Preparation method of a dendrobium candidum and astragalus membranaceus composition microcapsule and product thereof

Abstract

The present application provides a kind of dendrobium candidum astragalus composition microcapsule preparation method and its product, belong to capsule preparation technical field, it solves the existing dendrobium candidum and astragalus active ingredient due to the big difference of physical and chemical properties and leads to low oral bioavailability, and co-extract is easy to absorb moisture and is blocked, poor fluidity, poor thermal stability, easy to oxidize and deteriorate during storage The defect and the technical problem of unstable product quality in traditional capsule preparation process, low industrial production efficiency.A kind of dendrobium candidum astragalus composition microcapsule preparation method, comprising the following steps: S1, the preparation of dendrobium candidum and astragalus co-extract;S2, the preparation of multiple emulsion;S3, spray drying.In the present application, dendrobium candidum and astragalus are co-extracted, and the intermolecular interaction between the active ingredients of the two drugs, such as hydrogen bond and hydrophobic interaction, is utilized to improve the physical and chemical properties of the active ingredients of the two drugs, so that the hydrophobic components and polysaccharide components form weak self-assembled bodies.

Description

Technical Field

[0001] This invention belongs to the field of capsule preparation technology, and relates to a method for preparing microcapsules of a composition, particularly a method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition and the product thereof. Background Technology

[0002] Dendrobium officinale, the dried stem of Dendrobium officinale, a perennial epiphytic herb belonging to the genus Dendrobium of the Orchidaceae family, has the effects of nourishing the stomach and promoting the production of body fluids, nourishing yin and clearing heat. It is a traditional and precious Chinese medicinal material for nourishing yin. Its active ingredients are mainly Dendrobium officinale polysaccharides, supplemented by alkaloids such as Dendrobine and bibenzyl / phenanthrene secondary metabolites such as romaine / drumpet phenanthrene. It has antioxidant, anti-inflammatory, immunomodulatory, liver-protective and kidney-protective, and digestive-promoting effects. Astragalus membranaceus, the dried root of Astragalus membranaceus or Astragalus moniliforme, has the effects of invigorating qi and consolidating the exterior, replenishing qi and raising yang, promoting diuresis and reducing swelling, and nourishing blood and promoting the production of body fluids. Its medicinal materials are rich in chemical components, with the main active ingredients being astragalus polysaccharides, astragaloside A, and flavonoids such as romaine / drumpet phenanthrene. It has various effects in anti-fatigue, antiviral, immunomodulatory, and cardiovascular diseases.

[0003] In traditional Chinese medicine, Dendrobium officinale nourishes Yin and generates fluids, while Astragalus membranaceus tonifies Qi and raises Yang, forming a classic tonifying combination of Qi and Yin. Their physiological activities have been confirmed by modern pharmacology at multiple levels, including immune regulation, anti-fatigue, and organ protection. However, the core active ingredients of the two herbs exhibit significant differences in physicochemical properties. For example, hydrophobic active substances such as astragaloside A and romaine have extremely poor water solubility, while macromolecules such as Dendrobium officinale polysaccharides and Astragalus membranaceus polysaccharides, although possessing some amphiphilicity, are difficult to maintain a long-term stable colloidal dispersion in a single water extraction system, resulting in low oral bioavailability and hindering the synergistic effect of "tonifying both Qi and Yin." Therefore, it is necessary to co-extract and co-encapsulate Dendrobium officinale and Astragalus membranaceus. This aims to improve their physicochemical properties through intermolecular interactions during the co-extraction stage and achieve the stabilization and targeted delivery of active ingredients through subsequent co-encapsulation processes, thereby overcoming the bottlenecks of low dissolution rate and unstable components in traditional decoctions.

[0004] A search revealed a manufacturing process for a compound Dendrobium officinale capsule disclosed in Chinese patent literature [Application No.: CN201610789965.2; Publication No.: CN106266615A]. The weight parts of the raw materials for the contents of this Dendrobium officinale capsule are as follows: 20-30 parts of Dendrobium officinale stem, 1-2 parts of Acorus tatarinowii rhizome, 8-12 parts of Gynostemma pentaphyllum, 5-8 parts of Tribulus terrestris, 10-15 parts of soybean, 10-18 parts of Astragalus membranaceus, and 15-25 parts of Lentinus edodes. By combining the soaking and saponin extraction processes with a small amount of additives, the anti-stickiness of the capsule can be increased, giving the powdered contents excellent flowability.

[0005] Although the compound Dendrobium officinale capsule disclosed in this patent is made by extracting the active ingredients separately through maceration and saponin extraction processes, then mixing the extracts and adding excipients to form a capsule contents powder, the effective components of Dendrobium officinale and Astragalus membranaceus are simply mixed after separate extraction. This does not utilize the intermolecular interactions during the co-extraction stage to improve the physicochemical properties of the active ingredients. Moreover, the product form is a traditional capsule powder, without the use of microencapsulation technology to protect the active ingredients. This makes it difficult to solve the problems of low dissolution rate of hydrophobic components and easy moisture absorption and deterioration of polysaccharide components. Furthermore, the process does not have a systematic design for the stabilization and targeted delivery of active ingredients, and the oral bioavailability still needs to be improved. Summary of the Invention

[0006] The purpose of this invention is to address the aforementioned problems in existing technologies by proposing a method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus and the resulting product. The technical problem to be solved by this invention is: how to achieve the co-extraction and stable microencapsulation of the active ingredients of Dendrobium officinale and Astragalus membranaceus, improve the problem of poor dispersibility and low oral bioavailability of the active ingredients of the two drugs due to differences in physicochemical properties, and at the same time improve the thermal stability and storage stability of the co-extract.

[0007] The objective of this invention can be achieved through the following technical solutions: A method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition includes the following steps: S1. Preparation of the co-extract of Dendrobium officinale and Astragalus membranaceus: Dendrobium officinale and Astragalus membranaceus were pulverized into fine powder. The powders were weighed according to the prescription ratio, moistened with distilled water, and placed in a round-bottom flask. A condenser was connected for reflux extraction. After the liquid boiled, it was kept at a gentle boil for extraction. After extraction, the mixture was allowed to cool naturally. Water was added to make up for the weight loss due to evaporation. The mixture was then filtered under reduced pressure, and the filtrate was collected. The filtrate was centrifuged at high speed, the supernatant was discarded, and the precipitate was collected. After freeze-drying, the co-extract of Dendrobium officinale and Astragalus membranaceus was obtained. Using the above method, during the co-extraction process of Dendrobium officinale and Astragalus membranaceus, the active ingredients of the two drugs form weak self-assemblies through intermolecular forces such as hydrogen bonds and hydrophobic interactions. Hydrophobic components (such as astragaloside A and romaine) and polysaccharide components (such as Dendrobium officinale polysaccharide and Astragalus membranaceus polysaccharide) form a stable colloidal dispersion in the aqueous system. This method overcomes the technical bottleneck of easy stratification and incompatibility of active ingredients in the traditional simple mixing process after separate extraction, and lays a good foundation for subsequent microencapsulation.

[0008] S2. Preparation of double emulsion: The co-extract of Dendrobium officinale and Astragalus membranaceus obtained by S1 was used as the core material. An emulsifier was added, and deionized water was added and stirred until completely dissolved to form a primary emulsion. After adding the composite wall material solution, the mixture was placed in a constant temperature water bath and stirred. The mixture was then homogenized using a high-pressure homogenizer to form a secondary emulsion. The composite wall material is selected from any two of β-cyclodextrin, maltodextrin, gum arabic, and whey protein; Using the above method, a stable multi-emulsion system is formed through high-pressure homogenization, which allows the core material to be uniformly dispersed in the wall material solution. This provides a uniform emulsion prerequisite for the formation of microcapsules with complete encapsulation and dense structure after spray drying. The hydrophobic cavity structure and film-forming properties of each component in the composite wall material can achieve synergistic encapsulation of active ingredients with different properties.

[0009] S3, Spray drying: The compound emulsion obtained in S2 was spray-dried to obtain microcapsules of Dendrobium officinale and Astragalus membranaceus co-extract.

[0010] Using the above method, the moisture in the re-emulsion evaporates rapidly after spray drying, and the wall material quickly solidifies into a shell on the surface of the core material, forming microcapsules with a core-shell structure. Encapsulation and drying are completed in one step, making the process simple, efficient, and easy for continuous industrial production.

[0011] In S2, the mass ratio of the core material to the composite wall material is 1:1 to 1:5; The mass ratio of maltodextrin to β-cyclodextrin in the composite wall material is 2:1 to 1:4.

[0012] Using the above methods, within this core-to-wall ratio range, the wall material can effectively encapsulate the core material, avoiding problems such as core material exposure or wall adhesion caused by excessive wall material. Within this wall material ratio range, the film-forming properties of maltodextrin and the inclusion effect of β-cyclodextrin complement each other, jointly ensuring the encapsulation effect of microcapsules and product yield.

[0013] The mass ratio of the core material to the composite wall material is 1:3; The mass ratio of maltodextrin to β-cyclodextrin is 1:1.

[0014] Using the above method, under this optimal ratio, the system forms the most suitable viscosity and surface tension, which not only ensures that the emulsion is efficiently atomized into micron-sized uniform droplets under high-pressure atomization, but also provides the best film-forming kinetic conditions for the droplets to quickly solidify into a shell in the drying tower, so that the powder yield reaches the peak (about 40%), while the water content is reduced to the minimum (about 4.5%).

[0015] In S2, the emulsifier is glyceryl monostearate, and its addition amount is 0.05% to 0.5% of the core material weight; The pressure of the high-pressure homogenizer is 600–1000 bar; The solids content of the re-emulsion is 14% to 20%.

[0016] Using the above methods, monostearate fatty acid glycerides as emulsifiers can reduce the interfacial tension between oil and water and enhance the stability of the emulsion. Under high-pressure homogenization at 600–1000 bar, the emulsion particle size is refined and the distribution is uniform, forming a stable complex emulsion system. The solid content is controlled at 14%–20%, which not only ensures the drying efficiency of spray drying, but also avoids the atomization effect caused by excessive viscosity of the liquid due to excessive solid content, thus ensuring the integrity of the microcapsule product morphology and uniform particle size.

[0017] In step S3, the inlet air temperature for spray drying is 90–110°C, the vacuum degree is 0.02–0.05 MPa, and the feed rate is 3–7 rpm.

[0018] Using the above methods, efficient heat and mass transfer and rapid glass transition can be achieved within the inlet air temperature range, ensuring that the droplets solidify rapidly after atomization. Drying under vacuum conditions can reduce the material temperature and protect heat-sensitive active ingredients from high-temperature degradation. The moderate feed rate ensures a balance between atomization effect and drying efficiency, effectively avoiding wall sticking and bursting.

[0019] The inlet air temperature is 105℃, the vacuum degree is 0.03 MPa, and the feed rate is 5 rpm.

[0020] Using the above method, under this optimal combination of process parameters, the powder yield and moisture content both reach the best balance point (powder yield of about 40% and moisture content of about 4.5%). This avoids the problems of increased moisture content when the inlet air temperature is too low and surface hardening leading to microcapsule rupture when the temperature is too high. It is the best parameter combination that balances high efficiency, high quality and low energy consumption.

[0021] In S1, freeze drying includes a freezing stage, a primary drying stage, and a desorption drying stage; The centrifugation speed is 3000-5000 rpm, and the centrifugation time is 10-20 minutes.

[0022] Using the above method, through a three-stage freeze-drying process, water in the co-extract can be removed at low temperature, maximizing the preservation of the bioactivity of the active ingredients. High-speed centrifugation (3000–5000 rpm, 10–20 min) can effectively separate the precipitate in the extract, improving the purity of the co-extract.

[0023] The process optimization step is also included: based on single-factor experiments, core-to-wall ratio, composite wall material ratio and air inlet temperature are selected as key factors, and a quadratic regression model is established using the Box-Behnken design response surface method to determine the optimal preparation conditions. The optimal preparation conditions are: a maltodextrin to β-cyclodextrin mass ratio of 1:1 to 1:1.15, a core material to composite wall material mass ratio of 1:3.5 to 1:3.55, and an air inlet temperature of 105℃.

[0024] Using the above methods, a high-precision quadratic regression model (R²) was established through a system optimization strategy combining single-factor experiments and response surface methodology. 2 =0.9703), accurately reflecting the relationship between various factors and powder yield. Under the optimal preparation conditions (wall material ratio 1:1~1:1.15, core-wall ratio 1:3.5~1:3.55, inlet air temperature 105℃) determined by model prediction and verification experiments, the powder yield reached 38.24%±0.35%, which is highly consistent with the predicted value, proving the reliability of the optimization results. This method effectively solves the problems of strong subjectivity and poor reproducibility in traditional process parameter determination based on experience, and provides a scientific basis for industrial production.

[0025] A microcapsule of Dendrobium officinale and Astragalus membranaceus co-extract is prepared by the method described above.

[0026] The microcapsules prepared by the above method have a core material that is effectively embedded in the composite wall material, forming a stable core-shell structure. The active ingredients are effectively protected, and the thermal stability and storage stability of the product are significantly improved. They are suitable as raw materials for functional foods, health foods or pharmaceuticals.

[0027] The microcapsules are spherical or near-spherical, with a main particle size of 5-6 μm, a water content of 4%-5%, and a moisture absorption of ≤40% at a relative humidity of 80%-95%.

[0028] With the above structure, the microcapsules are spherical and intact, with a dense and smooth surface, clear particle boundaries, good dispersibility, and no obvious adhesion. This contrasts sharply with the unencapsulated co-extracts (which are irregular lumps, flocculent, and prone to moisture absorption and clumping). The low water content (4%–5%) and low moisture absorption (≤40%) under high humidity conditions ensure that the product is not prone to moisture absorption and sticking during storage, significantly extending the shelf life. The uniform particle size distribution ensures the consistency and stability of the product between batches, which is more conducive to subsequent formulation processing and application.

[0029] Compared with the prior art, the method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition and the product thereof of the present invention have the following advantages: 1. In this invention, by co-extracting Dendrobium officinale and Astragalus membranaceus, the intermolecular interactions between the active ingredients of the two drugs during the co-extraction stage, such as hydrogen bonds and hydrophobic interactions, are utilized to improve the physicochemical properties of the active ingredients. This allows the hydrophobic components and polysaccharide components to form weak self-assemblies, thereby improving the dispersion stability of the active ingredients in the aqueous system. This lays a good foundation for subsequent microencapsulation and effectively overcomes the technical bottleneck of easy stratification and incompatibility of active ingredients in the traditional single-extraction and mixing process.

[0030] 2. In this invention, maltodextrin and β-cyclodextrin are used as a composite wall material. By utilizing the excellent film-forming properties of maltodextrin and the unique hydrophobic cavity encapsulation properties of β-cyclodextrin, the hydrophilic and hydrophobic active ingredients in the co-extract are synergistically encapsulated. Through single-factor experiments and response surface methodology optimization, the optimal wall material ratio, core-to-wall ratio, and spray drying process parameters were determined. This significantly improved the powder yield of the microcapsules and reduced the product moisture content, resulting in excellent encapsulation effect. This solves the problems of severe powder adhesion to the wall and low yield in traditional spray drying.

[0031] 3. In this invention, through microencapsulation, a dense protective wall layer is formed on the outside of the core material, which effectively blocks heat conduction and oxygen diffusion. DSC results show that microencapsulation significantly improves the thermal stability of the co-extract, the high-temperature exothermic peak is significantly broadened and shifted towards the high temperature direction, and the co-extract's ability to resist thermal damage is greatly enhanced, solving the problem of easy oxidation and degradation of the heat-sensitive components of the co-extract.

[0032] 4. In this invention, the hygroscopicity of the co-extract is significantly reduced by microencapsulation. DVS results show that under high humidity conditions of 80% to 95%, the moisture absorption of the microcapsules is only about 60% of that of the co-extract, and most of the adsorbed water can be released. The microcapsules have a narrow hysteresis loop and excellent structural stability, which significantly improves the storage stability of the product and extends its shelf life.

[0033] 5. In this invention, microcapsules are prepared by spray drying, which is simple, easy to operate, has high production efficiency and low cost, and is easy to realize industrial continuous production. It provides a new technical approach for the development of Dendrobium officinale and Astragalus membranaceus related functional products and has good market application prospects. Moreover, the microcapsules prepared by this invention are regular spherical or near-spherical, with uniform particle size, dense and smooth surface, good dispersibility, and are not easy to absorb moisture and stick, which greatly improves the problem of poor flowability and easy moisture absorption and clumping of co-extract powder. Attached Figure Description

[0034] Figure 1 This is a graph showing the effect of the composite wall material composition on moisture content and powder yield in Experimental Example 1 of this invention. Figure 2 This is a graph showing the effect of wall material ratio on microcapsule moisture content and powder yield in Experimental Example 1 of this invention; Figure 3 This is a diagram comparing the water content and powder yield of microcapsules in the core wall of an experimental example of the present invention. Figure 4 This is a graph showing the effect of inlet air temperature on moisture content and powder output rate in Experiment Example 1 of this invention; Figure 5 These are contour plots and response surface plots showing the effect of the interaction between three factors on the powder yield of microcapsules in Experiment Example 1 of this invention. Figure 6This is a particle size distribution diagram of the microcapsules of Dendrobium officinale and Astragalus membranaceus co-extract in Experimental Example 2 of this invention; Figure 7 These are the morphology and scanning electron microscope images of the co-extract of Dendrobium officinale and Astragalus membranaceus and the microcapsule powder of the co-extract in Experimental Example 2 of this invention; Figure 8 These are the Fourier transform infrared spectra of MD+β-CD, DOCAE, and DOCAE-MCP in Experimental Example 2 of this invention. Figure 9 These are differential scanning calorigraphs of MD+β-CD, DOCAE, and DOCAE-MCP from Experimental Example 2 of this invention. Figure 10 This is a diagram showing the dynamic water vapor adsorption-desorption of DOCAE and DOCAE-MCP in Experimental Example 2 of this invention. Detailed Implementation

[0035] The following are specific embodiments of the present invention, described in conjunction with the accompanying drawings, to further illustrate the technical solution of the present invention. However, the present invention is not limited to these embodiments. Unless otherwise specified, specific conditions in the embodiments are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without a specified manufacturer are all commercially available conventional products.

[0036] Example 1 1. Instruments and Equipment The freeze dryer used in this embodiment is a Yamato DC801 freeze dryer, the spray drying equipment is a Shanghai Yacheng YC-510 vacuum low-temperature spray dryer, the particle size analysis equipment is a Malvern MASTERSIZER 3000 laser particle size analyzer, the SEM analysis equipment is a Hitachi SU8000 scanning electron microscope, the FT-IR analysis equipment is a Thermo Scientific iD7ATR Fourier transform infrared spectrometer, the TG analysis equipment is a Netzsch TG 209 F3 thermogravimetric analyzer, the DSC analysis equipment is a Netzsch DSC 214 Nevio differential scanning calorimeter, and the DVS analysis equipment is a Surface Measurement System Intrinsic Plus dynamic water vapor adsorption analyzer.

[0037] 2. Preparation of co-extract from Dendrobium officinale and Astragalus membranaceus Dendrobium officinale and Astragalus membranaceus were pulverized into fine powder. The powders were weighed at a mass ratio of 1:1, and 10 times the amount of distilled water was added to moisten them. The mixture was then placed in a round-bottom flask and refluxed using a condenser. After the liquid boiled, it was kept at a gentle boil for 2 hours. After extraction, the mixture was allowed to cool naturally. Water was added to make up for the weight loss due to evaporation. The mixture was then filtered under reduced pressure, and the filtrate was collected. The filtrate was centrifuged at 4000 rpm for 15 minutes, the supernatant was discarded, and the precipitate was collected. The precipitate was then freeze-dried in a freeze dryer (freezing temperature -40℃, first drying at -10℃ / 10Pa, and desorption drying at 20℃ / 5Pa) to obtain the co-extract of Dendrobium officinale and Astragalus membranaceus (hereinafter referred to as DOCAE).

[0038] 3. Preparation of microcapsules of co-extracted Dendrobium officinale and Astragalus membranaceus Microcapsules of a co-extractant of Dendrobium officinale and Astragalus membranaceus were prepared by spray drying.

[0039] Using the DOCAE obtained above as the core material, add 0.1% of monostearate as an emulsifier and deionized water, stirring thoroughly until completely dissolved to form a primary emulsion. Take maltodextrin and β-cyclodextrin mixed at a mass ratio of 1:1 to form a composite wall material. Weigh the composite wall material at a mass ratio of 1:3 (core material to composite wall material), add deionized water to prepare a wall material solution. Mix the primary emulsion and the composite wall material solution, and stir in a 60℃ constant temperature water bath for 30 minutes. Homogenize using a high-pressure homogenizer at a pressure of 800 bar to form a secondary emulsion. Control the solid content of the secondary emulsion to 18%. Then, perform vacuum spray drying on the secondary emulsion solution, setting the vacuum degree to 0.03 MPa, the inlet air temperature to 105℃, and the feed rate to 5 rpm to obtain microcapsules of Dendrobium officinale and Astragalus membranaceus co-extract (hereinafter referred to as DOCAE-MCP).

[0040] 4. Evaluation methods for microencapsulation effects 4.1 Determination of Microcapsule Powder Yield Powder yield (%) = W0 / (W1 + W2) × 100% Wherein, W0 is the mass (g) of the microcapsules collected after spray drying; W1 is the mass (g) of the core material; and W2 is the mass (g) of the wall material.

[0041] 4.2 Determination of water content in microcapsules After accurately weighing the clean, covered aluminum box to constant weight (m0), quickly take about 1g of DOCAE-MCP finished powder and spread it evenly inside the box, accurately weigh it to obtain m1, then remove the lid and place it in an electric heating drying oven preheated to 100℃ for 2 hours. After taking it out, cover it again while it is still hot, and transfer it to a desiccator containing color-changing silica gel to cool to room temperature for 30 minutes. Record the constant weight m2. Calculate the moisture content (%) according to the formula = (m1-m0) / (m1-m2)×100%. Perform two parallel determinations and take the average value. Immediately seal the remaining undetermined powder in a self-sealing bag with built-in desiccant, label it with the sample name, batch number, determination date and moisture content, and store it at 4℃ in the dark.

[0042] Example 2 The difference between this embodiment and Embodiment 1 is that maltodextrin and gum arabic are mixed at a mass ratio of 1:1 to form a composite wall material.

[0043] Example 3 The difference between this embodiment and Embodiment 1 is that β-cyclodextrin and whey protein are mixed at a mass ratio of 1:1 to form a composite wall material.

[0044] Example 4 The difference between this embodiment and Embodiment 1 is that gum arabic and whey protein are mixed in a mass ratio of 1:1 to form a composite wall material.

[0045] Experimental Example 1 1. Selection of composite wall materials Different composite wall material combinations were selected: maltodextrin + gum arabic (MD+GA), β-cyclodextrin + whey protein (β-CD+WP), maltodextrin + β-cyclodextrin (MD+β-CD), and gum arabic + whey protein (GA+WP). Different composite wall material solutions were prepared according to a 1:1 ratio of composite wall material.

[0046] Spray drying was performed using process parameters of 1:3 core material to composite wall material mass ratio, 20% solid content, 0.03 MPa vacuum degree, 105℃ inlet air temperature, and 5 rpm feed rate to prepare microcapsules with different composite wall material combinations. The appropriate composite wall material combination was selected based on the water content and powder yield of the microcapsules.

[0047] The results are as follows Figure 1As shown, different wall material combinations significantly affected the drying characteristics and physical stability of the Dendrobium officinale and Astragalus co-extract microcapsules. The maltodextrin-β-cyclodextrin (MD+β-CD) composite wall material performed best, with a powder yield of approximately 41%, significantly higher than other groups, and the lowest finished product moisture content (approximately 4.4%). This indicates that the system has good film-forming properties and moisture resistance, effectively reducing powder adhesion loss and promoting moisture evaporation. In contrast, the gum arabic-whey protein (GA+WP) group performed worst, with a powder yield of only 21% and a moisture content soaring to 6.1%. The maltodextrin+gum arabic (MD+GA) group and the β-cyclodextrin+whey protein (β-CD+WP) group fell between the two.

[0048] Therefore, maltodextrin + β-cyclodextrin (MD+β-CD) is the most ideal wall material choice in this microcapsule preparation process due to its significant advantages of high powder yield and low moisture content. It helps to improve the storage stability and process economy of the product. Therefore, maltodextrin + β-cyclodextrin (MD+β-CD) is selected as the best composite wall material combination.

[0049] 2. Single-factor experiment Using MD+β-CD as the composite wall material, the effects of three factors—the composite wall material ratio, the mass ratio of core material to composite wall material (core-to-wall ratio), and the inlet air temperature—on the powder yield and moisture content of the microcapsules were investigated. Single-factor design was conducted by changing one factor while keeping other factors constant.

[0050] The individual variables are as follows: The composite wall material formulations (maltodextrin:β-cyclodextrin) were 2:1, 1:1, 1:2, 1:3, and 1:4, respectively. The core-to-wall ratios (core material:wall material) are 1:1, 1:2, 1:3, 1:4, and 1:5, respectively. The inlet air temperatures are 90℃, 95℃, 100℃, 105℃, and 110℃, respectively. Fixed conditions: feed speed is 5 rpm; fan frequency is 45 Hz.

[0051] The effects of individual factors on the powder yield and moisture content of microcapsules of Dendrobium officinale and Astragalus membranaceus co-extract were analyzed.

[0052] Single-factor test results of composite wall material proportioning: The effect of composite wall material ratio on microcapsule spray drying efficiency and physicochemical properties, such as Figure 2As shown, with the increase of the proportion of β-cyclodextrin (β-CD), the powder yield first increases and then decreases, reaching a peak (40.34%) at a wall material ratio of 1:1, while the residual moisture content shows the opposite trend, decreasing to a minimum (4.56%) during the same period. When the proportion of β-CD in the composite wall material is low, the linear long chain of maltodextrin and the rigid hollow conical structure of cyclodextrin become entangled and interact with each other intermolecularly. When the core material to wall material ratio is 1:1, the system forms the most suitable viscosity and surface tension. This rheological property ensures that the emulsion can be efficiently atomized into micron-sized uniform droplets under the action of the high-pressure atomizer, and also provides the best film-forming kinetic conditions for the droplets to quickly solidify into a shell when in contact with hot air in the drying tower, thus promoting the powder yield to reach its peak. As the β-CD ratio increases further, the glass transition temperature of the system rises significantly. Premature surface solidification hinders the diffusion of internal moisture into the external gas phase, leading to a sharp increase in the vapor pressure inside the droplets. This can easily cause microcapsules to burst or severely adhere to the tower wall. Furthermore, excessively high viscosity can cause frequent nozzle clogging, resulting in a precipitous drop in atomization efficiency, directly manifested as a decrease in powder yield. In summary, a 1:1 ratio represents the optimal process window, balancing high yield with low residual water, providing a key physical basis for inhibiting core material degradation and extending shelf life.

[0053] Results of single-factor experiments on core-to-wall ratio: like Figure 3 As shown, the core-to-wall ratio has a significant impact on the spray drying efficiency and physicochemical properties of microcapsules. With increasing wall material ratio, the powder yield initially increases significantly and then decreases, reaching a peak (approximately 40.5%) at a core-to-wall ratio of 1:3. At a 1:1 ratio, the powder yield is low (approximately 14.22%), indicating that the wall material is insufficient to completely encapsulate and support the core material, leading to significant leakage or unformed material being discharged with the exhaust gas. As the wall material ratio increases to 1:3, the powder yield reaches its peak (approximately 40.5%). In this stage, sufficient wall material ensures that the emulsion droplets can quickly form a continuous protective film after atomization, preventing cracking and adhesion during the drying process. When the wall material ratio continues to increase (from 1:4 to 1:5), the powder yield decreases instead. This indicates that excessive wall material increases the total solids content of the system, leading to a significant increase in the viscosity of the liquid. Excessive viscosity deteriorated the atomizer's operating condition, leading to larger and more uneven droplet sizes, increased internal heat and mass transfer resistance, and ultimately resulting in some material failing to dry in time within the tower, forming wet lumps or severely adhering to the walls. Regarding moisture content, although it decreased with increasing wall material ratio in the 1:1 to 1:2 range, an anomalous rebound occurred in the high wall material ratio region (1:4), reaching a maximum value (5.05%). This indicates that excessive wall material formed a dense network structure in the system, severely hindering the migration and escape of internal moisture to the surface, while simultaneously enhancing the wall material's hygroscopic tendency, resulting in increased residual moisture in the final microcapsules. In conclusion, a core-to-wall ratio of 1:3 represents the optimal process window in this study, balancing high yield and low residual water content.

[0054] Results of single-factor test on inlet air temperature: As shown in Figure 4, the inlet air temperature has a significant nonlinear effect on the yield and moisture content of the microcapsule spray drying product. As the inlet air temperature increases from 90℃ to 105℃, the powder yield significantly increases, reaching a maximum of 40.34% at 105℃, while the residual moisture content decreases to a minimum (4.56%). This indicates that 105℃ is the optimal thermodynamic equilibrium point for achieving efficient heat and mass transfer and rapid glass transition, ensuring that droplets can quickly solidify into complete particles after atomization. When the inlet air temperature is further increased to 110℃, both the powder yield and moisture content show an abnormal decrease. This may be due to the "surface hardening" effect caused by the excessively high evaporation rate, leading to internal vapor pressure accumulation and inducing microcapsule rupture; in addition, extreme high temperatures may exacerbate the wall adhesion phenomenon, causing some incompletely dried high-moisture material to mix into the final product, thus deteriorating the overall process parameters. Therefore, 105℃ was determined as the optimal inlet air temperature parameter that balances high efficiency, high quality, and low energy consumption.

[0055] 3. Optimization of process conditions using response surface methodology Based on single-factor experiments, and according to the Box-Behnken design (BBD) principle, composite wall material ratio (A), core-to-wall ratio (B), and inlet air temperature (C) were selected as independent variables, with powder output rate (Y) as the response value. A three-factor, three-level response surface methodology was used for optimization. The factor level design is shown in Table 1. Table 1. Experimental Factors and Levels in the Box-Behnken Response Surface Methodology Experiment ; Based on the results of the single-factor experiments, a response surface methodology was designed using Design-ExPHrt software, with composite wall material ratio (A), core-to-wall ratio (B), and inlet air temperature (C) as independent variables and powder output rate (Y) as the dependent variable. The design and results of the response surface methodology are shown in Table 2. Table 2 Response Surface Experimental Design and Results ; By fitting the response values ​​of the microcapsule powder yield in Table 2, the simulated regression equation is obtained as follows: Y=37.67-0.6838A+1.18B+0.1038C+0.0475AB-0.4700AC-0.3225BC-2.52A 2 -1.07B 2 -4.00C 2 Table 3. Analysis of Variance for Regression Models ; Table 3 shows that the overall F-value of the model is 25.41, and the P-value is less than 0.001, indicating that the model has strong overall significance and is statistically significant. The coefficient of determination R² = 0.9703, and the corrected R² = 0.9321, indicating a good model fit. The P-value for the lack of fit is 0.5445, which is greater than 0.05, indicating that the lack of fit is not significant, and the model fits the experimental data well. The signal-to-noise ratio is 13.4133, which is much greater than 4, indicating sufficient signal strength. Therefore, this model can effectively reflect the relationship between various factors and response values ​​in the preparation of microcapsules of Dendrobium officinale and Astragalus membranaceus co-extractants and predict the optimal process conditions. The p-values ​​show that the first-order terms A and B have a significant impact on the microcapsule preparation process (p < 0.05), and the second-order terms A2, B2, and C2 also have a significant impact on the microcapsule preparation process (p < 0.05). By comparing the F-values, the order of influence of each factor on the microcapsule preparation process is: B > A > C, that is: core-to-wall ratio > composite wall material ratio > inlet air temperature.

[0056] according to Figure 5 Contour plots and corresponding surface plots illustrating the interaction between the three factors affecting the microcapsule powder yield clearly and intuitively demonstrate the pairwise interaction effects between the composite wall material ratio, core-wall ratio, and inlet air temperature, as well as the overall influence of different parameter combinations on the powder yield. In response surface analysis, the steepness of the surface directly reflects the intensity of the interaction between factors. The steeper the slope, the more significant the interaction effect of the two factors on the response value; even small changes in parameters can lead to drastic fluctuations in the response value. The accompanying contour plots serve as evidence; if the contour lines are densely packed ellipses, it indicates a significant interaction between the two factors; if they are sparsely packed circles, the interaction effect is weak. As shown in the figure, the interaction between the composite wall material ratio and the core-wall ratio (AB) is the most significant. Its three-dimensional response surface exhibits obvious tilting characteristics and a narrow peak region. The corresponding contour plot is typically elliptical and densely distributed, indicating a strong synergistic effect between the wall material composition and the core material loading, which together determine the compactness and curing efficiency of the microcapsule membrane. In contrast, the interactions between the composite wall material ratio and inlet air temperature (AC), and between the core wall ratio and inlet air temperature (BC), are relatively weak, with flatter response surfaces and contour lines approaching circular shapes, indicating a lower degree of synergistic influence on microcapsule powder extraction rate. Comprehensive graphical analysis reveals that the response value is highly sensitive to changes in the core wall ratio and composite wall material, representing a key interaction factor in regulating microcapsule powder extraction efficiency, consistent with the results of the analysis of variance.

[0057] Using the microcapsule powder yield as the response value, the optimal preparation process for the co-extracted microcapsules of Dendrobium officinale and Astragalus membranaceus was predicted by the response surface methodology Design Expert: a composite wall material ratio (MD:β-CD) of 1:1.15, a core-to-wall ratio (DOCAE:MD+β-CD) of 1:3.55, an inlet air temperature of 104.99℃, and a microcapsule powder yield of 38.04%. In the validation experiment, considering practical operation, the microcapsule preparation process was adjusted to a composite wall material ratio of 1:1, a core-to-wall ratio of 1:3.5, and an inlet air temperature of 105℃. Three parallel experiments were conducted, and the average value was taken, yielding a microcapsule powder yield of 38.24±0.35%, which is close to the model prediction. This indicates that the response surface methodology optimization results are reliable, and the model can be used to optimize the preparation process of the co-extracted microcapsules of Dendrobium officinale and Astragalus membranaceus.

[0058] Experimental Example 2 1. Microcapsule particle size analysis A certain mass of DOCAE-MCP sample was weighed, a dry dispersant was added, and dry particle size analysis was performed using a laser particle size analyzer. Measurement conditions: particle refractive index 1.520, particle absorptivity 0.100, dispersant refractive index 1.000, 1 measurement, hopper gap 2.00 mm, air pressure 2.5 barg, Mie model, and standard Venturi tube.

[0059] The results are as follows Figure 6 As shown, the particle size distribution of the microcapsule sample exhibits a distinct asymmetric bimodal characteristic. The distribution curve shows a significant main peak at 5.66 μm, corresponding to the average particle size (Dv50) of the system, indicating that the vast majority of capsules are within this size range. Simultaneously, weak fine particle peaks are observed in the range of 0.2–0.3 μm, with a Dv10 of 1.71 μm, suggesting slight secondary nucleation or mechanical fragmentation during the preparation process.

[0060] 2. Scanning electron microscopy (SEM) analysis DOCAE-MCP and unembedded DOCAE were gently sprinkled onto the conductive adhesive on the sample stage, and excess powder was blown away with a syringe. The samples were then sputtered with gold under vacuum conditions, and SEM characterization was performed after the gold sputtering was completed.

[0061] The results are as follows Figure 7 As shown. Figure 7 a shows the macroscopic morphology of the co-extract, which appears as a uniform pale yellow powder. Figure 7 b and Figure 7c shows the microscopic SEM images of the powder (magnifications of 500× and 3500×). Observation revealed that the unencapsulated co-extract exhibited irregular blocky, flocculent, and flaky structures with a rough surface and loose texture. Under a high magnification of 3500×, it was visible that it was composed of aggregates of fine particles or fragments, lacking an overall regular geometric shape. This morphology indicates that the co-extract is mainly composed of biomacromolecules such as polysaccharides, proteins, or phenols, with complex network structures formed between molecules through hydrogen bonds or hydrophobic interactions. Irreversible aggregation easily occurs during the drying process, resulting in poor flowability and extreme sensitivity to external environments (such as oxygen and light).

[0062] Figure 7 d shows the macroscopic morphology of the microencapsulated product. Compared with the precursor, the powder is slightly lighter in color, ranging from pale yellow to milky white. Figure 7 e and Figure 7 f shows microscopic SEM images of the microcapsules (magnifications of 250× and 3500×). Unlike the unencapsulated sample, the microencapsulated product exhibits distinct spherical or near-spherical particles with clear boundaries, good dispersibility, and no obvious adhesion. Under high magnification (3500×), the surfaces of these spherical particles are relatively dense and smooth, with slight wrinkles or irregular protrusions visible at the edges of some particles. This is due to the rapid evaporation of moisture during spray drying, causing uneven shrinkage of the microcapsule wall material and resulting in wrinkles. These spheres have diameters ranging from several micrometers to tens of micrometers, suggesting they are mononuclear or multinucleated microcapsules. The unencapsulated Dendrobium officinale and Astragalus membranaceus co-extract prepared by freeze-drying is hygroscopic and clumps easily, exhibiting poor flowability. In contrast, the Dendrobium officinale and Astragalus membranaceus co-extract microcapsules prepared by spray drying have better flowability and dispersibility, are less prone to moisture absorption, and are less likely to stick together. Therefore, compared to the unencapsulated co-extract, the co-extract microcapsules have better quality and are more suitable for process production and product preservation.

[0063] 3. Fourier Transform Infrared Spectroscopy (FT-IR) Detection The sample to be tested was evenly spread on the iD7 ATR accessory, with 32 scans, a resolution of 4 cm⁻¹, and a wavelength range of 550-4000 cm⁻¹.

[0064] The results are as follows Figure 8 As shown, the co-extracted microcapsules DOCAE-MCP exhibit a superposition effect of characteristic peaks from the wall material (MD+β-CD) and the core material co-extracted DOCAE, confirming the successful construction of the microcapsule system. In the characteristic region, approximately 3300 cm⁻¹... -1All three spectral lines exhibit significant broadening and strong absorption peaks, revealing the abundance of OH and NH groups within the system. For microcapsules, the absorption in this region suggests hydrogen bonding between the polysaccharide wall material and the phenolic or protein-based active ingredients in the extract; for the co-extract DOCAE, the absorption in this region reflects the characteristics of its contained active ingredients (such as polyphenols, proteins, or amino acids); while for the wall material system, it mainly originates from the abundant hydroxyl groups in cyclodextrin and maltodextrin molecules. (At ~3000–2800 cm⁻¹) 1 The absorption peaks in this range correspond to the CH stretching vibrations of methylene (-CH2-) and methyl (-CH3) groups. This characteristic is observed in both the co-extract and the sugar-containing wall material, reflecting the presence of aliphatic chains or sugar ring skeletons in the raw materials. In the fingerprint region (1200–950 cm⁻¹),... 1 The prominent COC and CO stretching vibration peaks within the microcapsule clearly reflect the integrity of the polysaccharide backbone. Notably, compared to the pure wall material, the CO bond vibration peak in the microcapsule spectrum shows a slight shift accompanied by peak broadening. This phenomenon provides direct spectroscopic evidence of non-covalent intermolecular interactions, indicating that the core material molecules are embedded in the hydrophobic cavity of the cyclodextrin or tightly bound to the wall material network via hydrogen bonds, rather than undergoing simple physical adsorption. In summary, these spectroscopic characteristics strongly support the effective encapsulation of the co-extract through hydrogen bonding and inclusion mechanisms, providing a molecular-level theoretical basis for the structural stability of the microcapsules.

[0065] 4. Differential Scanning Calorimetry (DSC) Detection Weigh 3-6 mg of the sample to be tested into an aluminum crucible, seal it, puncture it, and then place it in a differential scanning calorimeter for DSC testing. Use the same empty crucible as a reference. The test temperature range is 30-250℃, the heating rate is 10 K / min, and nitrogen is used as a protective gas at a flow rate of 40 mL / min.

[0066] The results are as follows Figure 9As shown in the DSC curve analysis, microencapsulation significantly optimized the thermal stability of the co-extract. Compared to the intense exothermic peak observed in the co-extract DOCAE in the 200–300℃ range, corresponding to the thermal decomposition / oxidation of the active ingredient, the heat flux rise rate of the co-extract microcapsule DOCAE-MCP significantly decreased in the low-temperature region (<150℃), indicating that the rigidity of the wall material system was enhanced, the movement of molecular chain segments was restricted, and the low-temperature volatilization and thermosensitive degradation of the core material were effectively inhibited. Crucially, the high-temperature exothermic peak of the microcapsule was significantly broader and shifted towards higher temperatures compared to the free core material. This is mainly attributed to the dense physical barrier formed by the wall material effectively blocking heat conduction and oxygen diffusion, thus delaying the oxidative degradation process of the thermosensitive active ingredient in the core material. Simultaneously, the intensity of the endothermic peak of the composite wall material in the 50–100℃ range was weakened in the microcapsule spectrum, suggesting strong intermolecular interactions between the wall material and the core material, leading to a reduction in the free volume of the wall material or restricted movement. In summary, DSC data thermodynamically confirm that microencapsulation successfully constructs a stable core-shell protection system by increasing the glass transition temperature and delaying the onset of thermal degradation, significantly enhancing the ability of the co-extract to resist thermal damage.

[0067] 5. Dynamic Water Vapor Adsorption (DVS) Detection Weigh 30-50 mg of the sample to be tested and place it in the dynamic water vapor adsorption instrument. Set the temperature to 25℃ and perform the measurement under a nitrogen atmosphere with a flow rate of 200 mL / min. Select the mode as 0-95-0% relative humidity (RH) adsorption and desorption of water vapor full cycle. Save the data every 5% RH step. The equilibrium standard for each step is dm / dt ≤ 0.002%.

[0068] The results are as follows Figure 10 As shown, there are significant differences in the hygroscopic and desorption behaviors between the co-extract of Dendrobium officinale and Astragalus membranaceus (DOCAE) and the microcapsule DOCAE-MCP. In the low humidity range (0–60% RH), the adsorption / desorption curves of both the co-extract and the microcapsule are relatively flat, with no obvious hysteresis loop, indicating good initial moisture resistance. When the relative humidity exceeds 60% RH, the hygroscopic rate of both samples increases significantly; in the high humidity stage (80%–95% RH), the hygroscopic capacity of the co-extract increases dramatically to approximately 62.7%, far exceeding the 37.3% of the microcapsule, indicating that the overall hygroscopic capacity of the co-extract is much greater than that of the microcapsule, making it easier to absorb moisture from the environment. Notably, the co-extract exhibits a very strong hygroscopic hysteresis effect under high humidity, with its desorption curve significantly lower than its adsorption curve, indicating that moisture is tightly bound inside the material and difficult to release, posing a significant risk of water retention. In contrast, although the adsorption and desorption curves of the microcapsule are separated, the difference is relatively small, and the hysteresis loop is narrower, indicating that most of the moisture adsorbed by the microcapsule can be released, demonstrating superior structural stability. Experimental results show that microencapsulation significantly reduces the hygroscopicity of the co-extract and improves its moisture-proof ability.

[0069] In summary, this invention achieves the preparation of microcapsules of Dendrobium officinale and Astragalus membranaceus co-extractants with intact microstructure, uniform particle size, good encapsulation effect, good dispersibility, and low hygroscopicity and adhesion through a simple and convenient preparation process. Related experiments have demonstrated that this method effectively encapsulates the Dendrobium officinale and Astragalus membranaceus co-extractants within a composite wall material, forming a new complex. This effectively improves the thermal and storage stability of the co-extractants, making them more suitable for industrial production. It provides a reference for the development and research of Dendrobium officinale and Astragalus membranaceus related products, and solves the technical problems of low oral bioavailability due to significant differences in the physicochemical properties of the active ingredients in existing Dendrobium officinale and Astragalus membranaceus products, as well as the defects of co-extractants such as easy hygroscopic clumping, poor flowability, poor thermal stability, and easy oxidation and deterioration during storage, and the unstable product quality and low industrial production efficiency in traditional capsule formulation processes.

[0070] The specific embodiments described herein are merely illustrative of the spirit of the invention. Those skilled in the art to which this invention pertains may make various modifications or additions to the described specific embodiments or use similar methods to substitute them, without departing from the spirit of the invention or exceeding the scope defined by the appended claims.

Claims

1. A method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus, characterized in that: Includes the following steps: S1. Preparation of the co-extract of Dendrobium officinale and Astragalus membranaceus: Dendrobium officinale and Astragalus membranaceus were pulverized into fine powder. The powders were weighed according to the prescription ratio, moistened with distilled water, and placed in a round-bottom flask. A condenser was connected for reflux extraction. After the liquid boiled, it was kept at a gentle boil for extraction. After extraction, the mixture was allowed to cool naturally. Water was added to make up for the weight loss due to evaporation. The mixture was then filtered under reduced pressure, and the filtrate was collected. The filtrate was centrifuged at high speed, the supernatant was discarded, and the precipitate was collected. After freeze-drying, the co-extract of Dendrobium officinale and Astragalus membranaceus was obtained. S2. Preparation of double emulsion: The co-extract of Dendrobium officinale and Astragalus membranaceus obtained by S1 was used as the core material. An emulsifier was added, and deionized water was added and stirred until completely dissolved to form a primary emulsion. After adding the composite wall material solution, the mixture was placed in a constant temperature water bath and stirred. The mixture was then homogenized using a high-pressure homogenizer to form a secondary emulsion. The composite wall material is selected from any two of β-cyclodextrin, maltodextrin, gum arabic, and whey protein; S3, Spray drying: The compound emulsion obtained in S2 was spray-dried to obtain microcapsules of Dendrobium officinale and Astragalus membranaceus co-extract.

2. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 1, characterized in that, In S2, the mass ratio of the core material to the composite wall material is 1:1 to 1:5; The mass ratio of maltodextrin to β-cyclodextrin in the composite wall material is 2:1 to 1:

4.

3. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 2, characterized in that, The mass ratio of the core material to the composite wall material is 1:3; The mass ratio of maltodextrin to β-cyclodextrin is 1:

1.

4. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 1, characterized in that, In S2, the emulsifier is glyceryl monostearate, and its addition amount is 0.05% to 0.5% of the core material weight; The pressure of the high-pressure homogenizer is 600–1000 bar; The solids content of the re-emulsion is 14% to 20%.

5. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 1, characterized in that, In step S3, the inlet air temperature for spray drying is 90–110°C, the vacuum degree is 0.02–0.05 MPa, and the feed rate is 3–7 rpm.

6. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 5, characterized in that, The inlet air temperature is 105℃, the vacuum degree is 0.03 MPa, and the feed rate is 5 rpm.

7. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 1, characterized in that, In S1, freeze drying includes a freezing stage, a primary drying stage, and a desorption drying stage; The centrifugation speed is 3000-5000 rpm, and the centrifugation time is 10-20 minutes.

8. The method for preparing microcapsules of Dendrobium officinale and Astragalus membranaceus composition according to claim 1, characterized in that, It also includes process optimization steps: based on single-factor experiments, core-to-wall ratio, composite wall material ratio and air inlet temperature are selected as key factors, and a quadratic regression model is established using the Box-Behnken design response surface method to determine the optimal preparation conditions; The optimal preparation conditions are: a maltodextrin to β-cyclodextrin mass ratio of 1:1 to 1:1.15, a core material to composite wall material mass ratio of 1:3.5 to 1:3.55, and an air inlet temperature of 105℃.

9. A microcapsule containing a co-extract of Dendrobium officinale and Astragalus membranaceus, characterized in that: Prepared by the method according to any one of claims 1 to 8.

10. The microcapsule of Dendrobium officinale and Astragalus membranaceus co-extract according to claim 9, characterized in that: The microcapsules are spherical or near-spherical, with a main particle size of 5-6 μm, a water content of 4%-5%, and a moisture absorption of ≤40% at a relative humidity of 80%-95%.

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