Dendrobium and radix asparagi granules and preparation method thereof

Abstract

The invention provides dendrobium and radix asparagi granules and a preparation method thereof, and relates to the technical field of traditional Chinese medicines, and the dendrobium and radix asparagi granules comprise the following components in parts by weight: 7-8 parts of radix asparagi, 11-12 parts of radix ophiopogonis, 2-4 parts of radix trichosanthis, 2-4 parts of radix scutellariae, 2-4 parts of rhizoma anemarrhenae, 2-4 parts of lotus leaves, 1-2 parts of ginseng, 1-2 parts of liquorice, 6-8 parts of dendrobium, 5-7 parts of rhizoma polygonati, 5-7 parts of radix polygonati officinalis and 1-2 parts of polysaccharide modified nano-liposome. According to the invention, the three medicinal materials, namely the dendrobium, the rhizoma polygonati and the radix polygonati officinalis, are creatively combined, so that a new three-yin-tonifying formula with a synergistic effect is constructed; the medicinal materials are pretreated by combining a liquid nitrogen quick-freezing crushing technology, and active ingredients of the medicinal materials are effectively reserved; an integrated preparation process comprising buffer system decoction, gradient concentration and pulse-spray combined drying is developed, and degradation of effective components is remarkably reduced; the beta-cyclodextrin inclusion technology is innovatively introduced to cooperate with the application of the dendrobium polysaccharide nano-liposome protective agent, so that the stability of the preparation is comprehensively enhanced.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to dendrobium and erdong granules and a preparation method thereof. Background Art

[0002] Erdong Decoction, a Chinese medicine formula, comes from Volume 3 of "Medical Enlightenment." This recipe moistens the lungs and clears the stomach, primarily treating upper digestive problems characterized by excessive thirst, frequent urination, and a weak pulse. In traditional prescriptions, Asparagus cochinchinensis and Ophiopogon japonicus are the main herbs, while Radix Trichosanthis, Rhizoma Anemarrhenae, and Radix Scutellariae Baicalensis are the secondary herbs. Lotus leaf and Panax ginseng are the adjuvant herbs, and Licorice root is the guiding herb. Modern research indicates that the polysaccharides and saponins in Asparagus cochinchinensis and Ophiopogon japonicus, the polysaccharides, saponins, and amino acids in Radix Trichosanthis, the flavonoids, saponins, polysaccharides, and diphenylpyrans in Rhizoma Anemarrhenae, the flavonoids in Radix Scutellariae Baicalensis, the flavonoids and alkaloids in Lotus leaf, the saponins and polysaccharides in Panax ginseng, and the flavonoids and triterpenoids in Licorice root are closely related to their moistening and heat-clearing properties.

[0003] Invention publication number CN117017923A discloses a preparation method of Erdong Decoction with a high powder yield and Erdong Decoction granules. Although the powder yield is improved, the original formula has obvious deficiencies in repairing the barrier function of the throat mucosa, and is unable to meet the needs of modern common yin deficiency and dryness-heat diseases such as chronic pharyngitis and Sjögren's syndrome for long-term fluid production and targeted repair; and the traditional decoction process is prone to degradation of heat-sensitive active ingredients, resulting in a decrease in the stability of the preparation and affecting the durability of the mucosal repair effect. Summary of the Invention

[0004] To address technical issues in existing technologies, such as the inadequate effect of existing formulas on laryngeal mucosal repair, degradation of heat-sensitive ingredients caused by traditional decoction processes, and poor formulation stability, the present invention provides Shihu Erdong Granules and a preparation method thereof. This invention utilizes the innovative combination of three medicinal ingredients—Dendrobium, Polygonatum, and Polygonatum—to create a novel "Three Yin Co-tonifying" formula with synergistic effects. Liquid nitrogen quick-freezing and fragmentation are used to pre-treat the medicinal ingredients, effectively preserving their active ingredients. An integrated preparation process, comprising decoction in a buffered system, gradient concentration, and pulse-spray drying, is developed to significantly reduce degradation of the active ingredients. Finally, the innovative introduction of β-cyclodextrin inclusion technology, combined with the use of Dendrobium polysaccharide nanoliposomes as a protective agent, comprehensively enhances formulation stability.

[0005] To achieve the above objectives, the present invention provides the following technical solutions: Disclosed are dendrobium and erdong granules comprising the following components in parts by weight: 7-8 parts of asparagus cochinchinensis, 11-12 parts of ophiopogon japonicus, 2-4 parts of trichosanthes root, 2-4 parts of scutellaria baicalensis, 2-4 parts of anemarrhena asphodeloides, 2-4 parts of lotus leaves, 1-2 parts of ginseng, 1-2 parts of liquorice, 6-8 parts of dendrobium, 5-7 parts of polygonatum, 5-7 parts of polygonatum odoratum, and 1-2 parts of polysaccharide-modified nanoliposomes.

[0006] This formula, centered on the Traditional Chinese Medicine (TCM) theory of "nourishing yin and moistening dryness, clearing heat and promoting fluid production, and replenishing qi and nourishing yin," is innovatively designed for symptoms of yin deficiency and dryness. Its compatibility adheres to the principle of "monarch, minister, assistant, and envoy": Monarch herbs Asparagus cochinchinensis and Ophiopogon japonicus primarily address lung and stomach yin deficiency, with Asparagus cochinchinensis specializing in nourishing yin and moistening dryness, and Ophiopogon japonicus excelling in promoting fluid production and relieving restlessness; Assistant herbs Trichosanthes kirilowii, Scutellaria baicalensis, and Anemarrhena rhizome collaboratively clearing excess heat in the upper Jiao, supplemented by nourishing yin and reducing internal heat; Adjuvant herbs Ginseng replenishes qi and protects the spleen, while Licorice harmonizes and detoxifies, preventing cold and dampness from damaging the body; Envoy herbs Dendrobium officinale, Polygonatum sibiricum, and Polygonatum odoratum guide the herbs to the meridians, collectively nourishing the three yin meridians to moisten the upper Jiao, nourish the stomach in the middle Jiao, and nourish the kidneys in the lower Jiao. The innovative introduction of Dendrobium polysaccharide nanoliposomes mimics the TCM "channel-guiding" effect, delivering them to the throat mucosa. Nano-scaled, the polysaccharide's yin-nourishing and moistening properties are doubled, while also providing mucosal repair, aligning with the concept of "nourishing the throat." This prescription is suitable for chronic pharyngitis and Sjögren's syndrome of yin deficiency and dryness-heat type. It treats both the symptoms and the root cause by "nourishing yin without stagnation" and "clearing away heat without damaging the body". Modern research has confirmed its mechanism: the components of Asparagus cochinchinensis / Ophiopogon japonicus upregulate AQP5 to promote saliva secretion, baicalin / Anemarrhena saponin inhibit the NF-κB inflammatory pathway, and Dendrobium nanoliposomes enhance mucosal repair, perfectly interpreting the TCM theory of "nourishing yin and regenerating muscles".

[0007] Preferably, the dendrobium is one or more of Huoshan dendrobium or officinale dendrobium. The polysaccharide content of the selected dendrobium variety is significantly higher than that of common dendrobium, which can specifically enhance the hydration of the throat mucosa and the immune regulation function.

[0008] Preferably, the ginseng particle size is 0.3-1.0 mm; the dendrobium, polygonatum, and polygonatum particle size is 0.1-0.5 mm. By precisely controlling the particle size of the medicinal materials, the specific surface area of ​​the medicinal materials is increased, and the dissolution efficiency of fat-soluble and large-molecule active ingredients such as ginsenosides and dendrobium polysaccharides is promoted.

[0009] Preferably, the polysaccharide-modified nanoliposomes are dendrobium polysaccharide nanoliposomes.

[0010] More preferably, the average particle size of the polysaccharide-modified nanoliposomes is 80 to 150 nm; the polysaccharide-modified nanoliposomes are prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0011] The present invention also provides a method for preparing Shihu Erdong granules, comprising the following steps: (1) Ginseng was crushed in a crusher, and dendrobium, polygonatum, and polygonatum were processed by liquid nitrogen quick freezing and crushing technology; (2) Mix asparagus, ophiopogon, trichosanthes root, scutellaria, anemarrhena, lotus leaf, and liquorice with 6 times the amount of buffer solution and decoct for the first time; then add ginseng, dendrobium, polygonatum, and polygonatum with 8 times the amount of water and decoct for the second time; combine the two decoctions and filter through an ultrasonic vibration sieve; (3) The filtrate is pre-concentrated by a ceramic membrane and then concentrated in a vacuum to obtain a clear paste; (4) The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, nanoliposomes were added and mixed evenly, pulse dried, and then centrifuged and spray dried to obtain a dry powder paste; (5) The dry paste powder is granulated using a differential speed roller to obtain the dendrobium and erdong granules.

[0012] Preferably, the buffer solution in step (2) has a pH of 6.5 to 7.0 and contains an aqueous solution of 0.1% sodium citrate and 0.05% L-ascorbic acid. The use of a neutral buffer system in combination with an antioxidant can effectively inhibit the oxidative hydrolysis of phenolic components such as baicalin and polygonatum saponin, thereby maintaining the stability of heat-sensitive components in the decoction.

[0013] Preferably, the filtrate in step (3) is pre-concentrated to a density of 1.05-1.08 (50°C) via a 50°C ceramic membrane, and then concentrated to a density of 1.28-1.32 (50°C) at a vacuum degree of -0.095 to -0.10 MPa and 45°C to obtain a clear paste. The gradient concentration process uses low-temperature conditions to reduce thermal degradation of heat-sensitive components such as polygonatum polysaccharides and ophiopogon saponins, while also reducing energy consumption during the concentration process.

[0014] More preferably, in step (3), a 300Da nanofiltration membrane is used for ceramic membrane pre-concentration, with a transmembrane pressure of 0.8-1.2 MPa and a membrane surface flow rate of 2.5-3.0 m / s. The nanofiltration membrane intercepts and accurately separates small molecular impurities such as tannins and starch, significantly improving the enrichment of effective ingredients.

[0015] Preferably, in step (5), the speed ratio of the fast roller to the slow roller during differential roller granulation is 1:1.5 to 1:2.0, and the roller gap is 0.8 to 1.2 mm. A porous network granule structure is formed through mechanical shearing and extrusion, accelerating granule disintegration and dissolution and release of the active ingredient.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) Through the innovative combination of Dendrobium, Polygonatum, and Polygonatum, a new formula of "three yin tonification" is formed, which synergistically enhances the effects of promoting fluid production and moistening the lungs and nourishing yin and moistening dryness, significantly improving the repair function of the throat mucosal barrier; (2) Liquid nitrogen quick freezing and crushing technology is used to process medicinal materials, accurately controlling the crushed particle size to ≤0.5mm, effectively protecting the molecular structure integrity of heat-sensitive active ingredients; (3) Through the integrated process of buffer system decoction, gradient concentration and pulse-spray combined drying, the extraction path is optimized and energy consumption is reduced, while the extraction rate of active ingredients and process stability are simultaneously improved; (4) Innovative application of β-cyclodextrin inclusion technology and dendrobium polysaccharide nanoliposome protective agent to form a multi-molecular stabilization barrier, significantly inhibiting the degradation of active ingredients and ensuring the stability of the physical and chemical properties of the preparation during storage and release. DETAILED DESCRIPTION

[0017] The present invention will be further described below with reference to the embodiments.

[0018] Example 1 This embodiment provides a total Shihu Erdong granule, which comprises the following components in parts by weight: 7-8 parts of asparagus, 11-12 parts of ophiopogon, 2-4 parts of trichosanthes, 2-4 parts of scutellaria, 2-4 parts of anemarrhena, 2-4 parts of lotus leaves, 1-2 parts of ginseng, 1-2 parts of liquorice, 6-8 parts of dendrobium, 5-7 parts of polygonatum, 5-7 parts of polygonatum, and 1-2 parts of polysaccharide-modified nanoliposomes.

[0019] In some preferred embodiments, the dendrobium is Huoshan dendrobium or candidum. The technical effect is that the polysaccharide content of the selected dendrobium variety is significantly higher than that of ordinary dendrobium, which can specifically enhance the hydration of the throat mucosa and the immune regulation function.

[0020] In some preferred embodiments, the ginseng particle size is 0.3-1.0 mm, and the dendrobium, polygonatum, and polygonatum particle size is 0.1-0.5 mm. The technical effect is that by precisely controlling the particle size of the medicinal materials, the specific surface area of ​​the medicinal materials is increased, promoting the dissolution efficiency of fat-soluble and large-molecule active ingredients such as ginsenosides and dendrobium polysaccharides.

[0021] In some preferred embodiments, the polysaccharide-modified nanoliposomes are dendrobium polysaccharide nanoliposomes. The technical effect is that by precisely controlling the particle size of the medicinal material, the specific surface area of ​​the medicinal material is increased, thereby promoting the dissolution efficiency of fat-soluble and macromolecular active ingredients such as ginsenosides and dendrobium polysaccharides.

[0022] In some preferred implementation cases, the average particle size of the polysaccharide-modified nanoliposomes is 80 to 150 nm; the polysaccharide-modified nanoliposomes are prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0023] This embodiment also provides a preparation method of total Shihu Erdong granules, which specifically comprises the following steps: (1) Ginseng was crushed in a crusher, and dendrobium, polygonatum, and polygonatum were processed by liquid nitrogen quick freezing and crushing technology; (2) Mix asparagus, ophiopogon, trichosanthes root, scutellaria, anemarrhena, lotus leaf, and liquorice with 6 times the amount of buffer solution and decoct for the first time; then add ginseng, dendrobium, polygonatum, and polygonatum with 8 times the amount of water and decoct for the second time; combine the two decoctions and filter through an ultrasonic vibration sieve; (3) The filtrate is pre-concentrated by a ceramic membrane and then concentrated in a vacuum to obtain a clear paste; (4) The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, nanoliposomes were added and mixed evenly, pulse dried, and then centrifuged and spray dried to obtain a dry powder paste; (5) The dry paste powder is granulated using a differential speed roller to obtain the dendrobium and erdong granules.

[0024] In some preferred embodiments, the buffer solution in step (2) has a pH of 6.5 to 7.0 and comprises an aqueous solution of 0.1% sodium citrate and 0.05% L-ascorbic acid. The technical effect is that the use of a neutral buffer system in combination with an antioxidant can effectively inhibit the oxidative hydrolysis of phenolic components such as baicalin and polygonatum saponin, thereby maintaining the stability of heat-sensitive components in the decoction.

[0025] In some preferred embodiments, the filtrate in step (3) is first pre-concentrated to a density of 1.05-1.08 (50°C) using a 50°C ceramic membrane, and then concentrated to a density of 1.28-1.32 (50°C) at a vacuum degree of -0.095 to -0.10 MPa and 45°C to obtain a clear paste. The technical effect of the gradient concentration process is that it reduces the thermal degradation of heat-sensitive components such as polygonatum polysaccharides and ophiopogon saponins under low temperature conditions, while also reducing energy consumption during the concentration process.

[0026] In some preferred embodiments, the ceramic membrane pre-concentration in step (3) uses a 300Da nanofiltration membrane, a transmembrane pressure of 0.8-1.2 MPa, and a membrane surface flow rate of 2.5-3.0 m / s. The technical effect is that small molecular impurities such as tannins and starch are precisely separated by the nanofiltration membrane, significantly improving the enrichment of the active ingredients.

[0027] In some preferred embodiments, the speed ratio of the fast roller to the slow roller during differential roller compaction in step (5) is 1:1.5 to 1:2.0, and the roller gap is 0.8 to 1.2 mm. The technical effect is that a porous network granule structure is formed through mechanical shearing and extrusion, accelerating granule disintegration and dissolution and release of the active ingredient.

[0028] Example 2 This embodiment provides a Shihu Erdong granule, which specifically comprises the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, 6 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0029] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0030] This embodiment also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0031] Example 3 This embodiment provides a Shihu Erdong granule, which specifically comprises the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 6 parts of Dendrobium, 5 parts of Polygonatum, 5 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0032] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0033] This embodiment also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0034] Example 4 This embodiment provides a Shihu Erdong granule, which specifically comprises the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 6 parts of Dendrobium, 7 parts of Polygonatum, 7 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0035] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0036] This embodiment also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0037] Comparative Example 1 The difference between this comparative example and Example 2 is that in step (2) of this comparative example, no segmented decocting is performed, and all raw materials are decocted together twice.

[0038] This comparative example provides a dendrobium and erdong granules, which specifically comprise the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, 6 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0039] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0040] This comparative example also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, Glycyrrhizae uralensis, Ginseng, Dendrobium, Polygonatum sibiricum, and Polygonatum odoratum with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add 8 times the amount of water, and decoct at 75°C for 40 minutes; filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0041] Comparative Example 2 The difference between this comparative example and Example 2 is that in step (2) of this comparative example, 6 times of water is added to the first decoction, and no buffer solution is added.

[0042] This comparative example provides a dendrobium and erdong granules, which specifically comprise the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, 6 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0043] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0044] This comparative example also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix asparagus, ophiopogon, trichosanthes root, scutellaria, anemarrhena, lotus leaf, and liquorice with 6 times the amount of water, and decoct at 85°C for 50 minutes; Second decoction: Add pre-treated ginseng, dendrobium, polygonatum, and polygonatum and 8 times the amount of water, and decoct at 75°C for 40 minutes; filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0045] Comparative Example 3 The difference between this comparative example and Example 2 is that in step (3) of this comparative example, no ceramic membrane system pre-concentration is performed.

[0046] This comparative example provides a dendrobium and erdong granules, which specifically comprise the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, 6 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0047] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0048] This comparative example also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Concentration: The filtrate is concentrated under vacuum at -0.10 MPa and 45°C to a relative density of 1.32 to obtain a clear paste; (4) Composite drying: the clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, and then with dendrobium polysaccharide nanoliposomes; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then transferred to centrifugal spray drying for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0049] Comparative Example 4 The difference between this comparative example and Example 2 is that only maltodextrin is added in step (4) of this comparative example.

[0050] This comparative example provides a dendrobium and erdong granules, which specifically comprise the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, 6 parts of Polygonatum odoratum, and 1 part of Dendrobium polysaccharide nanoliposomes.

[0051] The dendrobium is Dendrobium officinale; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:1.

[0052] This comparative example also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: the paste was mixed with maltodextrin in a ratio of 10:2, and dendrobium polysaccharide nanoliposomes were added; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then centrifugal spray drying was performed for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0053] Comparative Example 5 The difference between this comparative example and Example 2 is that in step (4) of this comparative example, no dendrobium polysaccharide nanoliposomes are added.

[0054] This comparative example provides a dendrobium and erdong granules, which specifically comprise the following components in parts by weight: 7.46 parts of Asparagus cochinchinensis, 11.19 parts of Ophiopogon japonicus, 3.73 parts of Radix Trichosanthis, 3.73 parts of Scutellaria baicalensis, 3.73 parts of Rhizoma Anemarrhenae, 3.73 parts of Lotus leaf, 1.87 parts of Ginseng, 1.87 parts of Licorice, 7 parts of Dendrobium, 6 parts of Polygonatum, and 6 parts of Polygonatum odoratum.

[0055] The dendrobium is Dendrobium officinale.

[0056] This comparative example also provides a method for preparing Shihu Erdong granules, which specifically comprises the following steps: (1) Raw material pretreatment: Ginseng was crushed into a crusher to a particle size of 0.3-1.0 mm, and Dendrobium, Polygonatum, and Polygonatum were processed by liquid nitrogen quick freezing and crushing technology to a particle size of ≤0.5 mm; (2) Decoction in stages: First decoction: Mix Asparagus cochinchinensis, Radix Ophiopogonis, Radix Trichosanthis, Radix Scutellariae, Rhizoma Anemarrhenae, Lotus Leaf, and Radix Glycyrrhizae with 6 times the amount of pH 7.0 buffer (containing 0.1% sodium citrate and 0.05% L-ascorbic acid), and decoct at 85°C for 50 minutes; Second decoction: Add pretreated Radix Ginseng, Dendrobium, Polygonatum, and Polygonatum odoratum and 8 times the amount of water, and decoct at 75°C for 40 minutes; Filter through a 200-mesh ultrasonic vibrating sieve; (3) Gradient concentration: The filtrate was pre-concentrated to a relative density of 1.05 at 50°C through a ceramic membrane system with a 300Da nanofiltration membrane (transmembrane pressure 1.2 MPa, membrane surface flow rate 3.0 m / s); and further concentrated to a relative density of 1.32 at a vacuum degree of -0.10 MPa and 45°C to obtain a clear paste; (4) Composite drying: The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1; pulse drying was performed at a temperature of 75°C and a vacuum degree of -0.095 MPa for 20 minutes, and then centrifugal spray drying was performed for 20 minutes; (5) Granulation: The dry paste powder was granulated using differential roller pressing (speed ratio of fast roller to slow roller 1:2.0, roller pressing gap 1.2 mm), the granule porosity was controlled to 40%, and the granules were passed through a 15-mesh sieve to obtain the Dendrobium Erdong granules.

[0057] Test example The dry paste rate, particle moisture absorption rate and particle forming rate of the Dendrobium Erdong granules prepared using the formula and method of Examples 2-5 and Comparative Examples 1-4 were tested, and the results are shown in Table 1.

[0058] The effective ingredient contents of the Shihu Erdong granules prepared in the examples and comparative examples were tested, and the results are shown in Table 2.

[0059] 1. Determination of dry paste rate: Accurately measure 20 mL of the filtrate after decoction and filtration of the medicinal materials, place it in an evaporating dish that has been dried to a constant weight, and weigh it to determine the weight W1. After evaporating to dryness on a water bath, dry it at 105°C for 3 hours, cool it in a desiccator for 30 minutes, and quickly and accurately weigh it to determine the weight W2. The calculation formula is as follows:

[0060] 2. Moisture Absorption Rate Determination Method: Take 2g of the test sample and spread it evenly in a weighing bottle (bottle weight m1). Weigh the weight (m2). Place the bottle with the lid open at a temperature of 25°C ± 2°C and a relative humidity of 60% ± 5% for 1 hour. Weigh the weight (m3). Calculate the moisture absorption rate using the formula: Moisture Absorption Rate = (m3 - m2) / (m2 - m1) * 100%.

[0061] Table 1 Group Dry paste rate (%) Moisture absorption rate (%) Forming rate (%) Example 2 44.66 4.7 47.01 Example 3 45.41 4.8 48.75 Example 4 43.79 4.9 45.98 Comparative Example 1 38.2 5.5 35 Comparative Example 2 40.1 6.2 28.6 Comparative Example 3 36.8 7.8 32.4 Comparative Example 4 42.5 5.1 39.48 Comparative Example 5 43.1 5.3 43

[0062] Table 2

[0063] As shown in Tables 1 and 2, the Shihu Erdong granules prepared in this invention demonstrate significant technical advantages in core quality indicators. Compared to traditional processes, the optimized gradient concentration, pulse-spray combined drying, and differential roller granulation process achieves a steady increase in dry paste yield, effective control of hygroscopic properties, and systematic improvements in molding performance and active ingredient content. The comparative group, however, exhibited varying degrees of degradation in all aspects due to the lack of key process steps, fully demonstrating the necessity of the process design of this invention.

[0064] Comparative Example 1 employed a simultaneous decoction process for all medicinal herbs. However, due to the failure to achieve staged temperature-controlled extraction of heat-sensitive components, the dissolution efficiency of the active ingredients from the precious and fine medicinal materials was significantly reduced. The core indicators of dry paste yield and characteristic active ingredient content were both lower than those of the examples of the present invention. Analysis showed that the high-temperature destructive effects of the mixed medicinal decoction and competitive inhibition of dissolution were the key factors contributing to the loss of active ingredients.

[0065] In Comparative Example 2, after the buffer solution system was removed, the phenolic active ingredients underwent significant oxidation degradation during the decoction process. While the content of characteristic flavonoid components decreased, the moisture absorption rate of the preparation increased abnormally, confirming the protective effect of the neutral buffer environment on the phenolic hydroxyl structure and the important influence of the antioxidant stabilization mechanism on the preparation quality.

[0066] Comparative Example 3, without membrane separation pre-concentration, used direct concentration, resulting in excessive impurity enrichment. The purity of the characteristic saponins was significantly reduced, and the dry paste yield fell short of the process benchmark. Studies have shown that the lack of nanofiltration membrane retention not only impairs the selective enrichment of active ingredients but also exacerbates thermal degradation of polysaccharides due to increased heat load.

[0067] In Comparative Example 4, omitting the β-cyclodextrin inclusion technology resulted in a simultaneous deterioration in both bitterness-masking and molding properties. The exposure of the characteristic bitter component resulted in an imbalance in the particle surface polarity, increasing its tendency to absorb moisture. Simultaneously, the imperfect dispersion of the fat-soluble component caused a loose particle structure, significantly degrading mechanical properties.

[0068] Comparative Example 5, which did not incorporate a nanoliposome protection system, significantly reduced the stability of the active ingredient during the drying process. The absence of the liposome bilayer exposed the dendrobium polysaccharide directly to the high-temperature drying environment, leading to molecular chain breakage and increased hygroscopicity. Furthermore, thermal stress during the drying process triggered isomerization of baicalin, reducing the stability of the formulation.

[0069] Unless otherwise specified, the raw materials and equipment used in the present invention are commonly used in the art; unless otherwise specified, the methods used in the present invention are conventional methods in the art. The above description is merely a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, alteration, or equivalent transformation of the above embodiment based on the technical essence of the present invention still falls within the scope of protection of the technical solution of the present invention.

Claims

1. A Dendrobium Erdong granule, characterized in that: The invention comprises the following components in parts by weight: 7-8 parts of asparagus cochinchinensis, 11-12 parts of ophiopogon japonicus, 2-4 parts of trichosanthes root, 2-4 parts of scutellaria baicalensis, 2-4 parts of anemarrhena asphodeloides, 2-4 parts of lotus leaf, 1-2 parts of ginseng, 1-2 parts of liquorice, 6-8 parts of dendrobium, 5-7 parts of polygonatum, 5-7 parts of polygonatum odoratum, and 1-2 parts of polysaccharide-modified nanoliposomes.

2. The Dendrobium Erdong granules according to claim 1, characterized in that The dendrobium is one or more of Huoshan dendrobium or officinale.

3. The Dendrobium Erdong granules according to claim 1, characterized in that The particle size of the ginseng is 0.3-1.0 mm; the particle sizes of the dendrobium, polygonatum and polygonatum are 0.1-0.5 mm.

4. The Dendrobium Erdong granules according to claim 1, characterized in that The polysaccharide modified nanoliposome is dendrobium polysaccharide nanoliposome.

5. The Dendrobium Erdong granules according to claim 1 or 4, characterized in that The average particle size of the polysaccharide-modified nanoliposome is 80-150 nm; the polysaccharide-modified nanoliposome is prepared from soybean lecithin, cholesterol and dendrobium polysaccharide extract in a ratio of 8:2:

1.

6. A method for preparing the Shihu Erdong granules according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) Ginseng was crushed in a crusher, and dendrobium, polygonatum, and polygonatum were processed by liquid nitrogen quick freezing and crushing technology; (2) Mix asparagus, ophiopogon, trichosanthes root, scutellaria, anemarrhena, lotus leaf, and liquorice with 6 times the amount of buffer solution and decoct for the first time; then add ginseng, dendrobium, polygonatum, and polygonatum with 8 times the amount of water and decoct for the second time; combine the two decoctions and filter through an ultrasonic vibration sieve; (3) The filtrate is pre-concentrated by a ceramic membrane and then concentrated in a vacuum to obtain a clear paste; (4) The clear paste was mixed with maltodextrin and β-cyclodextrin in a ratio of 10:2:1, nanoliposomes were added and mixed evenly, pulse dried, and then centrifuged and spray dried to obtain a dry powder paste; (5) The dry paste powder is granulated using a differential speed roller to obtain the dendrobium and erdong granules.

7. The preparation method according to claim 6, characterized in that The buffer solution in step (2) has a pH of 6.5 to 7.0 and contains an aqueous solution of 0.1% sodium citrate and 0.05% L-ascorbic acid.

8. The preparation method according to claim 6, characterized in that In the step (3), the filtrate is first pre-concentrated to a density of 1.05-1.08 (50°C) through a 50°C ceramic membrane, and then concentrated to a density of 1.28-1.32 (50°C) at a vacuum degree of -0.095 to -0.10 MPa and 45°C to obtain a clear paste.

9. The preparation method according to claim 6 or 8, characterized in that: In the step (3), a 300Da nanofiltration membrane is used for ceramic membrane pre-concentration, with a transmembrane pressure of 0.8 to 1.2 MPa and a membrane surface flow rate of 2.5 to 3.0 m / s.

10. The preparation method according to claim 6, characterized in that In the step (5), when the granules are compressed by differential speed rollers, the speed ratio of the fast roller to the slow roller is 1:1.5 to 1:2.0, and the roller pressing gap is 0.8 to 1.2 mm.

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