Phospholipid complex with high bioavailability as well as preparation method and application thereof

Abstract

The invention discloses a phospholipid complex with high bioavailability as well as a preparation method and application thereof. The compound consists of 30-70 parts of nutrients, 15-50 parts of phospholipid, 2-10 parts of a membrane layer framework material, 0.2-2 parts of an antioxidant, 5-30 parts of a wall material and 2-5 parts of an adhesive, and has a phospholipid-wall material double-layer or multi-layer embedding structure. The preparation method comprises the following steps: preparing membranized phospholipid powder by spray drying, modifying a wall material by plasma, co-crushing, granulating by a wet method, and cutting, spraying and coating. The product has good fluidity and low solvent residue lt; the nutrient loss rate is 100 ppm, and the nutrient loss rate is 1t; 2%, the retention rate gt after 20 days of acceleration at 60 DEG C; 90%; and the bioavailability is 2-3 times that of the raw materials, and the process can realize large-scale production and is low in cost. The compound is suitable for food, health care products or medicines and is used for efficiently delivering nutrients such as vitamins and minerals.

Description

Technical Field

[0001] This invention belongs to the field of food nutrition and health, specifically relating to a phospholipid complex with high bioavailability, its preparation method and application. Background Technology

[0002] Minerals and vitamins are essential micronutrients for maintaining normal physiological functions. However, these nutrients face many challenges in practical application. Many mineral ions are easily affected by factors such as pH, phytic acid, and oxalic acid in the gastrointestinal tract, forming insoluble precipitates and resulting in low absorption rates. Vitamins, especially water-soluble vitamins, are easily lost during production, processing, and storage, while fat-soluble vitamins suffer from difficulties in dissolution and low bioavailability. Furthermore, some vitamins and minerals interact with each other, accelerating degradation.

[0003] To improve the stability and bioavailability of these nutrients, microencapsulation technology has been widely used. Existing technologies include spray drying encapsulation and phospholipid encapsulation. However, despite extensive exploration of microencapsulation technology, existing methods inherently contradict each other in their technical approach, often resulting in compromises. Spray drying alone has limited efficiency in encapsulating minerals, while traditional phospholipid technology, although improving bioavailability, suffers from drawbacks such as easy leakage during storage and high costs associated with large-scale production. Chinese patent CN115006410B discloses a complex vitamin liposome, its preparation method, and its application. The preparation process requires heating and melting vitamins and other components at 150-160°C. For heat-sensitive vitamin components, this can cause significant degradation, potentially producing harmful decomposition products and making it difficult to guarantee product quality. Patent CN109497561B discloses a method for preparing vitamin B12 nanoliposomes, employing thin-film hydration, ultrasonic cell disruption, low-temperature centrifugation, and microporous membrane filtration. While this technology can achieve a high encapsulation rate, scale-up production is difficult, and the rotary evaporator temperature must be less than or equal to 20°C during solvent removal, making it challenging to guarantee solvent residue levels in the product. Patent CN120549866A discloses a calcium liposome for promoting bone health, its preparation method, and applications. The examples in the patent demonstrate high bioavailability; however, the phospholipid composition in the formulation consists of egg yolk lecithin, phosphatidylinositol, and distearate phosphatidylcholine in a mass ratio of 8~12:7~11:1~5. In reality, phospholipids are a mixture, and specifying only the proportions without limiting the purity of the phospholipid raw materials may lead to batch-to-batch product quality instability.

[0004] Therefore, there is an urgent need in this field for an innovative method and product that can fundamentally overcome the limitations of the above-mentioned technical paths, achieve stable, continuous and scalable production, and significantly improve its stability and bioavailability. Summary of the Invention

[0005] In view of the problems mentioned in the background art, such as poor stability of mineral and vitamin components, limited absorption effect, and difficulty in large-scale production, the present invention provides a phospholipid complex with high bioavailability and its preparation method.

[0006] One aspect of this invention is to protect a phospholipid complex with high bioavailability, comprising the following raw materials in parts by weight: 30-70 parts of nutrients, 15-50 parts of phospholipids, 2-10 parts of membrane framework material, 0.2-2 parts of antioxidant, 5-30 parts of wall material, and 2-5 parts of binder. More preferably, the parts by weight are: 30-48 parts of nutrients, 28-50 parts of phospholipids, 3-8.5 parts of membrane framework material, 1-2 parts of antioxidant, 10-30 parts of wall material, and 2.5-4 parts of binder; wherein: The phospholipids mentioned are selected from at least one of natural phospholipids, hydrogenated phospholipids, and synthetic phospholipids; The membrane framework material is selected from at least one of cholesterol, phytosterols, and phytosterol esters; The antioxidants mentioned include fat-soluble antioxidants and water-soluble antioxidants; The fat-soluble antioxidant is selected from at least one of the following: ascorbyl palmitate, mixed tocopherols, α-tocopherol, tocotrienol, β-carotene, lycopene, lutein, zeaxanthin, rosemary extract, carrageenan, rosmarinic acid, quercetin, glycyrrhizin, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and tert-butylhydroquinone. The wall material includes at least one of the following: sodium octenyl succinate starch, gum arabic octenyl succinate, corn starch, gum arabic, gelatin, carrageenan, pectin, xanthan gum, maltodextrin, solid corn syrup, resistant dextrin, inulin, maltodextrin, isomaltooligosaccharide, maltitol, whey protein concentrate, whey protein isolate, hydrolyzed whey protein, zein, casein, and sodium caseinate. The adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, polyethylene glycol, gum arabic, pectin, gelatin, and sodium alginate.

[0007] With respect to the technical solution described above, preferably, the phospholipid complex has a phospholipid-wall material double-layer or multi-layer encapsulation structure composed of the membrane-formed phospholipid and the wall material.

[0008] With respect to the technical solution described above, preferably, the angle of repose of the phospholipid complex is not greater than 45°; more preferably, it is ≤41°; even more preferably, the angle of repose is 35°~41°.

[0009] For the technical solution described above, preferably, the nutrient is a mineral, a vitamin, or a combination thereof.

[0010] For the technical solution described above, preferably, the vitamin is selected from at least one of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, and vitamin K. More preferably, it is selected from retinol, retinaldehyde, all-trans retinoic acid, retinyl palmitate, retinyl acetate, retinyl propionate, thiamine hydrochloride, thiamine nitrate, thiamine pyrophosphate (TPP), thiamine mononitrate, riboflavin, sodium riboflavin phosphate, niacin, nicotinamide, nicotinamide mononucleotide (NMN), nicotinamide adenine dinucleotide (NAD), nicotinamide ribose (NR), pantothenic acid, D-panthenol, D-calcium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate (PLP), pyridoxine 5-phosphate, biotin, biotin methyl ester, biotin ethyl ester, inositol, squalinositol, D-chiral inositol, chiro inositol, phytic acid, folic acid, and 5-methyltetrahydrofolate. 5-MTHF), 5-formyltetrahydrofolate, calcium folic acid, cyanocobalamin, methylcobalamin, adenosylcobalamin, hydroxycobalamin, L-ascorbic acid (vitamin C), magnesium ascorbate, sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbate palmitate, ascorbate stearate, ascorbate tetraisopalmitate, vitamin D3 (cholecalciferol), vitamin D2 (ergocalciferol), 25-hydroxyvitamin D3 (calciferiol), 1,25-dihydroxyvitamin D3 (calcitriol), calciferiol, α-tocopherol, dl-α-tocopherol, α-tocopherol acetate, α-tocopherol succinate, tocotrienol, mixed tocopherols, vitamin K1, vitamin K2.

[0011] For the technical solution described above, preferably, the mineral is selected from at least one of calcium, magnesium, zinc, iron, potassium, manganese, copper, sodium, chromium, selenium, iodine, and phosphorus. More preferably, it is selected from calcium glycinate, calcium L-aspartate, calcium L-lactic acid, calcium carbonate, calcium citrate, calcium citrate malate, calcium fructose borate, calcium malate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium glycerophosphate, calcium oxide, calcium sulfate, calcium gluconate, magnesium chloride, magnesium carbonate, magnesium oxide, magnesium glycinate, magnesium gluconate, magnesium hydrogen phosphate, magnesium taurate, magnesium sulfate, magnesium lactate, magnesium malate, magnesium fumarate, magnesium threonate, magnesium succinate (magnesium succinate), magnesium L-aspartate, ferrous glycinate, ferrous sulfate, ferrous pyrophosphate, ferrous fumarate, and sodium ferric ethylenediaminetetraacetate. The following are at least one of the following: ferrous gluconate, ferric citrate, ferrous ammonium citrate, ferric phosphate, zinc glycinate, zinc sulfate, zinc gluconate, zinc citrate, zinc oxide, zinc lactate, zinc chloride, zinc acetate, zinc malate, zinc L-aspartate, manganese glycinate, manganese sulfate, manganese chloride, manganese carbonate, manganese gluconate, manganese citrate, manganese L-aspartate, copper sulfate, copper glycinate, copper gluconate, copper citrate, copper carbonate, potassium chloride, potassium citrate, potassium dihydrogen citrate, potassium L-aspartate, potassium gluconate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium citrate, sodium chloride, sodium L-aspartate, sodium selenite, sodium selenate, potassium iodide, potassium iodate, sodium iodide, chromium sulfate, and chromium chloride.

[0012] For the technical solutions described above, preferably, natural phospholipids include soybean lecithin, sunflower lecithin, rapeseed lecithin, flaxseed lecithin, or egg yolk lecithin; hydrogenated phospholipids include hydrogenated soybean lecithin, hydrogenated sunflower lecithin, hydrogenated rapeseed lecithin, hydrogenated flaxseed lecithin, or hydrogenated egg yolk lecithin; and synthetic phospholipids include dipalmitoylphosphatidylcholine (DPPC), distearatelphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), or dimyristoylphosphatidylcholine (DMPC).

[0013] For the technical solutions described above, preferably, there are requirements on the purity of natural phospholipids and hydrogenated phospholipids. Preferably, the acetone-insoluble content in the phospholipids is greater than 60 wt%, more preferably, the acetone-insoluble content is greater than 90 wt%, and even more preferably, the acetone-insoluble content is greater than 95 wt%.

[0014] For the technical solution described above, preferably, the natural phospholipids and hydrogenated phospholipids are both mixtures, and their components include phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, glycolipids, etc. The technical solution of the present invention limits the content of phosphatidylcholine (PC) in natural phospholipids and hydrogenated phospholipids; preferably, the phosphatidylcholine content is greater than 70 wt%, more preferably, the phosphatidylcholine content is greater than 90 wt%.

[0015] For the technical solution described above, preferably, the weight ratio of the membrane skeleton material to the phosphatidylcholine component in the phospholipid is 1:3 to 1:15; more preferably, 1:3 to 1:12; even more preferably, 1:4 to 1:10; and even more preferably, 1:4 to 1:8.

[0016] For the technical solution described above, preferably, the membrane skeleton material includes at least one of cholesterol, phytosterols, mono- and diglycerides of fatty acids, fatty acids, and vegetable oils.

[0017] For the technical solution described above, preferably, based on the growing consumer demand for low-cholesterol diets, the membrane skeleton material is selected from at least one of phytosterols and phytosterol esters, and most preferably, it is selected from at least one of sitosterol and its sterol esters, stigmasterol and its sterol esters, rapeseed sterol and its sterol esters, ergosterol and its sterol esters, and microalgae sterol and its sterol esters.

[0018] For the technical solution described above, preferably, the water-soluble antioxidant is selected from at least one of ascorbic acid, sodium ascorbate, calcium ascorbate, D-isoascorbic acid, sodium D-isoascorbate, disodium EDTA, chlorogenic acid, cysteine, glutathione, tea polyphenols, citrus flavonoids, and proanthocyanidins.

[0019] Another aspect of the present invention relates to a method for preparing a phospholipid complex with high bioavailability, comprising the following steps: S1. Preparation of membrane-modified phospholipid powder: Phospholipids, membrane framework materials, fat-soluble nutrients and fat-soluble antioxidants are dissolved in an organic solvent to form a homogeneous and transparent phospholipid solution; then this solution is spray-dried to obtain membrane-modified phospholipid powder. S2. Plasma modification of wall materials: The wall materials are subjected to low-temperature plasma treatment to obtain modified wall materials; S3. Co-pulverization: The membrane-coated phospholipid powder obtained in step S1 is thoroughly mixed with non-fat-soluble nutrients and then pulverized. S4. Preparation of phospholipid complex: The water-soluble antioxidant and binder are completely dissolved in water to form a granulation slurry; the material obtained in step S3 is subjected to wet granulation; after preliminary molding, a portion of the modified wall material obtained in step S2 is added, and granulation and sizing are continued to obtain a phospholipid complex with uniform particle size. S5. Composite sustained-release layer encapsulation: The remaining modified wall material after step S4 is dispersed in water to prepare a coating solution; the phospholipid complex obtained in S4 is used as a substrate for coating and drying to obtain the final product.

[0020] For the technical solution described above, preferably, the organic solvent in S1 is at least one selected from methanol, ethanol, ethyl acetate, chloroform, diethyl ether, and petroleum ether. More preferably, the organic solvent is ethanol.

[0021] For the technical solution described above, preferably, the dissolution temperature in S1 is 50~70℃, and most preferably, the temperature is 60~65℃.

[0022] With respect to the technical solution described above, preferably, the spray drying in S1 is selected from closed-loop spray drying, and the inlet air temperature is 70~110℃; more preferably, the inlet air temperature is 80~100℃; and most preferably, the inlet air temperature is 85~95℃.

[0023] For the technical solution described above, preferably, the gas medium in S2 is at least one of air, nitrogen, oxygen, argon, helium, hydrogen, ammonia, methane, and carbon tetrafluoride; more preferably, the gas medium is air or oxygen.

[0024] For the technical solution described above, preferably, the pulverization in S3 involves mixing the membrane-treated phospholipid powder with nutrients and then pulverizing it, using one of the following methods: blade pulverization, hammer milling, grinding milling, or air jet milling. More preferably, the pulverization method is selected from air jet milling.

[0025] For the technical solution described above, preferably, the particle size D90 of the material after crushing in S3 is 10μm~100μm, and more preferably, D90 is 60μm~90μm.

[0026] For the technical solution described above, preferably, the S4 wet granulation involves dissolving a water-soluble antioxidant and a binder in water to form a slurry, and then wet granulating the co-pulverized material. For the technical solution described above, preferably, the S4 wet granulation involves adding 60wt% to 95wt% of the modified wall material prepared in step S2 during the granulation process. For the technical solution described above, preferably, the amount of wall material added in S4 is 70-90 wt% of the total wall material in the formula, and most preferably, it is 80-90 wt% of the total wall material in the formula.

[0027] For the technical solution described above, preferably, the S4 wet granulation involves granulating wet particles using a swaying granulator to obtain the core particles.

[0028] For the technical solution described above, preferably, the coating method in S5 is a fluidized bed coating process; it can be bottom spray coating or cut spray coating; more preferably, cut spray coating.

[0029] For the technical solution described above, preferably, during the S5 coating process, the inlet air temperature is controlled at 40~70℃, and the material temperature is maintained at 35~60℃; more preferably, the material temperature is 45~60℃; and most preferably, it is 50~55℃. This temperature control can ensure that the modified wall material forms a dense and continuous protective film on the particle surface, while avoiding the degradation of heat-sensitive nutrients.

[0030] For the technical solution described above, preferably, step S1 involves solvent spray drying to rapidly evaporate the organic solvent, resulting in a free-flowing film-formed phospholipid powder that can simultaneously load fat-soluble nutrients and fat-soluble antioxidants. Solvent spray drying requires a lower inlet air temperature and shorter heating time, avoiding thermal degradation of fat-soluble nutrients. The resulting film-formed phospholipid powder is a "pre-assembled" phospholipid layer structure, providing a good foundation for subsequent loading of active ingredients. Step S2, through plasma treatment, introduces hydrophilic groups such as hydroxyl and carboxyl groups onto the surface of the wall material without altering its bulk properties, thereby significantly improving the emulsification, water solubility, and film density of the wall material. In step S4, the nutrients are evenly dispersed and embedded with the membrane-modified phospholipids through the action of mechanical force and adhesive. On this basis, it is further combined with the plasma-treated wall material. In step S5, the composite slow-release layer is sprayed onto the surface of the composite particles in a fluidized state. During the spraying process, the water evaporates instantly, and the modified wall material forms a dense and continuous protective film on the particle surface, improving the encapsulation effect and stability of the product.

[0031] The phospholipid complex described in this invention exhibits significant effects in improving the bioavailability and stability of nutrients, and therefore can be widely used in a variety of products, including but not limited to the following levels: The first is to protect the application of the above-mentioned phospholipid complex in the preparation of foods, health products or drugs used to improve the bioavailability and stability of nutrients.

[0032] With respect to the technical solution described above, preferably, the use of the above-mentioned phospholipid complex in the preparation of food, dietary supplements or pharmaceuticals is protected.

[0033] With respect to the technical solution described above, preferably, the phospholipid complex prepared by the method described above is used in the preparation of products for promoting bone health or supplementing vitamins and minerals.

[0034] Beneficial effects of the present invention 1. The prepared phospholipid complex has good flowability, no unpleasant odor, and good sensory properties; 2. The process integrates solvent spray drying technology and mechanical granulation technology. The process does not involve high temperature, which can reduce the loss of nutrients. The retention rate of nutrients in the preparation process is higher than 98%, which is far better than the 5%-10% loss caused by high temperature treatment in traditional methods. 3. After multiple encapsulations, it exhibits excellent physical and chemical stability. After 20 days of accelerated treatment at 60℃, no problems such as clumping or deterioration of flavor or odor occurred, and the degradation rate was less than 9%. In contrast, traditional methods generally suffer from oxidation, clumping, and deterioration of flavor or odor. 4. By pretreating the membrane-modified phospholipid powder, the bioavailability of the phospholipid complex product can be significantly improved. The absorption efficiency of the product of this invention can reach 2-3 times that of ordinary raw materials. The improvement effect is comparable to that of liposomes prepared by traditional membrane hydration method. Moreover, it is easy to achieve large-scale production due to lower cost and simpler process. 5. "Pre-assembled" membrane-bound phospholipid powder is obtained through solvent spray drying process, which loads fat-soluble vitamins and avoids contact with minerals to accelerate degradation. 6. By designing a phospholipid-wall material bilayer encapsulation structure, the protection and delivery efficiency of small molecule peptides are synergistically optimized.

[0035] 7. Ethanol is preferred as a processing aid, as solvent recovery can be achieved during the process, without causing environmental pollution; 8. Most traditional technologies face bottlenecks such as strong equipment dependence and poor process stability when scaling up production; while the production cost of this invention is lower than that of common liposome preparation processes such as freeze drying and low temperature drying, making it more advantageous for large-scale scale-up. Detailed Implementation

[0036] The present invention will be further described below with reference to embodiments, but it should be understood that the scope of protection of the present invention is not limited to the embodiments. Unless otherwise stated, the chemical reagents and biological materials used in the present invention are all commercially available and processed and applied in accordance with standard operating procedures. All experimental steps were performed under normal laboratory conditions to ensure the repeatability and reliability of the technical solution.

[0037] Example 1 Weigh 40 parts of anhydrous ethanol, add 15 parts of soybean lecithin PC90 (PC90: phosphatidylcholine content ≥90%, the same below), 2 parts of stigmasterol and 0.2 parts of ascorbate palmitate, heat to 60℃ and stir until completely dissolved. Use a closed-loop spray dryer, set the inlet air temperature to 90℃ and the outlet air temperature to 45℃, and spray dry into powder to obtain a free-flowing film-formed phospholipid powder.

[0038] Weigh 10 parts of sodium caseinate and place them in a plasma treatment device. Select air as the reaction gas medium to modify the surface of the wall material.

[0039] The prepared membrane-modified phospholipid powder was mixed with 70 parts of magnesium glycine and pulverized using an air jet mill. The D90 was measured to be 86 μm. The mixture was then transferred to a wet granulator. 0.8 parts of sodium ascorbate and 2 parts of hydroxypropyl methylcellulose were dissolved in 30 parts of deionized water to prepare a homogeneous slurry. The slurry was wet-granulated for 3 minutes. Plasma-modified wall material (8.5 parts) with a total wall material weight of 85 wt% was added, and granulation was continued for 10 minutes. The granules were then sized using a swivel granulator to obtain wet particles with uniform particle size, which were then transferred to a fluidized bed.

[0040] The remaining 15 wt% of the modified wall material (1.5 parts) was dissolved in 15 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 60℃ and the material temperature to 52℃. Fluidized bed coating was carried out by cut-and-spray coating method. After coating, the material was dried at 55℃ for 30 minutes to obtain glycine magnesium phospholipid complex.

[0041] Example 2 Weigh 35 parts of anhydrous ethanol, add 20 parts of egg yolk lecithin PC70, 3 parts of cholesterol, 15 parts of vitamin D3, and 0.6 parts of mixed tocopherols, heat to 62°C, and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 88°C and the outlet air temperature set to 43°C to spray dry into powder, obtaining a free-flowing film-formed phospholipid powder.

[0042] Weigh 8 parts gum arabic and 4.5 parts concentrated whey protein, place them in a plasma treatment device, select oxygen as the reaction gas medium, and perform surface modification on the wall material.

[0043] The prepared membrane-modified phospholipid powder was mixed with 45 parts of calcium citrate and pulverized using an air jet mill. The particle size D90 was measured to be 75 μm, and the mixture was then transferred to a wet granulator. 1.4 parts of sodium D-isoascorbate and 2.5 parts of sodium carboxymethyl cellulose were dissolved in 25 parts of deionized water to prepare a homogeneous slurry. After wet granulation for 2 minutes, 80 wt% of plasma-modified wall material was added, and granulation continued for 8 minutes. The granules were then sized using a swivel granulator to obtain homogeneous wet particles, which were then transferred to a fluidized bed.

[0044] The remaining 20 wt% of the modified wall material was dissolved in 12 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 58 ℃ and the material temperature to 50 ℃. The coating was carried out by cutting and spraying. After coating, the mixture was dried at 52 ℃ for 25 minutes to obtain a calcium citrate-vitamin D3 compound phospholipid complex.

[0045] Example 3 Weigh 45 parts of anhydrous ethanol, add 35 parts of hydrogenated soybean lecithin PC90, 4 parts of sitosterol and 0.4 parts of rosemary extract, heat to 58°C and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 92°C and the outlet air temperature set to 46°C to spray dry into powder, obtaining film-coated phospholipid powder.

[0046] Weigh out 6 parts of pectin and 6 parts of resistant dextrin, place them in a plasma treatment device, and select air as the reaction gas medium for surface modification.

[0047] The membrane-treated phospholipid powder was mixed with 45 parts of ferrous glycine and pulverized using an air jet mill. The particle size D90 was measured to be 68 μm, and the mixture was then transferred to a wet granulator. 0.6 parts of tea polyphenols and 3 parts of polyethylene glycol were dissolved in 28 parts of deionized water to prepare a slurry. After wet granulation for 3 minutes, 85 wt% of modified wall material was added, and granulation continued for another 9 minutes. The granules were then sized using a swivel granulator and transferred to a fluidized bed.

[0048] The remaining 15 wt% of the modified wall material was dissolved in 10 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 62 ℃ and the material temperature to 53 ℃. After cutting and spraying the coating, it was dried at 55 ℃ for 30 minutes to obtain the glycine ferrous phospholipid complex.

[0049] Example 4 Weigh 40 parts of anhydrous ethanol, add 24 parts of dipalmitoylphosphatidylcholine (DPPC), 6 parts of mono- and diglycerides of fatty acids, and 0.4 parts of α-tocopherol, heat to 65°C, and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 85°C and the outlet air temperature set to 42°C to spray dry into powder, obtaining film-coated phospholipid powder.

[0050] Weigh out 5 parts gelatin and 7 parts oligomaltose, place them in a plasma treatment device, and use oxygen as the reaction gas medium to perform surface modification.

[0051] The membrane-coated phospholipid powder was mixed with 52 parts of zinc gluconate and pulverized using an air jet mill. The particle size D90 was measured to be 82 μm, and the mixture was then transferred to a wet granulator. 0.6 parts of calcium ascorbate and 5 parts of pectin were dissolved in 32 parts of deionized water to prepare a slurry. After wet granulation for 2.5 minutes, 82 wt% of modified wall material was added, and granulation continued for another 10 minutes. The granulated material was then transferred to a fluidized bed.

[0052] The remaining 18 wt% of the modified wall material was dissolved in 14 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 55℃ and the material temperature to 48℃. After cutting and spraying coating, the solution was dried at 50℃ for 28 minutes to obtain zinc gluconate phospholipid complex.

[0053] Example 5 Weigh 90 parts of anhydrous ethanol, add 28 parts of sunflower lecithin PC95, 4.5 parts of ergosterol, 4 parts of vitamin D3, 30 parts of retinyl acetate, and 0.3 parts of β-carotene. Heat to 60°C and stir until completely dissolved. Use a closed-loop spray dryer with an inlet air temperature of 87°C and an outlet air temperature of 44°C to spray dry into powder, obtaining a phospholipid powder loaded with vitamin D3 and retinyl acetate, with a particle size D90 of 70 μm.

[0054] Weigh 20 parts of octenyl succinate arabic ester and 10 parts of maltodextrin, place them in a plasma treatment device, and select air as the reaction gas medium for surface modification.

[0055] The membrane-coated phospholipid powder was transferred to a wet granulator. 0.5 parts of glutathione and 2.7 parts of gum arabic were dissolved in 26 parts of deionized water to prepare a slurry. After wet granulation for 3 minutes, 88 wt% of modified wall material was added, and granulation was continued for another 8 minutes. After granulation, the granules were transferred to a fluidized bed.

[0056] The remaining 12 wt% of the modified wall material was dissolved in 9 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 52 ℃ and the material temperature to 46 ℃. After cutting and spraying coating, the solution was dried at 48 ℃ for 25 minutes to obtain a vitamin A-vitamin D3 compound phospholipid complex.

[0057] Example 6 Weigh 78 parts of anhydrous ethanol, add 30 parts of DOPC, 10 parts of microalgae sterol and 0.2 parts of tert-butylhydroquinone (TBHQ), heat to 63°C and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 95°C and the outlet air temperature set to 47°C to spray dry into powder, obtaining film-coated phospholipid powder.

[0058] Weigh 7 parts of zein and 4 parts of inulin, place them in a plasma treatment device, and select air as the reaction gas medium for surface modification.

[0059] The membrane-modified phospholipid powder was mixed with 46 parts of folic acid and pulverized using an air jet mill. The particle size D90 was measured to be 65 μm, and the mixture was then transferred to a wet granulator. 0.4 parts of disodium ethylenediaminetetraacetate and 2.4 parts of sodium alginate were dissolved in 29 parts of deionized water to prepare a slurry. After wet granulation for 2 minutes, 85 wt% of modified wall material was added, and granulation continued for another 9 minutes. The granulated material was then transferred to a fluidized bed.

[0060] The remaining 15 wt% of the modified wall material was dissolved in 11 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 65℃ and the material temperature to 55℃. After cutting and spraying the coating, it was dried at 55℃ for 32 minutes to obtain the folic acid phospholipid complex.

[0061] Example 7 Weigh 100 parts of anhydrous ethanol, add 50 parts of flaxseed lecithin PC70, 8.5 parts of phytosterol esters, 0.2 parts of tea polyphenol palmitate, and 30 parts of vitamin E (dl-α-tocopherol acetate). Heat to 60°C and stir for 30 minutes until all fat-soluble components are completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 90°C and the outlet air temperature to 45°C to spray dry into powder, obtaining a film-coated phospholipid powder containing vitamin E.

[0062] Weigh out 5 parts guar gum and 4 parts maltitol, place them in a plasma treatment device, select oxygen as the reaction gas medium, set the power to 300W and the treatment time to 15 minutes, and perform surface modification on the wall material to enhance its compatibility with phospholipids.

[0063] The obtained vitamin E-containing membrane-modified phospholipid powder was separately transferred to an air jet mill, and the milling pressure was adjusted to 0.7 MPa. After milling, the particle size D90 was measured to be 72 μm, and then transferred to a wet granulator. 0.3 parts of sodium ascorbate and 2 parts of hydroxypropyl methylcellulose were dissolved in 27 parts of deionized water and stirred until completely dissolved to obtain a homogeneous slurry. This slurry was added to the wet granulator, and granulation was carried out at low speed for 2.5 minutes. Then, 83 wt% of plasma-modified wall material was added, and granulation was continued for 9 minutes. The granules were then sized using a 1.2 mm sieve vibrating granulator and transferred to a fluidized bed.

[0064] The remaining 17 wt% of the modified wall material was dissolved in 11 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 56℃, the material temperature to 49℃, and a cut-and-spray coating method was used. After coating, the inlet air temperature was maintained at 51℃ for drying for 26 minutes to obtain a vitamin E phospholipid complex.

[0065] Example 8 Weigh 56 parts of anhydrous ethanol, add 35 parts of soybean lecithin PC90, 3 parts of sitosterol, 2.5 parts of sterol esters and 0.4 parts of ascorbate palmitate, heat to 63°C and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 89°C and the outlet air temperature set to 44°C to spray dry into powder, obtaining film-coated phospholipid powder.

[0066] Weigh out 6 parts xanthan gum and 3.6 parts fructooligosaccharides, place them in a plasma treatment device, and select air as the reaction gas medium for surface modification.

[0067] The membrane-modified phospholipid powder was mixed with 25 parts of vitamin B2 (riboflavin) and 20 parts of vitamin B6 (pyridoxine hydrochloride), and pulverized using an air jet mill. The particle size D90 was measured to be 69 μm, and the mixture was then transferred to a wet granulator. 0.5 parts of citrus flavonoids and 4 parts of pectin were dissolved in 24 parts of deionized water to prepare a slurry. After wet granulation for 3 minutes, 86 wt% of modified wall material was added, and granulation continued for another 8 minutes. The granules were then sized using a swirl granulator and transferred to a fluidized bed.

[0068] The remaining 14 wt% of the modified wall material was dissolved in 10 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 54℃ and the material temperature to 47℃. After cutting and spraying coating, the solution was dried at 49℃ for 24 minutes to obtain a vitamin B2-B6 compound phospholipid complex.

[0069] Example 9 Weigh 90 parts of anhydrous ethanol, add 35 parts of hydrogenated sunflower lecithin PC95, 5 parts of sitosterol, 0.4 parts of α-tocopherol, 2 parts of retinyl acetate, 2 parts of vitamin D3, 2 parts of dl-α-tocopherol acetate, 2 parts of vitamin K1, and 2 parts of vitamin K2. Heat to 60°C and stir until completely dissolved. Use a closed-loop spray dryer with the inlet air temperature set to 86°C and the outlet air temperature set to 45°C to spray dry into powder, obtaining a membrane-bound phospholipid powder loaded with vitamins A, D, E, and K.

[0070] Six parts of sodium octenyl succinate starch and four parts of casein were weighed and placed in a plasma treatment device. Air was selected as the reaction gas medium for surface modification.

[0071] The membrane-treated phospholipid powder was mixed with 3 parts calcium gluconate, 3 parts magnesium glycine, 3 parts zinc gluconate, 3 parts ferrous fumarate, 3 parts sodium selenite, 3 parts potassium iodide, 2 parts vitamin B1, 2 parts vitamin B2, 2 parts vitamin B6, 2 parts vitamin B12, 2 parts nicotinic acid, 2 parts folic acid, and 4 parts vitamin C. The mixture was then pulverized using an air jet mill, and the particle size D90 was measured to be 80 μm. The pulverized powder was then transferred to a wet granulator. 1.6 parts tea polyphenols and 4 parts gum arabic were dissolved in 24 parts deionized water to prepare a slurry. After wet granulation for 3 minutes, 82 wt% of modified wall material was added, and granulation continued for 10 minutes. The granulated powder was then transferred to a fluidized bed after being granulated using a swivel granulator.

[0072] The remaining 18 wt% of the modified wall material was dissolved in 10 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 55℃ and the material temperature to 46℃. After cutting and spraying coating, the mixture was dried at 50℃ for 30 minutes to obtain a multi-dimensional and multi-mineral compound phospholipid complex.

[0073] In Examples 1-9 above, the following formulations were screened, as shown in the table below:

[0074] Based on the formulations and specifications of the raw materials used in the above embodiments, the actual weight ratio of the membrane skeleton material to the phosphatidylcholine (PC) component in the phospholipid can be calculated in each embodiment. Specifically, the weight ratio is calculated as follows: (weight parts of membrane skeleton material) ÷ ​​(weight parts of phospholipid × mass percentage of PC in the phospholipid).

[0075] The phosphatidylcholine (PC) content in Examples 1-9 was tested according to GB509.272. Based on the measured values, the actual weight ratio of the membrane framework material to the phosphatidylcholine (PC) component in the phospholipids in each example was calculated. The calculation results are shown in the table below:

[0076] As shown in the table above, the weight ratio of the membrane skeleton material to phosphatidylcholine (PC) in all embodiments is 1:3 to 1:15, and the weight ratio range of 1:4 to 1:8 is the preferred range of the present invention. This ensures the structural stability of the phospholipid complex, which can effectively improve the bioavailability of nutrients and resist degradation during processing and storage.

[0077] For the embodiments described above, this invention patent further compares and analyzes key factors from three aspects: process route, raw material addition amount, and process parameters. The comparison examples are as follows.

[0078] Comparative Example 1 (Comparison with liposome preparation by thin-film hydration method) Based on Example 2, the impact of the patented process route on product indicators was compared in this comparative example with the traditional thin-film hydration method for preparing liposomes.

[0079] Twenty parts of egg yolk lecithin PC70, three parts of cholesterol, 15 parts of vitamin D3, and 0.6 parts of mixed tocopherols were dissolved in chloroform and evaporated at 50°C and -0.09 MPa for 2 hours using a rotary evaporator to form a lipid film. Forty-five parts of calcium citrate were dispersed in 150 parts of water, and the phospholipid film was eluted with the calcium citrate aqueous solution. The mixture was homogenized using a high-speed shear mill for 5 minutes to obtain a liposome suspension, which was then freeze-dried to obtain calcium citrate-vitamin D3 complex liposomes.

[0080] Comparative Example 2 (Comparison with phospholipid compositions prepared by the mixed granulation method) Based on Example 3, the effects of the patented process route on product indicators were compared in this comparative example with those of the phospholipid composition prepared by the mixed granulation method.

[0081] Six parts of pectin and six parts of resistant dextrin were weighed and placed in a plasma treatment device. Air was selected as the reaction gas medium for surface modification. 45 parts of ferrous glycine, 35 parts of hydrogenated soybean lecithin PC90, 4 parts of sitosterol, 0.4 parts of rosemary extract, and 85 wt% of modified wall material were mixed and subjected to air jet milling. The particle size D90 was measured to be 82 μm. The pulverized material was transferred to a wet granulator. 0.6 parts of tea polyphenols and 3 parts of polyethylene glycol were dissolved in 28 parts of deionized water to prepare a slurry. This slurry was then wet granulated. After granulation, the granules were sized by a swivel granulator and then transferred to a fluidized bed.

[0082] The remaining 15 wt% of the modified wall material was dissolved in 10 parts of deionized water to prepare a coating solution. The fluidized bed inlet air temperature was set to 62°C and the material temperature to 53°C. After cutting and spraying the coating, it was dried at 55°C for 30 minutes to obtain a glycine ferrous phospholipid composition.

[0083] Comparative Example 3 (Comparison with phospholipid-encapsulated microcapsule powder prepared by spray drying process) Based on Example 5, the impact of the patented process route on product indicators was compared in this comparative example with that of phospholipid-encapsulated microcapsule powder prepared by conventional spray drying process.

[0084] Dissolve 20 parts of octenyl succinate arabinose and 10 parts of maltodextrin in water and stir at 60°C. Then add 28 parts of sunflower lecithin PC95 and 4.5 parts of ergosterol, and disperse by shearing. Add 0.5 parts of glutathione to dissolve. This is the aqueous phase.

[0085] Mix 30 parts of retinyl acetate with 4 parts of vitamin D3, melt in a 60°C water bath, and add 0.3 parts of β-carotene to form the oil phase.

[0086] The oil phase was added to the aqueous phase and stirred at 60°C for 1 hour. After shearing and homogenization, it was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 78°C to obtain vitamin A-vitamin D3 phospholipid-encapsulated microcapsule powder.

[0087] Comparative Example 4 (using unmodified plasma wall material) Based on Example 6, the impact of plasma modification treatment on product quality was compared. In this comparative example, unmodified wall material was used, and the amount of other raw materials added and process parameters were kept the same as in Example 6.

[0088] Weigh anhydrous ethanol, add DOPC, microalgae sterol, and TBHQ, and stir until completely dissolved. Use a closed-loop spray dryer to dry the solution into powder, obtaining film-coated phospholipid powder.

[0089] The membrane-treated phospholipid powder was mixed with folic acid, pulverized using an air jet mill, and then transferred to a wet granulator. Disodium EDTA and sodium alginate were dissolved in deionized water to prepare a slurry. After wet granulation for 2 minutes, 85 wt% of the total wall material (7 parts zein and 4 parts inulin) was added, and granulation was continued for another 9 minutes. After granulation, the granules were transferred to a fluidized bed.

[0090] The remaining 15 wt% of the wall material was added to water, sheared and dispersed to prepare a coating solution, which was then cut-sprayed and coated. After drying at 55°C for 32 minutes, the folic acid phospholipid complex was obtained.

[0091] Comparative Examples 5-6 (Comparison of the amount of phospholipids and membrane framework materials used) Based on Example 7, the effects of the amount of phospholipids and membrane skeleton materials on product indicators were compared. The formula is shown in the table below. The process is the same as in Example 7, and the vitamin E phospholipid complex is finally obtained.

[0092]

[0093] Comparative Example 7 (Comparison of inlet air temperature during spray drying) Based on Example 5, the effect of spray drying inlet air temperature on product indicators was compared. In this comparative example, the spray drying inlet air temperature was increased, while the amount of other raw materials added and process parameters remained the same as in Example 5.

[0094] Anhydrous ethanol was weighed and added to sunflower lecithin PC95, ergosterol, vitamin D3, retinyl acetate, and β-carotene. The mixture was heated to 60°C and stirred until completely dissolved. A closed-loop spray dryer was used, with the inlet air temperature set to 140°C and the outlet air temperature to 70°C, to dry the mixture into powder, obtaining a phospholipid powder loaded with vitamin D3 and retinyl acetate. The subsequent process was the same as in Example 5, ultimately yielding a vitamin A-vitamin D3 complex phospholipid compound.

[0095] Comparative Example 8 (without fluidized bed coating) Based on Example 8, the impact of not performing fluidized bed coating on product indicators was compared. In this comparative example, the amount of raw materials added and other process parameters were kept the same as in Example 8, except that all wall materials were added during the granulation stage.

[0096] Comparative Example 9 (Comparison of Fluidized Bed Coating Methods) Based on Example 8, the impact of fluidized bed coating method on product indicators was compared. In this comparative example, the traditional bottom spray coating method was used, and the amount of raw materials added and other process parameters were kept the same as in Example 8.

[0097] Effect Comparison Group 1. Sensory / Physicochemical Index Evaluation The phospholipid complexes, liposomes, and microcapsule powder samples prepared in Examples 1-9 and Comparative Examples 1-9 were evaluated based on the following indicators: product state, odor, angle of repose, solvent residue, and loss rate.

[0098] Status: Visual.

[0099] Smell: to smell.

[0100] Angle of repose: Measured using an angle of repose measuring instrument.

[0101] Solvent residue: determined using a headspace sampler in conjunction with gas chromatography.

[0102] Loss rate: The actual content of the target nutrient in the final sample is determined, and the loss rate is calculated as (theoretical content - actual content) / theoretical content * 100%.

[0103]

[0104] Based on the evaluation results of phospholipid complex indicators, the test results of product state, odor, angle of repose, and other indicators of different embodiments and comparative examples can be compared.

[0105] State: The phospholipid complexes in Examples 1-9 were all free-flowing fine particles, indicating excellent flowability. In contrast, the product in Comparative Example 1 was in fragmented form because it was freeze-dried. To achieve better flowability, further pulverization is often necessary. Comparative Example 7 exhibited slight pseudo-agglomeration because the high inlet air temperature during spray drying caused slight charring of the phospholipids and loaded nutrients, resulting in slight material adhesion and pseudo-agglomeration after subsequent product preparation.

[0106] Odor: The phospholipid complexes in Examples 1-9 have no obvious odor, while Comparative Examples 3 and 7 have a slight phospholipid odor. This is because the spray drying temperature is high, which causes the phospholipids to undergo a certain degree of oxidation, resulting in an oxidized odor.

[0107] Angle of repose: The angle of repose of particles is an important parameter describing the packing characteristics of particles (including powders) in a static state. It reflects the flowability of the powder; the smaller the angle of repose, the better the flowability of the particles. Better particle flowability improves process coordination and production efficiency in downstream processing such as tableting and capsule filling. The phospholipid complexes in Examples 1-9 have an angle of repose in the range of 36-41°, indicating very good flowability, while the angles of repose in Comparative Examples 1 and 7 are relatively larger, indicating relatively poorer flowability.

[0108] Solvent residue: The process of this patent can effectively remove the organic solvents used in the process. The solvent residue of the phospholipid complexes in Examples 1 to 9 is less than 100 ppm. Loss Rate: Nutrient loss during the process is a significant factor affecting product quality and cost. In Examples 1-9 of this invention, the loss rate of the target components of the phospholipid complexes is less than 2%, indicating excellent process control and maintenance of nutrient stability during preparation. In Comparative Examples 3 and 7, the loss rates of Vitamin A and Vitamin D are significantly increased due to improper process conditions, leading to thermal degradation of the nutrients. Compared to Example 6, Comparative Example 4 shows a slightly higher loss rate of folic acid because the wall material used was not plasma-modified, resulting in a slightly poorer encapsulation effect and causing a certain degree of degradation of the target component during drying. Compared to Example 7, Comparative Examples 5 and 6 also show a slightly higher loss rate of Vitamin E because the formulations in Comparative Examples 5 and 6 are not within the optimal range, leading to leakage of the loaded components and content loss during the preparation of the membrane-coated phospholipid powder.

[0109] The analysis of the above indicators only reflects the initial level of the product, so it is necessary to further compare the acceleration stability of each group.

[0110] Effect Comparison Group 2. Acceleration Stability Assessment The samples prepared in Examples 1-9 and Comparative Examples 1-9 were subjected to accelerated testing at 60°C to observe the product status and determine the retention rate of the target nutrients.

[0111] Retention rate: The actual content of the target nutrient in the sample before and after acceleration is determined, and the accelerated retention rate is calculated as (initial content - content after acceleration) / initial content * 100%.

[0112] Evaluation results of indicators for each group of samples after 20 days of accelerated testing

[0113] Sensory indicators: After 20 days of accelerated testing at 60°C, the state and odor of the phospholipid complexes in Examples 1-9 did not change significantly. Comparative Examples 1 and 7 showed more pseudo-agglomeration after acceleration, reflecting the relationship between product state and preparation process and parameters. Comparative Example 2 exhibited a metallic odor after acceleration, indicating that a simple and direct granulation process cannot achieve sufficient encapsulation; despite using hydrogenated phospholipids, the interaction with iron ions still produced an unpleasant odor. The phospholipid odor in Comparative Examples 3 and 7 after acceleration is due to the higher temperatures encountered during the process, which accelerated phospholipid oxidation, highlighting the necessity of the optimized process conditions for solvent spray drying in this invention.

[0114] Retention Rate: After 20 days of accelerated processing at 60°C, the phospholipid complexes of Examples 1-9 showed mineral retention rates exceeding 98% and vitamin retention rates exceeding 90%, demonstrating excellent accelerated stability. However, the nutrient retention rates in each comparative example decreased to varying degrees. For instance, compared to Example 2, Comparative Example 1 showed a lower vitamin D3 retention rate because it lacked wall material encapsulation, resulting in poor stability. Compared to Example 5, Comparative Examples 3 and 7 showed lower vitamin A and vitamin D3 retention rates because improper process methods and parameters led to degradation during product preparation, which in turn triggered further degradation. The retention rates of Comparative Examples 4, 5, and 6 were lower than those of Examples 6 and 7 because of inappropriate formulation selection (Comparative Example 4) or addition ratios outside the optimal range (Comparative Examples 5 and 6). Compared to Comparative Examples 8 and 9, Example 8 showed the highest retention rate, followed by Comparative Example 9. This is because Comparative Example 9 used bottom-spray coating, which improves retention compared to no coating process, while Example 8 used cut-spray coating, which further protects the core components, resulting in an even higher retention rate. Analysis of the retention rate indicators of various embodiments and comparative examples shows the importance of the preferred formulation, process, and process parameters in this invention patent for product quality.

[0115] The above results of the accelerated stability test further illustrate the necessity of optimizing the preparation process, process parameters, formulation selection, raw material ratio, and other conditions.

[0116] Effect Comparison Group 3. Bioavailability compared to liposomes Using a rat model, the differences in bioavailability between the phospholipid complex prepared by this invention and the corresponding raw materials and liposome products were investigated.

[0117] Eighteen rats were randomly divided into three groups of six each: the raw material group, the example group, and the comparative group. Calcium citrate and vitamin D3 (raw material group, a mixture of 45 parts calcium citrate and 15 parts vitamin D3), calcium citrate-vitamin D3 phospholipid complex (Example 2), and calcium citrate-vitamin D3 liposomes (Comparative Example 1) were dispersed and dissolved in 0.5% sodium carboxymethyl cellulose solution to prepare a suspension with a vitamin D3 concentration of 5 mg / mL.

[0118] Rats were fasted for 12 hours before gavage and resumed eating after gavage. Blood samples of 0.5 mL were collected from the orbital venous plexus of all rats at 0 h before administration and at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0 h, 12.0 h, and 24.0 h after administration. Plasma calcium levels were measured at each time point. 2+ Calculate the area under the blood drug concentration curve (AUC) based on the concentration of vitamin D3.

[0119] Using the relative bioavailability of the target component in the raw material group as 100%, the Ca2+ values ​​of the example group and the comparative group were calculated separately. 2+ The relative bioavailability of vitamin D3 is shown in the table below.

[0120] Each group of Ca 2+ Relative bioavailability:

[0121] Relative bioavailability of vitamin D3 in each group:

[0122] Compared to calcium citrate and vitamin D3 raw materials, both the calcium citrate-vitamin D3 phospholipid complex (Example 2) and the calcium citrate-vitamin D3 liposomes (Comparative Example 1) significantly improve bioavailability. Products prepared using this patented technology can significantly improve the bioavailability of nutrients, and their effects are comparable to traditional liposome products. However, in terms of process, this patented technology is more suitable for industrialization, and the process does not require freeze-drying, thus saving manufacturing costs. Regarding stability, due to the multi-layer encapsulation process employed in this patented technology, its stability is superior to that of traditional liposomes.

[0123] Taking all indicators into account, this invention patent can take into account the advantages of bioavailability, saving process costs, and improving shelf-life stability, and is generally superior to traditional liposome products.

[0124] Effect Comparison Group 4. Bioavailability compared with phospholipid-encapsulated microcapsule powder Using a rat model, the bioavailability differences between the phospholipid complex prepared by this invention and the corresponding raw materials and phospholipid-encapsulated microcapsule products were investigated.

[0125] Eighteen rats were randomly divided into three groups of six each: the raw material group, the example group, and the comparative group. Retinyl acetate (raw material group), vitamin A-vitamin D3 phospholipid complex (Example 5), and vitamin A-vitamin D3 phospholipid encapsulated powder (Comparative Example 3) were dispersed and dissolved in a 0.5% sodium carboxymethyl cellulose + 0.1% sucrose fatty acid ester solution to prepare a suspension with a vitamin A concentration of 5 mg / mL.

[0126] Rats were fasted for 12 hours before gavage and resumed eating after gavage. Blood samples of 0.5 mL were collected from the orbital venous plexus of all rats before administration (0 h) and at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0 h, 12.0 h, and 24.0 h after administration. The concentration of vitamin A in plasma was measured at each time point, and the area under the blood drug concentration curve (AUC) was calculated.

[0127] The relative bioavailability of vitamin A in the raw material group was taken as 100%. The relative bioavailability of vitamin A in the example group and the comparative group was calculated separately, as shown in the table below.

[0128] Relative bioavailability of vitamin A in each group:

[0129] Compared to retinyl acetate, both the vitamin A-vitamin D3 phospholipid complex (Example 5) and the vitamin A-vitamin D3 phospholipid-encapsulated microcapsule powder (Comparative Example 3) significantly improve bioavailability because they both alter the crystal structure of vitamin A, making it easier for the body to absorb. Furthermore, the phospholipid complex product prepared using this patented invention exhibits significantly higher bioavailability than ordinary phospholipid-encapsulated microcapsule powder, indicating a connection to the preparation process. This patented invention, through the pre-preparation of membrane-like phospholipid powder, enables phospholipids to spontaneously form a bilayer structure, rather than a colloidal or aggregated state. This, in turn, effectively improves bioavailability after further complexing with nutrients.

[0130] Effect Comparison Group 5. Comparison of Bioavailability Effects Among Different Formulations Using a rat model, the differences in bioavailability of phospholipid complexes prepared with different formulations according to this invention were investigated.

[0131] Eighteen rats were randomly divided into three groups of six each: the raw material group, the example group, and the comparative example group. dl-α-tocopherol acetate (raw material group) and vitamin E phospholipid complex (Example 7, Comparative Example 5) were dispersed and dissolved in a 0.5% sodium carboxymethyl cellulose + 0.1% sucrose fatty acid ester solution to prepare a suspension with a vitamin E concentration of 5 mg / mL.

[0132] Rats were fasted for 12 hours before gavage and resumed eating after gavage. Blood samples of 0.5 mL were collected from the orbital venous plexus of all rats before administration (0 h) and at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0 h, 12.0 h, and 24.0 h after administration. The concentration of vitamin E in plasma was measured at each time point, and the area under the blood drug concentration curve (AUC) was calculated.

[0133] The relative bioavailability of vitamin E in the raw material group was taken as 100%. The relative bioavailability of vitamin E in the example group and the comparative group was calculated separately, as shown in the table below.

[0134] Relative bioavailability of vitamin E in each group:

[0135] Compared to dl-α-tocopherol acetate, the vitamin E phospholipid complex (Example 7 and Comparative Example 5) significantly improves bioavailability because the preparation as a phospholipid complex allows it to form smaller droplets in the gastrointestinal environment, making it easier for the body to absorb. Furthermore, the vitamin E phospholipid complex prepared using the preferred formulation of this invention has higher bioavailability than the non-preferred formulation. In this comparative group, Comparative Example 5 appropriately reduced the amount of phospholipid and increased the amount of phytosterol esters, causing the weight ratio of the membrane framework material to the phosphatidylcholine component in its formulation to exceed the preferred range, resulting in poorer absorption and lower bioavailability than Example 7.

[0136] It should be understood that the above embodiments are only for illustrating the technical solutions of the present invention more clearly, and are not intended to limit the scope of protection thereof. Those skilled in the art can make various modifications and variations to the above embodiments without departing from the spirit and basic principles of the present invention, but these modifications and variations still fall within the protection scope of the claims of the present invention and their equivalents. The scope of protection of the present invention should be determined by the appended claims, and should not be limited to the specific embodiments described above.

Claims

1. A phospholipid complex with high bioavailability, characterized in that: Composed of the following raw materials in parts by weight: Nutrients 30-70 parts, phospholipids 15-50 parts, membrane skeleton material 2-10 parts, antioxidants 0.2-2 parts, wall material 5-30 parts, adhesive 2-5 parts; The phospholipids mentioned are selected from at least one of natural phospholipids, hydrogenated phospholipids, and synthetic phospholipids; The membrane framework material is selected from at least one of cholesterol, phytosterols, mono- and diglycerides of fatty acids, fatty acids, and vegetable oils; The antioxidants mentioned include fat-soluble antioxidants and water-soluble antioxidants; The fat-soluble antioxidant is selected from at least one of ascorbyl palmitate, mixed tocopherols, α-tocopherol, tocotrienols, β-carotene, lycopene, lutein, zeaxanthin, rosemary extract, carrageenan, rosmarinic acid, quercetin, glycyrrhizin, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and tert-butylhydroquinone. The water-soluble antioxidant is selected from at least one of ascorbic acid, sodium ascorbate, calcium ascorbate, D-isoascorbic acid, sodium D-isoascorbate, disodium EDTA, chlorogenic acid, cysteine, glutathione, tea polyphenols, citrus flavonoids, and proanthocyanidins. The wall material includes at least one of the following: sodium octenyl succinate starch, gum arabic octenyl succinate, corn starch, gum arabic, gelatin, carrageenan, pectin, xanthan gum, maltodextrin, solid corn syrup, resistant dextrin, inulin, maltodextrin, isomaltooligosaccharide, maltitol, whey protein concentrate, whey protein isolate, hydrolyzed whey protein, zein, casein, and sodium caseinate. The adhesive comprises at least one of methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, polyethylene glycol, gum arabic, pectin, gelatin, and sodium alginate.

2. The phospholipid complex according to claim 1, characterized in that: It has a phospholipid-wall material double or multilayer encapsulation structure composed of the membrane-formed phospholipid and the wall material.

3. The phospholipid complex according to claim 1, characterized in that: The nutrients mentioned are minerals, vitamins, or combinations thereof.

4. The phospholipid complex according to claim 3, characterized in that: The vitamins mentioned are selected from at least one of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, and vitamin K.

5. The phospholipid complex according to claim 3, characterized in that: The minerals mentioned are selected from at least one of calcium, magnesium, zinc, iron, potassium, manganese, copper, sodium, chromium, selenium, iodine, and phosphorus.

6. The phospholipid complex according to claim 3, characterized in that: The minerals mentioned are selected from calcium glycinate, calcium L-aspartate, calcium L-lactic acid, calcium carbonate, calcium citrate, calcium citrate-malate, calcium fructose-borate, calcium malate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, glycerol calcium phosphate, calcium oxide, calcium sulfate, calcium gluconate, magnesium chloride, magnesium carbonate, magnesium oxide, magnesium glycinate, magnesium gluconate, magnesium hydrogen phosphate, magnesium taurate, magnesium sulfate, magnesium lactate, magnesium malate, magnesium fumarate, magnesium threonate, magnesium succinate (magnesium succinate), magnesium L-aspartate, ferrous glycinate, ferrous sulfate, ferrous pyrophosphate, ferrous fumarate, ferric sodium EDTA, ferrous gluconate, ferrous citrate, ferric ammonium citrate, and ferric phosphate. The following are at least one of the following: zinc glycinate, zinc sulfate, zinc gluconate, zinc citrate, zinc oxide, zinc lactate, zinc chloride, zinc acetate, zinc malate, zinc L-aspartate, manganese glycinate, manganese sulfate, manganese chloride, manganese carbonate, manganese gluconate, manganese citrate, manganese L-aspartate, copper sulfate, copper glycinate, copper gluconate, copper citrate, copper carbonate, potassium chloride, potassium citrate, potassium dihydrogen citrate, potassium L-aspartate, potassium gluconate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium bicarbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium citrate, sodium chloride, sodium L-aspartate, sodium selenite, sodium selenate, potassium iodide, potassium iodate, sodium iodide, chromium sulfate, and chromium chloride.

7. The phospholipid complex according to claim 1, wherein the weight ratio of the membrane framework material to the phosphatidylcholine component in the phospholipid is 1:3 to 1:15; and the phosphatidylcholine content in the phospholipid is greater than 50 wt%.

8. The method for preparing the phospholipid complex according to claim 1, comprising the following steps: S1. Phospholipids, membrane framework materials, fat-soluble nutrients and fat-soluble antioxidants are dissolved in an organic solvent at 40~80℃ and spray-dried to obtain membrane-coated phospholipid powder. S2. The wall material is subjected to low-temperature plasma treatment to obtain the modified wall material; S3. Thoroughly mix the membrane-coated phospholipid powder obtained in step S1 with non-fat-soluble nutrients and then pulverize it; S4. Dissolve the water-soluble antioxidant and binder completely in water to make a granulation slurry; perform wet granulation on the material obtained in step S3; after preliminary molding, add some of the modified wall material obtained in step S2, and continue granulation and shaping to obtain a phospholipid complex with uniform particle size. S5. Disperse the remaining modified wall material after step S4 in water to prepare a coating solution; use the phospholipid complex obtained in S4 as a base material for coating and drying to obtain the final product.

9. The method according to claim 8, characterized in that: The spray drying in S1 is carried out using a closed-loop spray drying process, with the inlet air temperature controlled at 70°C to 110°C.

10. The method according to claim 8, characterized in that: The pulverization method is air jet milling, and the particle size D90 after pulverization is 10μm~100μm.

11. The method according to claim 8, characterized in that: The S4 wet granulation process involves adding 60wt% to 95wt% of the modified wall material obtained from S2 during the granulation process.

12. The method according to claim 8, characterized in that: The coating method in S5 is cut-and-spray coating. During the coating process, the air inlet temperature is controlled at 40~70℃ and the material temperature is maintained at 35~60℃.

13. The use of the phospholipid complex as described in claim 1 in the preparation of foods, health products or pharmaceuticals for improving the bioavailability and stability of nutrients.

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