microemulsion precursor with a food-grade solid carrier. The drug-loaded liquid self-microemulsion precursor comprises, by weight: 1-8 parts curcumin, 1-6 parts anthocyanin, 25-45 parts refined edible coconut oil, 30-50 parts food-grade nonionic surfactant, and 10-25 parts food-grade co-surfactant. Furthermore, the food-grade nonionic surfactant is selected from one or more of polyglycerol fatty acid esters or sucrose fatty acid esters; the food-grade co-surfactant is food-grade propylene glycol or edible anhydrous ethanol. The mass ratio of coconut oil to surfactant is limited to 0.5:1 to 1.5:1 to ensure the stability and efficiency of the self-emulsifying system. The food-grade solid carrier is composed of porous starch and microcrystalline cellulose in a mass ratio of 5:2, and its total mass accounts for 40% to 65% of the mass of the drug-loaded liquid self-microemulsion precursor. The porous structure of the porous starch can efficiently adsorb and encapsulate the drug-containing self-microemulsion, preventing oil leakage; while the microcrystalline cellulose provides excellent flowability and formability. Together, they solve the formulation problem of high oil-loading powders. All ingredients in this formula comply with the "Catalogue of Usable Raw Materials for Health Foods" and GB 2760 standard, and there are no chemical excipients. 2. Preparation method The present invention also provides a method for preparing the formulation, which is carried out entirely under light-protected or low-light conditions, and the steps include: (1) Preparation of drug-loaded liquid self-microemulsion stock solution: Weigh all liquid and active components according to the ratio, and stir in a water bath at 300-500 r / min for 25-40 min at 45-55°C to form a clear and transparent drug-loaded liquid self-microemulsion stock solution. (2) Preparation of carrier suspension: Mix porous starch and microcrystalline cellulose in a ratio of 5:2, add purified water, and prepare a suspension with a solid content of 25% to 35%. (3) Homogenization: The original solution obtained in step (1) is slowly added to the suspension in step (2), and homogenized under high pressure at 20-35 MPa or under high speed shear at 6000-12000 r / min for 8-15 min to obtain a homogeneous emulsion. (4) Spray drying solidification: The above emulsion is spray dried with the following specific process parameters: inlet air temperature 150-170°C, outlet air temperature 75-90°C, feed flow rate 15-30 mL / min, atomization pressure 0.25-0.4 MPa, and relative humidity ≤45%. After drying, it is passed through a 60-80 mesh sieve to obtain drug-loaded solid microemulsion powder. (5) Preparation of terminal dosage form: The obtained powder is packaged to obtain solid beverage; or it is dispersed in food-grade medium and pressed or filled to form soft capsules. 3. Beneficial effects Compared with the prior art, the present invention has the following significant advantages: Food-grade safety and compliance: The entire formula uses food-grade raw materials, abandoning traditional chemical auxiliaries, and is fully compatible with health food registration and large-scale production. Synergistic dual activity and high stability: Curcumin and anthocyanins are loaded in a self-microemulsion core-shell structure to avoid mutual interference. After 18 months of long-term storage, the activity retention rate is ≥96%, solving the problem of easy degradation of traditional compound formulations. Significantly improved bioavailability: The formulation self-emulsifies to form a nanoemulsion within 30 seconds after oral administration, significantly improving the dissolution and transmembrane absorption of the two components. Compared with conventional physical compounding, bioavailability can be increased by more than 45%. Precise and controllable process: The narrow window spray drying process effectively overcomes the problems of coconut oil-based materials sticking to the wall, oil seepage, and deactivation of heat-sensitive components, resulting in excellent product flowability and stable yield. Attached Figure Description Figure 1 Schematic diagram of a coconut oil-based solid self-microemulsion dual-active loading structure In the picture: 1. The outer layer is a porous starch and microcrystalline cellulose composite solid carrier, which serves to fix the shape and prevent leakage. 2. The intermediate coconut oil encapsulates and fixes the fat-soluble curcumin in the microemulsion layer. 3. The internal space is used to disperse water-soluble anthocyanins, with zoned loading to avoid mutual interference between components. 4. Upon immersion in water, the outer carrier dissociates, rapidly forming a nanoscale microemulsion, thus improving absorption and utilization rates. Detailed Implementation The present invention will be further described in detail below through examples and comparative examples. Example 1 Weigh out the following components by weight: 4 parts curcumin, 3 parts anthocyanins, 32 parts refined coconut oil, 38 parts food-grade polyglycerol fatty acid ester, and 18 parts food-grade propylene glycol. Stir at 400 r / min for 30 minutes in a 50°C, light-protected water bath to obtain a transparent drug-loaded liquid microemulsion stock solution, totaling 95 parts. Weigh out 42 parts of porous starch and 16.8 parts of microcrystalline cellulose in a mass ratio of 5:2. The total weight of the carrier is 58.8 parts, accounting for 61.9% of the precursor mass. Add 176.4 parts of purified water to disperse into a suspension with a solid content of 25%. Add the stock solution to the suspension and homogenize under high pressure of 30 MPa for 10 minutes to obtain a homogeneous emulsion. Spray drying was performed, with the inlet air temperature controlled at 160°C, the outlet air temperature at 82°C, the feed flow rate at 22 mL / min, the atomization pressure at 0.32 MPa, and the relative humidity at ≤45%. The powder was collected and passed through a 70-mesh sieve to obtain a white, dry solid microemulsion powder with a yield of 81%. The powder can be dispensed into solid beverages; or it can be dispersed in an appropriate amount of medium-chain triglycerides and compressed into soft capsules. Example 2 Weigh out: 1 part curcumin, 1 part anthocyanin, 25 parts refined coconut oil, and 50 parts food-grade polyglycerol fatty acid ester. Stir at 55°C in the dark for 40 minutes to obtain the drug-loaded stock solution. Combine with 30 parts porous starch and 12 parts microcrystalline cellulose, with a carrier ratio of 54.5%, to prepare a suspension with a 25% solid content. Homogenize at 25 MPa pressure for 12 minutes. Spray dry the powder with inlet air temperature of 150°C, outlet air temperature of 75°C, and feed flow rate of 15 mL / min. The final powder meets all performance standards. Example 3 Weigh out: 8 parts curcumin, 6 parts anthocyanins, 45 parts refined coconut oil, 35 parts food-grade sucrose fatty acid ester, and 20 parts food-grade propylene glycol. Prepare the stock solution by stirring at 45°C in the dark. Select 45 parts porous starch and 18 parts microcrystalline cellulose as carriers, with a carrier ratio of 55.3%. Spray drying is performed using parameters of 170°C inlet air, 90°C outlet air, and a feed flow rate of 30 mL / min. The finished powder meets the physicochemical properties standards and exhibits stable activity without loss. Comparative Example 1 (System without self-microemulsification) Equal amounts of curcumin and anthocyanins were directly and physically mixed with porous starch and microcrystalline cellulose without preparing a self-microemulsion. The remaining operations were the same as in Example 1. Results: A self-emulsifying system could not be formed, the active ingredients were unevenly dispersed, and the anthocyanins oxidized and changed color rapidly. Comparative Example 2 (Inlet air temperature exceeds the upper limit) The raw material ratio and operating procedures were kept consistent with Example 1, except that the spray drying inlet air temperature was adjusted to 185°C. Results: Anthocyanins showed severe oxidation and fading, curcumin underwent significant thermal degradation, and the activity retention rate was less than 65%. Comparative Example 3 (solid carrier dosage below the lower limit) The basic raw material ratio was the same as in Example 1, but the carrier dosage was reduced to 25% of the precursor mass, while the rest of the process remained unchanged. Results: The powder surface showed severe oil seepage and clumping, loss of flowability, and activity leakage occurred after one month of storage. Product efficacy verification The powder obtained in Example 1 was tested according to the standard methods in the 2020 edition of the Chinese Pharmacopoeia. The test results are as follows: Self-emulsifying properties: When 1g of powder is added to 100mL of 37°C warm water, it spontaneously forms a uniform microemulsion with an average particle size of 95-135nm within 30 seconds. Flowability: The powder has an angle of repose of 32°, indicating excellent flowability. Storage stability: After being stored in a sealed, light-protected environment at 25°C±2°C for 18 months, the activity retention rate was ≥96%, and no abnormal changes were observed in the appearance of the powder or its self-emulsifying properties.

Claims

1. A curcumin / anthocyanin oral formulation containing a self-microemulsifying coconut oil characterized in that, It is made by solidification of a drug-loaded liquid self-microemulsion precursor and a food-grade solid carrier; The drug-loaded liquid self-microemulsion precursor is composed of the following components by weight: 1-8 parts curcumin, 1-6 parts anthocyanin, 25-45 parts refined edible coconut oil, 30-50 parts food-grade nonionic surfactant, and 10-25 parts food-grade co-surfactant. The food-grade solid carrier is composed of porous starch and microcrystalline cellulose in a mass ratio of 5:2, and its mass is 40% to 65% of the mass of the drug-loaded liquid microemulsion precursor.

2. The oral preparation according to claim 1, characterized by The food-grade nonionic surfactant is any one or a combination of two of polyglycerol fatty acid esters or sucrose fatty acid esters; the food-grade co-surfactant is food-grade propylene glycol or edible anhydrous ethanol.

3. The oral preparation according to claim 1, characterized by, In the drug-loaded liquid microemulsion precursor, the mass ratio of coconut oil to food-grade nonionic surfactant is 0.5:1 to 1.5:

1.

4. The oral preparation according to claim 1, characterized by, The final product form of the oral formulation is a solid beverage or a soft capsule.

5. A process for the preparation of an oral formulation as claimed in any one of claims 1 to 4, characterized in that, Includes the following steps: (1) Weigh out curcumin, anthocyanin, refined edible coconut oil, food-grade nonionic surfactant and food-grade co-surfactant according to the ratio, and stir at 300-500 r / min for 25-40 min in a water bath at 45-55℃ and in the dark to obtain a clear and uniform drug-loaded liquid microemulsion stock solution. (2) Mix porous starch and microcrystalline cellulose at a mass ratio of 5:2, and add purified water to prepare a carrier suspension with a solid content of 25% to 35%; (3) Add the drug-loaded liquid microemulsion stock solution from step (1) to the carrier suspension from step (2), and use high pressure homogenization or high speed shear mixing. The homogenization pressure is 20-35 MPa or the shear speed is 6000-12000 r / min. The mixture is processed for 8-15 min to obtain a uniform drug-loaded emulsion. (4) Spray dry the drug-loaded emulsion from step (3), controlling the inlet air temperature to be 150-170℃, the outlet air temperature to be 75-90℃, the feed flow rate to be 15-30 mL / min, the atomization pressure to be 0.25-0.4 MPa, and the relative humidity of the drying environment to be ≤45%. After drying, pass through a 60-80 mesh sieve to obtain drug-loaded solid self-microemulsion powder. (5) The powder obtained in step (4) is directly packaged into solid beverages or dispersed in food-grade dispersion medium to form soft capsules.

6. The preparation method according to claim 5, characterized in that, The high-pressure homogenization pressure in step (3) is 25-35 MPa, and the high-speed shearing speed is 8000-12000 r / min.

7. The use of an oral formulation as described in any one of claims 1-4 in the preparation of a health food product with antioxidant function.

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