Granules for tonifying primordial qi and preparation method thereof

Abstract

The invention provides primordial qi tonifying granules and a preparation method thereof.The primordial qi tonifying granules comprise main components and auxiliary materials, and the main components comprise, by weight, 20-35 parts of astragalus membranaceus, 20-35 parts of codonopsis pilosula, 15-20 parts of rhizoma atractylodis macrocephalae fried with bran, 15-20 parts of cynomorium songaricum, 15-20 parts of fructus corni, 8-12 parts of angelica sinensis, 8-12 parts of pericarpium citri reticulatae, 8-12 parts of rhizoma cimicifugae, 8-12 parts of bupleurum chinense and 8-12 parts of honey-fried licorice roots; the auxiliary material is dextrin; the weight ratio of the main component to the auxiliary material is (1-2): 1. The invention provides a traditional Chinese medicine composition for treating chronic obstructive pulmonary disease, which can inhibit pathological injury of lung tissue, reduce airway collagen deposition and improve airway remodeling.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a kind of invigorating granules and a preparation method thereof. Background Art

[0002] For patients with chronic obstructive pulmonary disease, the airway collagen deposition accounts for a large area, which is easy to cause airway remodeling, and some patients have the following symptoms: shortness of breath, which is aggravated by movement, coldness, cold limbs, thin body, dark tongue, thin white or slightly greasy tongue coating, weak pulse, right Guan partial stringy and slippery, right Cun mostly thin and slippery, two Chi pulse weak, etc. The condition is lingering and does not heal for a long time.

[0003] Traditional Chinese medicine has unique advantages in the treatment of chronic obstructive pulmonary disease. Therefore, developing a Chinese medicine composition for the treatment of chronic obstructive pulmonary disease, inhibiting pathological damage to lung tissue, reducing airway collagen deposition, and improving airway remodeling are technical problems that need to be solved by those skilled in the art. Summary of the invention

[0004] To this end, the present invention proposes a Buyuan granule and a preparation method thereof, so as to develop a Chinese medicine composition for treating chronic obstructive pulmonary disease.

[0005] One aspect of the present invention provides a Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 20-35 parts of Astragalus, 20-35 parts of Codonopsis, 15-20 parts of Rhizoma Atractylodis Macrocephalae, 15-20 parts of Cynomorium songaricum, 15-20 parts of Fructus Corni, 8-12 parts of Angelica sinensis, 8-12 parts of Citrus reticulatae, 8-12 parts of Cimicifuga heracleifolia, 8-12 parts of Radix Bupleuri, and 8-12 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = (1-2):1.

[0006] Another aspect of the present invention provides a method for preparing the above-mentioned Buyuan granules, the preparation method comprising the following steps: Step 1, weighing the main component and auxiliary materials in proportion, adding water to the main component and decocting it twice, adding 10-10.5 times the amount of water for the first time and decocting it for 1 hour, adding 9.5-10 times the amount of water for the second time and decocting it for 1 hour, combining the extracts, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.10-1.20 at 60°C; Step 2, performing pulsating vacuum drying on the extract, wherein the water tank of the pulsating vacuum drying is controlled at a temperature of 70-75° C. and a vacuum degree of -0.09-0.08 MPa, to obtain an extract powder with a water content of <8%; Step 3, adding auxiliary materials, wetting agents, and flavoring agents to the extract powder, mixing and granulating, and then passing through a 14-mesh sieve to obtain wet granules; Step 4, drying the wet granules to prepare the Buyuan granules.

[0007] The formula of the Buyuan granules provided by the present invention is as follows: The Astragalus in the formula greatly replenishes the vital energy to protect the skin and hair. Codonopsis, roasted liquorice and Atractylodes help Astragalus to replenish the spleen and stomach and generate vitality. Blood is the mother of Qi, so Angelica is sent to nourish blood and nourish the body. Tangerine peel not only strengthens the spleen and eliminates phlegm, but also regulates Qi to clear the stagnation of tonics. Cimicifuga and Bupleurum raise yang, while Cynomorium songaricum and Cornus officinalis assist yang and benefit the vital energy. All the medicines in the formula have the power to invigorate qi and warm yang, so as to replenish the ancestral Qi to embody the spleen Qi and stomach Qi, so that breathing is even, qi and blood are harmonized, and biochemistry is active.

[0008] Lord: Astragalus, Codonopsis; Minister: stir-fried Atractylodes macrocephala, Cynomorium songaricum, and Cornus officinalis Adjuvant: Angelica sinensis, dried orange peel; Ingredients: Cimicifuga heracleifolia, Bupleurum chinense, and roasted liquorice root

[0009] The present invention experimentally studies the effect of Buyuan granules on the lungs of rats with chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide. The experiment illustrates the protective effect of Buyuan granules on the lungs of rats induced by cigarette smoke and lipopolysaccharide. Buyuan granules can inhibit pathological damage to lung tissue, reduce airway collagen deposition, and thus improve airway remodeling.

[0010] The preparation method of the Buyuan granules of the present invention adopts dextrin as an auxiliary material, and limits the weight ratio of the main component to the auxiliary material to: main component: auxiliary material = (1-2): 1. In conjunction with the optimized preparation process of the present invention, firstly, the main component is decocted with water twice, the amount of water added and the decocting time are reasonably set, and the filtrate is decompressed and concentrated to an extract with a relative density of 1.10-1.20 at 60°C, and then pulse vacuum drying is performed to obtain an extract powder with a water content of less than 8%, and then auxiliary materials, a wetting agent, and a flavoring agent are added, mixed and granulated, and then passed through a 14-mesh sieve to obtain wet granules, and finally the wet granules are dried to prepare the Buyuan granules. Experimental results show that the granules obtained by the method have good medicinal effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 This is the HPLC chart of loganin; Figure 2 It is the linear regression equation diagram of loganin content determination; Figure 3 This is the HE staining observation of lung tissue of rats in the control group; Figure 4 This is the HE staining observation picture of the lung tissue of rats in the model group; Figure 5 This is the HE staining observation picture of the lung tissue of rats in the Buyuan Granules 1 group; Figure 6 This is the HE staining observation of lung tissue of rats in Buyuan Granule Group 2; Figure 7is the observation picture of Masson staining of lung tissue of rats in the control group; Figure 8 is the Masson staining observation picture of lung tissue of rats in the model group; Fig. 9 This is the Masson staining observation picture of the lung tissue of rats in the Buyuan Granules 1 group; Fig.10 This is the Masson staining observation picture of lung tissue of rats in the Buyuan Granules group 2. DETAILED DESCRIPTION

[0012] In order to facilitate understanding of the present invention, the present invention will be described more fully below with reference to various embodiments, but the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0013] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0014] The following is a further description of the embodiments of the present invention in multiple embodiments. The embodiments of the present invention are not limited to the following specific embodiments. Within the scope of the unchanged main rights, appropriate changes can be made to the implementation.

[0015] Embodiment 1: A Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 20 parts of Astragalus, 20 parts of Codonopsis, 15 parts of Rhizoma Atractylodis Macrocephalae, 17 parts of Cynomorium songaricum, 18 parts of Fructus Corni, 8 parts of Angelica sinensis, 8 parts of Citrus reticulatae, 10 parts of Cimicifuga heracleifolia, 9 parts of Radix Bupleuri, and 11 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = 1:1.

[0016] Embodiment 2: A Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 30 parts of Astragalus, 25 parts of Codonopsis, 16 parts of Rhizoma Atractylodis Macrocephalae, 20 parts of Cynomorium songaricum, 15 parts of Fructus Corni, 9 parts of Angelica sinensis, 12 parts of Citrus reticulatae, 8 parts of Cimicifuga heracleifolia, 11 parts of Radix Bupleuri, and 8 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = 2:1.

[0017] Embodiment 3: A Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 28 parts of Astragalus, 35 parts of Codonopsis, 17 parts of Rhizoma Atractylodis Macrocephalae, 15 parts of Cynomorium songaricum, 20 parts of Fructus Corni, 8 parts of Angelica sinensis, 9 parts of Citrus reticulatae, 10 parts of Cimicifuga heracleifolia, 12 parts of Radix Bupleuri, and 12 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = 1:1.

[0018] Embodiment 4: A Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 25 parts of Astragalus, 30 parts of Codonopsis, 20 parts of Rhizoma Atractylodis Macrocephalae, 17 parts of Cynomorium songaricum, 18 parts of Fructus Corni, 12 parts of Angelica sinensis, 11 parts of Citrus reticulatae, 9 parts of Cimicifuga heracleifolia, 8 parts of Radix Bupleuri, and 12 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main component to the auxiliary material is: Main ingredient: auxiliary ingredient = 2:1.

[0019] Embodiment 5: A Buyuan granule, comprising a main component and auxiliary materials, wherein the main component comprises 35 parts of Astragalus, 28 parts of Codonopsis, 15 parts of Rhizoma Atractylodis Macrocephalae, 18 parts of Cynomorium songaricum, 16 parts of Fructus Corni, 9 parts of Angelicae Sinensis, 8 parts of Citrus Reticulatae, 12 parts of Cimicifuga heracleifolia, 9 parts of Radix Bupleuri, and 9 parts of Radix Glycyrrhizae Preparata; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = 1:1.

[0020] Example 6 A method for preparing a supplementary granule comprises the following steps: Step 1, weighing the main component and the auxiliary materials according to the proportion of Example 1, decocting the main component with water twice, adding 10 times the amount of water for the first time, decocting for 1 hour, filtering with a 100-mesh filter cloth, adding 9.5 times the amount of water for the second time, decocting for 1 hour, filtering with a 100-mesh filter cloth, combining the extracts, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.10 at 60° C., and the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 70° C., and time 6 hours; Step 2, performing pulsating vacuum drying on the extract, wherein the water tank of the pulsating vacuum drying is controlled at a temperature of 70° C. and a vacuum degree of -0.09 to -0.08 MPa, to obtain an extract powder with a water content of <8%; Step 3, adding auxiliary materials, 85% ethanol, and sucralose to the extract powder, mixing and granulating, the conditions of the mixed granulation are: the stirring paddle speed is 300 rpm, the granulating knife speed is 1000 rpm, mixing for 2 minutes, and then passing through a 14-mesh sieve to obtain wet granules, the weight ratio of the extract powder to 85% ethanol is: extract powder: 85% ethanol = 4:1, and the amount of sucralose added is 0.1% of the extract powder; Step 4, drying the wet granules at 75°C for 4 hours to prepare Buyuan granules.

[0021] Example 7 A method for preparing a supplementary granule comprises the following steps: Step 1, weighing the main component and auxiliary materials according to the proportion of Example 1, decocting the main component with water twice, adding 10.5 times the amount of water for the first time, decocting for 1 hour, filtering with a 100-mesh filter cloth, adding 9.5 times the amount of water for the second time, decocting for 1 hour, filtering with a 100-mesh filter cloth, combining the extracts, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.20 at 60° C., and the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 80° C., and time 6 hours; Step 2, performing pulsating vacuum drying on the extract, wherein the water tank of the pulsating vacuum drying is controlled at a temperature of 75° C. and a vacuum degree of -0.09 to -0.08 MPa, to obtain an extract powder with a water content of <8%; Step 3, adding auxiliary materials, 85% ethanol, and sucralose to the extract powder, mixing and granulating, the conditions of the mixed granulation are: the stirring paddle speed is 200 rpm, the granulating knife speed is 1200 rpm, mixing for 2 minutes, and then passing through a 14-mesh sieve to obtain wet granules, the weight ratio of the extract powder to 85% ethanol is: extract powder: 80% ethanol = 4:1, and the amount of sucralose added is 0.1% of the extract powder; Step 4, drying the wet granules at 75°C for 4 hours to prepare Buyuan granules.

[0022] Example 8 A method for preparing a supplementary granule comprises the following steps: Step 1, weighing the main component and the auxiliary materials according to the proportion of Example 1, decocting the main component with water twice, adding 10 times the amount of water for the first time, decocting for 1 hour, filtering with a 100-mesh filter cloth, adding 10 times the amount of water for the second time, decocting for 1 hour, filtering with a 100-mesh filter cloth, combining the extracts, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.10 at 60° C., and the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 70° C., and time 6 hours; Step 2, performing pulsating vacuum drying on the extract, wherein the water tank of the pulsating vacuum drying is controlled at a temperature of 70° C. and a vacuum degree of -0.09 to -0.08 MPa, to obtain an extract powder with a water content of <8%; Step 3, adding auxiliary materials, 85% ethanol, and sucralose to the extract powder, mixing and granulating, the conditions of the mixed granulation are: the stirring paddle speed is 300 rpm, the granulating knife speed is 1500 rpm, mixing for 2 minutes, and then passing through a 14-mesh sieve to obtain wet granules, the weight ratio of the extract powder to 85% ethanol is: extract powder: 85% ethanol = 4:1, and the amount of sucralose added is 0.1% of the extract powder; Step 4, drying the wet granules at 75°C for 4 hours to prepare Buyuan granules.

[0023] Example 9 Example 9 is basically the same as Example 6, except that the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 80° C., and time 6 h.

[0024] Example 10 Example 10 is basically the same as Example 6, except that the filtrate is concentrated under reduced pressure to an extract with a relative density of 1.20 at 60°C.

[0025] Embodiment 11 Example 11 is basically the same as Example 6, except that the temperature of the water tank for pulsating vacuum drying is controlled at 75°C.

[0026] Example 12 Example 12 is basically the same as Example 6, except that the weight ratio of the main ingredient to the auxiliary material is: main ingredient: auxiliary material = 2:1.

[0027] Embodiment 13 Example 13 is basically the same as Example 6, except that the stirring paddle speed is 200 rpm.

[0028] Embodiment 14 Example 14 is basically the same as Example 6, except that the pelletizing knife speed is 1500 rpm.

[0029] Comparative Example 1 Comparative Example 1 is substantially the same as Example 6, except that 6 times the amount of water is added for the first time.

[0030] Comparative Example 2 Comparative Example 2 is substantially the same as Example 6, except that 12 times the amount of water is added for the first time.

[0031] Comparative Example 3 The control example 3 is basically the same as the embodiment 6, except that the first decoction time is 1.5 h.

[0032] Comparative Example 4 The control example 4 is basically the same as the embodiment 6, except that the first decoction time is 2 hours.

[0033] Comparative Example 5 Comparative Example 5 is substantially the same as Example 6, except that 8 times the amount of water is added the second time.

[0034] Comparative Example 6 Comparative Example 6 is substantially the same as Example 6, except that 12 times the amount of water is added the second time.

[0035] Comparative Example 7 The control example 7 is basically the same as the embodiment 6, except that the second decoction time is 0.5h.

[0036] Comparative Example 8 The control example 8 is basically the same as the embodiment 6, except that the second decoction time is 1.5 h.

[0037] Comparative Example 9 Control Example 9 is basically the same as Example 6, except that the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 60° C., and time 6 h.

[0038] Comparative Example 10 Control Example 10 is basically the same as Example 6, except that the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 85° C., and time 6 h.

[0039] Comparative Example 11 Comparative Example 11 is substantially the same as Example 6, except that the filtrate is concentrated under reduced pressure to an extract having a relative density of 1.00 at 60°C.

[0040] Comparative Example 12 Comparative Example 12 is substantially the same as Example 6, except that the filtrate is concentrated under reduced pressure to an extract having a relative density of 1.23 at 60°C.

[0041] Comparative Example 13 Comparative Example 13 is basically the same as Example 6, except that the water tank temperature of the pulsating vacuum drying is controlled at 60°C.

[0042] Comparative Example 14 Comparative Example 14 is basically the same as Example 6, except that the water tank temperature of the pulsating vacuum drying is controlled at 85°C.

[0043] Comparative Example 15 Control Example 15 is basically the same as Example 6, except that the weight ratio of the main component to the auxiliary material is: main component: auxiliary material = 3:1.

[0044] Comparative Example 16 Control Example 16 is basically the same as Example 6, except that the auxiliary material is starch.

[0045] Comparative Example 17 Control Example 17 is basically the same as Example 6, except that the auxiliary material consists of dextrin and powdered sugar, and the weight ratio of each component in the auxiliary material is: dextrin: powdered sugar = 4:1.

[0046] Comparative Example 18 Control Example 18 is basically the same as Example 6, except that the auxiliary material consists of starch and powdered sugar, and the weight ratio of each component in the auxiliary material is: starch: powdered sugar = 4:1.

[0047] Comparative Example 19 Control Example 19 is basically the same as Example 6, except that auxiliary materials, 50% ethanol, and sucralose are added to the extract powder, and the mixture is mixed and granulated.

[0048] Comparative Example 20 Comparative Example 20 is substantially the same as Example 6, except that auxiliary materials, 75% ethanol, and sucralose are added to the extract powder, and the mixture is mixed and granulated.

[0049] Comparative Example 21 Control Example 21 is basically the same as Example 6, except that auxiliary materials, 90% ethanol, and sucralose are added to the extract powder and mixed for granulation.

[0050] Comparative Example 22 Control Example 22 is substantially the same as Example 6, except that the stirring paddle speed is 100 rpm.

[0051] Comparative Example 23 Control Example 23 is substantially the same as Example 6, except that the stirring paddle speed is 350 rpm.

[0052] Comparative Example 24 Comparative Example 24 is substantially the same as Example 6, except that the pelletizing knife speed is 900 rpm.

[0053] Comparative Example 25 Control Example 25 is substantially the same as Example 6, except that the pelletizing knife speed is 1700 rpm.

[0054] Comparative Example 26 Control Example 26 is basically the same as Example 6, except that the drying conditions are: 50° C., 3 h.

[0055] Comparative Example 27 Comparative Example 27 is basically the same as Example 6, except that the drying conditions are: 50° C., 4 h.

[0056] Comparative Example 28 Comparative Example 28 is basically the same as Example 6, except that the drying conditions are: 75° C., 3 h.

[0057] The present invention is verified as follows Experiment 1 Selection of criteria for evaluating granulation effect According to the Buyuan formula, the main drugs are Astragalus and Codonopsis, the assistant drugs are Rhizoma Atractylodis Macrocephalae, Cynomorium songaricum and Fructus Corni, the adjuvant drugs are Radix Angelicae Sinensis and Pericarpium Citri Reticulatae, and the guiding drugs are Rhizoma Cimicifugae, Radix Bupleuri and Radix Glycyrrhizae Preparata. The present invention adopts loganin, the main active ingredient of Fructus Corni, as the standard for evaluating the granulation effect.

[0058] Verify the feasibility of loganin as an evaluation of granulation effect: 1.1 Preparation of reference solution Preparation of reference solution: Take an appropriate amount of loganin reference substance, weigh it accurately, and add 70% methanol to prepare a stock solution of a certain concentration; accurately measure the stock solution, add 70% methanol to prepare a reference solution containing 60 μg loganin per 1 mL.

[0059] 1.2 Preparation of test solution Take the Buyuan granules obtained in Example 6 to prepare a Buyuan granule concentrate, shake well, take the supernatant, filter through a microporous filter membrane (0.22 μm), and obtain a test solution.

[0060] 1.3 Preparation of negative sample solution According to the prescription of Buyuan Granules, a negative sample without Cornus officinalis was prepared, 10 times the amount of water was added, and the extraction was performed once for 1 hour each time. After extraction and filtration, the water extract was obtained, and the extract was shaken well. The supernatant was taken and filtered through a microporous filter membrane (0.22 μm) to obtain a negative sample solution.

[0061] 1.4 Chromatographic conditions C18 chromatographic column (Diamonsil 5μm, 4.6×250mm), mobile phase: methanol (A)-0.1% phosphoric acid solution (B), detection wavelength: loganin 237nm, column temperature: 35℃.

[0062] Table 1 Mobile phase ratio

[0063] 1.5 System suitability test Take the negative sample solution, test solution and reference solution respectively, and inject and measure under the chromatographic conditions of 1.4. The results are shown in Figure 1 .

[0064] from Figure 1It can be seen that the elution positions of the test solution and the reference solution have corresponding peaks at the same retention time, while the negative control has no corresponding peak, indicating that other components in the sample have no interference with the determination of loganin. The results preliminarily show that it is feasible to use loganin to evaluate the granulation effect.

[0065] 1.6 Linear relationship test Accurately pipette an appropriate amount of loganin reference solution, dilute it into a series of reference solution concentrations, inject it according to the chromatographic conditions in 1.4, and record the peak area of ​​the chromatographic peak. Draw a standard curve with loganin concentration (X) as the horizontal coordinate and chromatographic peak area (Y) as the vertical coordinate. The regression equation is y=16770.93709x+17130.78797, R²=0.99996, indicating that loganin concentration (μg / mL) and peak area have a good linear relationship in the range of 13.042~579.645μg / mL. The results are shown in Figure 2 and Table 2.

[0066] Table 2 Linear relationship between loganin and peak area

[0067] 1.7 Precision test Accurately pipette 10 μL of the loganin reference solution, repeat the injection 6 times according to the determined chromatographic conditions, and record the peak area values ​​respectively. The results are shown in Table 3.

[0068] Table 3 Precision test results

[0069] As shown in Table 3, the RSD% of the loganin peak area was 0.33%, indicating that the instrument had good precision.

[0070] 1.8 Repeatability test Take samples from the same batch and prepare 6 test solutions in parallel according to the method in 1.2. Measure them under the determined chromatographic conditions and record the peak areas. The results are shown in Table 4.

[0071] Table 4 Repeatability test results

[0072] As shown in Table 4, the RSD% of loganin was 0.50%, indicating that the repeatability results were good.

[0073] 1.9 Stability test Take an appropriate amount of the same test solution and place it at room temperature for 0, 3, 6, 12, 18, 24, and 27 hours, inject 10 μL of each solution, and measure the peak area. The results are shown in Table 5.

[0074] Table 5 Stability test results

[0075] As can be seen from Table 5, the peak area RSD% of loganin was 1.52%, indicating that it was stable within 27 h.

[0076] 1.10 Sample recovery test Take 9 portions of known complementary granules of the same concentration (equivalent to 100% concentration level) and weigh them accurately. Add different concentrations (equivalent to 80%, 100%, and 120% concentration levels) of loganin mixed reference substances accurately respectively. Each group has 3 parallel portions. The solution is prepared according to the test sample preparation method and measured under the determined chromatographic conditions. The results are shown in Table 6.

[0077] Table 6 Results of sample recovery test

[0078] As shown in Table 6, the average recovery rate of loganin was 104.23% and the RSD% was 0.85%, indicating that the method had good accuracy.

[0079] The above results finally showed that it was feasible to use loganin as a test to evaluate the granulation effect.

[0080] Experiment 2 In Example 6, Example 7, Control Example 1 and Control Example 2, after the first decoction, the filtrate was taken to determine the solid content of the extract and the content of loganin, and the transfer rate of loganin and the extract yield were calculated. The results are shown in Table 7.

[0081] Table 7

[0082] As can be seen from Table 7, compared with Control Examples 1 and 2, the loganin transfer rate and extract yield of Examples 6 and 7 are increased. Considering the production cycle and energy saving, it is determined that 10 to 10.5 times the amount of water is added in the first decoction.

[0083] Experiment 3 In Example 6, Control Example 3 and Control Example 4, after the first decoction, the filtrate was taken to determine the solid content of the extract and the content of loganin, and the transfer rate of loganin and the extract yield were calculated. The results are shown in Table 8.

[0084] Table 8

[0085] It can be seen from Table 8 that with the increase of the first decoction time, the index component transfer rate and extract yield do not change significantly. Considering the production cycle, the first decoction time is determined to be 1 hour.

[0086] Experiment 4 In Example 6, Example 8, Comparative Example 5 and Comparative Example 6, after the second decoction, the filtrate was taken to determine the solid content of the extract and the content of loganin, and the transfer rate of loganin and the extract yield were calculated. The results are shown in Table 9.

[0087] Table 9

[0088] As can be seen from Table 9, compared with Control Examples 5 and 6, the loganin transfer rate and extract yield of Examples 6 and 8 are increased. Considering the production cycle and energy saving, 9.5 to 10 times the amount of water is added in the second decoction.

[0089] Experiment 5 In Example 6, Control Example 7 and Control Example 8, after the second decoction, the filtrate was taken to determine the solid content of the extract and the content of loganin, and the transfer rate of loganin and the extract yield were calculated. The results are shown in Table 10.

[0090] Table 10

[0091] It can be seen from Table 10 that with the increase of extraction time, the index component transfer rate and extract yield do not change significantly. Considering the production cycle, the second decoction time is determined to be 1 hour.

[0092] Experiment 6 For the extracts and concentrated solutions obtained in Example 6, Example 9, Control Example 9 and Control Example 10, the solid content of the extracts and the content of loganin were measured respectively, and the transfer rate of loganin and the extract yield were calculated. The results are shown in Table 11.

[0093] Table 11

[0094] It can be seen from Table 11 that the loganin transfer rates of Examples 6 and 9 are significantly better than those of Control Examples 9 and 10. Therefore, the conditions for reduced pressure concentration are determined as follows: pressure 0.08 MPa, temperature 70-80° C., and time 6 h.

[0095] Experiment 7 The extract powders after pulsating vacuum drying in Example 6, Example 10, Control Example 11 and Control Example 12 were collected, the powder rate was calculated, and the water content of the extract powder was measured. The results are shown in Table 12.

[0096] Table 12

[0097] It can be seen from Table 12 that the extract powder yields of Examples 6 and 10 are better than those of Control Examples 11 and 12. Therefore, the relative density of the liquid medicine is determined to be controlled at 1.10-1.20 (60°C).

[0098] Experiment 8 The extract powders after pulsating vacuum drying in Example 6, Example 11, Comparative Example 13 and Comparative Example 14 were collected, the powder rate was calculated, and the water content of the extract powder was measured. The results are shown in Table 13.

[0099] Table 13

[0100] It can be seen from Table 13 that as the temperature of the pulsating vacuum water tank increases, the water content of the extract powder gradually decreases; the powder yields of Example 6 and Example 11 are relatively high. Considering the production cycle and energy saving, the control temperature of the pulsating vacuum water tank is determined to be 70-75°C.

[0101] Experiment 9 The particle yields of Example 6, Example 12, and Control Example 15 were calculated, and the solubility of the particles was tested. The results are shown in Table 14.

[0102] Table 14

[0103] It can be seen from Table 14 that the granulation difficulty of Example 6 and Example 12 is easier and the particle yield is higher. Therefore, the weight ratio of the main component to the auxiliary material is determined as: main component: auxiliary material = (1~2): 1.

[0104] Experiment 10 The particle yields of Example 6, Control Example 16, Control Example 17, and Control Example 18 were calculated, and the solubility of the particles was tested. The results are shown in Table 15.

[0105] Table 15

[0106] It can be seen from Table 15 that the granulation difficulty of Example 6 is the easiest and the granule yield is higher, so the auxiliary material is determined to be dextrin.

[0107] Experiment 11 The particle yields of Example 6, Control Example 19, Control Example 20, and Control Example 21 were calculated, and the solubility of the particles was tested. The results are shown in Table 16.

[0108] Table 16

[0109] As shown in Table 16, the granulation difficulty of Example 6 is the easiest and the granule yield is the highest. The change of the wetting agent ethanol concentration will affect the granule properties. When the ethanol concentration is too high, the wetting agent is easy to disperse and the soft material is moderate. When the ethanol concentration is too low, the wetting agent is not easy to disperse, the soft material is easy to agglomerate, and granulation is difficult. Therefore, it is determined that the wetting agent is 85% ethanol.

[0110] Experiment 12 The particle yields of Example 6, Example 13, Example 14, Control Example 22, Control Example 23, Control Example 24, and Control Example 25 were calculated, and the solubility of the particles was tested. The results are shown in Table 17.

[0111] Table 17

[0112] It can be seen from Table 17 that Examples 6, 13, and 14 are easy to granulate and have a high granule yield. Therefore, the conditions for mixed granulation are determined as follows: the stirring paddle speed is 200-300 rpm, the granulating knife speed is 1000-1500 rpm, and the mixing time is 2 min.

[0113] Experiment 13 The moisture content of the particles of Example 6, Control Example 26, Control Example 27, and Control Example 28 was calculated. The results are shown in Table 18.

[0114] Table 18

[0115] It can be seen from Table 18 that the moisture content of the particles in Example 6 is lower than that in Control Examples 26, 27, and 28. In order to save energy, the drying conditions are determined to be: 75° C., 4 h.

[0116] Experiment 14 The effects of Buyuan granules on the lungs of COPD rats induced by cigarette smoke and lipopolysaccharide (LPS) were experimentally studied.

[0117] (1) Animal grouping The rats were randomly divided into 6 groups (n=10 / group), namely: control group, model group, Buyuan Granules group 1, and Buyuan Granules group 2.

[0118] (2) Drug preparation The granules used in Buyuan Granules Group 1 were prepared by the method of Example 6, and the granules used in Buyuan Granules Group 2 were prepared by the method of Example 7.

[0119] (3) Modeling and drug administration The rat model of stable COPD was established by cigarette smoke exposure combined with LPS airway instillation. On the 1st and 14th days, the rats in the model group, Buyuan Granule 1 group, and Buyuan Granule 2 group were intraperitoneally anesthetized with 10% ammonia hydrate (0.3 mL / 100 g) and LPS (1 mg / kg, 0.9% sodium chloride solution prepared into 1 mg / mL solution) was instilled into the airway, and the control group was instilled with an equal amount of 0.9% sodium chloride solution; cigarette fumigation was performed in a homemade fumigation box for 30 minutes, twice a day, with an interval of 4 hours, for 28 consecutive days, and no fumigation was performed on the day of LPS instillation.

[0120] 28 days after modeling, the drug was administered orally for 4 weeks, twice a day. The daily dosage of the drug was calculated according to the "Equivalent Dose Ratio Table between Humans and Animals Based on Body Surface Area". The control group and the model group were given an equal volume of 0.9% sodium chloride solution. The body weight was measured every other day after administration, and the dosage of the drug was adjusted according to the change of body weight.

[0121] Rats were anesthetized by intraperitoneal injection of 10% aminal hydrate (0.3 mL / 100 g), blood was drawn from the abdominal aorta, and then the rats were killed. The lung tissues were then isolated and dissected.

[0122] (4) Detection indicators (4.1) Hematoxylin-eosin staining (HE) observation Paraffin sections of lung tissue were dewaxed in xylene, hydrated with gradient ethanol, and stained with HE. Pathological damage of lung tissue was observed under an optical microscope.

[0123] (4.2) Masson staining observation Routine dewaxing, hydration, hematoxylin, ponceau acid fuchsin staining, drying, sealing, and photography were performed. Three fields of view were randomly selected and the area of ​​airway collagen deposition in lung tissue was analyzed using Image-Pro Plus 6.0 software. The ratio of collagen deposition to tissue area was calculated and the average value was taken.

[0124] (5) Experimental results Chronic obstructive pulmonary disease induced by cigarette smoke combined with lipopolysaccharide is a widely used experimental model for studying the pathogenesis of lung diseases and promoting the development of new drugs. The lung tissues of rats in each group were paraffin-embedded and stained with HE and Masson staining to evaluate the pathological damage of rat lung tissues. Figures 3 to 10As shown in the figure, compared with the control group, the lung tissue structure of the model group was destroyed, the bronchial smooth muscle was significantly thickened, a large amount of collagen deposition and inflammatory cell infiltration around the bronchus and between the lung tissues, and the airway wall was thickened. In contrast, the lung tissue structure of the control group was intact, the bronchial smooth muscle was not significantly thickened, and there was no obvious inflammatory cell infiltration around the bronchus and between the lung tissues. The results showed that the rat chronic obstructive pulmonary disease model induced by cigarette smoke combined with lipopolysaccharide has been successfully established. Compared with the model group, the pathological damage and airway collagen deposition in the Buyuan Granules 1 and Buyuan Granules 2 groups were significantly improved, and the airway wall was thinned. In addition, eosinophils, lymphocytes and plasma cells were infiltrated to varying degrees in the bronchial wall and surrounding lung tissue of the Buyuan Granules 1 and Buyuan Granules 2 groups, the thickness of the airway smooth muscle was thinner than that of the model group, the epithelial structure of some lung tissues was incomplete, the degree of collagen fiber deposition was different, some cilia were obviously shed, a small amount of goblet cells proliferated, and the alveoli expanded and fused. These results indicate that Buyuan Granules significantly reduced lung tissue pathological damage and airway collagen deposition in rats, and Buyuan Granules 1 group showed more significant therapeutic effects.

[0125] The present invention experimentally studies the effect of Buyuan granules on the lungs of rats with chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide. The experiment illustrates the protective effect of Buyuan granules on the lungs of rats with chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide. Buyuan granules can improve airway remodeling by inhibiting pathological damage to lung tissue and reducing airway collagen deposition.

[0126] In summary, the present invention experimentally studied the effect of Buyuan Granules on the lungs of rats with chronic obstructive pulmonary disease induced by cigarette smoke and lipopolysaccharide. The experiment clarified the protective effect of Buyuan Granules on the lungs of rats induced by cigarette smoke and lipopolysaccharide. Buyuan Granules can inhibit pathological damage to lung tissue, reduce airway collagen deposition, and thus improve airway remodeling.

[0127] The preparation method of the Buyuan granules of the present invention adopts dextrin as an auxiliary material, and limits the weight ratio of the main component to the auxiliary material to: main component: auxiliary material = (1-2): 1. In conjunction with the optimized preparation process of the present invention, firstly, the main component is decocted with water twice, the amount of water added and the decocting time are reasonably set, and the filtrate is decompressed and concentrated to an extract with a relative density of 1.10-1.20 at 60°C, and then pulse vacuum drying is performed to obtain an extract powder with a water content of less than 8%, and then auxiliary materials, a wetting agent, and a flavoring agent are added, mixed and granulated, and then passed through a 14-mesh sieve to obtain wet granules, and finally the wet granules are dried to prepare the Buyuan granules. Experimental results show that the granules obtained by the method have good medicinal effects.

[0128] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

Claims

1. A supplementary granule, characterized in that: The invention comprises a main component and auxiliary materials, wherein the main component comprises 20-35 parts of astragalus, 20-35 parts of codonopsis, 15-20 parts of bran-fried atractylodes, 15-20 parts of cynomorium songaricum, 15-20 parts of cornus fruit, 8-12 parts of angelica, 8-12 parts of tangerine peel, 8-12 parts of cimicifuga, 8-12 parts of bupleurum, and 8-12 parts of roasted liquorice; The auxiliary material is dextrin; The weight ratio of the main ingredient to the auxiliary material is: Main ingredient: auxiliary ingredient = (1-2):

1.

2. The method for preparing the supplementary granules according to claim 1, characterized in that: The following steps are involved: Step 1, weighing the main component and auxiliary materials in proportion, adding water to the main component and decocting it twice, adding 10-10.5 times the amount of water for the first time and decocting it for 1 hour, adding 9.5-10 times the amount of water for the second time and decocting it for 1 hour, combining the extracts, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.10-1.20 at 60°C; Step 2, performing pulsating vacuum drying on the extract, wherein the water tank of the pulsating vacuum drying is controlled at a temperature of 70-75° C. and a vacuum degree of -0.09-0.08 MPa, to obtain an extract powder with a water content of <8%; Step 3, adding auxiliary materials, wetting agents, and flavoring agents to the extract powder, mixing and granulating, and then passing through a 14-mesh sieve to obtain wet granules; Step 4, drying the wet granules to prepare the Buyuan granules.

3. The method for preparing the supplementary granules according to claim 2, characterized in that: In step 1, the conditions for reduced pressure concentration are: pressure 0.08 MPa, temperature 70-80° C., and time 6 h.

4. The method for preparing the supplementary granules according to claim 2, characterized in that: Step 1 specifically includes: Weigh the main ingredient and auxiliary materials in proportion, add water to the main ingredient and boil it twice, add 10-10.5 times the amount of water for the first time, boil it for 1 hour, filter it with a 100-mesh filter cloth, add 9.5-10 times the amount of water for the second time, boil it for 1 hour, filter it with a 100-mesh filter cloth, combine the extracts, filter, and concentrate the filtrate under reduced pressure to an extract with a relative density of 1.10-1.20 at 60°C.

5. The method for preparing the Buyuan granules according to claim 2, characterized in that: In step 3, the wetting agent is 85% ethanol, and the weight ratio of the extract powder to the wetting agent is: Extract powder: wetting agent = 4:

1.

6. The method for preparing the Buyuan granules according to claim 2, characterized in that: In step 3, the flavoring agent is sucralose, and the amount of the flavoring agent added is 0.1% of the extract powder.

7. The method for preparing the Buyuan granules according to claim 2, characterized in that: In step 3, the conditions for mixing and granulating are: the stirring paddle speed is 200-300 rpm, the granulating knife speed is 1000-1500 rpm, and the mixing time is 2 min.

8. The method for preparing the Buyuan granules according to claim 2, characterized in that: The drying conditions in step 4 are: 75° C., 4 h.

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