Liver-protecting tablet and its preparation method

Abstract

This invention provides a method for preparing liver-protecting tablets, comprising the following steps: (1) Angelica sinensis, Aucklandia lappa, Cyperus rotundus, Ligusticum chuanxiong, and Citrus aurantium are pulverized into mixed medicinal powder I, and water and mixed enzymes are added for enzymatic hydrolysis to obtain mixed enzymatic hydrolysate I, which is then subjected to supercritical CO2 extraction to obtain extract I; (2) Bupleurum chinense, Codonopsis pilosula, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata are pulverized into mixed medicinal powder II, and water and mixed enzymes are added for enzymatic hydrolysis to obtain mixed enzymatic hydrolysate II, which is then subjected to percolation extraction. The percolated residue is ultrasonically extracted to obtain ultrasonic extract, and the percolation liquid and ultrasonic extract are combined and filtered to obtain extract II; (3) Extract I and extract II are concentrated and mixed with trehalose and sorbitol, spray-dried to obtain spray-mixed medicinal powder, and then mixed with magnesium stearate and croscarmellose sodium, and compressed into tablets to obtain liver-protecting tablets. This invention, through a reasonable preparation method, can more efficiently retain the active ingredients in the raw materials, reduce losses, and maintain their stability.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a liver-protecting tablet and its preparation method. Background Technology

[0002] Ganling Tablets, also known as Zhonghua Ganling Tablets, are a traditional Chinese medicine. They are composed of Bupleurum (processed with vinegar), Codonopsis pilosula, Magnolia officinalis (processed with ginger), Panax notoginseng, Angelica sinensis, Aucklandia lappa, Cyperus rotundus (processed with vinegar), Ligusticum chuanxiong, Carapax Trionycis (processed with vinegar), Curcuma longa, Citrus reticulata (processed with vinegar), and Citrus aurantium (stir-fried with wheat bran). They have the effects of soothing the liver and strengthening the spleen, regulating qi and relieving pain, promoting blood circulation and removing blood stasis, and softening and dispersing masses. They are used for liver qi stagnation and blood obstruction, accumulations that are difficult to resolve, distending pain in the hypochondriac region, poor appetite and loose stools, ecchymosis on the tongue, and a deep, weak, and hesitant pulse. Traditionally, the preparation of Ganling Tablets involves directly decocting the raw materials with water to extract the active ingredients. However, this method still suffers from low extraction efficiency, easy oxidation of active ingredients, and significant loss of active ingredients. In particular, the content of active ingredients in raw materials such as Magnolia officinalis, Angelica sinensis, and Ligusticum chuanxiong, which are beneficial for liver damage repair, protecting liver cell function, and improving liver microcirculation, is low, making it difficult to effectively control the quality of Ganling Tablets. Summary of the Invention

[0003] In view of this, the present invention proposes a liver-protecting tablet and its preparation method to solve the above problems.

[0004] The technical solution of this invention is implemented as follows:

[0005] A method for preparing liver-protecting tablets includes the following steps:

[0006] (1): Take Angelica sinensis, Costus root, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed powder I. Then add water and mixed enzymes for enzymatic hydrolysis and enzyme inactivation to obtain mixed enzymatic hydrolysate I. Perform supercritical CO2 extraction on mixed enzymatic hydrolysate I. Then evaporate the extraction solvent through an evaporation system to obtain extract I.

[0007] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Turtle shell, Curcuma longa and Citrus reticulata peel and grind them into mixed medicinal powder II. Then add water and mixed enzymes for enzymatic hydrolysis, inactivate the enzymes, and obtain mixed enzymatic hydrolysate II. Percolate extract mixed enzymatic hydrolysate II, collect the percolate, and use ethanol solution to ultrasonically extract the filter residue after percolation to obtain ultrasonic extract. Combine the percolate and ultrasonic extract, filter, and obtain extract II.

[0008] (3): After mixing extract I and extract II, concentrate to a relative density of 1.01-1.30. Mix the extract with trehalose and sorbitol and spray dry to obtain spray-mixed drug powder. Then mix the spray-mixed drug powder with magnesium stearate and croscarmellose sodium and compress to obtain liver-protecting tablets.

[0009] Furthermore, the concentration temperature is 45°C and the vacuum is controlled at -0.075 MPa.

[0010] Further, in step (1), the particle size of the mixed powder I is 80-120 mesh; the amount of water added is 8-12 times the weight of the mixed powder I; the amount of the mixed enzyme added is 0.1-0.5% of the weight of the mixed powder I; the mixed enzyme includes cellulase, amylase, β-glucanase, and mannanase in a mass ratio of (6-8):(0.6-2):(0.5-3):(1-1.8).

[0011] Furthermore, in step (1), the CO2 supercritical extraction temperature is 30-50℃, the extraction pressure is 8.0-10.5MPa, the CO2 flow rate is 15-30L / h, and the extraction time is 60-120min.

[0012] Furthermore, the particle size of the mixed powder II is 60-80 mesh; the amount of water added is 12-15 times the weight of the mixed powder I; the amount of the mixed enzyme added is 0.5-1.2% of the weight of the mixed powder I; the mixed enzyme includes cellulase, amylase, β-glucanase, and mannanase in a mass ratio of (8-10):(0.8-1.6):(1-3):(2-3).

[0013] Furthermore, the enzymatic hydrolysis is carried out at a temperature of 20–30°C for 1–3 hours.

[0014] Furthermore, in step (2), the percolation extraction rate is 2-5 ml / min, the percolation process temperature is 30-40℃, the ethanol solution concentration is 70-80 wt%, and the amount of ethanol solution added is 5-8 times the mass of the filter residue.

[0015] Furthermore, in step (2), the ultrasonic extraction process is performed twice. The first extraction conditions are: ultrasonic power 300-400W, temperature 30-40℃, and extraction time 120-180min. The second extraction conditions are: ultrasonic power 600-800W, temperature 50-60℃, and extraction time 60-90min.

[0016] Furthermore, in step (3), the amount of trehalose added is 3-5% of the total weight of the extract; the amount of sorbitol added is 0.05-0.1% of the total weight of the extract; the amount of magnesium stearate added is 0.1-1% of the weight of the spray-mixed powder; and the amount of croscarmellose sodium added is 0.5-3% of the weight of the spray-mixed powder.

[0017] Furthermore, in step (3), during the spray drying process, the atomizer speed is 250-300 Hz, the inlet air temperature is 150-190°C, and the outlet air temperature is 80-110°C.

[0018] Furthermore, the Liver-Clearing Tablets comprise the following raw materials in parts by weight: Bupleurum chinense 5-8 parts, Codonopsis pilosula 4-7 parts, Magnolia officinalis 28-35 parts, Panax notoginseng 4-8 parts, Angelica sinensis 28-35 parts, Aucklandia lappa 10-14 parts, Cyperus rotundus 18-26 parts, Ligusticum chuanxiong 9-13 parts, Trionyx sinensis 20-26 parts, Curcuma longa 18-25 parts, Citrus reticulata 26-34 parts, Citrus aurantium 26-34 parts.

[0019] Furthermore, after compression, the weight of the liver-protecting tablets is 0.3g, the weight difference is (±4%), the compression speed is <50HZ, and the hardness is 20N~70N.

[0020] Compared with the prior art, the beneficial effects of the present invention are:

[0021] This invention utilizes a combination of enzymatic hydrolysis, supercritical CO2 extraction, percolation, and ultrasonic extraction. By controlling the conditions of supercritical CO2 extraction, percolation, and ultrasonic extraction, the various steps work synergistically to ensure the full release of active ingredients in the raw materials of Ganling tablets. This allows for the effective extraction of active ingredients and maintains a high content of active ingredients such as magnolol and ligustilide.

[0022] In the extraction process of this invention, a complex enzyme composed of cellulase, amylase, β-glucanase, and mannanase is first used to enzymatically hydrolyze mixed powder I and mixed powder II separately. This process can more thoroughly break down the cell walls of the raw materials, allowing the active ingredients to be fully exposed. Furthermore, specific extraction methods are used for mixed powder I and mixed powder II according to their active ingredient composition, which can better preserve the content of active ingredients and improve extraction efficiency. Mixed powder I mainly extracts volatile oils. A specific extraction process is used to fully extract the volatile oils and other active ingredients in mixed powder I while minimizing the destruction of active ingredients. Mixed powder II is extracted using a percolation combined with ultrasonic extraction. After percolation, most of the water-soluble active ingredients are obtained from mixed powder II, but alcohol-soluble components still remain in the filter residue. Therefore, by subjecting the percolated filter residue to specific ethanol ultrasonic extraction conditions, the active ingredients in mixed powder II can be more fully extracted, minimizing their loss.

[0023] The liver-soothing tablets prepared by this invention have the effects of soothing the liver and strengthening the spleen, regulating qi and relieving pain, promoting blood circulation and removing blood stasis, and softening and dispersing masses. They can be used for patients with liver qi stagnation and blood stasis, unresolved masses, distending pain in the hypochondriac region, poor appetite and loose stools, ecchymosis on the tongue, and a deep, weak, and hesitant pulse. Detailed Implementation

[0024] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0025] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0026] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0027] Example 1

[0028] The Liver-Clearing Tablets of this embodiment include the following raw materials in parts by weight: Bupleurum 6 parts, Codonopsis 7 parts, Magnolia officinalis 28 parts, Panax notoginseng 4 parts, Angelica sinensis 35 parts, Aucklandia lappa 14 parts, Cyperus rotundus 18 parts, Ligusticum chuanxiong 9 parts, Trionyx sinensis 20 parts, Curcuma longa 22 parts, Citrus reticulata 26 parts, Citrus aurantium 26 parts.

[0029] The preparation method of this liver-protecting tablet includes the following steps:

[0030] (1): Take Angelica sinensis, Aucklandia lappa, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed medicinal powder I with a particle size of 80 mesh. Then add water and mixed enzyme and carry out enzymatic hydrolysis at 20℃ for 3h (wherein, the amount of water added is 8 times the weight of mixed medicinal powder I, the amount of mixed enzyme added is 0.1% of the weight of mixed medicinal powder I, and the mixed enzyme includes cellulase, amylase, β-glucanase and mannanase in a mass ratio of 8:0.6:3:1). Inactivate the enzyme to obtain mixed enzymatic hydrolysate I. Carry mixed enzymatic hydrolysate I under CO2 supercritical extraction for 120min at a temperature of 50℃, an extraction pressure of 9.0MPa and a CO2 flow rate of 15L / h. Then evaporate the extraction solvent through an evaporation system to obtain extract I.

[0031] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 80 mesh. Then add water and mixed enzymes and carry out enzymatic hydrolysis at 20℃ for 2 hours (wherein, the amount of water added is 15 times the weight of mixed medicinal powder I, and the amount of mixed enzymes added is 0.8% of the weight of mixed medicinal powder I; the mixed enzymes include cellulase, amylase, β-glucanase, and mannanase in a mass ratio of 10:1:3:2). Inactivate the enzymes to obtain mixed enzymatic hydrolysate II. Put the mixed enzymatic hydrolysate II into the solution... Percolation extraction was performed at a percolation rate of 5 ml / min and a temperature of 40℃. The percolation liquid was collected. The filter residue after percolation was first extracted with an 80 wt% ethanol solution under ultrasonic power of 300 W and a temperature of 40℃ for 120 min, and then under ultrasonic power of 700 W and a temperature of 50℃ for 90 min to obtain an ultrasonic extract (where the amount of ethanol solution added was 8 times the mass of the filter residue). The percolation liquid and the ultrasonic extract were combined, filtered, and extract II was obtained.

[0032] (3): Extract I and Extract II are mixed and concentrated to a relative density of 1.01 under the conditions of 45℃ and vacuum degree of -0.075MPa. The extract is mixed with trehalose and sorbitol and then spray-dried under the conditions of 300HZ atomizer speed, 190℃ inlet air temperature and 80℃ outlet air temperature to obtain spray-mixed drug powder (wherein, the amount of trehalose added is 5% of the total weight of the extract; the amount of sorbitol added is 0.05% of the total weight of the extract). Then, the spray-mixed drug powder is mixed with magnesium stearate and croscarmellose sodium and then compressed into tablets (wherein, the amount of magnesium stearate added is 0.8% of the weight of the spray-mixed drug powder; the amount of croscarmellose sodium added is 3% of the weight of the spray-mixed drug powder) to obtain liver-protecting tablets.

[0033] Example 2

[0034] The Liver-Clearing Tablets of this embodiment include the following raw materials in parts by weight: Bupleurum chinense 5 parts, Codonopsis pilosula 4 parts, Magnolia officinalis 35 parts, Panax notoginseng 8 parts, Angelica sinensis 28 parts, Aucklandia lappa 10 parts, Cyperus rotundus 20 parts, Ligusticum chuanxiong 13 parts, Trionyx sinensis 23 parts, Curcuma longa 25 parts, Citrus reticulata 34 parts, Citrus aurantium 30 parts.

[0035] The preparation method of this liver-protecting tablet includes the following steps:

[0036] (1): Take Angelica sinensis, Aucklandia lappa, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed medicinal powder I with a particle size of 100 mesh. Then add water and mixed enzyme and carry out enzymatic hydrolysis at 30℃ for 1h (wherein, the amount of water added is 10 times the weight of mixed medicinal powder I, the amount of mixed enzyme added is 0.5% of the weight of mixed medicinal powder I, and the mixed enzyme includes cellulase, amylase, β-glucanase and mannanase in a mass ratio of 6:1:2:1.8). Inactivate the enzyme to obtain mixed enzymatic hydrolysate I. Carry mixed enzymatic hydrolysate I under CO2 supercritical extraction at 30℃, extraction pressure of 10.5MPa and CO2 flow rate of 30L / h for 60min. Then evaporate the extraction solvent through the evaporation system to obtain extract I.

[0037] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 60 mesh. Then add water and mixed enzymes and carry out enzymatic hydrolysis at 25℃ for 1 hour (wherein, the amount of water added is 12 times the weight of mixed medicinal powder I, and the amount of mixed enzymes added is 0.5% of the weight of mixed medicinal powder I; the mixed enzymes include cellulase, amylase, β-glucanase, and mannanase in a mass ratio of 9:0.8:2:3). Inactivate the enzymes to obtain mixed enzymatic hydrolysate II. Mixed enzymatic hydrolysate II Percolation extraction was performed at a percolation rate of 2 ml / min and a temperature of 35℃. The percolate was collected, and the filter residue after percolation was first extracted with a 70 wt% ethanol solution under ultrasonic power of 400 W and a temperature of 35℃ for 150 min, and then under ultrasonic power of 600 W and a temperature of 60℃ for 60 min to obtain an ultrasonic extract (wherein, the amount of ethanol solution added was 7 times the mass of the filter residue). The percolate and ultrasonic extract were combined, filtered, and extract II was obtained.

[0038] (3): Extract I and Extract II are mixed and concentrated to a relative density of 1.30 under the conditions of 45℃ and vacuum degree of -0.075MPa. The extract is mixed with trehalose and sorbitol and spray-dried under the conditions of 250HZ atomizer speed, 150℃ inlet air temperature and 110℃ outlet air temperature to obtain spray-mixed drug powder (wherein, the amount of trehalose added is 3% of the total weight of the extract; the amount of sorbitol added is 0.1% of the total weight of the extract). Then, the spray-mixed drug powder is mixed with magnesium stearate and croscarmellose sodium and then compressed into tablets (wherein, the amount of magnesium stearate added is 0.1% of the weight of the spray-mixed drug powder; the amount of croscarmellose sodium added is 3% of the weight of the spray-mixed drug powder) to obtain liver-protecting tablets.

[0039] Example 3

[0040] The Liver-Clearing Tablets of this embodiment include the following raw materials in parts by weight: Bupleurum chinense 8 parts, Codonopsis pilosula 5 parts, Magnolia officinalis 30 parts, Panax notoginseng 7 parts, Angelica sinensis 32 parts, Aucklandia lappa 12 parts, Cyperus rotundus 25 parts, Ligusticum chuanxiong 12 parts, Trionyx sinensis 26 parts, Curcuma longa 18 parts, Citrus reticulata 30 parts, Citrus aurantium 34 parts.

[0041] The preparation method of this liver-protecting tablet includes the following steps:

[0042] (1): Take Angelica sinensis, Aucklandia lappa, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed medicinal powder I with a particle size of 120 mesh. Then add water and mixed enzyme and carry out enzymatic hydrolysis at 25℃ for 2h (wherein, the amount of water added is 12 times the weight of mixed medicinal powder I, the amount of mixed enzyme added is 0.4% of the weight of mixed medicinal powder I, and the mixed enzyme includes cellulase, amylase, β-glucanase and mannanase in a mass ratio of 7:2:0.5:1.4). Inactivate the enzyme to obtain mixed enzymatic hydrolysate I. Carry mixed enzymatic hydrolysate I under CO2 supercritical extraction at 40℃, extraction pressure of 8.0MPa and CO2 flow rate of 20L / h for 90min. Then evaporate the extraction solvent through the evaporation system to obtain extract I.

[0043] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 70 mesh. Then add water and mixed enzymes and carry out enzymatic hydrolysis at 30℃ for 3 hours (wherein, the amount of water added is 14 times the weight of mixed medicinal powder I, and the amount of mixed enzymes added is 1.2% of the weight of mixed medicinal powder I; the mixed enzymes include cellulase, amylase, β-glucanase, and mannanase in a mass ratio of 8:1.6:1:2). Inactivate the enzymes to obtain mixed enzymatic hydrolysate II. Percolation extraction was performed at a percolation rate of 4 ml / min and a temperature of 30℃. The percolation liquid was collected. The filter residue after percolation was first extracted with a 75 wt% ethanol solution under ultrasonic power of 350 W and a temperature of 30℃ for 180 min, and then under ultrasonic power of 800 W and a temperature of 50℃ for 70 min to obtain an ultrasonic extract (wherein, the amount of ethanol solution added was 5 times the mass of the filter residue). The percolation liquid and the ultrasonic extract were combined, filtered, and extract II was obtained.

[0044] (3): Extract I and Extract II are mixed and concentrated to a relative density of 1.10 under the conditions of 45℃ and vacuum degree of -0.075MPa. The extract is mixed with trehalose and sorbitol and then spray-dried under the conditions of 290HZ atomizer speed, 170℃ inlet air temperature and 90℃ outlet air temperature to obtain spray-mixed drug powder (wherein, the amount of trehalose added is 4% of the total weight of the extract; the amount of sorbitol added is 0.08% of the total weight of the extract). Then, the spray-mixed drug powder is mixed with magnesium stearate and croscarmellose sodium and then compressed into tablets (wherein, the amount of magnesium stearate added is 1% of the weight of the spray-mixed drug powder; the amount of croscarmellose sodium added is 2% of the weight of the spray-mixed drug powder) to obtain liver-protecting tablets.

[0045] Comparative Example 1

[0046] The difference between this embodiment and Embodiment 3 is that neither mixed powder I nor mixed powder II underwent an enzymatic hydrolysis step in step (1). Specifically:

[0047] The preparation method of this liver-protecting tablet includes the following steps:

[0048] (1): Take Angelica sinensis, Costus root, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed powder I with a particle size of 120 mesh. Then, carry out supercritical CO2 extraction for 90 min at a temperature of 40℃, an extraction pressure of 8.0 MPa and a CO2 flow rate of 20 L / h. Then, evaporate the extraction solvent through an evaporation system to obtain extract I.

[0049] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 70 mesh. Then add water with a weight of 14 times that of mixed medicinal powder I and perform percolation extraction at a percolation rate of 4 ml / min and a temperature of 30℃. Collect the percolation liquid. The filter residue after percolation is first extracted with 75 wt% ethanol solution at an ultrasonic power of 350 W and a temperature of 30℃ for 180 min, and then extracted at an ultrasonic power of 800 W and a temperature of 50℃ for 70 min to obtain ultrasonic extract (wherein, the amount of ethanol solution added is 5 times the mass of the filter residue). Combine the percolation liquid and ultrasonic extract, filter, and obtain extract II.

[0050] (3): Extract I and Extract II are mixed and concentrated to a relative density of 1.10 under the conditions of 45℃ and vacuum degree of -0.075MPa. The extract is mixed with trehalose and sorbitol and then spray-dried under the conditions of 290HZ atomizer speed, 170℃ inlet air temperature and 90℃ outlet air temperature to obtain spray-mixed drug powder (wherein, the amount of trehalose added is 4% of the total weight of the extract; the amount of sorbitol added is 0.08% of the total weight of the extract). Then, the spray-mixed drug powder is mixed with magnesium stearate and croscarmellose sodium and then compressed into tablets (wherein, the amount of magnesium stearate added is 1% of the weight of the spray-mixed drug powder; the amount of croscarmellose sodium added is 2% of the weight of the spray-mixed drug powder) to obtain liver-protecting tablets.

[0051] Comparative Example 2

[0052] The difference between this embodiment and Embodiment 3 is that the conditions for supercritical CO2 extraction are changed in step (1). Specifically, the mixed enzymatic hydrolysate I is subjected to supercritical CO2 extraction for 60 min at a temperature of 80°C, an extraction pressure of 5.0 MPa, and a CO2 flow rate of 12 L / h. Then, the extraction solvent is evaporated through an evaporation system to obtain extract I.

[0053] Comparative Example 3

[0054] The difference between this embodiment and Embodiment 3 is that, in step (2), after enzymatic hydrolysis, only ultrasonic extraction is performed. Specifically:

[0055] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 70 mesh. Then add water and mixed enzymes and enzymatically hydrolyze at 30℃ for 3h (wherein, the amount of water added is 14 times the weight of mixed medicinal powder I, and the amount of mixed enzymes added is 1.2% of the weight of mixed medicinal powder I; the mixed enzymes include cellulase, amylase, β-glucanase, and mannanase in a mass ratio of 8:1.6:1:2). Inactivate the enzymes to obtain mixed enzymatic hydrolysate II. Add 6 times the mass of mixed enzymatic hydrolysate II to a 75wt% ethanol solution and extract for 120min under ultrasonic power of 500W and temperature of 50℃. Filter and concentrate to a relative density of 1.1 to obtain extract II.

[0056] Comparative Example 4

[0057] The difference between this embodiment and Embodiment 3 is that, in step (2), after enzymatic hydrolysis, only percolation extraction is performed. Specifically:

[0058] (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II with a particle size of 70 mesh. Then add water and mixed enzyme and carry out enzymatic hydrolysis at 30℃ for 3h (wherein, the amount of water added is 14 times the weight of mixed medicinal powder I, and the amount of mixed enzyme added is 1.2% of the weight of mixed medicinal powder I; the mixed enzyme includes cellulase, amylase, β-glucanase and mannanase in a mass ratio of 8:1.6:1:2). Inactivate the enzyme to obtain mixed enzymatic hydrolysate II. Percolate extract mixed enzymatic hydrolysate II at a percolation rate of 1ml / min and a temperature of 30℃. Collect the percolate, filter, and concentrate to a relative density of 1.1 to obtain extract II.

[0059] Performance testing

[0060] Magnolia officinalis has the effects of drying dampness and resolving phlegm, relieving asthma and reversing adverse flow of qi, and eliminating stagnation and promoting qi circulation. It also works with Cyperus rotundus, Aucklandia lappa, and Citrus aurantium to soothe the liver and strengthen the spleen. Angelica sinensis has the effects of nourishing blood and softening the liver, while Ligusticum chuanxiong has the effects of promoting blood circulation, removing blood stasis, and improving liver microcirculation. Therefore, by determining the content of magnolol in Magnolia officinalis and the most important active ingredient in Angelica sinensis volatile oil—ligustilide (Ligusticum chuanxiong also contains a certain amount of ligustilide), the content of active ingredients in the liver-strengthening tablets obtained by the preparation method of this invention can be further reflected.

[0061] The contents of magnolol and ligustilide in the liver-protecting tablets prepared in Examples 1-3 and Comparative Examples 1-5 were determined by high performance liquid chromatography.

[0062] (1) Chromatographic conditions for magnolol:

[0063] Column: ZORBAX SB-C 18 (250mm×4.6mm, 5μm)

[0064] Mobile phase: methanol-0.5% phosphoric acid solution (volume ratio 75:25)

[0065] Flow rate: 1.0 ml / min

[0066] Detection wavelength: 294nm

[0067] Column temperature: 30℃

[0068] Injection volume: 10 μL.

[0069] (2) Chromatographic conditions for ligustilide:

[0070] Column: ZORBAX SB-C 18 (250mm×4.6mm, 5μm)

[0071] Mobile phase: methanol-0.5% acetic acid solution (volume ratio 65:35)

[0072] Detection wavelength: 324nm

[0073] Flow rate: 1.0 mL / min

[0074] Column temperature: 30℃

[0075] Injection volume: 10 μL.

[0076] (3) Preparation of sample solution: The liver-cleansing tablets prepared in Examples 1-3 and Comparative Examples 1-5 were ground into fine powder. About 0.5g of fine powder was accurately weighed and placed in a 100mL stoppered conical flask. Then, 50mL of 50% methanol was added, and the mixture was ultrasonically extracted for 40min. After filtration, the filtrate was diluted to a volumetric flask with 50% methanol to obtain the sample solution. Five samples were taken from each group of sample solutions and measured three times on average. The average value of the measurement results is shown in Table 1 below.

[0077] Example 1 1.25 27.14 Example 2 1.19 26.85 Example 3 1.34 28.63 Comparative Example 1 0.75 22.91 Comparative Example 2 0.96 24.38 Comparative Example 3 0.60 27.10 Comparative Example 4 0.45 26.72

[0078] The above results indicate that the raw material formulations of Examples 1-3 of this invention, after enzymatic hydrolysis, followed by CO2 supercritical extraction and percolation combined with ultrasonic extraction for different raw materials, can dissolve more active ingredients such as magnolol and ligustilide in the raw materials, resulting in higher levels of active ingredients in the tablets. The magnolol content in Examples 1-3 was 1.19–1.34 mg / g, and the ligustilide content was 26.85–28.63 mg / g. In contrast, the magnolol content in Comparative Examples 1-4 was 0.45–0.96 mg / g, and the ligustilide content was 22.91–27.10 mg / g, showing a decrease in content. Compared with Comparative Example 1, Example 3, using a composite enzyme composed of cellulase, amylase, β-glucanase, and mannanase, can effectively break down the plant cell walls in the raw materials, allowing for better enzymatic hydrolysis of active ingredients such as magnolol and ligustilide. Compared with Comparative Example 2, Example 3 demonstrates that the use of optimized CO2 supercritical extraction conditions can also improve the extraction efficiency of active ingredients such as ligustilide. Compared with Comparative Example 3 and Comparative Example 4, Example 3 demonstrates that the use of percolation combined with ultrasonic extraction can reduce the extraction loss of active ingredients such as magnolol and increase the extraction content of these active ingredients.

[0079] In addition, the liver-protecting tablets prepared in the manner of Examples 1-3 of the present invention were tested according to the Guidelines for Stability Testing of Raw Materials and Preparations in Appendix 9001 of the 2020 Edition of the Chinese Pharmacopoeia, Part IV. After 6 months of testing, there were no significant changes in indicators such as disintegration time, moisture content, magnolol content, and ligustilide, indicating good stability.

[0080] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing Ganling tablets, characterized in that, Includes the following steps: (1): Take Angelica sinensis, Aucklandia lappa, Cyperus rotundus, Ligusticum chuanxiong and Citrus aurantium and grind them into mixed powder I. Then add water and mixed enzymes for enzymatic hydrolysis and enzyme inactivation to obtain mixed enzymatic hydrolysate I. Perform supercritical CO2 extraction on mixed enzymatic hydrolysate I. Then evaporate the extraction solvent through an evaporation system to obtain extract I. The supercritical CO2 extraction temperature is 30~50℃, the extraction pressure is 8.0~10.5MPa, the CO2 flow rate is 15~30L / h, and the extraction time is 60~120min. (2): Take Bupleurum, Codonopsis, Magnolia officinalis, Panax notoginseng, Carapax Trionycis, Curcuma longa, and Citrus reticulata peel and grind them into mixed medicinal powder II. Then add water and mixed enzymes for enzymatic hydrolysis and enzyme inactivation to obtain mixed enzymatic hydrolysate II. Percolate extract mixed enzymatic hydrolysate II and collect the percolate. Use ethanol solution to ultrasonically extract the filter residue after percolation to obtain ultrasonic extract. Combine the percolate and ultrasonic extract, filter, and obtain extract II. The ultrasonic extraction process is performed twice. The first extraction conditions are: ultrasonic power 300~400W, temperature 30~40℃, extraction time 120~180min. The second extraction conditions are: ultrasonic power 600~800W, temperature 50~60℃, extraction time 60~90min. (3): After mixing extract I and extract II, concentrate to a relative density of 1.01-1.

30. Mix the extract with trehalose and sorbitol and spray dry to obtain spray-mixed drug powder. Then mix the spray-mixed drug powder with magnesium stearate and croscarmellose sodium and compress to obtain liver-protecting tablets.

2. The preparation method of Ganling tablets according to claim 1, characterized in that, In step (1), the particle size of the mixed powder I is 80-120 mesh; the amount of water added is 8-12 times the weight of the mixed powder I; the amount of the mixed enzyme added is 0.1-0.5% of the weight of the mixed powder I; the mixed enzyme includes cellulase, amylase, β-glucanase and mannanase in a mass ratio of (6-8):(0.6-2):(0.5-3):(1-1.8).

3. The preparation method of Ganling tablets according to claim 1, characterized in that, The particle size of the mixed powder II is 60-80 mesh; the amount of water added is 12-15 times the weight of the mixed powder I; the amount of the mixed enzyme added is 0.5-1.2% of the weight of the mixed powder I; the mixed enzyme includes cellulase, amylase, β-glucanase, and mannanase in a mass ratio of (8-10):(0.8-1.6):(1-3):(2-3).

4. The preparation method of Ganling tablets according to claim 1, characterized in that, The enzymatic hydrolysis is carried out at a temperature of 20~30℃ for 1~3 hours.

5. The method for preparing liver-protecting tablets according to claim 1, characterized in that, In step (2), the percolation rate of the percolation extraction is 2~5 ml / min, the percolation temperature is 30~40℃, the concentration of the ethanol solution is 70~80 wt%, and the amount of ethanol solution added is 5~8 times the mass of the filter residue.

6. The preparation method of Ganling tablets according to claim 1, characterized in that, In step (3), the amount of trehalose added is 3-5% of the total weight of the extract; the amount of sorbitol added is 0.05-0.1% of the total weight of the extract; the amount of magnesium stearate added is 0.1-1% of the weight of the spray-mixed powder; and the amount of croscarmellose sodium added is 0.5-3% of the weight of the spray-mixed powder.

7. The preparation method of Ganling tablets according to claim 1, characterized in that, In step (3), during the spray drying process, the atomizer speed is 250~300HZ, the inlet air temperature is 150~190℃, and the outlet air temperature is 80~110℃.

8. The Ganling tablet prepared according to the method of any one of claims 1-7, wherein, It is made from the following raw materials in parts by weight: Bupleurum chinense 5-8 parts, Codonopsis pilosula 4-7 parts, Magnolia officinalis 28-35 parts, Panax notoginseng 4-8 parts, Angelica sinensis 28-35 parts, Aucklandia lappa 10-14 parts, Cyperus rotundus 18-26 parts, Ligusticum chuanxiong 9-13 parts, Trionyx sinensis 20-26 parts, Curcuma longa 18-25 parts, Citrus reticulata peel 26-34 parts, Citrus aurantium 26-34 parts.