Granules for treating chronic obstructive pulmonary disease and preparation method thereof

Abstract

The invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to granules for treating chronic obstructive pulmonary diseases and a preparation method of the granules. The granules for treating the chronic obstructive pulmonary disease are prepared from main medicines including codonopsis pilosula, astragalus membranaceus, fructus lycii, fructus perillae, radix ranunculi ternati, poria cocos, processed rhizoma pinelliae, pericarpium citri reticulatae, roasted rhizoma atractylodis macrocephalae, peach kernels, almonds, radix rehmanniae preparata and earthworms and a medicinal auxiliary material, namely soluble starch, and the medicinal auxiliary material further comprises beta-cyclodextrin. The granules for treating the chronic obstructive pulmonary disease, provided by the invention, have the advantages that the content of effective components is higher, and the treatment effect is better; the preparation method is suitable for industrial production, and the process steps are relatively simplified.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine preparations, and specifically relates to a granule for treating chronic obstructive pulmonary disease and a preparation method thereof. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is known as an injurious lung disease, which is closely related to abnormal inflammation of the lungs caused by stimulation of pathogens, polluted gases, and toxic particles such as CS. The main complaints of patients are dyspnea, expectoration, and frequent coughing. It is characterized by restricted gas flow during breathing, and this restriction is not completely reversible, often showing a progressive evolution. With the increase of air pollutants in today's society, the burning of fuels such as firewood, coal, and animal manure, and the increase in the number of smokers, the prevalence of COPD has been increasing year by year. It is expected that by 2030, COPD will still be on the list of various high-mortality diseases in the world and will move forward to the 3rd place. With the increase in the incidence and mortality of lung cancer, COPD, as a high-risk factor for lung cancer, has gradually become the focus of urgent attention in both basic and clinical fields. Currently, the commonly used drugs for treating COPD in clinical practice include bronchodilators, inhaled corticosteroids, etc. These drugs have a rapid onset of action and obvious effects of relieving spasm and asthma, but long-term use of such drugs will cause side effects such as liver and kidney function damage, and drug resistance may also occur.

[0003] Different from the single-target treatment method of western medicine, traditional Chinese medicine has unique advantages in adjusting the internal environment and regulating the body balance. The applicant filed a patent application for an invention titled "Preparation method of granules for treating chronic obstructive pulmonary disease by the method of internal administration of acupoint transdermal drug delivery for strengthening the spleen, tonifying the kidney, and resolving phlegm" on June 14, 2018. The preparation method involved in this patent application includes: (1) preparing Codonopsis pilosula extract, (2) preparing Astragalus membranaceus extract, (3) preparing Lycium barbarum extract, (4) drying and grinding dry Perilla seed into powder, (5) drying and grinding Cat's Claw into powder, (6) drying and grinding Poria cocos slices into powder, (7) preparing Pinellia ternata extract, (8) preparing Citrus reticulata extract, (9) stir-frying Atractylodes macrocephala and drying it into powder, (10) drying and grinding Prunus persica into powder; (11) drying and grinding Armeniaca vulgaris into powder, (12) drying and grinding Rehmannia glutinosa into powder, (13) drying and grinding Pheretima into powder, (14) concentration: mixing the above-mentioned extracts and powders and concentrating them into an extract; (15) granulation: adding soluble starch to the extract, stirring and mixing evenly, drying, then pulverizing, and finally adding ethanol and mixing evenly, sieving, to obtain the granules. The applicant found in further research that this method not only has a complex process and cumbersome steps, but also has limited efficacy.

[0004] In view of this, the present invention is specifically proposed. Summary of the Invention

[0005] The object of the present invention is to provide a granule for treating chronic obstructive pulmonary disease and a preparation method thereof. The granule for treating chronic obstructive pulmonary disease provided by the present invention has a higher content of active ingredients and better treatment effects; its preparation method is suitable for industrial production and relatively simplifies the process steps.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A granule for treating chronic obstructive pulmonary disease, comprising main drugs Codonopsis pilosula, Astragalus membranaceus, Lycium barbarum, Perilla frutescens, Ranunculus ternatus, Poria cocos, Pinellia ternata preparata, Citrus reticulata Blanco, Atractylodes macrocephala Koidz stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa, Pheretima aspergillum and a medicinal adjuvant soluble starch, wherein the medicinal adjuvant further comprises β-cyclodextrin.

[0008] Further, the dosage of the β-cyclodextrin is 40-50 wt% of the total amount of Codonopsis pilosula and Astragalus membranaceus.

[0009] Further, the main drugs are composed of the following ratios:

[0010] 10-30 parts by weight of Codonopsis pilosula, 20-60 parts by weight of Astragalus membranaceus, 20-60 parts by weight of Lycium barbarum, 5-15 parts by weight of Perilla frutescens, 10-25 parts by weight of Ranunculus ternatus, 10-30 parts by weight of Poria cocos slices, 5-15 parts by weight of Pinellia ternata preparata, 5-15 parts by weight of Citrus reticulata Blanco, 10-30 parts by weight of Atractylodes macrocephala Koidz stir-fried, 5-15 parts by weight of Prunus persica, 5-15 parts by weight of Armeniaca vulgaris, 5-15 parts by weight of Rehmannia glutinosa, 5-15 parts by weight of Pheretima aspergillum.

[0011] The present invention also provides a preparation method of the granule, which comprises the following steps:

[0012] S1. Respectively crush Codonopsis pilosula and Astragalus membranaceus, mix them evenly, after pretreatment, add water for decoction, filter to obtain a filtrate and residues; crush the residues, add an ethanol aqueous solution for reflux extraction to obtain a first extract; add β-cyclodextrin to the filtrate, mix evenly, and dry to obtain a mixture;

[0013] S2. Respectively crush Lycium barbarum, Poria cocos and Pinellia ternata preparata, mix them evenly and add water for decoction, and combine the decoction liquids to obtain a second extract;

[0014] S3. Add water to Citrus reticulata Blanco for steam distillation to extract volatile oil, and separate the volatile oil of Citrus reticulata Blanco; add water to the residues after distillation for decoction, and combine the decoction liquids to obtain a third extract;

[0015] S4. Respectively crush Perilla frutescens, Ranunculus ternatus, Atractylodes macrocephala Koidz stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima aspergillum, and mix them evenly to obtain a mixed powder;

[0016] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3, and the mixed powder obtained in step S4, and then concentrate to obtain an extract paste.

[0017] S6. Mix the extract paste with the mixture obtained in step S1, add soluble starch, mix well, dry, pulverize, add ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of tangerine peel separated in step S3 with ethanol, evenly spray it on the surface of the granules, and dry to obtain the granule agent.

[0018] Further, in step S1, the pretreatment is as follows: add 10 - 20 times of 15 - 25% ethanol aqueous solution to the mixed powder obtained by pulverizing and mixing codonopsis pilosula and astragalus membranaceus, stir evenly, cool to -5 - 0 °C at room temperature, keep for 20 - 30 minutes, then heat up to room temperature and keep for 20 - 30 minutes.

[0019] Further, the particle size of the pulverized filter residue is 200 - 300 mesh, the volume fraction of the ethanol aqueous solution is 55 - 65%, and the dosage of β - cyclodextrin is 40 - 50 wt% of the total amount of codonopsis pilosula and astragalus membranaceus.

[0020] Further, step S3 is as follows: add 8 - 12 times of water to tangerine peel and distill to extract volatile oil for 3 - 5 hours, separate the volatile oil of tangerine peel; add 5 - 8 times of water to the residue after distillation and decoct, decoct 2 - 4 times, each time for 30 - 50 min, combine the decoction liquids to obtain the third extract.

[0021] Further, in step S1, the water decoction is to add 10 - 20 times of water and decoct for 30 - 50 min.

[0022] Further, in step S2, the water decoction is to add 30 - 50 times of water and decoct, decoct 2 - 4 times, each time for 30 - 50 min.

[0023] Further, step S6 is as follows: mix the extract paste with the mixture obtained in step S1, add 60 - 80 wt% of soluble starch, mix well, dry at 50 - 60 °C, then pulverize to 50 - 60 mesh, add 65 - 75% ethanol and mix well, granulate, and finally spray the volatile oil of tangerine peel separated in step S3 to obtain the granule agent.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] (1) The content of the active ingredients in the granule agent for treating chronic obstructive pulmonary disease provided by the present invention is higher, and the treatment effect is better.

[0026] (2) The preparation method provided by the present invention is suitable for industrial production, and relatively simplifies the process steps. Detailed Embodiments

[0027] The following are the detailed embodiments of the present invention. The described embodiments are for further describing the present invention rather than limiting it.

[0028] Embodiment 1

[0029] Prepare 30 g of Codonopsis pilosula, 50 g of Astragalus membranaceus, 20 g of Lycium barbarum, 10 g of Perilla frutescens, 20 g of Ranunculus ternatus, 25 g of Poria cocos slices, 10 g of Pinellia ternata processed, 9 g of Citrus reticulata, 20 g of Atractylodes macrocephala stir-fried, 10 g of Prunus persica, 10 g of Armeniaca vulgaris, 10 g of Rehmannia glutinosa, and 10 g of Pheretima aspergillum.

[0030] Prepare the granule according to the following method:

[0031] S1. Crush Codonopsis pilosula and Astragalus membranaceus to 100 meshes respectively, mix them evenly, add 15 times of 20% ethanol aqueous solution, stir evenly, cool down to -2°C at room temperature, keep for 25 minutes, then heat up to room temperature and keep for 25 minutes, add 15 times of water and decoct for 40 min, filter to obtain filtrate and residue; crush the residue, pass through a 250-mesh sieve, add ethanol aqueous solution with a volume fraction of 60% and reflux extract for 1 h to obtain the first extract; add 45 wt% of β-cyclodextrin based on the total amount of Codonopsis pilosula and Astragalus membranaceus to the filtrate, mix evenly, and dry to a water content of 2 wt% to obtain a mixture;

[0032] S2. Crush Lycium barbarum, Poria cocos and Pinellia ternata processed to 100 meshes respectively, mix evenly and decoct with 40 times of water for 3 times, each time for 40 min, combine the decoction liquids to obtain the second extract;

[0033] S3. Distill and extract the volatile oil from Citrus reticulata with 10 times of water for 4 hours to separate the volatile oil of Citrus reticulata; decoct the residue after distillation with water for 3 times, each time for 40 min, combine the decoction liquids to obtain the third extract;

[0034] S4. Crush Perilla frutescens, Ranunculus ternatus, Atractylodes macrocephala stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima aspergillum to 100 meshes respectively, and mix evenly to obtain a mixed powder;

[0035] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4, and concentrate to an extract at 50 - 60°C. The relative density of the extract is 1.15 - 1.2;

[0036] S6. Mix the extract paste with the mixture obtained in step S1, add 70 wt% soluble starch, mix well, dry at 55 °C, then crush to 55 mesh, add 70% ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of tangerine peel separated in step S3 with 75% ethanol, evenly spray it on the surface of the granules, dry in a 70 °C forced-air oven for 12 min, and package at 10 g / bag to obtain the granule agent as described.

[0037] Example 2

[0038] Prepare 10 g of Codonopsis pilosula, 20 g of Astragalus membranaceus, 20 g of Lycium barbarum, 5 g of Perilla seed, 10 g of Ranunculus ternatus, 10 g of Poria cocos slices, 5 g of Rhizoma Pinelliae preparatum, 5 g of Tangerine peel, 10 g of Atractylodes macrocephala stir-fried, 5 g of Prunus persica, 5 g of Armeniaca vulgaris, 5 g of Rehmannia glutinosa, 5 g of Pheretima.

[0039] Prepare the granule agent by the following method:

[0040] S1. Crush Codonopsis pilosula and Astragalus membranaceus to 80 mesh respectively, mix well, add 10 times of 15% ethanol aqueous solution, stir evenly, cool to -5 °C at room temperature, keep for 20 minutes, then warm to room temperature and keep for 20 minutes, decoct with 10 times of water for 30 min, filter to obtain the filtrate and filter residue; crush the filter residue, pass through a 200-mesh sieve, add ethanol aqueous solution with a volume fraction of 55% and reflux for 1.5 h to obtain the first extract; add 40 wt% of β-cyclodextrin based on the total amount of Codonopsis pilosula and Astragalus membranaceus to the filtrate, mix well, dry to a water content of 2 wt% to obtain a mixture.

[0041] S2. Crush Lycium barbarum, Poria cocos and Rhizoma Pinelliae preparatum to 80 mesh respectively, mix well and decoct with 30 times of water, decoct twice, 30 min each time, combine the decoction liquids to obtain the second extract.

[0042] S3. Distill and extract the volatile oil of tangerine peel with 8 times of water for 3 hours, separate the volatile oil of tangerine peel; decoct the residue after distillation with water, decoct twice, 30 min each time, combine the decoction liquids to obtain the third extract.

[0043] S4. Crush Perilla seed, Ranunculus ternatus, Atractylodes macrocephala stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima to 80 mesh respectively, mix evenly to obtain a mixed powder.

[0044] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4, and concentrate to an extract paste at 50 - 60 °C, and the relative density of the extract paste is 1.15 - 1.2.

[0045] S6. Mix the extract paste with the mixture obtained in step S1, add 60 wt% soluble starch, mix well, dry at 50 - 60 °C, then crush to 50 mesh, add 65% ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of tangerine peel separated in step S3 with 70% ethanol, evenly spray it on the surface of the granules, dry in a 70 °C forced air oven for 8 min, and package at 10 g / bag to obtain the granule agent as described.

[0046] Example 3

[0047] Prepare 30 g of Codonopsis pilosula, 60 g of Astragalus membranaceus, 60 g of Lycium barbarum, 15 g of Perilla frutescens, 25 g of Ranunculus ternatus, 30 g of Poria cocos slices, 15 g of Rhizoma Pinelliae preparatum, 15 g of Citrus reticulata Blanco, 30 g of Atractylodes macrocephala Koidz stir-fried, 15 g of Prunus persica, 15 g of Armeniaca vulgaris, 15 g of Rehmannia glutinosa, 15 g of Pheretima aspergillum.

[0048] Prepare the granule agent by the following method:

[0049] S1. Crush Codonopsis pilosula and Astragalus membranaceus to 120 mesh respectively, mix well, add 20 times of 25% ethanol aqueous solution, stir evenly, cool to 0 °C at room temperature, keep for 30 minutes, then heat up to room temperature and keep for 30 minutes, decoct with 20 times of water for 50 min, filter to obtain filtrate and filter residue; crush the filter residue, pass through a 300 - mesh sieve, add ethanol aqueous solution with a volume fraction of 65% and reflux for 2 h to obtain the first extract; add 50 wt% of β - cyclodextrin based on the total amount of Codonopsis pilosula and Astragalus membranaceus to the filtrate, mix well, dry to a water content of 2 wt% to obtain a mixture.

[0050] S2. Crush Lycium barbarum, Poria cocos and Rhizoma Pinelliae preparatum to 120 mesh respectively, mix well and decoct with 50 times of water, decoct 4 times, each time for 50 min, combine the decoction liquids to obtain the second extract.

[0051] S3. Distill and extract the volatile oil of Citrus reticulata Blanco with 12 times of water for 5 h, separate the volatile oil of tangerine peel; add water to the residue after distillation and decoct, decoct 4 times, each time for 50 min, combine the decoction liquids to obtain the third extract.

[0052] S4. Crush Perilla frutescens, Ranunculus ternatus, Atractylodes macrocephala Koidz stir - fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima aspergillum to 120 mesh respectively, mix evenly to obtain a mixed powder.

[0053] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4, and concentrate to an extract paste at 50 - 60 °C, and the relative density of the extract paste is 1.15 - 1.2.

[0054] S6. Mix the extract paste with the mixture obtained in step S1, add 80 wt% soluble starch, mix well, dry at 60 °C, then grind to 60 mesh, add 75% ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of tangerine peel separated in step S3 with 80% ethanol, evenly spray it on the surface of the granules, dry in a forced-air oven at 70 °C for 15 min, and package at 10 g / bag to obtain the granule agent as described above.

[0055] Example 4

[0056] Prepare 25 g of Codonopsis pilosula, 40 g of Astragalus membranaceus, 30 g of Lycium barbarum, 12 g of Perilla frutescens, 18 g of Ranunculus ternatus, 22 g of Poria cocos slices, 12 g of processed Pinellia ternata, 8 g of Citrus reticulata, 26 g of stir-fried Atractylodes macrocephala, 12 g of Prunus persica, 8 g of Armeniaca vulgaris, 8 g of Rehmannia glutinosa, and 12 g of Pheretima aspergillum.

[0057] Prepare the granule agent by the following method:

[0058] S1. Grind Codonopsis pilosula and Astragalus membranaceus to 110 mesh respectively, mix well, add 16 times of 22% ethanol aqueous solution, stir evenly, cool to 2 °C at room temperature, keep for 22 minutes, then warm to room temperature and keep for 22 minutes, add 16 times of water and decoct for 38 min, filter to obtain filtrate and filter residue; grind the filter residue, pass through a 250-mesh sieve, add ethanol aqueous solution with a volume fraction of 60% and reflux extract for 1 time to obtain the first extract; add 42 wt% of β-cyclodextrin based on the total amount of Codonopsis pilosula and Astragalus membranaceus to the filtrate, mix well, and dry to a water content of 2 wt% to obtain a mixture.

[0059] S2. Grind Lycium barbarum, Poria cocos and processed Pinellia ternata to 100 mesh respectively, mix well and decoct with 36 times of water for 3 times, each time for 42 min, combine the decoction liquids to obtain the second extract.

[0060] S3. Distill and extract the volatile oil of Citrus reticulata with 9 times of water for 3.5 hours, separate the volatile oil of tangerine peel; decoct the residue after distillation with water for 3 times, each time for 45 min, combine the decoction liquids to obtain the third extract.

[0061] S4. Grind Perilla frutescens, Ranunculus ternatus, stir-fried Atractylodes macrocephala, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima aspergillum to 100 mesh respectively, mix evenly to obtain a mixed powder.

[0062] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4, and concentrate to an extract paste at 50 - 60 °C, and the relative density of the extract paste is 1.15 - 1.2.

[0063] S6. Mix the extract paste with the mixture obtained in step S1, add 65 wt% soluble starch, mix well, dry at 55 °C, then crush to 55 mesh, add 72% ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of tangerine peel separated in step S3 with 75% ethanol, evenly spray it on the surface of the granules, dry in a 70 °C forced-air oven for 10 min, and package at 10 g / bag to obtain the granule agent.

[0064] Example 5

[0065] Prepare 18 g of Codonopsis pilosula, 42 g of Astragalus membranaceus, 38 g of Lycium barbarum, 13 g of Perilla frutescens, 18 g of Ranunculus ternatus, 26 g of Poria cocos slices, 11 g of Rhizoma Pinelliae preparata, 9 g of Citrus reticulata, 24 g of Atractylodes macrocephala stir-fried, 13 g of Prunus persica, 9 g of Armeniaca vulgaris, 7 g of Rehmannia glutinosa, 14 g of Pheretima aspergillum.

[0066] Prepare the granule agent by the following method:

[0067] S1. Crush Codonopsis pilosula and Astragalus membranaceus to 110 mesh respectively, mix well, add 12 times of 18% ethanol aqueous solution, stir evenly, cool to -1 °C at room temperature, keep for 26 minutes, then heat to room temperature and keep for 26 minutes, add 18 times of water and decoct for 42 min, filter to obtain filtrate and filter residue; crush the filter residue, pass through a 250-mesh sieve, add ethanol aqueous solution with a volume fraction of 60% and reflux for 1.5 h to obtain the first extract; add 46 wt% of β-cyclodextrin based on the total amount of Codonopsis pilosula and Astragalus membranaceus to the filtrate, mix well, dry to a water content of 2 wt% to obtain a mixture;

[0068] S2. Crush Lycium barbarum, Poria cocos and Rhizoma Pinelliae preparata to 100 mesh respectively, mix well and decoct with 34 times of water for 3 times, each time for 46 min, combine the decoction liquids to obtain the second extract;

[0069] S3. Distill and extract the volatile oil of Citrus reticulata with 9 times of water for 4 h, separate the volatile oil of tangerine peel; add water to the residue after distillation and decoct for 3 times, each time for 45 min, combine the decoction liquids to obtain the third extract;

[0070] S4. Crush Perilla frutescens, Ranunculus ternatus, Atractylodes macrocephala stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa and Pheretima aspergillum to 100 mesh respectively, mix evenly to obtain a mixed powder;

[0071] S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4, and concentrate to an extract paste at 50 - 60 °C, and the relative density of the extract paste is 1.15 - 1.2;

[0072] S6. Mix the extract paste with the mixture obtained in step S1, add soluble starch at 72 wt%, mix well, dry at 55 °C, then crush to 55 mesh, add 70% ethanol and mix well, granulate to obtain granules; dissolve the volatile oil of dried tangerine peel separated in step S3 with 75% ethanol, evenly spray it on the surface of the granules, dry in a forced-air oven at 70 °C for 14 min, and package at 10 g / bag to obtain the granule agent.

[0073] Comparative Example 1

[0074] Prepare the granule agent according to the method of CN108452129A, specifically as follows:

[0075] Prepare 30 g of Codonopsis pilosula, 50 g of Astragalus membranaceus, 20 g of Lycium barbarum, 10 g of Perilla frutescens, 20 g of Ranunculus ternatus, 25 g of Poria cocos slices, 10 g of Rhizoma Pinelliae preparata, 9 g of dried tangerine peel, 20 g of Atractylodes macrocephala stir-fried, 10 g of Prunus persica, 10 g of Armeniaca vulgaris, 10 g of Rehmannia glutinosa, and 10 g of Pheretima aspergillum.

[0076] Prepare the granule agent according to the following method:

[0077] (1) Prepare the extract of Codonopsis pilosula: Dry and grind Codonopsis pilosula into powder, pass through a 100-mesh sieve to obtain 100-mesh Codonopsis pilosula powder, mix the Codonopsis pilosula powder with water at a weight ratio of 1:40 and decoct for 3 times, 30 min each time, combine the decoction liquids to obtain the extract of Codonopsis pilosula;

[0078] (2) Prepare the extract of Astragalus membranaceus: Dry and grind Astragalus membranaceus into powder, pass through a 100-mesh sieve to obtain 100-mesh Astragalus membranaceus powder, mix the Astragalus membranaceus powder with water at a weight ratio of 1:45 and decoct for 4 times, 40 min each time, combine the decoction liquids to obtain the extract of Astragalus membranaceus;

[0079] (3) Prepare the extract of Lycium barbarum: Dry and grind Lycium barbarum into powder, pass through a 100-mesh sieve to obtain 100-mesh Lycium barbarum powder, mix the Lycium barbarum powder with water at a weight ratio of 1:30 and decoct for 4 times, 35 min each time, combine the decoction liquids to obtain the extract of Lycium barbarum;

[0080] (4) Dry and grind dry Perilla frutescens into powder, pass through a 100-mesh sieve to obtain 100-mesh Perilla frutescens powder;

[0081] (5) Dry and grind Ranunculus ternatus into powder, pass through a 100-mesh sieve to obtain 100-mesh Ranunculus ternatus powder;

[0082] (6) Dry and grind Poria cocos slices into powder, pass through a 100-mesh sieve to obtain 100-mesh Poria cocos powder; mix the Poria cocos powder with water at a weight ratio of 1:46 and decoct for 2 times, 35 min each time, combine the decoction liquids to obtain the extract of Poria cocos;

[0083] (7) Dry the processed Pinellia ternata and grind it into powder, sieve it through a 100-mesh sieve to obtain 100-mesh processed Pinellia ternata powder; mix the processed Pinellia ternata powder and water at a weight ratio of 1:33 for decoction, decoct for 3 times, 46 minutes each time, combine the decoction liquids to obtain the processed Pinellia ternata extract;

[0084] (8) Dry the dried tangerine peel and grind it into powder, sieve it through a 100-mesh sieve to obtain 100-mesh dried tangerine peel powder; mix the dried tangerine peel powder and water at a weight ratio of 1:48 for decoction, decoct for 4 times, 42 minutes each time, combine the decoction liquids to obtain the dried tangerine peel extract;

[0085] (9) Dry the stir-fried Atractylodes macrocephala and grind it into powder, sieve it through a 100-mesh sieve to obtain 100-mesh stir-fried Atractylodes macrocephala powder;

[0086] (10) Dry the peach kernels and grind them into powder, sieve them through a 100-mesh sieve to obtain 100-mesh peach kernel powder;

[0087] (11) Dry the apricot kernels and grind them into powder, sieve them through a 100-mesh sieve to obtain 100-mesh apricot kernel powder;

[0088] (12) Dry the prepared Rehmannia glutinosa and grind it into powder, sieve it through a 100-mesh sieve to obtain 100-mesh prepared Rehmannia glutinosa powder;

[0089] (13) Dry the earthworms and grind them into powder, sieve them through a 100-mesh sieve to obtain 100-mesh earthworm powder;

[0090] (14) Concentration: Mix the above-mentioned extracts and powders, concentrate them into an extract at 50 - 60 °C; the relative density of the extract is 1.15 - 1.2.

[0091] (15) Granulation: Add 70 wt% soluble starch to the extract, stir and mix evenly, dry at 55 °C, then crush to 50 - 60 mesh, finally add 70% ethanol and mix evenly, granulate, and package in 10 g / bags to obtain the product.

[0092] Test Example 1

[0093] This test example investigated the contents of total polysaccharides, total flavonoids, and total saponins in the granules prepared by different methods.

[0094] I. Content determination method

[0095] 1. Determination of the content of total polysaccharides in the granules

[0096] 1.1. Preparation of the reference solution

[0097] Precisely weigh 15.26 mg of D-glucose reference standard, transfer it to a 10 mL volumetric flask, dissolve it with water and dilute to the mark to obtain a mother solution of D-glucose reference standard with a concentration of 1.5260 mg / mL. Then take 1 mL of the mother solution of D-glucose reference standard and dilute it to 5 mL to obtain a D-glucose reference standard solution with a concentration of 0.3052 mg / mL.

[0098] 1.2 Preparation of Test Solution

[0099] Accurately weigh 0.1 g of the granule, place it in a 100 mL round-bottom flask, add 50 mL of water, reflux at 100 °C for 60 min, cool to room temperature, make up the lost mass with water, filter, accurately transfer 20 mL to a 50 mL round-bottom flask, concentrate under reduced pressure, place it in a 10 mL volumetric flask, dilute to the mark with water, shake well, then take 1 mL and dilute it to 5 mL with water to obtain the solution.

[0100] 1.3 Determination of Total Polysaccharide Content in Granule by Phenol-Sulfuric Acid Colorimetry

[0101] Accurately pipette 0.8 mL of the test solution into a stoppered test tube, add water to 1 mL, add 1 mL of 5% phenol, quickly add 5 mL of concentrated sulfuric acid, shake well, cool to room temperature in a cold water bath, then heat in a boiling water bath for 15 min, and then cool to room temperature in a cold water bath. Conduct a blank control in parallel, and measure the absorbance at 490 nm.

[0102] 2 Determination of Total Flavonoid Content in Granule

[0103] 2.1 Preparation of Reference Solution

[0104] Accurately weigh 5.45 mg of rutin reference substance, place it in a 5 mL volumetric flask, add an appropriate amount of 70% ethanol to dissolve it completely, dilute to the mark, shake well to obtain a 1.09 mg / mL rutin reference solution.

[0105] 2.2 Preparation of Test Solution

[0106] Take 0.2 g of the granule, accurately weigh it, extract it ultrasonically with 20 mL of 70% ethanol for 30 min, filter, evaporate the solvent to dryness, dissolve the residue in 70% ethanol and dilute to 10 mL to obtain the solution.

[0107] 2.3 Determination of Total Flavonoid Content in Granule by Sodium Nitrite-Aluminum Nitrate-Sodium Hydroxide Colorimetry

[0108] Accurately measure 1 mL of the test solution into a 25 mL volumetric flask, add 5 mL of water, add 1 mL of 5% NaNO2 solution, shake well, add 1 mL of 10% Al(NO3)3 solution after 6 min, shake well, add 5 mL of 10% NaOH solution after 6 min, dilute to the mark with distilled water, conduct a blank control in parallel, and measure the absorbance at 510 nm after 10 min.

[0109] 3 Determination of Total Saponin Content in Granule

[0110] 3.1 Preparation of Reference Solution

[0111] Accurately weigh 12.01 mg of glycyrrhizic acid reference substance, place it in a 2-mL volumetric flask, dissolve it with methanol, make up the volume to the scale, shake well, and obtain a mother solution of glycyrrhizic acid reference substance with a concentration of 6 mg / mL. Then take 1 mL of the mother solution of glycyrrhizic acid reference substance and dilute it to 10 mL to obtain a glycyrrhizic acid reference substance solution with a concentration of 0.6 mg / mL.

[0112] 3.2 Preparation of test solution

[0113] Accurately weigh 0.1 g of the granule, ultrasonically extract it with 20 mL of distilled water for 20 min, defat it twice with 20 mL of ether, place the aqueous layer in a separating funnel, and extract it 4 times with 50 mL of n-butanol saturated with water. Collect the n-butanol solution, wash it twice with 2 times the volume of 5% ammonia test solution, and then wash it 3 times with n-butanol solution saturated with water, 100 mL each time. Evaporate the n-butanol to dryness and make up the volume to 5 mL with methanol in a volumetric flask, filter, transfer 1 mL from the continuous filtrate to a 10-mL volumetric flask, make up the volume to the scale with methanol, shake well, and then obtain the solution.

[0114] 3.3 Determination of the total saponin content in the granule by 1% vanillin acetic acid-perchloric acid colorimetry

[0115] Accurately measure 1 mL of the test solution into a 10-mL stoppered graduated test tube, evaporate the methanol in a water bath, cool it, accurately add 0.5 mL of 1% vanillin acetic acid-perchloric acid solution (2:8), shake well immediately, mix thoroughly in a constant temperature water bath at 60 °C and heat for 15 min, take it out, immediately cool it in an ice bath, accurately add 5 mL of 77% sulfuric acid solution, and shake well. Make a blank control in parallel, and measure the absorbance at 437 nm.

[0116] II. Determination results

[0117] Take the granules prepared in Example 1 and Comparative Example 1 of the present invention, and detect the contents of total polysaccharides, total flavonoids and total saponins in the granules prepared by different methods according to the above content determination method. The results are shown in Table 1 below:

[0118] Table 1. Determination results of the contents of total polysaccharides, total flavonoids and total saponins in different granules

[0119] Granules Total polysaccharide (mg / g) Total flavonoids (mg / g) Total saponins (mg / g) Example 1 203.138 40.149 21.621 Control Example 1 153.247 28.912 11.429

[0120] It can be seen from the results in Table 1 above that the content of the active ingredients in the granules prepared by the method of the present invention is higher than that of Comparative Example 1.

[0121] Test Example 2

[0122] 1. Data and methods

[0123] 1.1 General data

[0124] A total of 90 patients with chronic obstructive pulmonary disease (phlegm-obstructing lung syndrome) admitted to our hospital from March 2020 to August 2023 were selected and randomly divided into two groups (experimental group and control group), with 45 cases in each group.

[0125] There were 23 males and 22 females in the experimental group; the age ranged from 46 to 82 years, with an average age of (65.13±1.62) years; the course of disease ranged from 1 to 10 years, with an average course of disease of (7.18±0.68) years; the severity of the disease was moderate in 25 cases and severe in 20 cases.

[0126] There were 24 males and 21 females in the control group; the age ranged from 47 to 80 years old, with an average age of (65.37±1.72) years; the course of disease ranged from 1.5 to 12 years, with an average course of disease of (7.28±0.81) years; the severity of the disease was moderate in 27 cases and severe in 18 cases.

[0127] There was no statistically significant difference in general information between the two groups.

[0128] 1.2 Inclusion and Exclusion Criteria

[0129] Inclusion criteria: ① All patients met the diagnostic criteria for COPD in the Global Initiative for Chronic Obstructive Pulmonary Disease and the Guiding Principles for Clinical Research of New Chinese Medicines, and were diagnosed with phlegm-turbidity obstructing the lungs according to TCM syndrome differentiation; ② All patients signed the informed consent form.

[0130] Exclusion criteria: ① the presence of other lung diseases, such as lung cancer, bronchiectasis, etc.; ② allergies to the drugs used in the study or contraindications to treatment; ③ mental or intellectual abnormalities leading to inability to cooperate with treatment; ④ failure to take medication as prescribed by the doctor.

[0131] 1.3 Treatment methods

[0132] Both groups received routine treatment, including basic treatments such as antispasmodic and antiasthmatic, expectorant and antitussive, anti-infection, and oxygen inhalation. Nasal cannula oxygen inhalation was given at an oxygen flow rate of 1 to 2 L / min. Sputum culture was collected before treatment and sensitive antibiotics were given. Inhalation of budesonide suspension 2 mg + ipratropium bromide solution 500 μg was given by nebulization inhalation, twice a day.

[0133] The control group was treated with the granules prepared in Comparative Example 1 on the basis of conventional treatment, three times a day, one bag each time, taken with warm water, and both groups continued the treatment for 2 weeks.

[0134] The experimental group was treated with the granules prepared in Example 1 on the basis of conventional treatment, 1 bag three times a day, taken with warm water, and both groups continued the treatment for 2 weeks.

[0135] 1.4 Observation indicators

[0136] The curative effect was evaluated 2 weeks after treatment. Clinical control: the syndrome score decreased by ≥95%; Marked effect: the syndrome score decreased by 70% - 94%; Effective: the syndrome score decreased by 30% - 69%; Ineffective: the syndrome score decreased by <30%.

[0137] 2. Results

[0138] 2.1 Comparison of curative effects

[0139] The total effective rate of the experimental group (97.78%) was higher than that of the control group (86.67%), as shown in Table 2.

[0140] Table 2. Comparison of curative effects

[0141] Group Clinical control Marked effect Effective Invalid Total effective Test group (n = 45) 21 18 4 2 43(95.56％) Control group (n = 45) 15 18 6 6 39(86.67％)

[0142] Clinical experiments have shown that the effective rate of the granule prepared by the method of the present invention for chronic obstructive pulmonary disease reaches 95.56%, and the number of ineffective cases is small, and the treatment effect is good.

[0143] The embodiments described above are some, but not all, of the embodiments of the present invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely represents selected embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

Claims

1. A granule for treating chronic obstructive pulmonary disease, comprising main drugs Codonopsis pilosula, Astragalus membranaceus, Lycium barbarum, Perilla frutescens, Ranunculus ternatus, Poria cocos, Rhizoma Pinelliae Praeparatum, Citrus reticulata Blanco, Rhizoma Atractylodis Macrocephalae Praeparatum, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa, Pheretima and pharmaceutical adjuvant soluble starch, characterized in that, The pharmaceutical excipients also include β-cyclodextrin.

2. The granule according to claim 1, characterized in that, The dosage of the β-cyclodextrin is 40-50 wt% of the total amount of Codonopsis pilosula and Astragalus membranaceus.

3. The granule according to claim 1 or 2, characterized in that, The main drugs are composed of the following ratios: 10-30 parts by weight of Codonopsis pilosula, 20-60 parts by weight of Astragalus membranaceus, 20-60 parts by weight of Lycium barbarum, 5-15 parts by weight of Perilla frutescens, 10-25 parts by weight of Ranunculus ternatus, 10-30 parts by weight of Poria cocos slices, 5-15 parts by weight of Rhizoma Pinelliae Praeparatum, 5-15 parts by weight of Citrus reticulata Blanco, 10-30 parts by weight of Atractylodes macrocephala Koidz stir-fried, 5-15 parts by weight of Prunus persica, 5-15 parts by weight of Armeniaca vulgaris, 5-15 parts by weight of Rehmannia glutinosa Libosch., 5-15 parts by weight of Pheretima.

4. A method for preparing the granule according to any one of claims 1-3, characterized in that, The preparation method includes the following steps: S1. Crush Codonopsis pilosula and Astragalus membranaceus separately, mix them evenly, add water for decoction after pretreatment, filter to obtain a filtrate and filter residues; crush the filter residues, add an ethanol aqueous solution for reflux extraction to obtain a first extract; add β-cyclodextrin to the filtrate, mix evenly, and dry to obtain a mixture; S2. Crush Lycium barbarum, Poria cocos and Rhizoma Pinelliae Praeparatum separately, mix them evenly and add water for decoction, combine the decoction liquids to obtain a second extract; S3. Distill Citrus reticulata Blanco with water to extract volatile oil and separate the volatile oil of Citrus reticulata Blanco; decoct the residue after distillation with water, combine the decoction liquids to obtain a third extract; S4. Crush Perilla frutescens, Ranunculus ternatus, Atractylodes macrocephala Koidz stir-fried, Prunus persica, Armeniaca vulgaris, Rehmannia glutinosa Libosch. and Pheretima separately, and mix them evenly to obtain a mixed powder; S5. Mix the first extract obtained in step S1, the second extract obtained in step S2, the third extract obtained in step S3 and the mixed powder obtained in step S4 evenly, and concentrate to obtain an extract; S6. Mix the extract and the mixture obtained in step S1 evenly, add soluble starch, mix evenly, dry, crush, add ethanol and mix evenly, granulate to obtain granules; dissolve the volatile oil of Citrus reticulata Blanco separated in step S3 with ethanol, evenly spray it on the surface of the granules, and dry to obtain the granules.

5. The preparation method according to claim 4, characterized in that, In step S1, the pretreatment is: add 10-20 times of 15-25% ethanol aqueous solution to the mixed powder obtained by crushing and mixing Codonopsis pilosula and Astragalus membranaceus, stir evenly, cool to -5-0 °C at room temperature, keep for 20-30 minutes, then heat up to room temperature and keep for 20-30 minutes.

6. The preparation method according to claim 4, wherein, The particle size of the crushed filter residues is 200-300 mesh, the volume fraction of the ethanol aqueous solution is 55-65%, and the dosage of the β-cyclodextrin is 40-50 wt% of the total amount of Codonopsis pilosula and Astragalus membranaceus.

7. The preparation method according to claim 4, characterized in that, Step S3 is: distill Citrus reticulata Blanco with 8-12 times of water to extract volatile oil for 3-5 hours, separate the volatile oil of Citrus reticulata Blanco; decoct the residue after distillation with 5-8 times of water, decoct for 2-4 times, 30-50 minutes each time, combine the decoction liquids to obtain a third extract.

8. The preparation method according to claim 4, characterized in that, In step S1, the addition of water for decoction is to add 10-20 times of water for decoction for 30-50 minutes.

9. The preparation method according to claim 4, wherein In step S2, the addition of water for decoction is to add 30-50 times of water for decoction, decoct for 2-4 times, 30-50 minutes each time.

10. The preparation method according to claim 4, characterized in that, Step S6 is as follows: Mix the extract with the mixture obtained in Step S1, add soluble starch at 60-80 wt%, mix well, dry at 50-60 °C, then crush to 50-60 mesh, add ethanol at 65-75% and mix well, granulate, and finally spray the volatile oil of tangerine peel separated in Step S3 to obtain the granule.