Salidroside multilayer microcapsule powder

Abstract

The present application provides a salidroside multilayer microcapsule powder comprising salidroside; an inner layer covering the salidroside, the inner layer comprising chitosan or gelatin, and gum arabic; and an outer layer covering the inner layer, the outer layer comprising resistant dextrin, trehalose, and hydrolyzed whey protein or hydrolyzed soy protein. The present application also discloses a food, beverage, nutritional product, dietary supplement, or cosmetic comprising the salidroside multilayer microcapsule powder, and a method for preparing the salidroside multilayer microcapsule powder.

Description

Technical Field

[0001] This invention belongs to the technical fields of health food, cosmetics, and pharmaceutical preparations. Specifically, this invention relates to a multilayer microcapsule powder of rhodioloside prepared by complex coagulation method using gum arabic and chitosan as wall materials. Background Technology

[0002] Rhodiola rosea has historically been used as a valuable herbal supplement due to its remarkable adaptogenic properties. Rhodioloside is the main active compound isolated from Rhodiola rosea. Rhodioloside possesses various pharmacological effects, including anti-fatigue, immunomodulatory, and free radical scavenging. As a compound with broad pharmacological activity, rhodioloside exhibits multifaceted health-promoting effects. It has broad application prospects in health products, pharmaceuticals, and cosmetics.

[0003] Rhodioloside has a strong bitter taste, which would severely affect the palatability of oral liquids, solid beverages, and other food and health products if used directly, thus limiting its application. Furthermore, rhodioloside is sensitive to light, heat, oxygen, and acid / alkaline environments, and is highly susceptible to degradation during routine food or pharmaceutical processing (such as high-temperature sterilization) and long-term storage, leading to the loss of its active ingredients.

[0004] To overcome the problems associated with rhodioloside-related products, some studies have utilized chitosan-sodium alginate microencapsulation technology to encapsulate crude rhodioloside extracts. However, the rhodioloside content in the crude extracts is low, and the in vivo sustained-release performance is unclear. He Lili et al. prepared rhodioloside-chitosan nanoparticles using a solvent diffusion-ion crosslinking method, which showed some sustained-release efficacy in in vitro drug release experiments, but the average particle size was greater than 200 nm, resulting in poor stability. Chen Sha et al. prepared thermosensitive mesoporous silica nanoparticles loaded with rhodioloside; however, unprotected rhodioloside is easily destroyed by highly acidic gastric juices when passing through the stomach, failing to reach the intestines intact for absorption, leading to low bioavailability.

[0005] Fan Minghui conducted a systematic study on rhodioloside nanoliposomes. CN113041169A discloses lyophilized rhodioloside liposome powder, and CN107898758A discloses a method for preparing PEGylated nanoliposomes encapsulated with rhodioloside. Although liposome technology improves stability and bioavailability to some extent, the preparation process is complex and requires the use of large amounts of organic solvents such as ethanol and chloroform, resulting in high requirements for industrial production and posing safety and pollution risks. In addition, rhodioloside liposomes have strong lipid solubility, which can trigger an immune response and be rapidly cleared by macrophages in the reticuloendothelial system, leading to a rapid decrease in blood drug concentration.

[0006] Traditional single-layer complex coagulated microcapsules (such as those using only chitosan and gum arabic) have thin walls, which are prone to rupture or wall collapse during the subsequent high-temperature spray drying process, resulting in low encapsulation efficiency; in addition, the water solubility and intestinal-targeted release control capabilities of single-layer microcapsule powders are somewhat insufficient.

[0007] Therefore, developing a multilayer rhodioloside formulation with high encapsulation efficiency, high safety, strong heat resistance and stability, precise intestinal targeted release, high bioavailability, excellent flavor masking and instant dissolution properties, which can be used in food, beverages, nutritional products, dietary supplements or cosmetics, has important practical significance and application value. Summary of the Invention

[0008] This invention uses gum arabic, chitosan, and / or gelatin as wall materials, and initiates a complex coagulation reaction by adjusting the pH to form primary microcapsules; then hydrolyzed protein, as well as excipients such as trehalose and resistant dextrin as protective agents, are added to form multilayer microcapsules; and then spray drying is used to obtain rhodioloside multilayer microcapsule powder.

[0009] In one aspect, the present invention provides a rhodioloside multilayer microcapsule powder comprising rhodioloside; an inner layer coating the rhodioloside, the inner layer comprising chitosan or gelatin and gum arabic; and an outer layer coating the inner layer, the outer layer comprising resistant dextrin, trehalose, and hydrolyzed whey protein or hydrolyzed soy protein.

[0010] In some embodiments, the mass ratio of chitosan or gelatin to gum arabic is 1:5 to 1:2. In some embodiments, the mass ratio of chitosan or gelatin to gum arabic can be 1:4 to 1:2, preferably 1:3.

[0011] In some implementations, the inner layer may also contain PEG400.

[0012] In some implementations, the mass ratio of resistant dextrin to hydrolyzed whey protein or hydrolyzed soy protein is 3:10 to 3:5.

[0013] In some embodiments, the outer layer may also contain excipients such as sodium dihydrogen phosphate and / or potassium dihydrogen phosphate, sodium caseinate, etc. In some embodiments, the outer layer may also contain sodium dihydrogen phosphate. In some embodiments, the outer layer may also contain sodium caseinate.

[0014] In some embodiments, the mass ratio of rhodioloside, inner layer, and outer layer is (5-8):(1-3):(0.5-1.5). In some embodiments, the mass ratio of rhodioloside, inner layer, and outer layer can be (6-7):(1.5-2.5):(1-1.2).

[0015] On the other hand, the present invention also provides the application of rhodioloside multilayer microcapsule powder in solid beverages, compressed candies, baked goods, or health foods with intestinal controlled release requirements.

[0016] In another aspect, the present invention provides a food, beverage, nutritional product, dietary supplement or cosmetic comprising the rhodioloside multilayer microcapsule powder as described above.

[0017] In another aspect, the present invention provides a method for preparing rhodioloside multilayer microcapsule powder, comprising: Step (1) Dissolve rhodioloside and gum arabic in water to obtain solution A; Step (2) Dissolve chitosan or gelatin in an acidic aqueous solution to obtain solution B; add solution B to solution A, adjust the pH to 2.5-5.0 using an acidic aqueous solution, and stir at 40-50℃ to obtain a suspension; Step (3) Centrifuge the suspension, discard the supernatant, and obtain the primary microcapsule precipitate; Step (4) Dissolve sodium dihydrogen phosphate and / or potassium dihydrogen phosphate, resistant dextrin, hydrolyzed whey protein or hydrolyzed soy protein, and trehalose in water to obtain solution C; add solution C to the primary microcapsule precipitate to obtain a multilayer microcapsule suspension; Step (5) Dry the multilayer microcapsule suspension to obtain rhodioloside multilayer microcapsule powder.

[0018] In some embodiments, in step (1), stirring is performed at 40-50°C and 200-400 rpm. In some embodiments, in step (1), stirring is performed at 45°C and 300 rpm.

[0019] In some implementations, PEG400 may also be dissolved in solution A.

[0020] In some embodiments, the acidic aqueous solution is an aqueous solution of acetic acid or citric acid with a mass fraction of 1-12%.

[0021] In some implementations, in step (2), chitosan or gelatin is dissolved in an aqueous solution of acetic acid or citric acid with a mass fraction of 1-3%.

[0022] In some embodiments, solution B is added dropwise to solution A. In some embodiments, the dropping rate is 1-5 mL / min, preferably 2-4 mL / min.

[0023] In some implementations, in step (2), the pH is adjusted to 3.0-4.5 using an aqueous solution of acetic acid or citric acid with a mass fraction of 8-12%, preferably 10%.

[0024] In some embodiments, in step (2), after adjusting the pH, the water bath temperature is maintained at 42-48°C, and the stirring is carried out at 400-600 rpm. In some embodiments, in step (2), after adjusting the pH, the water bath temperature is maintained at 45°C, and the stirring is carried out at 500 rpm.

[0025] In some embodiments, in step (2), the mass ratio of chitosan or gelatin to gum arabic in the suspension is 1:5 to 1:2. In some embodiments, in step (2), the mass ratio of chitosan or gelatin to gum arabic in the suspension can be 1:4 to 1:2, preferably 1:3.

[0026] In some implementations, in step (3), centrifugation is performed at 1500-2500 rpm, preferably 1800-2200 rpm, and more preferably 2000 rpm.

[0027] In some embodiments, after solution C is added, the mixture is stirred at 400-600 rpm, preferably 500 rpm.

[0028] In some implementations, in solution C, the mass ratio of resistant dextrin to hydrolyzed whey protein or hydrolyzed soy protein is 3:10 to 3:5.

[0029] In some implementations, sodium caseinate may also be dissolved in solution C.

[0030] In some embodiments, the drying is spray drying, with an inlet air temperature of 150-200°C and an outlet air temperature of 65-100°C. In some embodiments, the drying is spray drying, with an inlet air temperature of 160-180°C and an outlet air temperature of 75-90°C.

[0031] The beneficial effects of this invention include:

[0032] 1. This invention constructs a dense, multi-layered structure. The dual physical barriers significantly improve stability, effectively isolating oxygen, light, and moisture. Combined with the thermotropic protective effect of trehalose, the material remains intact even under the high-temperature thermal shearing of spray drying, improving the retention rate of rhodioloside during processing and storage. The microcapsule powder prepared by this invention has a high encapsulation rate and excellent powder flowability, without adhesion, solving the problem of the difficulty in directly spray-drying highly active substances into powder.

[0033] 2. This invention utilizes hydrolyzed whey protein, gum arabic, chitosan, and sodium dihydrogen phosphate to form a three-dimensional multilayer network system, which can provide a strong thermal barrier. The microcapsule powder of this invention can not only be used for room temperature preparation, but also has wide applicability in food and beverage products that require baking, hot pressing, and high-temperature sterilization (such as functional baked goods and hot-canned beverages).

[0034] 3. The multiple physical wall materials of this invention completely encapsulate rhodioloside, effectively masking its original bitter taste. The resulting rhodioloside multilayer microcapsule powder has a pure taste and can be directly added to various solid beverages, compressed candies, and baked goods. The outermost wall material contains highly water-soluble hydrolyzed whey protein and resistant dextrin, and trehalose reduces the hygroscopicity of the powder. Sodium dihydrogen phosphate makes the complex cohesive network more robust, resulting in uniform rhodioloside multilayer microcapsule powder particles, good flowability, and resistance to clumping. It exhibits excellent dispersibility and rapid solubility in both hot and cold water, without sticking to the wall or significant stratification. Furthermore, it avoids the phenomenon of lipid floating matter and slow dispersion that easily occurs when liposome freeze-dried powder is added to water.

[0035] 4. The resistant dextrin in the outer layer of this invention is a dietary fiber that cannot be digested by gastric enzymes. It acts as a protective barrier in the extremely acidic environment of gastric juice and the presence of pepsin, preventing the active ingredients from being destroyed by gastric acid. When the microcapsules enter the weakly alkaline intestinal environment, components such as chitosan in the primary microcapsules swell and dissociate, promoting the targeted and sustained release of rhodioloside in the intestine. In contrast, conventional monolayer microcapsules and liposomes suffer severe damage and drug leakage at the front of the gastrointestinal tract. This invention has advantages in targeted delivery to the human body and improved bioavailability.

[0036] 5. The process of this invention does not use any flammable or highly toxic organic solvents, eliminating solvent residue issues and requiring less sophisticated production equipment, making it suitable for most production systems. By employing a step-by-step control method—first purifying the primary microcapsules by centrifugation, then adding an external wall material solution for secondary coagulation—loss of free material due to charge disorder in various systems is avoided. Furthermore, unlike expensive and time-consuming liposome freeze-drying equipment, this invention can be completed using conventional centrifugation and spray drying equipment, resulting in high continuous production efficiency and low cost. Detailed Implementation

[0037] The present invention will now be further described with reference to preferred embodiments thereof. While the invention will be described in conjunction with preferred embodiments, it should be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the spirit and scope of the invention as defined in the claims.

[0038] As used herein, the term “or” is intended to include both “and” and “or”. In other words, the term “or” can also be replaced with “and / or”.

[0039] As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” are intended to include the plural forms as well.

[0040] As used herein, the term “comprising” or “including” or variations thereof means, in its non-restrictive sense, the inclusion of the item following the word, but does not exclude items not specifically mentioned. It also includes the more restrictive verbs 'consistently made up of' and 'comprises from'.

[0041] In this invention, unless otherwise stated, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the laboratory procedures used herein are standard procedures widely used in the relevant fields. Unless otherwise specified, all raw materials and reagents used in this invention are commercially available. All reagents are commercial grade and used according to received standards. Example 1

[0042] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0043] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0044] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0045] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0046] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 2

[0047] Dissolve 6.11 g of rhodioloside and 2.03 g of gum arabic in 20 g of purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0048] Dissolve 0.5 g of chitosan in 10 g of 1% acetic acid aqueous solution and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 3.0 with 10% acetic acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0049] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0050] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, and 0.11 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0051] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 3

[0052] Dissolve 7.01 g rhodioloside and 1.04 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0053] Dissolve 0.5 g of gelatin in 10 g of 1% acetic acid aqueous solution and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 4.0 with 10% acetic acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0054] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0055] Dissolve 0.02 g sodium dihydrogen phosphate, 0.35 g resistant dextrin, 0.64 g hydrolyzed whey protein, and 0.10 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0056] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 4

[0057] Dissolve 6.50 g rhodioloside and 1.56 g gum arabic in 15 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0058] Dissolve 0.5 g of highly water-soluble chitosan in 10 g of purified water and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 4.0 with 10% acetic acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0059] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0060] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.10 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0061] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 5

[0062] Dissolve 6.01 g rhodioloside and 2.00 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0063] 0.5 g of acid-soluble chitosan was dissolved in 8 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0064] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0065] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.82 g hydrolyzed soy protein, and 0.10 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0066] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 6

[0067] Dissolve 6.13 g of rhodioloside and 2.13 g of gum arabic in 20 g of purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0068] 0.5 g of acid-soluble chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.0 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0069] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0070] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, and 0.11 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0071] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 160°C and an outlet air temperature of 75°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 7

[0072] Dissolve 6.12 g rhodioloside, 1.50 g gum arabic, and 0.5 g PEG400 in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0073] Dissolve 0.5 g of chitosan in 10 g of 1% acetic acid aqueous solution and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 4.0 with 10% acetic acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0074] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0075] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, and 0.11 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0076] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 8

[0077] Dissolve 6.02 g rhodioloside and 2.01 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0078] Dissolve 0.5 g of chitosan in 10 g of 3% citric acid aqueous solution and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 4.0 with 10% citric acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0079] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0080] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, and 0.11 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0081] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 9

[0082] Dissolve 7.04 g rhodioloside and 2.10 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0083] 0.5 g of acid-soluble chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.0 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0084] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0085] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, 0.11 g trehalose, and 0.5 g sodium caseinate in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0086] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Example 10

[0087] Dissolve 6.03 g rhodioloside and 2.10 g gum arabic in 15 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0088] 0.5 g of acid-soluble chitosan was dissolved in 10 g of 1% (w / w) aqueous acetic acid solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 4 mL / min. After the addition was complete, the pH of the system was adjusted to 4.0 using 10% aqueous acetic acid solution. The system was then maintained at a water bath temperature of 45°C and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0089] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0090] Dissolve 0.02 g sodium dihydrogen phosphate, 0.32 g resistant dextrin, 0.62 g hydrolyzed whey protein, and 0.11 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0091] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 160°C and an outlet air temperature of 75°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 1

[0092] Weigh out 6.02 g of rhodioloside, 2.03 g of gum arabic, 0.51 g of chitosan, 0.02 g of sodium dihydrogen phosphate, 0.30 g of resistant dextrin, 0.61 g of hydrolyzed whey protein, and 0.12 g of trehalose, and dissolve and disperse them in 40 g of purified water for later use.

[0093] The solution was spray-dried at an inlet temperature of 180°C and an outlet temperature of 85°C. The powder was then collected to obtain rhodioloside microcapsule powder. Comparative Example 2

[0094] Weigh out 7.51 g of rhodioloside, 2.55 g of egg yolk lecithin, and 1.01 g of cholesterol, mix them thoroughly, and then dissolve them in 20 g of anhydrous ethanol.

[0095] The solution prepared in step 1 was added dropwise to 80 g of purified water and stirred at 200 rpm to obtain a dispersion.

[0096] The dispersion was homogenized to obtain a rhodioloside liposome dispersion.

[0097] Add 1.5% trehalose to the homogenized dispersion as a freeze-drying protectant, pre-freeze at -80℃, and freeze-dry to obtain rhodioloside liposome freeze-dried powder. Comparative Example 3

[0098] Weigh out 6.50 g of rhodioloside, 2.50 g of egg yolk lecithin, 0.8 g of cholesterol, and 1.0 g of PEG400. Mix them thoroughly and then dissolve them in 25 g of anhydrous ethanol.

[0099] The solution obtained in step 1 was placed into a rotary evaporator and evaporated under reduced pressure until all the anhydrous ethanol evaporated, yielding a liposome film.

[0100] Add PBS 7.0 buffer solution to a rotary evaporator flask, shake for 3 min, and sonicate for 20 min to obtain liposome hydrated dispersion.

[0101] Add 1.5% trehalose and 5% resistant dextrin to the dispersion in step 3, and then spray dry to obtain rhodioloside liposome powder. Comparative Example 4

[0102] Dissolve 6.02 g rhodioloside and 1.05 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0103] 1.05 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0104] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0105] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0106] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 5

[0107] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0108] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0109] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0110] Dissolve 0.02 g sodium dihydrogen phosphate, 0.60 g resistant dextrin, 0.60 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0111] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 6

[0112] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0113] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 5.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0114] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0115] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0116] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 7

[0117] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0118] Dissolve 0.51 g of pectin in 10 g of 1% acetic acid aqueous solution and stir until clear and transparent to obtain solution B. Add solution B dropwise to solution A at a rate of 2 mL / min. After the addition is complete, adjust the pH of the system to 4.5 with 10% acetic acid aqueous solution, maintain the water bath temperature at 45℃, and stir at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0119] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0120] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0121] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 8

[0122] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0123] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0124] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0125] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g maltodextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0126] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 9

[0127] Dissolve 6.02 g rhodioloside and 2.03 g gum arabic in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0128] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0129] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0130] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed rice protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add this solution entirely to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0131] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Comparative Example 10

[0132] Dissolve 6.02 g rhodioloside and 2.03 g carrageenan in 20 g purified water, keep warm at 45°C, and stir at 300 rpm for 10 min to obtain solution A.

[0133] 0.51 g of chitosan was dissolved in 10 g of 1% acetic acid aqueous solution and stirred until clear and transparent to obtain solution B. Solution B was added dropwise to solution A at a rate of 2 mL / min. After the addition was complete, the pH of the system was adjusted to 4.5 using 10% acetic acid aqueous solution. The system was then maintained at a water bath temperature of 45℃ and stirred at 500 rpm for 30 min to obtain a primary complex coagulated suspension.

[0134] The suspension obtained in step 2 was centrifuged at 2000 rpm for 10 min, and the supernatant was discarded to obtain a loose precipitate of primary microcapsules.

[0135] Dissolve 0.02 g sodium dihydrogen phosphate, 0.30 g resistant dextrin, 0.61 g hydrolyzed whey protein, and 0.12 g trehalose in 10 g purified water to obtain a secondary wall material solution. Add all of this solution to the primary microcapsule precipitate obtained in step 3, and stir at 500 rpm for 30 min at room temperature to obtain a multilayer microcapsule suspension.

[0136] The multilayer microcapsule suspension obtained in step 4 was spray-dried at an inlet air temperature of 180°C and an outlet air temperature of 90°C. The powder was then collected to obtain rhodioloside multilayer microcapsule powder. Test Example 1: Powder Appearance and Encapsulation Efficiency Test

[0137] The moisture content and encapsulation efficiency of rhodioloside in each group of powders were determined. Encapsulation efficiency = (rhodioloside content in microcapsules / total rhodioloside content) × 100%. The test results are shown in the table below:

[0138] This invention, through secondary complex coagulation and the protective effect of trehalose, not only improves the encapsulation rate of rhodioloside (over 94%), but also ensures excellent powder morphology. In contrast, Comparative Example 3 (liposome spray drying) suffered from significant leakage of rhodioloside due to the easy rupture of the liposome bilayer under the high-temperature thermal shear of spray drying, resulting in the lowest encapsulation rate. Comparative Example 1 (monolayer) had a thin shell and its encapsulation ability was also inferior to the multilayer structure of this invention. The encapsulation rates of other comparative examples were all less than 80%, and their flowability was poor. Test Example 2: Masking of Undesirable Flavors and Sensory Evaluation Test

[0139] Twenty trained sensory evaluators were recruited. Each group of samples was dissolved in room temperature water at the same amount of rhodioloside equivalent to prepare aqueous solutions. The evaluators conducted blind evaluations, scoring the solutions on their "bitterness" and "dispersibility" out of 10 (higher scores indicate weaker bitterness and better dispersibility). The test results are shown in the table below:

[0140] The solutions in the example groups had no obvious bitter taste and dissolved in water very quickly, thanks to the excellent water solubility of the outer resistant dextrin and hydrolyzed whey protein, as well as the ability to lock in flavor through dense, multi-layered structures. Comparative Example 1 had a strong bitter taste after reconstitution due to a large amount of unencapsulated rhodioloside; Comparative Example 2, although well-encapsulated, dispersed slowly in water, easily resulting in lipid floaters; Comparative Example 3 had a strong bitter taste after reconstitution and contained some lipid floaters; the other comparative examples did not achieve optimal encapsulation, exhibited bitterness, and had poor reconstitution and dispersibility. Test Example 3: Heat Resistance Stability Test

[0141] Each group of samples was heated in a constant temperature water bath at 85℃ for 60 minutes (simulating a common food and beverage pasteurization / heat processing process), and then the retention rate of rhodioloside was determined. The results are shown in the table below:

[0142] Liposome structures are extremely sensitive to heat (Comparative Examples 2 and 3), undergoing phase transitions and rupture at high temperatures, leading to rapid degradation of rhodioloside. The present invention utilizes a multi-layered, thick-walled structure formed by the cross-linking of polysaccharides and proteins, effectively resisting high-temperature damage with a retention rate exceeding 91%, making it suitable for subsequent complex high-temperature food processing, while the retention rates of the comparative examples were all no higher than 75%. Test Example 4: In vitro simulated gastrointestinal fluid digestion and release test

[0143] Simulated gastric juice (SGF, pH 1.2, containing pepsin) and simulated intestinal juice (SIF, pH 6.8, containing trypsin) were prepared according to pharmacopoeia standards. The samples were first digested in SGF for 2 hours, then transferred to SIF for 4 hours of digestion. The cumulative release rate of rhodioloside at each stage was determined. The test results are shown in the table below:

[0144] This invention features an outer wall material containing resistant dextrin that is difficult for human gastric enzymes to digest, and an internally intact primary complex coagulation nucleus. Therefore, it is stable in highly acidic gastric juice (release rate less than 18% in 2 hours, even as low as 12.4%). Upon entering the weakly alkaline intestine, due to changes in chitosan solubility and swelling of the internal and external structures, rhodioloside is released in large quantities and continuously (total release rate approximately 90%), demonstrating intestinal targeting and significantly improving the in vivo bioavailability of rhodioloside. In contrast, monolayer microcapsules are prone to wall material erosion in gastric acid, while liposomes easily demulsify in the low pH and enzymatic environment of gastric juice; other comparative formulations also show rapid release in gastric juice (release rate exceeding 25% in 2 hours, some even approaching 70%). Therefore, this invention has an advantage in controlled release in vivo.

[0145] The rhodioloside multilayer microcapsule powder of this invention has the following technical effects: Through secondary coagulation and encapsulation combined with the protective effect of trehalose, the encapsulation rate of rhodioloside is improved (exceeding 94%), ensuring excellent powder morphology and excellent flowability. It exhibits excellent dispersibility after reconstitution and dispersion, with no obvious bitter taste. Based on the multilayer thick-walled structure formed by the cross-linking of polysaccharides and proteins, it has excellent heat resistance and stability, with a retention rate exceeding 91% after 60 minutes in an 85°C constant temperature water bath, effectively resisting high-temperature damage and suitable for subsequent complex high-temperature food processing. Furthermore, it is stable in strongly acidic gastric juice, with a release rate of less than 18% after 2 hours; upon entering the weakly alkaline intestine, it can release a large amount and continuously (total release rate of approximately 90%), demonstrating intestinal targeting and significantly improving the in vivo bioavailability of rhodioloside, offering advantages in in vivo release control.

[0146] While specific embodiments and examples of the invention have been described herein, those skilled in the art will understand that any modifications and variations can be made without departing from the principles of the invention. The above embodiments and descriptions do not limit the scope of the invention. Any combination of embodiments of the invention, as well as any obvious extensions or analogies thereof, are within the scope of the invention. Furthermore, the invention covers any arrangement intended to achieve the same purpose, and all such variations and modifications falling within the scope of the appended claims.

Claims

1. A multilayer microcapsule powder containing rhodioloside, characterized in that, The rhodioloside multilayer microcapsule powder comprises rhodioloside; an inner layer coating the rhodioloside, the inner layer comprising chitosan or gelatin and gum arabic; and an outer layer coating the inner layer, the outer layer comprising resistant dextrin, trehalose, and hydrolyzed whey protein; the mass ratio of chitosan or gelatin to gum arabic is 1:5 to 1:2; the mass ratio of resistant dextrin to hydrolyzed whey protein is 3:10 to 3:5; the method for preparing the rhodioloside multilayer microcapsule powder includes: Step (1) Dissolve rhodioloside and gum arabic in water to obtain solution A; Step (2) Dissolve chitosan or gelatin in an acidic aqueous solution to obtain solution B; add solution B to solution A, adjust the pH to 2.5-5.0 with an acidic aqueous solution, and stir at 40-50℃ to obtain a suspension; Step (3) Centrifuge the suspension, discard the supernatant, and obtain the primary microcapsule precipitate; Step (4) Dissolve sodium dihydrogen phosphate and / or potassium dihydrogen phosphate, resistant dextrin, hydrolyzed whey protein, and trehalose in water to obtain solution C; add solution C to the primary microcapsule precipitate to obtain a multilayer microcapsule suspension; Step (5) Dry the multilayer microcapsule suspension to obtain the rhodioloside multilayer microcapsule powder.

2. The rhodioloside multilayer microcapsule powder according to claim 1, characterized in that, The mass ratio of the rhodioloside, the inner layer, and the outer layer is (5-8):(1-3):(0.5-1.5).

3. The rhodioloside multilayer microcapsule powder according to claim 1, characterized in that, In step (1), the mixture is stirred at 40-50℃ and 200-400 rpm.

4. The rhodioloside multilayer microcapsule powder according to claim 1, characterized in that, The acidic aqueous solution is an aqueous solution of acetic acid or citric acid with a mass fraction of 1-12%.

5. The rhodioloside multilayer microcapsule powder according to claim 1, characterized in that, In step (2), after adjusting the pH, the water bath temperature is maintained at 42-48℃ and the mixture is stirred at 400-600 rpm.

6. The rhodioloside multilayer microcapsule powder according to claim 1, characterized in that, The drying process is spray drying, with an inlet air temperature of 150-200℃ and an outlet air temperature of 65-100℃.

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