A quercetin-eucalyptus-oil composition for clearing and protecting the lungs

Abstract

The present invention discloses a quercetin-eucalyptus-oil composition for clearing and protecting the lungs, relating to the technical field of functional foods. The composition comprises active functional components and a three-phase layered targeted-delivery system. The active functional components comprise, in parts by weight, 5-20 parts quercetin, 1-8 parts eucalyptus oil, 2-10 parts bromelain, 10-30 parts dihydromyricetin, 1-6 parts perillaldehyde, 3-15 parts icariin, and 1-5 parts ultra-low-molecular-weight sodium hyaluronate. The three-phase layered targeted-delivery system comprises three independent encapsulation units, namely enteric-protective microspheres encapsulating bromelain, nano mixed micelles encapsulating quercetin, dihydromyricetin, and icariin, and sustained-release microcapsules encapsulating eucalyptus oil and perillaldehyde. By scientifically combining the seven active functional components with the three-phase layered targeted-delivery system and by improving the preparation process, the present invention solves the problems of component incompatibility and easy inactivation in conventional compositions, improves ingredient utilization, enables large-scale production, and enhances the storage stability of the composition.

Description

[0001] DESCRIPTION

[0002] A quercetin-eucalyptus-oil composition for clearing and protecting the lungs TECHNICAL FIELD

[0003] The present invention relates to the technical field of functional foods, and in particular to a quercetin-eucalyptus-oil composition for clearing and protecting the lungs.

[0004] BACKGROUND ART

[0005] The lungs are important respiratory organs of the human body. Long-term smoking, exposure to kitchen oil fumes, smog weather, and occupational dust encountered by workers in industries such as mining and construction can all damage the lungs and respiratory tract, causing discomfort such as coughing, excessive sputum, chest tightness, and dry throat; with long-term accumulation, such damage may also induce diseases such as chronic bronchitis and chronic obstructive pulmonary disease. At present, most lung-clearing and lung-protective products on the market contain only a single active ingredient. Although some products attempt to combine multiple ingredients, they lack rational combination design and dedicated delivery systems, and therefore cannot enable the ingredients to exert their effects synergistically. As people pay increasing attention to lung health, there is an urgent market demand for lung-clearing and lung-protective compositions having rational ingredient combinations, precise delivery, comprehensive efficacy, and good stability, as well as preparation methods capable of large-scale production and effective preservation of ingredient activity.

[0006] Traditional lung-clearing and lung-protective compositions have many obvious defects. Most products do not employ dedicated delivery systems, and the active ingredients are readily destroyed by gastric acid, volatilized, or oxidized, resulting in low absorption and utilization of the ingredients by the human body and a substantial decline in lung-protective efficacy. Although DESCRIPTION some compositions combine multiple ingredients, they do not resolve incompatibility conflicts among the ingredients, so that ingredient inactivation and mutual interference readily occur and synergistic enhancement cannot be achieved. Meanwhile, traditional preparation processes lack reasonable temperature-control and oxygen-control measures, so that the active ingredients are readily thermally inactivated or oxidatively decomposed during preparation, and because process parameters lack unified standards, product quality varies substantially from batch to batch, making industrial-scale production difficult. In addition, some products also have problems such as irritation to mucous membranes and poor storage stability, and therefore cannot satisfy the practical needs of long-term lung care and large-scale product promotion.

[0007] SUMMARY OF THE INVENTION

[0008] An object of the present invention is to overcome the shortcomings of the prior art by providing a quercetin-eucalyptus-oil composition for clearing and protecting the lungs. By scientifically combining seven active functional components including quercetin and eucalyptus oil, together with a three-phase layered targeted-delivery system design and an improved dedicated preparation process, the present invention develops a quercetin-eucalyptus-oil composition for clearing and protecting the lungs. The three independent encapsulation units of the system are adapted to the characteristics of the respective components, thereby achieving precise encapsulation and targeted release of the active ingredients, solving the problems in conventional compositions of component incompatibility and the tendency of components to be destroyed by gastric acid, inactivated, or volatilized, and greatly improving ingredient utilization. The preparation process adopts independent phase-by-phase preparation and full-process temperature and oxygen control, with accurate and controllable parameters and no need for customized special equipment, thereby enabling DESCRIPTION industrial-scale production. The obtained composition has strong tolerance to gastric acid and excellent storage stability, can maintain good performance under different ratios, and effectively solves the core problems of traditional lung-clearing and lung-protective products.

[0009] In order to solve the above technical problems, the present invention provides the following technical solutions. In one aspect, the present invention provides a quercetin-eucalyptus-oil composition for clearing and protecting the lungs, wherein the composition comprises active functional components and a three-phase layered targeted-delivery system;

[0010] The active functional components comprise, in parts by weight, 5-20 parts quercetin, 1-8 parts eucalyptus oil, 2-10 parts bromelain, 10-30 parts dihydromyricetin, 1-6 parts perillaldehyde, 3-15 parts icariin, and 1-5 parts ultra-low-molecular-weight sodium hyaluronate;

[0011] The three-phase layered targeted-delivery system comprises three independent encapsulation units, namely enteric-protective microspheres encapsulating bromelain, nano mixed micelles encapsulating quercetin, dihydromyricetin, and icariin, and sustained-release microcapsules encapsulating eucalyptus oil and perillaldehyde.

[0012] Further, the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa.

[0013] Furthermore, the enteric-protective microspheres employ a composite wall material comprising chitosan, sodium alginate, and sodium caseinate, the mass ratio of the three being 0.5-1.5: 1.5-2.5:0.5-1.5, the microsphere particle size being 10-20 pm, and the encapsulation efficiency of bromelain being not lower than 95%.

[0014] Furthermore, the nano mixed micelles employ a composite carrier comprising D-a-tocopheryl polyethylene glycol succinate, soybean lecithin, and chitosan oligosaccharide, the mass ratio of the three being 2-4 : 1 -3 : 0.5- 1 .5, the micelle particle size being 20-50 nm, and the encapsulation efficiency of DESCRIPTION the flavonoid components being not lower than 90%; the flavonoid components are a mixture of quercetin, dihydromyricetin, and icariin.

[0015] Furthermore, the sustained-release microcapsules employ hydroxypropyl-P-cyclodextrin as an inclusion wall material and ethyl cellulose as a sustained-release coating material, the total mass ratio of hydroxypropyl-P-cyclodextrin to eucalyptus oil and perillaldehyde being 6-10:1, the amount of ethyl cellulose solids being 5%-15% of the solid mass of the hydroxypropyl- P-cyclodextrin inclusion complex, the microcapsule particle size being 5-10 pm, and the encapsulation efficiency of the volatile components being not lower than 92%; the volatile components are a mixture of eucalyptus oil and perillaldehyde.

[0016] Furthermore, the mass ratio of the core material to the wall material in the enteric-protective microspheres is 1:15-1:25, and trehalose at a mass fraction of l%-2% is added to the core-material solution as a freeze-drying protectant.

[0017] Furthermore, the mass ratio of the total flavonoid active ingredients to the composite carrier in the nano mixed micelles is 1:5-1 :10; the total flavonoid active ingredients are a mixture of quercetin, dihydromyricetin, and icariin.

[0018] In another aspect, the present invention provides a method for preparing the quercetin-eucalyptus-oil composition for clearing and protecting the lungs, the method comprising the following steps:

[0019] 51. Preparation of enteric-protective microspheres: at 4 °C-10 °C, enteric-protective microspheres encapsulating bromelain are prepared by using high-voltage electrostatic microsphere technology; a core-material solution and a wall-material solution are first prepared, and after the two are mixed, high-voltage electrostatic dripping, curing, washing, and freeze-drying are carried out to obtain enteric-protective microsphere powder;

[0020] 52. Preparation of nano mixed micelles: at a temperature not higher than DESCRIPTION

[0021] 35 °C and under nitrogen protection, nano mixed micelles encapsulating flavonoid active components are prepared by using low-temperature high-pressure homogenization technology; an oil phase and an aqueous phase are first prepared, and after the two are mixed and stirred to form a primary emulsion, high-pressure homogenization, rotary evaporation for solvent removal, and freeze-drying are carried out to obtain nano mixed micelle powder;

[0022] 53. Preparation of sustained-release microcapsules: at a temperature not higher than 35 °C and under closed conditions, sustained-release microcapsules encapsulating volatile components are prepared by using cyclodextrin inclusion combined with spray-drying technology; a wall-material aqueous solution and a core-material solution are first prepared, and after the core-material solution is mixed with the wall-material aqueous solution, constant-temperature inclusion, standing under refrigeration, filtration, addition of a sustained-release coating material, and spray-drying are carried out to obtain sustained-release microcapsule powder;

[0023] 54. Mixing of the finished product: at a temperature not higher than 25 °C in a closed environment under nitrogen protection, the enteric-protective microsphere powder, nano mixed micelle powder, sustained-release microcapsule powder, and ultra-low-molecular-weight sodium hyaluronate are uniformly mixed according to the prescribed ratio to obtain the finished composition.

[0024] Furthermore, in step SI, the core-material solution is prepared by dissolving bromelain in a phosphate buffer solution at pH 6.5, the wall-material solution is prepared by dissolving chitosan, sodium alginate, and sodium caseinate in purified water, the volume ratio of the core-material solution to the wall-material solution is 1:8-1: 12, the preparation voltage of the high-voltage electrostatic microspheres is 15-25 kV, and the feed rate is 0.5-2 mL / min; the pre-freezing temperature for freeze-drying is -40 °C, the DESCRIPTION pre-freezing time is 4 h, the sublimation-drying temperature is -10 °C to 0 °C, and the final drying temperature is not higher than 25 °C.

[0025] Furthermore, in step S3, spray-drying is carried out by using closed-cycle equipment with nitrogen protection introduced throughout the entire process, the inlet-air temperature for spray-drying is 120 °C- 140 °C, the outlet-air temperature is 50 °C-60 °C, the feed rate is 5-10 mL / min, and the atomization pressure is 0.2-0.4 MPa; in step S4, the mixing speed is 30-50 r / min, and the mixing time is 15-30 min.

[0026] Compared with the prior art, the quercetin-eucalyptus-oil composition for clearing and protecting the lungs provided by the present invention has the following beneficial effects:

[0027] I. By scientifically combining seven active functional components including quercetin, eucalyptus oil, bromelain, dihydromyricetin, perillaldehyde, icariin, and ultra-low-molecular-weight sodium hyaluronate with the three independent encapsulation units of the three-phase layered targeted-delivery system, the present invention achieves precise delivery of each active ingredient and synergistic action thereof. Each encapsulation unit is specially designed according to the characteristics of the corresponding components, thereby effectively solving the problems in conventional compositions of incompatibility conflicts among ingredients, easy inactivation, and high volatility, ensuring that the ingredients are precisely released at the corresponding sites of action, improving utilization of the active ingredients, and at the same time reducing irritation of the ingredients to mucous membranes.

[0028] II. By improving the preparation process and adopting key measures of independent phase-by-phase preparation, full-process low-temperature control, DESCRIPTION and inert-gas protection, together with precise process parameters at each step, the present invention can effectively preserve the biological activity of the active ingredients and avoid oxidation and thermal inactivation of the ingredients during preparation. The equipment used in the preparation process consists of common equipment, the process parameters are easy to control, the quality of products from different batches is stable, industrial- scale production can be achieved without the need for customized special equipment, and the prepared composition has strong stability, high retention of active ingredients during storage, and no need for special storage conditions, thereby solving the problems of cumbersome traditional preparation processes, low active-ingredient retention, and difficulty in large-scale production.

[0029] Other advantages, objectives, and features of the present invention will be set forth in part in the following description, and in part will become apparent to those skilled in the art upon examination of the following disclosure, or may be learned from practice of the invention.

[0030] BRIEF DESCRIPTION OF THE DRAWINGS

[0031] To describe the technical solutions in the embodiments of the present invention or in the prior art more clearly, the drawings required for describing the embodiments or the prior art are briefly introduced below. Obviously, the drawings in the following description merely illustrate certain embodiments of the present invention, and those of ordinary skill in the art can derive other drawings therefrom without inventive effort.

[0032] Figure 1 is a flow chart of the preparation method of the quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to the present invention; DESCRIPTION

[0033] Figure 2 is a schematic diagram of the three-phase layered targeted-delivery system in the present invention.

[0034] DETAILED DESCRIPTION

[0035] In order to further illustrate the technical means and effects adopted by the present invention to achieve the intended objectives, the specific implementation, structure, features, and effects of the present invention are described in detail below in conjunction with the accompanying drawings and preferred embodiments.

[0036] Embodiment 1:

[0037] The present invention provides a quercetin-eucalyptus-oil composition for clearing and protecting the lungs in this embodiment, the composition comprising the following components:

[0038] In parts by weight, the active functional components of the quercetin-eucalyptus-oil composition for clearing and protecting the lungs comprise 12 parts quercetin, 4 parts eucalyptus oil, 6 parts bromelain, 20 parts dihydromyricetin, 3 parts perillaldehyde, 8 parts icariin, and 3 parts ultra-low-molecular-weight sodium hyaluronate, wherein the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa; as shown in Figure 2, the three-phase layered targeted-delivery system of the composition comprises three independent encapsulation units, namely enteric-protective microspheres encapsulating bromelain, nano mixed micelles encapsulating quercetin, dihydromyricetin, and icariin, and sustained-release microcapsules encapsulating eucalyptus oil and perillaldehyde.

[0039] As shown in Figure 1, the preparation method of the composition comprises steps S1-S4, and the specific preparation method is as follows:

[0040] SI . Preparation of enteric-protective microspheres: at 8 °C, enteric-protective microspheres encapsulating bromelain are prepared by using high-voltage electrostatic microsphere technology. Bromelain is slowly DESCRIPTION added to a phosphate buffer solution at pH 6.5 and stirred at low speed until completely dissolved, thereby obtaining a core-material solution. Chitosan, sodium alginate, and sodium caseinate are respectively dissolved in purified water at a mass ratio of 1:2:1 and then mixed and stirred until the system becomes uniform, thereby obtaining a wall-material solution. The volume ratio of the core-material solution to the wall-material solution is 1:10, and after the two are mixed, the mixture is stirred at low speed for 30 min until uniformly mixed. The mixture is transferred to a medical syringe, 1.5% aqueous calcium chloride solution is added into the receiving tank, the high-voltage electrostatic dripping voltage is set at 20 kV, the feed rate is 1 mL / min, and the vertical distance between the needle tip and the liquid surface of the calcium chloride aqueous solution is 12 cm. After completion of uniform dripping, curing is carried out at 8 °C for 40 min. The cured microspheres are washed three times with purified water, collected by filtration and uniformly spread on trays, and then placed in freeze-drying equipment, with a pre-freezing temperature of -40 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of -5 °C, a vacuum degree of <10 Pa, and a sublimation time of 22 h, and a final drying temperature of 20 °C, a vacuum degree of <10 Pa, and a final drying time of 6 h. After drying is completed, enteric-protective microsphere powder is obtained.

[0041] S2. Preparation of nano mixed micelles: at 30 °C under nitrogen protection throughout the entire process, nano mixed micelles encapsulating flavonoid active components are prepared by using low-temperature high-pressure homogenization technology. D-a-tocopheryl polyethylene glycol succinate, soybean lecithin, and chitosan oligosaccharide are added to absolute ethanol at a mass ratio of 3:2:1 and stirred at low speed in a 30 °C water bath until completely dissolved, thereby obtaining an oil phase. Purified water is purged with high-purity nitrogen for 30 min to remove dissolved oxygen, thereby obtaining an aqueous phase, and the volume ratio of the oil DESCRIPTION phase to the aqueous phase is 1:8. The oil phase is slowly injected into the aqueous phase at a rate of 1 mL / min, and high-speed stirring at 1000 r / min is carried out for 40 min to form a uniform primary emulsion. The primary emulsion is transferred into a high-pressure homogenizer, cooling water in the jacket is used to control the material temperature at <8 °C, the homogenization pressure is set at 1000 bar, and circulating homogenization is performed four times. The homogenized micellar solution is transferred into a rotary evaporator, and absolute ethanol is removed by rotary evaporation in a 30 °C water bath at a vacuum degree of <-0.09 MPa. The solution is then placed in freeze-drying equipment, with a pre-freezing temperature of -45 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of 0 °C, a vacuum degree of <10 Pa, and a sublimation time of 20 h, and a final drying temperature of 25 °C, a vacuum degree of <10 Pa, and a final drying time of 6 h. After drying is completed, nano mixed micelle powder is obtained.

[0042] S3. Preparation of sustained-release microcapsules: at 32 °C under closed conditions throughout the entire process, sustained-release microcapsules encapsulating volatile components are prepared by using cyclodextrin inclusion combined with spray-drying technology. Hydroxypropyl-P-cyclodextrin is added into purified water and stirred at a constant temperature of 32 °C until completely dissolved, thereby obtaining a wall-material aqueous solution having a mass fraction of 20%. Eucalyptus oil and perillaldehyde are added into absolute ethanol and stirred until completely dissolved, thereby obtaining a core-material solution, wherein the total mass ratio of hydroxypropyl- P-cyclodextrin to eucalyptus oil and perillaldehyde is 8:1. The core-material solution is added dropwise into the wall-material aqueous solution at a rate of 1 mL / min, inclusion is carried out at 32 °C and 500 r / min under constant-temperature stirring for 3 h, and the solution is then allowed to stand under refrigeration at 0-4 °C for 10 h. Insoluble matter is removed through filtration with a 0.45 pm microporous membrane, thereby io DESCRIPTION obtaining an inclusion-complex solution. An aqueous ethyl cellulose dispersion is added into the inclusion-complex solution, the amount of ethyl cellulose solids being 10% of the solid mass of the hydroxypropyl-P-cyclodextrin inclusion complex, and the mixture is stirred at low speed for 30 min until uniformly mixed. Drying is then carried out by using closed-cycle spray-drying equipment with nitrogen protection introduced throughout the entire process, with an inlet-air temperature of 130 °C, an outlet-air temperature of 55 °C, a feed rate of 8 mL / min, an atomization pressure of 0.3 MPa, and an induced-draft frequency of 35 Hz. After drying is completed, sustained-release microcapsule powder is obtained.

[0043] S4. Mixing of the finished product: at 20 °C in a closed environment under nitrogen protection, the enteric-protective microsphere powder, nano mixed micelle powder, sustained-release microcapsule powder, and ultra-low-molecular-weight sodium hyaluronate are added into a three-dimensional motion mixer according to the prescribed ratio, the mixing speed is set at 40 r / min, the mixing time is 20 min, and the uniformity of mixing is controlled at an RSD of <5%. After completion of mixing, the finished composition is obtained.

[0044] In this embodiment, the active functional components adopt the medium-value ratio scheme of the present invention, and the process parameters of each preparation step are adapted to the requirements of this ratio scheme and are precisely controlled. The obtained enteric-protective microspheres have a particle size of 15 pm and a bromelain encapsulation efficiency of 97.2%; the obtained nano mixed micelles have a particle size of 35 nm and a flavonoid-component encapsulation efficiency of 92.6%; and the obtained sustained-release microcapsules have a particle size of 8 pm and a volatile-component encapsulation efficiency of 94.5%, all reaching the design specifications and showing excellent encapsulation and particle-size control effects. In the composition, bromelain retains 98.5% of its activity after ii DESCRIPTION incubation for 2 h in a gastric-acid environment at pH 1.2, and the total retention rate of the active components after sealed storage at 25 °C for 6 months is 96.3%, thereby greatly improving gastric-acid tolerance and storage stability. Throughout the preparation process, the components do not interfere with one another, the material reaction is sufficient and the operation is controllable, and the finished product shows good mixing uniformity, thereby effectively achieving targeted encapsulation protection and synergistic action of the active ingredients.

[0045] Embodiment 2

[0046] The present invention provides a quercetin-eucalyptus-oil composition for clearing and protecting the lungs in this embodiment, the composition comprising the following components:

[0047] In parts by weight, the active functional components of the quercetin-eucalyptus-oil composition for clearing and protecting the lungs comprise 5 parts quercetin, 1 part eucalyptus oil, 2 parts bromelain, 10 parts dihydromyricetin, 1 part perillaldehyde, 3 parts icariin, and 1 part ultra-low-molecular-weight sodium hyaluronate, wherein the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa.

[0048] The preparation method of the composition comprises steps S1-S4, and the specific preparation method is as follows:

[0049] SI . Preparation of enteric-protective microspheres: at 4 °C, enteric-protective microspheres encapsulating bromelain are prepared by using high-voltage electrostatic microsphere technology. Bromelain is slowly added to a phosphate buffer solution at pH 6.5 and stirred at low speed until completely dissolved, thereby obtaining a core-material solution. Chitosan, sodium alginate, and sodium caseinate are respectively dissolved in purified water at a mass ratio of 0.5:1.5:0.5 and then mixed and stirred until the system becomes uniform, thereby obtaining a wall-material solution. The volume DESCRIPTION ratio of the core-material solution to the wall-material solution is 1:8, and after the two are mixed, the mixture is stirred at low speed for 25 min until uniformly mixed. The mixture is transferred to a medical syringe, 1% aqueous calcium chloride solution is added into the receiving tank, the high-voltage electrostatic dripping voltage is set at 15 kV, the feed rate is 0.5 mL / min, and the vertical distance between the needle tip and the liquid surface of the calcium chloride aqueous solution is 10 cm. After completion of uniform dripping, curing is carried out at 4 °C for 30 min. The cured microspheres are washed three times with purified water, collected by filtration and uniformly spread on trays, and then placed in freeze-drying equipment, with a pre-freezing temperature of -40 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of -10 °C, a vacuum degree of <10 Pa, and a sublimation time of 24 h, and a final drying temperature of 20 °C, a vacuum degree of <10 Pa, and a final drying time of 5 h. After drying is completed, enteric-protective microsphere powder is obtained.

[0050] S2. Preparation of nano mixed micelles: at 25 °C under nitrogen protection throughout the entire process, nano mixed micelles encapsulating flavonoid active components are prepared by using low-temperature high-pressure homogenization technology. D-a-tocopheryl polyethylene glycol succinate, soybean lecithin, and chitosan oligosaccharide are added to absolute ethanol at a mass ratio of 2: 1 :0.5 and stirred at low speed in a 25 °C water bath until completely dissolved, thereby obtaining an oil phase. Purified water is purged with high-purity nitrogen for 30 min to remove dissolved oxygen, thereby obtaining an aqueous phase, and the volume ratio of the oil phase to the aqueous phase is 1:8. The oil phase is slowly injected into the aqueous phase at a rate of 1 mL / min, and high-speed stirring at 800 r / min is carried out for 30 min to form a uniform primary emulsion. The primary emulsion is transferred into a high-pressure homogenizer, cooling water in the jacket is used to control the material temperature at <8 °C, the DESCRIPTION homogenization pressure is set at 800 bar, and circulating homogenization is performed three times. The homogenized micellar solution is transferred into a rotary evaporator, and absolute ethanol is removed by rotary evaporation in a 28 °C water bath at a vacuum degree of <-0.09 MPa. The solution is then placed in freeze-drying equipment, with a pre-freezing temperature of -45 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of -5 °C, a vacuum degree of <10 Pa, and a sublimation time of 22 h, and a final drying temperature of 20 °C, a vacuum degree of <10 Pa, and a final drying time of 5 h. After drying is completed, nano mixed micelle powder is obtained.

[0051] S3. Preparation of sustained-release microcapsules: at 30 °C under closed conditions throughout the entire process, sustained-release microcapsules encapsulating volatile components are prepared by using cyclodextrin inclusion combined with spray-drying technology. Hydroxypropyl-P-cyclodextrin is added into purified water and stirred at a constant temperature of 30 °C until completely dissolved, thereby obtaining a wall-material aqueous solution having a mass fraction of 15%. Eucalyptus oil and perillaldehyde are added into absolute ethanol and stirred until completely dissolved, thereby obtaining a core-material solution, wherein the total mass ratio of hydroxypropyl- P-cyclodextrin to eucalyptus oil and perillaldehyde is 6:1. The core-material solution is added dropwise into the wall-material aqueous solution at a rate of 1 mL / min, inclusion is carried out at 30 °C and 400 r / min under constant-temperature stirring for 2 h, and the solution is then allowed to stand under refrigeration at 0-4 °C for 8 h. Insoluble matter is removed through filtration with a 0.45 pm microporous membrane, thereby obtaining an inclusion-complex solution. An aqueous ethyl cellulose dispersion is added into the inclusion-complex solution, the amount of ethyl cellulose solids being 5% of the solid mass of the hydroxypropyl-P-cyclodextrin inclusion complex, and the mixture is stirred at low speed for 25 min until uniformly mixed. Drying is then carried out by DESCRIPTION using closed-cycle spray-drying equipment with nitrogen protection introduced throughout the entire process, with an inlet-air temperature of 120 °C, an outlet-air temperature of 50 °C, a feed rate of 5 mL / min, an atomization pressure of 0.2 MPa, and an induced-draft frequency of 30 Hz. After drying is completed, sustained-release microcapsule powder is obtained.

[0052] S4. Mixing of the finished product: at 18 °C in a closed environment under nitrogen protection, the enteric-protective microsphere powder, nano mixed micelle powder, sustained-release microcapsule powder, and ultra-low-molecular-weight sodium hyaluronate are added into a three-dimensional motion mixer according to the prescribed ratio, the mixing speed is set at 30 r / min, the mixing time is 15 min, and the uniformity of mixing is controlled at an RSD of <5%. After completion of mixing, the finished composition is obtained.

[0053] The process parameters of each preparation step are adaptively reduced according to the ingredient ratio, and all parameters remain stable and controllable throughout the entire process. The obtained enteric-protective microspheres have a particle size of 10 pm and a bromelain encapsulation efficiency of 95.5%; the obtained nano mixed micelles have a particle size of 20 nm and a flavonoid-component encapsulation efficiency of 90.8%; and the obtained sustained-release microcapsules have a particle size of 5 pm and a volatile-component encapsulation efficiency of 92.3%, all reaching the design specifications and showing qualified encapsulation-protection performance. In the composition, bromelain retains 98.1% of its activity after incubation for 2 h in a gastric-acid environment at pH 1.2, and the total retention rate of the active components after sealed storage at 25 °C for 6 months is 95.8%, demonstrating excellent gastric-acid tolerance and storage stability. Throughout the preparation process, no active ingredient is inactivated or oxidized, the materials react sufficiently at each step, the finished product shows good dispersibility, and the controlled-release characteristics of the DESCRIPTION active ingredients are highly consistent with the design requirements.

[0054] Embodiment 3

[0055] The present invention provides a quercetin-eucalyptus-oil composition for clearing and protecting the lungs in this embodiment, the composition comprising the following components:

[0056] In parts by weight, the active functional components of the quercetin-eucalyptus-oil composition for clearing and protecting the lungs comprise 20 parts quercetin, 8 parts eucalyptus oil, 10 parts bromelain, 30 parts dihydromyricetin, 6 parts perillaldehyde, 15 parts icariin, and 5 parts ultra-low-molecular-weight sodium hyaluronate, wherein the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa.

[0057] The preparation method of the composition comprises steps S1-S4, and the specific preparation method is as follows:

[0058] SI . Preparation of enteric-protective microspheres: at 10 °C, enteric-protective microspheres encapsulating bromelain are prepared by using high-voltage electrostatic microsphere technology. Bromelain is slowly added to a phosphate buffer solution at pH 6.5 and stirred at low speed until completely dissolved, thereby obtaining a core-material solution. Chitosan, sodium alginate, and sodium caseinate are respectively dissolved in purified water at a mass ratio of 1.5:2.5: 1.5 and then mixed and stirred until the system becomes uniform, thereby obtaining a wall-material solution. The volume ratio of the core-material solution to the wall-material solution is 1:12, and after the two are mixed, the mixture is stirred at low speed for 35 min until uniformly mixed. The mixture is transferred to a medical syringe, 2% aqueous calcium chloride solution is added into the receiving tank, the high-voltage electrostatic dripping voltage is set at 25 kV, the feed rate is 2 mL / min, and the vertical distance between the needle tip and the liquid surface of the calcium chloride aqueous solution is 15 cm. After completion of uniform DESCRIPTION dripping, curing is carried out at 10 °C for 50 min. The cured microspheres are washed three times with purified water, collected by filtration and uniformly spread on trays, and then placed in freeze-drying equipment, with a pre-freezing temperature of -40 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of 0 °C, a vacuum degree of <10 Pa, and a sublimation time of 20 h, and a final drying temperature of 25 °C, a vacuum degree of <10 Pa, and a final drying time of 7 h. After drying is completed, enteric-protective microsphere powder is obtained.

[0059] S2. Preparation of nano mixed micelles: at 35 °C under nitrogen protection throughout the entire process, nano mixed micelles encapsulating flavonoid active components are prepared by using low-temperature high-pressure homogenization technology. D-a-tocopheryl polyethylene glycol succinate, soybean lecithin, and chitosan oligosaccharide are added to absolute ethanol at a mass ratio of 4:3: 1.5 and stirred at low speed in a 35 °C water bath until completely dissolved, thereby obtaining an oil phase. Purified water is purged with high-purity nitrogen for 30 min to remove dissolved oxygen, thereby obtaining an aqueous phase, and the volume ratio of the oil phase to the aqueous phase is 1:8. The oil phase is slowly injected into the aqueous phase at a rate of 1 mL / min, and high-speed stirring at 1200 r / min is carried out for 50 min to form a uniform primary emulsion. The primary emulsion is transferred into a high-pressure homogenizer, cooling water in the jacket is used to control the material temperature at <8 °C, the homogenization pressure is set at 1200 bar, and circulating homogenization is performed five times. The homogenized micellar solution is transferred into a rotary evaporator, and absolute ethanol is removed by rotary evaporation in a 32 °C water bath at a vacuum degree of <-0.09 MPa. The solution is then placed in freeze-drying equipment, with a pre-freezing temperature of -45 °C and a pre-freezing time of 4 h, a sublimation-drying temperature of 5 °C, a vacuum degree of <10 Pa, and a sublimation time of 18 h, and a final drying DESCRIPTION temperature of 30 °C, a vacuum degree of <10 Pa, and a final drying time of 7 h. After drying is completed, nano mixed micelle powder is obtained.

[0060] 53. Preparation of sustained-release microcapsules: at 35 °C under closed conditions throughout the entire process, sustained-release microcapsules encapsulating volatile components are prepared by using cyclodextrin inclusion combined with spray-drying technology. Hydroxypropyl-P-cyclodextrin is added into purified water and stirred at a constant temperature of 35 °C until completely dissolved, thereby obtaining a wall-material aqueous solution having a mass fraction of 25%. Eucalyptus oil and perillaldehyde are added into absolute ethanol and stirred until completely dissolved, thereby obtaining a core-material solution, wherein the total mass ratio of hydroxypropyl- P-cyclodextrin to eucalyptus oil and perillaldehyde is 10:1. The core-material solution is added dropwise into the wall-material aqueous solution at a rate of 1 mL / min, inclusion is carried out at 35 °C and 600 r / min under constant-temperature stirring for 4 h, and the solution is then allowed to stand under refrigeration at 0-4 °C for 12 h. Insoluble matter is removed through filtration with a 0.45 pm microporous membrane, thereby obtaining an inclusion-complex solution. An aqueous ethyl cellulose dispersion is added into the inclusion-complex solution, the amount of ethyl cellulose solids being 15% of the solid mass of the hydroxypropyl-P-cyclodextrin inclusion complex, and the mixture is stirred at low speed for 35 min until uniformly mixed. Drying is then carried out by using closed-cycle spray-drying equipment with nitrogen protection introduced throughout the entire process, with an inlet-air temperature of 140 °C, an outlet-air temperature of 60 °C, a feed rate of 10 mL / min, an atomization pressure of 0.4 MPa, and an induced-draft frequency of 40 Hz. After drying is completed, sustained-release microcapsule powder is obtained.

[0061] 54. Mixing of the finished product: at 25 °C in a closed environment under nitrogen protection, the enteric-protective microsphere powder, nano DESCRIPTION mixed micelle powder, sustained-release microcapsule powder, and ultra-low-molecular-weight sodium hyaluronate are added into a three-dimensional motion mixer according to the prescribed ratio, the mixing speed is set at 50 r / min, the mixing time is 30 min, and the uniformity of mixing is controlled at an RSD of <5%. After completion of mixing, the finished composition is obtained.

[0062] In this embodiment, the active functional components adopt the high-value ratio scheme of the present invention, and the process parameters of each preparation step are adaptively increased for the high-ratio components, with no parameter exceeding its prescribed limit throughout the entire process. The obtained enteric-protective microspheres have a particle size of 20 pm and a bromelain encapsulation efficiency of 96.8%; the obtained nano mixed micelles have a particle size of 50 nm and a flavonoid-component encapsulation efficiency of 91.5%; and the obtained sustained-release microcapsules have a particle size of 10 pm and a volatile-component encapsulation efficiency of 93.8%, all reaching the design specifications, and the high-ratio components show no agglomeration or insufficient dissolution, with satisfactory encapsulation-protection effects. In the composition, bromelain retains 98.3% of its activity after incubation for 2 h in a gastric-acid environment at pH 1.2, and the total retention rate of the active components after sealed storage at 25 °C for 6 months is 96.1%, showing excellent core performance. Throughout the preparation process, all active ingredients are effectively protected, the finished product shows good mixing uniformity, and the material load and process parameters of each preparation stage are well matched, thereby satisfying the requirements for large-scale preparation of high-ratio compositions and achieving efficient encapsulation and synergistic action of the active ingredients.

[0063] Comparative Example 1

[0064] The ingredients and ratios of the composition in this comparative DESCRIPTION example are as follows:

[0065] In parts by weight, the active functional components of the composition comprise 12 parts quercetin, 4 parts eucalyptus oil, 6 parts bromelain, 20 parts dihydromyricetin, 3 parts perillaldehyde, 8 parts icariin, and 3 parts ultra-low-molecular-weight sodium hyaluronate, wherein the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa, and the ingredients and ratios are exactly the same as those of Embodiment 1.

[0066] The specific preparation method is as follows:

[0067] The raw-material powders of quercetin, eucalyptus oil, bromelain, dihydromyricetin, perillaldehyde, icariin, and ultra-low-molecular-weight sodium hyaluronate are directly added into mixing equipment according to the prescribed ratio in an open environment at 25 °C, the mixing speed is set at 40 r / min, and the mixing time is 20 min. No ingredient-encapsulation treatment step is employed, and no precise temperature- or atmosphere-control measures are taken. After completion of mixing, the finished composition is obtained.

[0068] In this comparative example, the ratio of the active functional components is exactly the same as that of Embodiment 1, but no preparation process related to ingredient encapsulation or targeted delivery is employed, and the raw-material powders are merely subjected to simple physical mixing, so that no design indexes such as encapsulation efficiency or particle size are available for reference. In this mixture, direct contact between bromelain and the flavonoid components produces obvious mutual interference, and eucalyptus oil and perillaldehyde suffer significant volatilization loss during the open mixing process. Bromelain retains only 6.8% of its activity after incubation for 2 h in a gastric-acid environment at pH 1.2, and the total retention rate of the active components after sealed storage at 25 °C for 6 months is only 32.5%, showing no gastric-acid protection or storage- stability effect whatsoever. No ingredient-protection measure is adopted throughout DESCRIPTION the preparation process, mutual interaction among the ingredients occurs during material mixing, product-quality stability is extremely poor, and the active ingredients are readily inactivated and lost under the influence of the external environment, so that effective protection and synergistic action of the active ingredients cannot be achieved.

[0069] Performance comparison table between the embodiments and the comparative example:

[0070] As can be seen from the above table, the three embodiments respectively DESCRIPTION adopt the medium-, low-, and high-value ratios of the active functional components. After treatment by the three-phase layered targeted-delivery system and dedicated preparation process of the present invention, all of them achieve the required particle-size indexes, and the encapsulation efficiencies of bromelain, flavonoid components, and volatile components are respectively not lower than 95.5%, 90.8%, and 92.3%; the activity retention rate of bromelain in a gastric-acid environment is in all cases higher than 98%, and the total retention rate of the active components after sealed storage at 25 °C for 6 months is in all cases higher than 95%. This fully verifies that the core process of the present invention can effectively achieve precise encapsulation and particle-size control of the active ingredients under different ratios, greatly improve the gastric-acid tolerance and storage stability of the composition, and possesses good adaptability, controllability, and stability, thereby preventing mutual interference among the ingredients and achieving synergistic action of the active ingredients. By contrast, because the comparative example does not adopt the core process of the present invention, no encapsulation or particle-size control effect is achieved, and the protection and retention effects for the active ingredients are extremely poor. The sharp contrast between the two directly demonstrates that the three-phase layered targeted-delivery system and preparation process of the present invention are the key to solving the core defects of traditional lung-clearing and lung-protective compositions, such as active ingredients being readily destroyed by gastric acid, readily inactivated or volatilized, and having poor storage stability.

[0071] The above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention has been disclosed above by preferred embodiments, these are not intended to limit the present invention. Any person skilled in the art, without departing from the scope of the technical DESCRIPTION solutions of the present invention, may make some changes or modifications using the technical content disclosed above to form equivalent embodiments with equivalent variations. However, any simple modification, equivalent variation, or modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solutions of the present invention shall still fall within the scope of the technical solutions of the present invention.

Claims

CLAIMS1. A quercetin-eucalyptus-oil composition for clearing and protecting the lungs, characterized in that the composition comprises active functional components and a three-phase layered targeted-delivery system;The active functional components comprise, in parts by weight, 5-20 parts quercetin, 1-8 parts eucalyptus oil, 2-10 parts bromelain, 10-30 parts dihydromyricetin, 1-6 parts perillaldehyde, 3-15 parts icariin, and 1-5 parts ultra-low-molecular-weight sodium hyaluronate;The three-phase layered targeted-delivery system comprises three independent encapsulation units, namely enteric-protective microspheres encapsulating bromelain, nano mixed micelles encapsulating quercetin, dihydromyricetin, and icariin, and sustained-release microcapsules encapsulating eucalyptus oil and perillaldehyde.

2. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the ultra-low-molecular-weight sodium hyaluronate has a molecular weight of less than 10 kDa.

3. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the enteric-protective microspheres employ a composite wall material comprising chitosan, sodium alginate, and sodium caseinate, the mass ratio of the three being 0.5-1.5: 1.5-2.5:0.5-1.5, the microsphere particle size being 10-20 pm, and the encapsulation efficiency of bromelain being not lower than 95%.

4. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the nano mixed micelles employ a composite carrier comprising D-a-tocopheryl polyethylene glycol succinate, soybean lecithin, and chitosan oligosaccharide, the mass ratio of the three being 2-4: 1-3: 0.5- 1.5, the micelle particle size being 20-50 nm, and the encapsulation efficiency of the flavonoid components being not lower than 90%; the flavonoid components are a mixture of quercetin, dihydromyricetin, andCLAIMS icariin.

5. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the sustained-release microcapsules employ hydroxypropyl- P-cyclodextrin as an inclusion wall material and ethyl cellulose as a sustained-release coating material, the total mass ratio of hydroxypropyl- P-cyclodextrin to eucalyptus oil and perillaldehyde being 6-10:1, the amount of ethyl cellulose solids being 5%-15% of the solid mass of the hydroxypropyl- P-cyclodextrin inclusion complex, the microcapsule particle size being 5-10 pm, and the encapsulation efficiency of the volatile components being not lower than 92%; the volatile components are a mixture of eucalyptus oil and perillaldehyde.

6. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the mass ratio of the core material to the wall material in the enteric-protective microspheres is 1:15-1 :25, and trehalose at a mass fraction of l%-2% is added to the core-material solution as a freeze-drying protectant.

7. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the mass ratio of the total flavonoid active ingredients to the composite carrier in the nano mixed micelles is 1:5-1 :10; the total flavonoid active ingredients are a mixture of quercetin, dihydromyricetin, and icariin.

8. The quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 1, characterized in that the preparation method of the composition comprises the following steps:SI . Preparation of enteric-protective microspheres: at 4 °C-10 °C, enteric-protective microspheres encapsulating bromelain are prepared by using high-voltage electrostatic microsphere technology; a core-material solution and a wall-material solution are first prepared, and after the two are mixed, high-voltage electrostatic dripping, curing, washing, and freeze-drying areCLAIMS carried out to obtain enteric-protective micro sphere powder;52. Preparation of nano mixed micelles: at a temperature not higher than 35 °C and under nitrogen protection, nano mixed micelles encapsulating flavonoid active components are prepared by using low-temperature high-pressure homogenization technology; an oil phase and an aqueous phase are first prepared, and after the two are mixed and stirred to form a primary emulsion, high-pressure homogenization, rotary evaporation for solvent removal, and freeze-drying are carried out to obtain nano mixed micelle powder;53. Preparation of sustained-release microcapsules: at a temperature not higher than 35 °C and under closed conditions, sustained-release microcapsules encapsulating volatile components are prepared by using cyclodextrin inclusion combined with spray-drying technology; a wall-material aqueous solution and a core-material solution are first prepared, and after the core-material solution is mixed with the wall-material aqueous solution, constant-temperature inclusion, standing under refrigeration, filtration, addition of a sustained-release coating material, and spray-drying are carried out to obtain sustained-release microcapsule powder;54. Mixing of the finished product: at a temperature not higher than 25 °C in a closed environment under nitrogen protection, the enteric-protective microsphere powder, nano mixed micelle powder, sustained-release microcapsule powder, and ultra-low-molecular-weight sodium hyaluronate are uniformly mixed according to the prescribed ratio to obtain the finished composition.

9. The method for preparing the quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 8, characterized in that, in step SI, the core-material solution is prepared by dissolving bromelain in a phosphate buffer solution at pH 6.5, the wall-material solution is prepared by dissolving chitosan, sodium alginate, and sodium caseinate in purified water,CLAIMS the volume ratio of the core-material solution to the wall-material solution is 1:8-1: 12, the preparation voltage of the high-voltage electrostatic microspheres is 15-25 kV, and the feed rate is 0.5-2 mL / min; the pre-freezing temperature for freeze-drying is -40 °C, the pre-freezing time is 4 h, the sublimation-drying temperature is -10 °C to 0 °C, and the final drying temperature is not higher than 25 °C.

10. The method for preparing the quercetin-eucalyptus-oil composition for clearing and protecting the lungs according to claim 8, characterized in that, in step S3, spray-drying is carried out by using closed-cycle equipment with nitrogen protection introduced throughout the entire process, the inlet-air temperature for spray-drying is 120 °C- 140 °C, the outlet-air temperature is 50 °C-60 °C, the feed rate is 5-10 mL / min, and the atomization pressure is 0.2-0.4 MPa; in step S4, the mixing speed is 30-50 r / min, and the mixing time is 15-30 min.

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