Preparation method of medicinal and edible compound composition for treating sarcoidosis

Abstract

The invention discloses a preparation method of a medicinal and edible compound composition for treating sarcoidosis, and relates to the technical field of medicines and foods. The method comprises the following steps: A, carrying out low-temperature superfine grinding, namely respectively and accurately weighing the raw materials of red tangerine peel, perilla frutescens and semen brassicae, putting into a superfine grinding machine in a liquid nitrogen environment at the temperature of 40 DEG C below zero, and grinding for 30 minutes; through low-temperature superfine grinding and sectional cold extraction, volatile and heat-sensitive components of raw materials such as exocarpium citri rubrum and brassica juncea are protected, various effective components such as flavonoid glycoside and total flavonoids are completely reserved, anti-cancer components are activated through targeted enzymolysis, the drug effect is enhanced through hot-phase transduction concentration, the mucous membrane adhesion microsphere and nano-composite technology is combined, and the anti-cancer effect is achieved. The compound prepared from the medicinal and edible raw materials can be used for medicines, health care products and functional foods, provides choices for treatment, prevention and adjuvant treatment of sarcoidosis, is high in safety, and is suitable for long-term use.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine and food, and particularly relates to a preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis. Background Art

[0002] Sarcoidosis, as a multi-system and multi-organ granulomatous disease with unknown etiology, seriously affects the physical health and quality of life of patients. At present, there are many limitations in the clinical treatment methods for sarcoidosis. For example, traditional drug treatments are often accompanied by side effects to varying degrees, and long-term use may damage liver and kidney functions; surgical treatments have problems such as large trauma, long recovery time, and recurrence risks. Therefore, it is urgent to develop safe and effective new treatment methods and drugs.

[0003] Medicine-food homologous substances are widely sourced and highly safe. Compound compositions developed based on them have gradually attracted attention in the fields of disease treatment and prevention. However, traditional medicine-food homologous compounds face many challenges in the preparation and application processes. On the one hand, conventional processes such as crushing, extraction, and concentration cannot fully retain the active ingredients in the raw materials, especially thermosensitive and volatile ingredients, resulting in a significant reduction in the efficacy of the products. For example, during the high-temperature and long-time treatment process of traditional water decoction methods, a large amount of volatile ingredients such as limonene in tangerine peel and allyl isothiocyanate in white mustard seeds will be lost, reducing the therapeutic effect of the drugs. On the other hand, ordinary preparation processes are difficult to improve the bioavailability of the active ingredients in the compound, resulting in a large amount of active ingredients not being fully absorbed and utilized by the human body. For example, the intestinal absorption rate of medicine-food homologous compounds prepared by traditional processes is generally low and cannot meet the clinical treatment requirements.

[0004] Therefore, we provide a preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis to solve the above problems. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis, which solves the problems of side effects and large trauma in the existing treatment methods for sarcoidosis, as well as the easy loss of active ingredients and low bioavailability in the preparation process of medicine-food homologous compounds.

[0006] To solve the above technical problems, the present invention is realized through the following technical solutions.

[0007] The present invention is a preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis, including the following steps:

[0008] A. Low-temperature ultrafine grinding: After accurately weighing the raw materials of tangerine peel, perilla, and white mustard seeds, place them in an ultrafine grinder in a -40°C liquid nitrogen environment and grind for 30 minutes to protect 5% of the limonene in tangerine peel and 3% of the allyl isothiocyanate volatile components in white mustard seeds;

[0009] B. Stepwise cold extraction:

[0010] Cold extraction of Hangzhou white chrysanthemum and lily: Take 150 g of Hangzhou white chrysanthemum and 250 g of lily, add 5000 mL of 50% ethanol solution, and cold extract at a constant temperature of 25°C for 2 hours to retain flavonoid glycosides. Cold extraction of passion fruit and seabuckthorn (assisted by pectinase at pH 4.0): Take 500 g of passion fruit and 200 g of seabuckthorn, add 3000 mL of pectinase solution with a pH of 4.0 (pectinase mass concentration is 0.5%), and extract at 30°C for 3 hours to release total flavonoids;

[0011] C. Targeted enzymatic hydrolysis:

[0012] White mustard seeds + β-glucosidase (40°C, pH 6.0, 1 h): Mix 200 g of white mustard seeds with 10 g of β-glucosidase, add 2000 mL of phosphate buffer solution with a pH of 6.0, and react at 40°C for 1 hour to activate the anti-cancer components. Reed stem + cellulase (50°C, 2 h): Take 600 g of reed stem, add 15 g of cellulase, place it in 3000 mL of acetic acid-sodium acetate buffer solution with a pH of 4.8, and react at 50°C for 2 hours to increase the polysaccharide dissolution;

[0013] D. Thermal phase change energy concentration:

[0014] Enzymatic hydrolysate and astragalus membranaceus, licorice extract: Mix the above enzymatic hydrolysate with the 2000 mL extract obtained by water extraction of 200 g of astragalus membranaceus and 150 g of licorice, and concentrate under reduced pressure to 1000 mL at 80°C and a vacuum degree of 0.08 MPa to enhance the medicinal effect through intermolecular hydrogen bond recombination. Encapsulation of dried ginger volatile oil (β-cyclodextrin nanocarrier): Take 10 mL of volatile oil extracted from 100 g of dried ginger, and encapsulate it with 100 g of β-cyclodextrin nanocarrier at 35°C and a stirring speed of 200 r / min for 2 hours;

[0015] E. Bioavailability Enhancement Technology: Formation of Mucoadhesive Microspheres by Adding Passion Fruit Pectin: 20 g of pectin was extracted from 500 g of passion fruit and dissolved in 1000 mL of deionized water to prepare a 2% pectin solution. The emulsification-crosslinking method was used, with liquid paraffin as the oil phase (oil phase volume: 1500 mL), Span-80 as the emulsifier (emulsifier mass: 15 g), and calcium chloride as the crosslinking agent (crosslinking agent mass: 10 g). The reaction was carried out at 45 °C with a stirring speed of 400 r / min for 1.5 hours to form mucoadhesive microspheres. Jin'ejin-Yam Nanocomposite: 150 g of Jin'ejin and 200 g of yam were respectively pulverized to 100 mesh, mixed in a mass ratio of 1:1.3, and a nanocomposite was prepared by the co-precipitation method under the conditions of 60 °C and a stirring speed of 250 r / min for 2.5 hours.

[0016] The present invention is further configured such that in the low-temperature ultrafine pulverization step, the pulverization particle size of the ultrafine pulverizer is controlled between 10 - 50 microns. Before pulverization, the ultrafine pulverizer is cleaned and calibrated, and a sample with a standard particle size is used to test the pulverization effect of the equipment to ensure that the target pulverization particle size range is achieved.

[0017] The present invention is further configured such that in the segmented cold extraction step, after the cold extraction of Hangzhou White Chrysanthemum and Lily, the extraction solution is separated by filtration. A filter membrane with a pore size of 0.45 μm and a filter membrane material of polyethersulfone is used, and a vacuum filtration device is adopted during filtration, with the vacuum degree maintained at 0.05 - 0.06 MPa.

[0018] The present invention is further configured such that in the segmented cold extraction step, after the pH 4.0 pectinase-assisted extraction of passion fruit and seabuckthorn, the extraction solution needs to be concentrated under reduced pressure. The temperature for concentration under reduced pressure is set at 40 °C, the vacuum degree is controlled at 0.06 MPa, and it is concentrated to 1 / 3 of the original volume. Before concentration under reduced pressure, the extraction solution is first transferred to a round-bottom flask of a rotary evaporator, and the volume of the round-bottom flask is 3 - 4 times the volume of the extraction solution. The rotary evaporator is started, and the rotation speed is set at 60 - 80 revolutions per minute.

[0019] The present invention is further configured such that in the targeted enzymatic hydrolysis step, after the reaction between Brassica alba and β-glucosidase ends, β-glucosidase is inactivated by heating to 80 °C and maintaining for 10 minutes. A constant temperature water bath is used as the heating device. The reaction solution is transferred to a heat-resistant glass container and placed in a preheated constant temperature water bath at 80 °C. A stirrer is used to slowly stir the reaction solution at a speed of 50 - 80 revolutions per minute. After heating for 10 minutes, the reaction solution is quickly taken out and placed in an ice bath to cool to room temperature.

[0020] The present invention is further configured such that in the targeted enzymatic hydrolysis step, for the enzymatic hydrolysate after the reed stalk reacts with cellulase, small molecule impurities therein are removed by dialysis. The cut-off molecular weight of the dialysis bag is 5000 Da. Before use, the dialysis bag is pre-treated by boiling in deionized water for 10 minutes.

[0021] The present invention is further configured such that in the thermal phase change energy concentration step, after the enzymatic hydrolysate is mixed with the extracts of Astragalus membranaceus and Glycyrrhiza uralensis, ultrasonic treatment is first performed for 15 minutes before vacuum concentration. The ultrasonic power is 300 W. An ultrasonic cleaner is used for the ultrasonic treatment. The mixed solution is placed in a glass container, and the glass container is placed in a constant temperature water bath at 25°C. When performing the ultrasonic treatment, the ultrasonic frequency is set to 40 kHz.

[0022] The present invention is further configured such that in the thermal phase change energy concentration step, during the embedding process of the volatile oil of dried ginger, the particle size of the β-cyclodextrin nanocarrier is 50 - 200 nm. When preparing the β-cyclodextrin nanocarrier, the reverse microemulsion method is used to control the particle size of the nanocarrier. After preparation, a transmission electron microscope is used to detect the particle size of the β-cyclodextrin nanocarrier. At least 50 nanoparticles are randomly selected for measurement, and their particle size distribution is statistically analyzed. If the particle size does not meet the requirements, the preparation process parameters are adjusted and re-prepared.

[0023] The present invention is further configured such that the mucoadhesive microspheres and the nanocomplex of chicken gizzard-membrane and Chinese yam prepared in the bioavailability enhancement technology step are respectively subjected to freeze-drying treatment before being added to the compound composition. The freeze-drying conditions are -50°C, the vacuum degree is 10 Pa, and the drying time is 24 hours.

[0024] The present invention is further configured such that the medicated and edible homologous compound composition prepared by the preparation method is used for preparing drugs, health products, and functional foods for treating sarcoidosis.

[0025] The present invention has the following beneficial effects.

[0026] 1. Through low-temperature ultrafine pulverization and segmented cold extraction, the present invention protects the volatile and thermosensitive components of raw materials such as tangerine peel and white mustard seeds, completely retains various active ingredients such as flavone glycosides and total flavonoids, targets enzymatic hydrolysis to activate anti-cancer components, enhances the medicinal effect through thermal phase change energy concentration, combines mucoadhesive microsphere and nanocomplex technologies, improves intestinal absorption rate and lymphatic targeting efficiency, enhances the overall bioavailability. The compound prepared from medicated and edible homologous raw materials can be used for drugs, health products, and functional foods, providing options for the treatment, prevention, and adjuvant treatment of sarcoidosis, with high safety and being suitable for long-term use. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for describing the embodiments will be briefly introduced below.

[0028] Figure 1 It is a flow chart of a preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis.

[0029] Figure 2 It is a flow chart of cryogenic ultrafine grinding in the preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis.

[0030] Figure 3 It is a flow chart of segmented cold extraction in the preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis.

[0031] Figure 4 It is a flow chart of targeted enzymatic hydrolysis in the preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis.

[0032] Figure 5 It is a flow chart of thermal phase change energy concentration in the preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis.

[0033] Figure 6 It is a flow chart of bioavailability enhancement technology in the preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis. Specific embodiments

[0034] Next, the technical solutions in the embodiments of the present invention will be described in conjunction with the accompanying drawings in the embodiments of the present invention. The described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0035] Embodiment 1

[0036] Please refer to Figures 1-6 , the present invention is a preparation method of a medicine and food homologous compound composition for the treatment of sarcoidosis, including the following steps:

[0037] A. Cryogenic ultrafine grinding: Weigh the raw materials of tangerine peel, perilla, and white mustard seeds accurately and place them in an ultrafine grinder in a -40°C liquid nitrogen environment, and grind for 30 minutes to protect 5% of the limonene in tangerine peel and 3% of the volatile allyl isothiocyanate in white mustard seeds.

[0038] B. Segmented cold extraction:

[0039] Cold extraction of Hangzhou white chrysanthemum and lily: Take 150 g of Hangzhou white chrysanthemum and 250 g of lily, add 5000 mL of 50% ethanol solution, and cold extract for 2 hours in a constant temperature environment at 25°C to retain flavonoid glycosides. Passion fruit and seabuckthorn (pH 4.0 pectinase-assisted extraction): Take 500 g of passion fruit and 200 g of seabuckthorn, add 3000 mL of pectinase solution with pH 4.0 (pectinase mass concentration is 0.5%), and extract for 3 hours at 30°C to release total flavonoids.

[0040] C. Targeted enzymatic hydrolysis:

[0041] Semen brassicae + β-glucosidase (40°C, pH 6.0, 1 h): Mix 200 g of Semen brassicae with 10 g of β-glucosidase, add 2000 mL of phosphate buffer solution with pH 6.0, and react for 1 hour at 40°C to activate the anti-cancer components. Reed rhizome + cellulase (50°C, 2 h): Take 600 g of reed rhizome, add 15 g of cellulase, place it in 3000 mL of acetic acid-sodium acetate buffer solution with pH 4.8, and react for 2 hours at 50°C to increase the polysaccharide dissolution.

[0042] D. Thermal phase change concentration:

[0043] Enzymatic hydrolysate and Astragalus membranaceus, Glycyrrhiza glabra extract: Mix the above enzymatic hydrolysate with 2000 mL of extract obtained by water extraction from 200 g of Astragalus membranaceus and 150 g of Glycyrrhiza glabra, and concentrate it under reduced pressure to 1000 mL at 80°C and a vacuum degree of 0.08 MPa to enhance the drug efficacy through intermolecular hydrogen bond recombination. Inclusion of Zingiber officinale volatile oil (β-cyclodextrin nanocarrier): Take 10 mL of volatile oil extracted from 100 g of Zingiber officinale, and include it with 100 g of β-cyclodextrin nanocarrier at 35°C and a stirring speed of 200 r / min for 2 hours.

[0044] E. Bioavailability enhancement technology: Addition of Passiflora edulis Sims pectin to form mucoadhesive microspheres: Extract 20 g of pectin from 500 g of Passiflora edulis Sims, add 1000 mL of deionized water to prepare a 2% pectin solution, and use the emulsification cross-linking method with liquid paraffin as the oil phase (oil phase volume is 1500 mL), Span-80 as the emulsifier (emulsifier mass is 15 g), and calcium chloride as the cross-linking agent (cross-linking agent mass is 10 g), and react at 45°C and a stirring speed of 400 r / min for 1.5 hours to form mucoadhesive microspheres. Nano-complex of Endothelium corneum galli - Dioscorea opposita: Grind 150 g of Endothelium corneum galli and 200 g of Dioscorea opposita to 100 meshes respectively, mix them according to a mass ratio of 1:1.3, and use the co-precipitation method to prepare the nano-complex at 60°C and a stirring speed of 250 r / min for 2.5 hours.

[0045] Example 2: Preparation of a drug for treating sarcoidosis

[0046] Low-temperature ultrafine pulverization: Accurately weigh 200 g of Exocarpium citri rubrum, 150 g of Perilla frutescens, and 100 g of Semen brassicae, put them into an ultrafine pulverizer in a -40°C liquid nitrogen environment that has been cleaned, calibrated, and tested to meet the standards, and pulverize for 30 minutes with the pulverization particle size controlled within 10 - 50 microns.

[0047] Segmented cold extraction: Measure 5000 mL of 50% ethanol solution, add 150 g of Chrysanthemum morifolium Ramat. and 250 g of Lilium brownii var. viridulum Baker, and perform cold extraction at a constant temperature of 25°C for 2 hours. After the cold extraction is completed, use a filter membrane with a pore size of 0.45 μm and a material of polyethersulfone to separate the extract through a vacuum filtration device with a vacuum maintained at 0.05 MPa. Separately, take 3000 mL of a pectinase solution with a pH of 4.0 and a pectinase mass concentration of 0.5%, add 500 g of Passiflora edulis Sims and 200 g of Hippophae rhamnoides L., and perform extraction at 30°C for 3 hours. After extraction, transfer the extract to a round-bottom flask with a volume 3 times that of the extract, and perform vacuum concentration at 40°C and 0.06 MPa until the volume is reduced to 1 / 3 of the original volume. Set the rotation speed of the rotary evaporator to 60 revolutions per minute.

[0048] Targeted enzymatic hydrolysis: Add 200 g of Brassica juncea (L.) Czern. et Coss. and 10 g of β-glucosidase to 2000 mL of a pH 6.0 phosphate buffer solution, and react at 40°C for 1 hour. After the reaction is completed, transfer the reaction solution to a high-temperature resistant glass container, place it in a constant temperature water bath preheated to 80°C, stir at 50 revolutions per minute for 10 minutes, and then quickly take it out and place it in an ice bath to cool to room temperature. Take 600 g of Phragmites communis Trin. stems, add 15 g of cellulase, place it in 3000 mL of a pH 4.8 acetic acid-sodium acetate buffer solution, and react at 50°C for 2 hours. After the reaction, use a dialysis bag with a cut-off molecular weight of 5000 Da and pretreated by boiling in deionized water for 10 minutes to dialyze and remove small molecule impurities.

[0049] Thermal phase change energy concentration: Mix the above enzymatic hydrolysis solution with 2000 mL of an extract obtained by water extraction of 200 g of Astragalus membranaceus (Fisch.) Bunge and 150 g of Glycyrrhiza glabra L., place it in a glass container, and put it into an ultrasonic cleaner in a 25°C constant temperature water bath. Perform ultrasonic treatment at a power of 300 W and a frequency of 40 kHz for 15 minutes. Then, perform vacuum concentration at 80°C and 0.08 MPa until the volume is reduced to 1000 mL. Take 10 mL of volatile oil extracted from 100 g of Zingiber officinale Rosc., and mix it with 100 g of β-cyclodextrin nanoparticles with a particle size of 50 - 200 nm (qualified by reverse microemulsion method and transmission electron microscope detection). Perform inclusion at 35°C and a stirring speed of 200 r / min for 2 hours.

[0050] Bioavailability enhancement technology: Extract 20 g of pectin from 500 g of Passiflora edulis Sims, add 1000 mL of deionized water to prepare a 2% pectin solution. Use 1500 mL of liquid paraffin as the oil phase, 15 g of Span-80 as the emulsifier, and 10 g of calcium chloride as the cross-linking agent. React at 45°C and a stirring speed of 400 r / min for 1.5 hours to form mucoadhesive microspheres. Grind 150 g of Gallus gallus domesticus Brisson and 200 g of Dioscorea opposita Thunb. to 100 meshes respectively, mix them according to a mass ratio of 1:1.3, and use the co-precipitation method to react at 60°C and a stirring speed of 250 r / min for 2.5 hours to prepare a nanocomposite. Freeze-dry the mucoadhesive microspheres and the Gallus gallus domesticus Brisson-Dioscorea opposita Thunb. nanocomposite (-50°C, 10 Pa, 24 hours), and then add them to the above concentrated solution to prepare a drug for treating sarcoidosis.

[0051] Example 3: Preparation of health products for preventing sarcoidosis

[0052] Low-temperature ultrafine grinding: Accurately weigh 180g of tangerine peel, 130g of perilla, and 90g of mustard seeds, thoroughly clean the ultrafine grinder to remove residual impurities from the last use, and then calibrate the equipment with samples of standard particle size to ensure that its grinding accuracy meets the requirements, put the weighed raw materials into the ultrafine grinder in a liquid nitrogen environment that has been cooled to -40℃, start the equipment to grind for 30 minutes, during which time the particle size monitoring device built into the equipment is used to monitor the grinding particle size in real time to ensure that it is controlled between 10-50 microns.

[0053] Segmented cold brew

[0054] Cold extraction of chrysanthemum and lily: Accurately measure 5000mL of 50% ethanol solution, pour it into a clean extraction container, carefully add 150g of chrysanthemum and 250g of lily into the solution, place it in a shaker or constant temperature water bath oscillator at a constant temperature of 25℃, and oscillate cold extraction at a speed of 150r / min for 2 hours to allow the flavonoid glycosides in chrysanthemum and lily to fully dissolve in the ethanol solution.

[0055] Passion fruit and sea buckthorn extraction and treatment: prepare 3000mL of pectinase solution with pH 4.0 and pectinase mass concentration of 0.5%, weigh 500g of passion fruit and 200g of sea buckthorn, wash and chop them respectively and add them to the pectinase solution, and use a magnetic stirrer to stir and extract at a speed of 200r / min for 3 hours at 30°C. After the extraction, transfer the extract to a round-bottom flask of a rotary evaporator, the volume of the round-bottom flask is 3 times the volume of the extract, start the rotary evaporator, set the temperature to 35°C, the vacuum degree to 0.05MPa, the speed to 70 rpm, and concentrate under reduced pressure to 1 / 2 of the original volume.

[0056] Separation of the extract: After cold extraction of chrysanthemum and lily, select a filter membrane with a pore size of 0.45μm and a material of polyethersulfone and install it on a vacuum filtration device, slowly pour the cold extract into the filtration funnel, turn on the vacuum pump, maintain the vacuum degree at 0.05MPa, perform suction filtration separation, and collect the clarified extract.

[0057] Targeted enzymatic digestion

[0058] Enzymatic hydrolysis and inactivation of Brassica alba: Accurately weigh 200 g of Brassica alba and 10 g of β-glucosidase, add them to a reaction vessel containing 2000 mL of pH 6.0 phosphate buffer solution, place the reaction vessel in a constant temperature water bath at 40 °C, and use a magnetic stirrer to stir the reaction at a speed of 120 r / min for 1 hour to activate the anti-cancer components in Brassica alba. After the reaction, transfer the reaction solution to a heat-resistant glass container, place it in a preheated constant temperature water bath at 80 °C, and at the same time use a stirrer to slowly stir the reaction solution at a speed of 50 revolutions per minute to keep it for 10 minutes to inactivate β-glucosidase. Then quickly take out the reaction solution and cool it to room temperature in an ice bath.

[0059] Enzymatic hydrolysis of reed stems and removal of impurities: Weigh 600 g of reed stems, add 15 g of cellulase, and put them into a reaction vessel containing 3000 mL of pH 4.8 acetic acid-sodium acetate buffer solution. Place the reaction vessel in a constant temperature incubator at 50 °C and react for 2 hours to increase the polysaccharide dissolution. After the reaction is completed, use a dialysis bag with a molecular weight cut-off of 5000 Da. After pre-treating the dialysis bag by boiling it in deionized water for 10 minutes, fill it with the enzymatic hydrolysis solution and place it in a large amount of deionized water for dialysis to remove small molecule impurities. The dialysis time is 12 hours, and the dialysis solution is changed 3 times during this period.

[0060] Thermal phase change energy concentration

[0061] Ultrasonic treatment: Mix the above enzymatic hydrolysis solution evenly with 2000 mL of the extraction solution obtained by water extraction of 200 g of Astragalus membranaceus and 150 g of Glycyrrhiza uralensis, transfer it to a glass container, place the glass container in a constant temperature water bath at 25 °C, and then place it in an ultrasonic cleaner. Set the ultrasonic power to 250 W and the ultrasonic frequency to 40 kHz, and perform ultrasonic treatment for 15 minutes to promote the recombination of intermolecular hydrogen bonds.

[0062] Vacuum concentration and encapsulation of volatile oil: After ultrasonic treatment, transfer the mixed solution to a vacuum concentration device and concentrate it to 1000 mL under the conditions of 80 °C and a vacuum degree of 0.08 MPa. Weigh 100 g of dried ginger and extract 10 mL of volatile oil. Another 100 g of β-cyclodextrin nanocarrier is taken, and the volatile oil and the nanocarrier are added to the reaction vessel and encapsulated at 35 °C and a stirring speed of 200 r / min for 2 hours.

[0063] Bioavailability enhancement technology

[0064] Preparation of mucoadhesive microspheres: Extract 20 g of pectin from 500 g of passion fruit, add 1000 mL of deionized water, heat and stir to completely dissolve it, and prepare a 2% pectin solution. Add 1500 mL of liquid paraffin as the oil phase to the reaction vessel, then add 12 g of Tween-80 as the emulsifier, stir evenly to form a stable emulsion, and then add 10 g of calcium chloride as the cross-linking agent. Place the reaction vessel in a constant temperature water bath at 40 °C, and use a stirrer to stir and react at a speed of 350 r / min for 1.2 hours to form mucoadhesive microspheres.

[0065] Preparation of gallus gallus domesticus - dioscorea opposita nanocomposite: Crush 150 g of gallus gallus domesticus and 200 g of dioscorea opposita to 100 meshes respectively, accurately weigh and mix them evenly according to the mass ratio of 1:1.3. Using the coprecipitation method, add the mixture to the reaction solution containing the precipitating agent, and under the environment of 55 °C, use a stirrer to stir and react at a speed of 220 r / min for 2 hours to prepare the gallus gallus domesticus - dioscorea opposita nanocomposite.

[0066] Freeze-drying and mixing: Transfer the prepared mucoadhesive microspheres and gallus gallus domesticus - dioscorea opposita nanocomposite to the trays of the freeze-drying equipment respectively. Set the freeze-drying conditions as -50 °C, the vacuum degree as 10 Pa, and the drying time as 24 hours. After drying, take out both and mix them evenly to make granular health products, which can be packaged and stored.

[0067] Example 4: Preparation of functional food for adjuvant treatment of sarcoidosis

[0068] Low-temperature ultrafine grinding: Weigh 160 g of tangerine peel, 120 g of perilla, and 80 g of brassica alba. Process the ultrafine grinder according to the same equipment cleaning and calibration process as in Example 3. Put the raw materials into the ultrafine grinder in a -40 °C liquid nitrogen environment and grind for 30 minutes to ensure that the grinding particle size is 10 - 50 microns.

[0069] Segmented cold extraction

[0070] Cold extraction of chrysanthemum morifolium ramat. and lilium brownii var. viridulum baker: Measure 5000 mL of 50% ethanol solution into the extraction container, add 150 g of chrysanthemum morifolium ramat. and 250 g of lilium brownii var. viridulum baker, place the extraction container in a constant temperature environment at 25 °C, and use static cold extraction for 1.5 hours to allow flavonoid glycosides to fully dissolve.

[0071] Passion fruit and seabuckthorn extraction and treatment: Prepare 3000 mL of pectinase solution with a pH of 4.0 and a pectinase mass concentration of 0.5%. After washing and cutting 500 g of passion fruit and 200 g of seabuckthorn, add them to the pectinase solution. In an environment of 28 °C, use a stirrer to stir and extract at a speed of 180 r / min for 3 hours. After the extraction is completed, transfer the extract to a round-bottom flask of a rotary evaporator (the volume is 3 times the volume of the extract), and under the conditions of 40 °C and 0.06 MPa, concentrate under reduced pressure to 1 / 3 of the original volume. The rotation speed of the rotary evaporator is set at 70 revolutions per minute.

[0072] Separation of the extract: The same operation as separating the extract after cold extraction of Chrysanthemum morifolium Ramat. and Lilium brownii F.E.Br. var. viridulum Baker in Example 3 is used. A filter membrane with a pore size of 0.45 μm and a material of polyethersulfone and a vacuum filtration device with a vacuum degree maintained at 0.05 MPa are used for separation.

[0073] Targeted enzymatic hydrolysis: The operation steps are exactly the same as those of targeted enzymatic hydrolysis in Example 3, including the processes of sinigrin enzymatic hydrolysis, enzyme inactivation, and reed stem enzymatic hydrolysis and impurity removal.

[0074] Thermal phase change energy concentration

[0075] Ultrasonic treatment and concentration under reduced pressure: Mix the enzymolysis solution with 2000 mL of the extract obtained by water extraction of 200 g of Astragalus membranaceus (Fisch.) Bge. and 150 g of Glycyrrhiza uralensis Fisch., transfer it to a glass container, and place it in an ultrasonic cleaner in a 25 °C constant temperature water bath. Ultrasonic treatment is carried out at a power of 300 W and a frequency of 40 kHz for 15 minutes, and then concentrated under reduced pressure to 1000 mL under the conditions of 80 °C and 0.08 MPa.

[0076] Embedding of volatile oil from dried ginger: Take 10 mL of volatile oil extracted from 100 g of dried ginger, and encapsulate it with 100 g of β-cyclodextrin nanocarrier at 35 °C and a stirring speed of 180 r / min for 2 hours.

[0077] Bioavailability enhancement technology

[0078] Preparation of mucoadhesive microspheres: Extract 20 g of pectin from 500 g of passion fruit, add 1000 mL of deionized water to prepare a 3% pectin solution. Add 1200 mL of liquid paraffin as the oil phase, 10 g of Span-60 as the emulsifier, and stir evenly. Then add 12 g of calcium lactate as the cross-linking agent. Place the reaction container in a 42 °C constant temperature water bath and stir and react at a speed of 380 r / min for 1.3 hours to form mucoadhesive microspheres.

[0079] Preparation of nano-complex of Endothelium Corneum Gigeriae Galli and Chinese yam: The same preparation method as that of the nano-complex of Endothelium Corneum Gigeriae Galli and Chinese yam in Example 3 is used. Grind 150 g of Endothelium Corneum Gigeriae Galli and 200 g of Chinese yam to 100 meshes respectively, mix them according to a mass ratio of 1:1.3, and react at 55 °C and a stirring speed of 220 r / min for 2 hours to prepare the nano-complex.

[0080] Freeze-drying and food forming: The mucoadhesive microspheres and the nano-complex of chicken gizzard-membrane and Chinese yam were freeze-dried respectively (-50 °C, 10 Pa, 24 hours). After drying, an appropriate amount of edible pigment, sweetener (such as xylitol), and gelling agent (such as carrageenan, with an addition amount of 2% of the total mass) were added thereto, and it was heated to 80 °C to completely dissolve and mix evenly. The mixed solution was poured into a jelly mold and cooled to form at room temperature to make a jelly-like functional food for adjuvant treatment of sarcoidosis.

[0081] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific embodiments described. These embodiments are selected and specifically described in this specification in order to better explain the principle and practical application of the present invention, so that those skilled in the art can well understand and utilize the present invention.

Claims

1. A preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis, characterized in that: It includes the following steps: A. Low-temperature ultrafine grinding: Accurately weigh the raw materials of tangerine peel, perilla, and white mustard seeds, and place them in an ultrafine grinder in a -40°C liquid nitrogen environment. Grind for 30 minutes to protect 5% of the limonene in tangerine peel and 3% of the allyl isothiocyanate volatile components in white mustard seeds; B. Segmented cold extraction: Cold extraction of Hangzhou white chrysanthemum and lily: Take 150 g of Hangzhou white chrysanthemum and 250 g of lily, add 5000 mL of 50% ethanol solution, and perform cold extraction at a constant temperature of 25°C for 2 hours to retain flavonoid glycosides. Cold extraction of passion fruit and seabuckthorn (assisted by pH 4.0 pectinase): Take 500 g of passion fruit and 200 g of seabuckthorn, add 3000 mL of pectinase solution with pH 4.0 (pectinase mass concentration is 0.5%), and extract at 30°C for 3 hours to release total flavonoids; C. Targeted enzymatic hydrolysis: White mustard seeds + β-glucosidase (40°C, pH 6.0, 1 h): Mix 200 g of white mustard seeds with 10 g of β-glucosidase, add 2000 mL of phosphate buffer solution with pH 6.0, and react at 40°C for 1 hour to activate anti-cancer components. Reed stem + cellulase (50°C, 2 h): Take 600 g of reed stem, add 15 g of cellulase, place it in 3000 mL of acetic acid-sodium acetate buffer solution with pH 4.8, and react at 50°C for 2 hours to increase the polysaccharide dissolution; D. Thermal phase change energy concentration: Enzymatic hydrolysate and astragalus membranaceus, licorice extract: Mix the above enzymatic hydrolysate with 200 g of astragalus membranaceus and 150 g of licorice, and the 2000 mL extract obtained by water extraction. Under the conditions of 80°C and a vacuum degree of 0.08 MPa, concentrate it under reduced pressure to 1000 mL, and enhance the medicinal effect through intermolecular hydrogen bond recombination. Encapsulation of dried ginger volatile oil (β-cyclodextrin nanocarrier): Take 10 mL of volatile oil extracted from 100 g of dried ginger, and encapsulate it with 100 g of β-cyclodextrin nanocarrier at 35°C and a stirring speed of 200 r / min for 2 hours; E. Bioavailability enhancement technology: Add passion fruit pectin to form mucoadhesive microspheres: Extract 20 g of pectin from 500 g of passion fruit, add 1000 mL of deionized water to prepare a 2% pectin solution. Using the emulsification cross-linking method, with liquid paraffin as the oil phase (oil phase volume is 1500 mL), Span-80 as the emulsifier (emulsifier mass is 15 g), and calcium chloride as the cross-linking agent (cross-linking agent mass is 10 g), react at 45°C and a stirring speed of 400 r / min for 1.5 hours to form mucoadhesive microspheres. Nano-complex of chicken gizzard-membrane and Chinese yam: Grind 150 g of chicken gizzard-membrane and 200 g of Chinese yam to 100 mesh respectively, mix them according to a mass ratio of 1:1.3, and use the co-precipitation method to react at 60°C and a stirring speed of 250 r / min for 2.5 hours to prepare the nano-complex.

2. The preparation method of a medicine-food homologous compound composition for treating sarcoidosis according to claim 1, characterized in that: In the low-temperature ultrafine grinding step, the grinding particle size of the ultrafine grinder is controlled between 10 - 50 microns. Before grinding, clean and calibrate the ultrafine grinder, and use a sample with a standard particle size to test the grinding effect of the equipment to ensure that the target grinding particle size range is reached.

3. The preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis according to claim 1, characterized in that: In the segmented cold extraction step, after the Hangzhou white chrysanthemum and lily are cold extracted, the extract is separated by filtration. A filter membrane with a pore size of 0.45 μm and a filter membrane material of polyethersulfone is used. During filtration, a vacuum filtration device is adopted, and the vacuum degree is maintained at 0.05 - 0.06 MPa.

4. The preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis according to claim 1, wherein: In the segmented cold extraction step, after the passion fruit and seabuckthorn are assisted in extraction with pectinase at pH 4.0, the extract needs to be concentrated under reduced pressure. The temperature for concentration under reduced pressure is set at 40°C, the vacuum degree is controlled at 0.06 MPa, and it is concentrated to 1 / 3 of the original volume. Before concentration under reduced pressure, the extract is first transferred to a round-bottom flask of a rotary evaporator. The volume of the round-bottom flask is 3 - 4 times the volume of the extract. The rotary evaporator is started, and the rotation speed is set at 60 - 80 revolutions per minute.

5. The preparation method of a medicine-food homologous compound composition for treating sarcoidosis according to claim 1, characterized in that: In the targeted enzymatic hydrolysis step, after the reaction between brassica seeds and β-glucosidase ends, β-glucosidase is inactivated by heating to 80°C and maintaining for 10 minutes. A constant temperature water bath is used as the heating device. The reaction solution is transferred to a heat-resistant glass container and placed in a constant temperature water bath preheated to 80°C. A stirrer is used to slowly stir the reaction solution at a speed of 50 - 80 revolutions per minute. After heating for 10 minutes, the reaction solution is quickly taken out and placed in an ice bath to cool to room temperature.

6. The preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis according to claim 1, wherein: In the targeted enzymatic hydrolysis step, the enzymatic hydrolysate after the reaction between reed stems and cellulase is treated by dialysis to remove small molecule impurities therein. The cut-off molecular weight of the dialysis bag is 5000 Da. Before use, the dialysis bag is pre-treated by boiling in deionized water for 10 minutes.

7. The preparation method of a medicine and food homologous compound composition for treating sarcoidosis according to claim 1, characterized in that: In the thermal phase change energy concentration step, after the enzymatic hydrolysate is mixed with the extracts of astragalus membranaceus and licorice, ultrasonic treatment is carried out for 15 minutes before concentration under reduced pressure. The ultrasonic power is 300 W. An ultrasonic cleaner is used for ultrasonic treatment. The mixed solution is placed in a glass container, and the glass container is placed in a constant temperature water bath at 25°C. When carrying out ultrasonic treatment, the ultrasonic frequency is set at 40 kHz.

8. The preparation method of a medicine and food homologous compound composition for treating sarcoidosis according to claim 1, wherein: In the thermal phase change energy concentration step, during the process of entrapping the volatile oil of dried ginger, the particle size of the β-cyclodextrin nanocarrier is 50 - 200 nm. When preparing the β-cyclodextrin nanocarrier, the particle size of the nanocarrier is regulated by the reverse microemulsion method. After preparation, a transmission electron microscope is used to detect the particle size of the β-cyclodextrin nanocarrier. At least 50 nanoparticles are randomly selected for measurement, and their particle size distribution is statistically analyzed. If the particle size does not meet the requirements, the preparation process parameters are adjusted and re-prepared.

9. The preparation method of a medicine-food homologous compound composition for treating sarcoidosis according to claim 1, characterized in that: Before adding to the compound composition, the mucoadhesive microspheres and the nano-complex of chicken gizzard-membrane and Chinese yam prepared in the bioavailability enhancement technology step are respectively subjected to freeze-drying treatment. The conditions for freeze-drying are -50°C, a vacuum degree of 10 Pa, and a drying time of 24 hours.

10. The preparation method of a medicine-food homologous compound composition for the treatment of sarcoidosis according to claim 1, characterized in that: The medicine-food homologous compound composition prepared by the preparation method is used for preparing drugs, health products, and functional foods for treating sarcoidosis.

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