CN114392322A - Traditional Chinese medicine granule and preparation method and application thereof - Google Patents

Traditional Chinese medicine granule and preparation method and application thereof Download PDF

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Publication number
CN114392322A
CN114392322A CN202210216166.1A CN202210216166A CN114392322A CN 114392322 A CN114392322 A CN 114392322A CN 202210216166 A CN202210216166 A CN 202210216166A CN 114392322 A CN114392322 A CN 114392322A
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radix
chinese medicine
traditional chinese
lung
preparata
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CN114392322B (en
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黄璐琦
张水寒
胡学军
谢谊
周融融
曾宏亮
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HUNAN ACADEMY OF CHINESE MEDICINE
Institute of Materia Medica of CAMS
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HUNAN ACADEMY OF CHINESE MEDICINE
Institute of Materia Medica of CAMS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/41—Crassulaceae (Stonecrop family)
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/18—Magnoliophyta (angiosperms)
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    • A61K36/18—Magnoliophyta (angiosperms)
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Abstract

The invention discloses a traditional Chinese medicine granule as well as a preparation method and application thereof, belonging to the technical field of medicines. The traditional Chinese medicine particles are prepared from the following raw materials in parts by weight: 200-300 g of rhodiola rosea, 200-300 g of radix astragali preparata, 100-300 g of radix ophiopogonis, 100-150 g of rhizoma polygonati, 100-200 g of salvia miltiorrhiza, 100-200 g of exocarpium citri rubrum, 150-200 g of semen lepidii (north), 150-200 g of rhizoma pinellinae praeparata, 150-200 g of Japanese ardisia, 50-100 g of herba ephedrae preparata, 100-200 g of schisandra chinensis, 50-100 g of radix sileris and 100-200 g of radix glycyrrhizae preparata. The invention is mainly positioned in the treatment of the remission stage and the prolonged stage of diseases such as chronic obstructive pulmonary disease, chronic bronchitis and the like, improves the functions of viscera, strengthens physique, relieves symptoms, delays and reduces the relapse of cough and asthma phlegm symptoms of patients with lung (spleen) and kidney deficiency, and is suitable for industrial popularization and application.

Description

Traditional Chinese medicine granule and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a traditional Chinese medicine granule, a preparation method thereof, and application of the traditional Chinese medicine granule in tonifying lung and kidney and preventing and treating chronic obstructive pulmonary disease.
Background
Chronic Obstructive Pulmonary Disease (COPD) is a progressive and destructive chronic lung disease, and if not timely controlled, airflow limitation is further aggravated, leading to pulmonary hypertension and finally pulmonary heart disease, however, patients with COPD in the stable phase have the main symptoms of slight cough, expectoration and asthma, and the pathological changes are as follows: the number of alveolar spaces decreases and the alveolar septa break down, leading to fusion of the alveoli forming large alveoli with inflammatory cell infiltration.
In the aspect of western medicine, bronchodilators, receptor agonists or inhaled glucocorticoid control is mainly applied to stable-phase COPD treatment clinically, and after treatment, only COPD symptoms can be relieved, but the long-term curative effect is not significant; in the aspect of traditional Chinese medicine, the chronic obstructive pulmonary disease belongs to the categories of cough, asthma and lung account, and the traditional Chinese medicine for treating COPD has the unique advantages of multi-target comprehensive treatment, less side effect, syndrome differentiation and treatment and the like.
However, chronic obstructive pulmonary disease is frequently encountered in many patients and the disease is repeatedly attacked. Although the traditional Chinese medicine has advantages of treating symptoms of chronic obstructive pulmonary disease and reducing the disease period, no new medicine or Chinese patent medicine is available in the market, and the clinical observation period is long and the investment is large. Therefore, the technical problem to be solved by those skilled in the art is how to provide a Chinese medicinal granule for tonifying lung and kidney and preventing and treating chronic obstructive pulmonary disease.
Disclosure of Invention
In view of the above, the present invention aims to provide a traditional Chinese medicine granule for preventing and treating chronic obstructive pulmonary disease, which aims at the problems existing in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
the traditional Chinese medicine granule is prepared from the following raw materials in parts by weight: 200-300 g of rhodiola rosea, 200-300 g of radix astragali preparata, 100-300 g of radix ophiopogonis, 100-150 g of rhizoma polygonati, 100-200 g of salvia miltiorrhiza, 100-200 g of exocarpium citri rubrum, 150-200 g of semen lepidii (north), 150-200 g of rhizoma pinellinae praeparata, 150-200 g of Japanese ardisia, 50-100 g of herba ephedrae preparata, 100-200 g of schisandra chinensis, 50-100 g of radix sileris and 100-200 g of radix glycyrrhizae preparata.
The Chinese medicinal granules disclosed by the invention are a compound preparation consisting of a plurality of Chinese medicaments such as Chinese magnoliavine fruit, red sage root, roasted ephedra herb, roasted astragalus, rhodiola rosea and dwarf lilyturf tuber, wherein the Chinese magnoliavine fruit has the functions of astringing lung, relieving cough and asthma, the red sage root has the functions of expanding peripheral blood vessels and improving microcirculation, the roasted ephedra herb has the functions of moistening lung and relieving cough, is mostly used for relieving exterior symptoms, relieving asthma and cough, the roasted astragalus has the functions of tonifying qi and blood, and is suitable for treating lung deficiency, short breath, qi deficiency and blood weakness, and the rhodiola rosea contains a plurality of scopolamine, kaempferol and other antibacterial and anti-inflammatory components; the tannin content is the most, the product has astringency, can protect the mucosa surface, and has curative effect on cough and expectoration caused by lung inflammation; the dwarf lilyturf tuber has the effects of nourishing yin and moistening lung, and is used for treating yin deficiency and lung dryness, dry cough, over-heat hemoptysis and other symptoms, and the cough, the asthma and the lung tent symptoms induced by the chronic obstructive pulmonary disease in the stable stage are synergistically improved by combining the medicines.
The invention also aims to provide a preparation method of the traditional Chinese medicine granule.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a preparation method of traditional Chinese medicine granules specifically comprises the following steps:
(1) weighing rhodiola rosea, radix astragali preparata, radix ophiopogonis, rhizoma polygonati, salvia miltiorrhiza, exocarpium citri rubrum, semen lepidii (north), rhizoma pinellinae praeparata, Japanese ardisia herb, herba ephedrae preparata, schisandra chinensis, radix sileris and radix glycyrrhizae preparata respectively according to the disclosed formula for later use;
(2) crushing the salvia miltiorrhiza, the schisandra chinensis and the roasted ephedra to 20-80 meshes, carrying out reflux extraction twice by using 65-75% ethanol, and filtering to obtain ethanol extraction filtrate;
(3) decocting the residue after ethanol extraction with radix Rhodiolae, radix astragali Preparata, radix Ophiopogonis, rhizoma Polygonati, exocarpium Citri rubrum, semen Lepidii (North), rhizoma Pinelliae Preparata, herba Ardisiae Japonicae, radix Saposhnikoviae and radix Glycyrrhizae Preparata with water twice, and filtering to obtain water extraction filtrate;
(4) mixing the ethanol extraction filtrate and the water extraction filtrate, concentrating under reduced pressure to obtain fluid extract, and vacuum belt drying and pulverizing to obtain dry extract powder;
(5) adding dextrin and sweetener into the dry paste powder, mixing well, and granulating to obtain the traditional Chinese medicine granules.
Preferably, in the step (2), the first extraction time is 2-4 h, and the second extraction time is 1-3 h; and the addition amount of the 70% ethanol is 4-8 times of the mass of the coarse powder.
Further, in the step (2), the first extraction time is 2 hours, and the second extraction time is 1.5 hours; and the addition amount of the 70% ethanol is 5-6 times of the mass of the coarse powder.
Preferably, in the step (3), the first water adding and decocting time is 2-4 hours, and the second water adding and decocting time is 1-3 hours; and the water adding amount is 6-10 times of the mass of the medicinal materials.
Further, in the step (3), the first water adding decoction time is 2 hours, and the second water adding decoction time is 1.5 hours; and the water adding amount is 6-8 times of the mass of the medicinal materials.
Preferably, in the step (4), the vacuum degree during the reduced pressure concentration is-0.07 to-0.08 Mpa, the temperature is 60 to 65 ℃, and the density of the clear paste measured at 60 ℃ is 1.15 to 1.25, preferably 1.20 to 1.25.
Further preferably, the vacuum degree during the vacuum belt type drying is-99.0 to-100.0 Kpa, and the temperature of the first area is 90-115 ℃; the temperature of the second area is 70-90 ℃; the temperature of the three zones is 30-50 ℃; .
Preferably, in the step (5), 1-20 g of sweetener is added.
Specifically, the preparation method of the traditional Chinese medicine granule for preventing and treating chronic obstructive pulmonary disease comprises the following steps:
crushing the salvia miltiorrhiza, the schisandra chinensis and the roasted ephedra to 20-60 meshes, carrying out reflux extraction for 2 times by using 65-75% ethanol, carrying out extraction for 2-4 hours by adding 5-8 times of ethanol for the first time, carrying out extraction for 1-3 hours by adding 4-6 times of ethanol for the second time, filtering, and mixing the filtrates for later use; decocting the dregs after alcohol extraction and the rest eleven medicines such as rhodiola rosea and the like in water twice, adding 8-10 times of water for decocting for 2-4 h for the first time, adding 6-8 times of water for decocting for 1-3 h for the second time, merging decoction, filtering, merging with the standby alcohol extraction filtrate, and concentrating under reduced pressure (vacuum degree-0.07 to-0.08 Mpa, temperature of about 60-65 ℃) to obtain clear paste with relative density of 1.15-1.25 (60 ℃); then carrying out vacuum belt drying (the vacuum degree is-99.0 to-100.0 Kpa, the temperature of a first area is 90-115 ℃, the temperature of a second area is 70-90 ℃, and the temperature of a third area is 30-50 ℃) to obtain dry paste, and crushing; adding a proper amount of dextrin and about 1-20 g of flavoring agent into the dry paste powder, uniformly mixing, granulating, and drying to prepare 1000g of the dry paste powder.
The invention also requests to protect the application of the traditional Chinese medicine granules in the field of medicine.
Furthermore, the traditional Chinese medicine granules are applied to tonifying lung and kidney and preventing and treating chronic obstructive pulmonary disease.
Furthermore, the traditional Chinese medicine granules have the functions of tonifying lung, tonifying kidney, strengthening spleen, regulating qi, blood and yin and yang, and have the functions of tonifying lung, tonifying kidney, strengthening spleen and stomach, ventilating lung, descending qi, and relieving cough and asthma. Can be used for treating deficiency of lung (spleen) and kidney, manifested by cough and asthma, cough with white phlegm, difficulty in expectoration, anorexia, chest distress, discomfort or palpitation, soreness of waist and knees, and clear and abundant urine; those with the above symptoms in the remission stage (stationary phase) and prolonged period of chronic obstructive pulmonary disease, chronic bronchitis, asthma, pulmonary heart disease, etc.
Specifically, the traditional Chinese medicine particles are mainly clinically positioned in the treatment of the remission stage and the prolonged stage of diseases such as chronic obstructive pulmonary disease, chronic bronchitis and the like, improve the functions of viscera, strengthen physique, relieve symptoms and delay and reduce the relapse of the diseases; and is different from the general cough and asthma relieving medicine in that: the recipe treats both principal and secondary aspects of diseases, and mainly treats the root cause;
furthermore, the difference between the present invention and the general medicine for tonifying kidney and relieving asthma is that: it has the actions of both lung, spleen and kidney, and treats both the upper, middle and lower energizers, and also has the actions of ascending, descending, exiting and entering of visceral qi; the product has appropriate amount of lung-ventilating, qi-descending, asthma-relieving, cough-relieving and phlegm-resolving herbs while regulating qi activity of viscera and qi and blood and yin and yang of human body, so the key point is to strengthen physique and slow down the recurrence of cough and phlegm symptoms of patients with lung (spleen) and kidney deficiency; the kidney tonifying granule is mainly used for frequent micturition, nocturia, soreness and weakness of waist and knees and the like caused by kidney-yang deficiency.
According to the technical scheme, compared with the prior art, the traditional Chinese medicine granule and the preparation method and the application thereof provided by the invention have the following excellent effects:
the traditional Chinese medicine particles prepared by the invention can obviously reduce the level of white blood cells and cytokines in the lung, can obviously relieve the lung ventilation function damage of COPD, can reduce the partial pressure of carbon dioxide in blood and increase the partial pressure of oxygen in blood. Therefore, the traditional Chinese medicine granules have obvious treatment effect on different types of chronic obstructive pulmonary diseases.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 shows pathological sections (HE X100) of rat lung tissues, in which (a) shows a normal control group and (b) shows a model group.
FIG. 2 is a schematic view of an experimental rabbit atomizing device.
FIG. 3 is a schematic diagram of lung tissue visual observation of dead animals.
FIG. 4 shows lung pathological section (HE X100) of experimental rabbit in molding stage, wherein (a) shows normal control group and (b) shows model group.
FIG. 5 is a pathological section (HE X100) of lung tissue of an experimental rabbit before administration, wherein (a) is a normal control group and (b) is a model group.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention discloses a traditional Chinese medicine granule for preventing and treating chronic obstructive pulmonary disease and a preparation method thereof.
The present invention will be further specifically illustrated by the following examples for better understanding, but the present invention is not to be construed as being limited thereto, and certain insubstantial modifications and adaptations of the invention by those skilled in the art based on the foregoing disclosure are intended to be included within the scope of the invention.
The technical solution of the present invention will be further described with reference to specific experiments.
The contents of the present invention are not limited to the contents of the following experimental examples.
Example 1:
a traditional Chinese medicine granule for preventing and treating chronic obstructive pulmonary disease:
the formula is as follows: 240g of rhodiola rosea, 240g of radix astragali preparata, 120g of radix ophiopogonis, 120g of rhizoma polygonati, 200g of salvia miltiorrhiza, 120g of exocarpium citri rubrum, 160g of semen lepidii (north), 160g of rhizoma pinellinae praeparata, 160g of Japanese ardisia, 80g of herba ephedrae preparata, 120g of schisandra chinensis, 80g of radix sileris and 120g of honey-fried licorice root.
The preparation method comprises the following steps: (1) weighing rhodiola rosea, radix astragali preparata, radix ophiopogonis, rhizoma polygonati, salvia miltiorrhiza, exocarpium citri rubrum, semen lepidii (north), rhizoma pinellinae praeparata, Japanese ardisia herb, herba ephedrae preparata, schisandra chinensis, radix sileris and radix glycyrrhizae preparata respectively according to the disclosed formula for later use;
(2) pulverizing the salvia miltiorrhiza, the schisandra chinensis and the roasted ephedra to 20-60 meshes, performing reflux extraction twice by using 70% ethanol, and filtering to obtain ethanol extraction filtrate;
(3) decocting the residue after ethanol extraction with radix Rhodiolae, radix astragali Preparata, radix Ophiopogonis, rhizoma Polygonati, exocarpium Citri rubrum, semen Lepidii (North), rhizoma Pinelliae Preparata, herba Ardisiae Japonicae, radix Saposhnikoviae and radix Glycyrrhizae Preparata with water twice, and filtering to obtain water extraction filtrate;
(4) mixing the ethanol extraction filtrate and the water extraction filtrate, concentrating under reduced pressure to obtain fluid extract, and vacuum belt-type pulverizing to obtain dry extract powder;
(5) adding dextrin and a sweetening agent into the dry paste powder, uniformly mixing, and granulating to obtain the traditional Chinese medicine granules;
in the step (2), the first extraction time is 2 hours, and the second extraction time is 1.5 hours; and the addition amount of the 70% ethanol is 5-6 times of the mass of the coarse powder.
In the step (3), the first water adding decoction time is 2 hours, and the second water adding decoction time is 1.5 hours; and the water adding amount is 6-8 times of the mass of the medicinal materials.
In the step (4), the vacuum degree during the reduced pressure concentration is-0.07 to-0.08 Mpa, the temperature is 60 to 65 ℃, and the density of the clear paste measured at 60 ℃ is 1.20 to 1.25.
And the vacuum degree during vacuum belt drying is-99.0 to-100.0 Kpa, and the temperature of the first area is 100 ℃; the temperature of the second zone is 85 ℃; the temperature in the three zones was 37 ℃.
In the step (5), 1g of sweetener is added.
Example 2:
a traditional Chinese medicine granule for preventing and treating chronic obstructive pulmonary disease:
the formula is as follows: 200g of rhodiola rosea, 200g of radix astragali preparata, 150g of radix ophiopogonis, 150g of rhizoma polygonati, 150g of salvia miltiorrhiza, 150g of exocarpium citri rubrum, 200g of semen lepidii (north), 200g of rhizoma pinellinae praeparata, 150g of Japanese ardisia, 100g of herba ephedrae preparata, 100g of schisandra chinensis, 100g of radix sileris and 150g of honey-fried licorice root.
The preparation method comprises the following steps:
(1) weighing rhodiola rosea, radix astragali preparata, radix ophiopogonis, rhizoma polygonati, salvia miltiorrhiza, exocarpium citri rubrum, semen lepidii (north), rhizoma pinellinae praeparata, Japanese ardisia herb, herba ephedrae preparata, schisandra chinensis, radix sileris and radix glycyrrhizae preparata respectively according to the disclosed formula for later use;
(2) crushing the salvia miltiorrhiza, the schisandra chinensis and the roasted ephedra to 40-80 meshes, carrying out reflux extraction twice by using 75% ethanol, and filtering to obtain ethanol extraction filtrate;
(3) decocting the residue after ethanol extraction with radix Rhodiolae, radix astragali Preparata, radix Ophiopogonis, rhizoma Polygonati, exocarpium Citri rubrum, semen Lepidii (North), rhizoma Pinelliae Preparata, herba Ardisiae Japonicae, radix Saposhnikoviae and radix Glycyrrhizae Preparata with water twice, and filtering to obtain water extraction filtrate;
(4) mixing the ethanol extraction filtrate and the water extraction filtrate, concentrating under reduced pressure to obtain fluid extract, and vacuum belt-type pulverizing to obtain dry extract powder;
(5) adding dextrin and sweetener into the dry paste powder, mixing well, and granulating to obtain the traditional Chinese medicine granules.
In the step (2), the first extraction time is 2.5 hours, and the second extraction time is 2 hours; and the addition amount of the 75% ethanol is 6-8 times of the mass of the coarse powder.
In the step (3), the first water adding decoction time is 2.5 hours, and the second water adding decoction time is 2 hours; and the water adding amount is 7-9 times of the mass of the medicinal materials.
In the step (4), the vacuum degree during the reduced pressure concentration is-0.07 to-0.08 Mpa, the temperature is 60 to 65 ℃, and the density of the clear paste measured at 60 ℃ is 1.15 to 1.20.
And the vacuum degree during vacuum belt drying is-99.0 to-100.0 Kpa, and the temperature of the first area is 95 ℃; the temperature of the second zone is 80 ℃; the temperature in the three zones was 40 ℃.
In the step (5), 5g of a sweetener is added.
In order to further verify that the traditional Chinese medicine granules for preventing and treating chronic obstructive pulmonary disease prepared by the invention have excellent technical effects, the inventor also carries out the following performance measurement experiments.
It should be noted that the "chronic obstructive pulmonary disease granule" mentioned in the following experiments 1 and 2 is the traditional Chinese medicine granule prepared in the present disclosure.
Experiment 1: effect of Chronic obstructive pulmonary particles on rat COPD model
The invention adopts Lipopolysaccharide (LPS) and smoke to induce rats to establish a chronic obstructive pulmonary disease model, and performs histopathological examination on trachea and lung by analyzing lung function indexes, blood gas and alveolar lavage fluid cytokines and evaluating the drug effect of chronic obstructive pulmonary particles on the rat chronic obstructive pulmonary disease model.
1. Test materials
1.1 test article
Slow obstructive pulmonary particles (traditional Chinese medicine particles prepared by example 1), lot number: 200901, content: 1g of dry extract is equivalent to 3.47g of crude drug, and the effective period is as follows: 2022.08.31. the functional indications are as follows: tonify lung, tonify kidney, invigorate spleen, regulate qi, blood and yin and yang. For the stationary phase of Chronic Obstructive Pulmonary Disease (COPD). The symptoms are that the patient takes time to sleep for a long time, the patient is particularly acute when taking the patient, cough, white phlegm, unsmooth expectoration, anorexia, chest distress, discomfort or palpitation, soreness and weakness of waist and knees, clear and long urine. The usage and dosage are as follows: 48g crude drug/day for 1 month. Production unit: new exchange pharmaceutical products of Hunan province, Inc.
1.2 Positive control drugs
Jinshuibao capsule, batch number: the specification is as follows based on actual use batch number: 0.33 g/pellet, 9 pellets × 8 plates/box, pot life up to: the practical use is the standard. Indications are as follows: tonifying lung and kidney, replenishing essence and invigorating qi. Can be used for treating deficiency of lung and kidney, deficiency of vital essence and energy, chronic cough, asthma, listlessness, asthenia, insomnia, amnesia, soreness of the lower back and knee joints, menoxenia, sexual impotence, and premature ejaculation; chronic bronchitis is seen in the above syndromes. The usage and dosage are as follows: is administered orally. 3 granules at a time, 3 times a day. Production unit: jiangxi Jinshuibao pharmaceutical Co.
1.3 Primary reagents
Hibiscus rose cigarette (tar amount 11mg, nicotine content in smoke 0.9mg, carbon monoxide in smoke 13mg, Hunan Heidel cigarette factory); lipopolysaccharide (LPS), specification: 10 mg/bottle, batch number: 0000110640, respectively; the validity period is as follows: the year after the opening. Production unit: sigma; rat TNF-alpha, IL-6, IL-8 kit, batch number: 092021, production Unit: jiangsu enzyme Immunity Co.
And (3) preparing 1mg/mL of LPS solution, namely weighing 25mg of LPS, adding 25mL of LPS into 0.9% sodium chloride injection, and preparing the LPS solution with the mass concentration of 1 mg/mL.
1.4 Main Instrument
PFT lung function detection system (Shanghai Tawang intelligent science and technology Co., Ltd.), BG-800 type blood gas electrolyte analyzer (Shenzhen Medicong medical electronics Co., Ltd.), BC-5000Vet type five-classification blood cell analyzer for animals (Shenzhen Merrill Co., Ltd.), Spectra Max i3x type multifunctional enzyme-labeled analyzer (Shanghai Merrill), B203LED type biomicroscope (Chongqing Oltte optical instruments Co., Ltd.), RM2235 type paraffin microtome (German Leica), TP1020 type full-automatic dehydrator (German Leica), HI1220 type baking machine (German Leica), HI1210 type spreading machine (German Leica), EG1150H + C type tissue embedding machine (German Leica), DFC 420C type pathology imaging system (German Leica).
2. Experimental methods
2.1 modeling, grouping and administration
Selecting 100 male SD rats qualified for quarantine, performing SPF (specific pathogen free) grade, taking 87 of the male SD rats as a model group, and injecting 0.2 mL/one of 1mg/mL Lipopolysaccharide (LPS) solution into the lanes 1, 7, 15 and 21, wherein the specific operation method comprises the following steps: rats were anesthetized with ether, exposed under an otoscope, and the trachea was rapidly inserted from the glottis with a micro-syringe and the LPS solution was injected into the trachea. The rats are placed in a self-made smoking box for passive smoking for 1 time and 30 min/time on days 2-6, 8-14, 16-20 and 22-56. The remaining 13 rats served as normal controls and were injected with an equal volume of 0.9% sodium chloride injection into the airways using the same method only at 1 st, 7 th, 15 th and 21 st. After 56 days of modeling, 3 rats are randomly selected from a normal control group and a model group respectively, and are subjected to lung function and lung tissue pathological examination, the results show that the lung function airway resistance of the model group animals is obviously increased, the compliance is obviously reduced, and the lung tissue pathological results show that alveolar cavities are enlarged and are accompanied with a large amount of inflammatory exudation. Selecting 50 model rats, randomly dividing the rats into 5 groups according to weight, wherein the weight is 424.5-522.8 g, and the rats are respectively a model control group, a Jinshuibao capsule group (0.27g/kg), a slow obstructive pulmonary granule low, medium and high dose group (2.16, 4.32 and 8.64g crude drugs/kg), and each group comprises 10 animals. The rats of each group are gavaged with 10mL/kg of liquid medicine with corresponding dose, and the rats of the normal control group and the rats of the model control group are gavaged with pure water with the same volume for 1 time/day and are continuously administrated for 28 days.
2.2 index detection
2.2.1 Effect on Lung function
After the last administration, rats of each group are injected with 60mg/kg of Shutai 50 in the tail abdominal cavity for anesthesia, an inverted T-shaped opening is formed in a trachea, the trachea is intubated, and indexes such as pulmonary function airway resistance (Penh), lung compliance (Cpyn), tidal Volume (VT), Forced Vital Capacity (FVC), maximum expired air volume (FEV200) of expired air 200s, maximum expiratory flow rate (PEF), maximum inspiratory flow rate (PIF) and the like are detected by a PFT pulmonary function detection system.
2.2.2 Effect on partial pressure of arterial blood oxygen, partial pressure of carbon dioxide and pH
The abdominal aorta was sampled after each group of rats examined lung function and partial pressure of blood oxygen (PaO) was measured2) Partial pressure of carbon dioxide (PaCO)2)。
2.2.3 Effect on IL-8, TNF-alpha levels in alveolar lavage fluid
The rats in each group were exsanguinated and euthanized, and 6mL of 0.9% sodium chloride injection was injected into the right lung from the opening of the trachea to perform alveolar lavage, and alveolar lavage fluid was collected, and alveolar lavage fluid white blood cell count and classification were detected using a five-classification animal hemocyte analyzer, and alveolar lavage fluid TNF- α, IL-6, and IL-8 levels were detected using a rat ELISA kit.
2.2.4 Effect on Lung histopathology
Taking lungs of rats in each group, slicing the rats in 10% neutral formalin solution, carrying out HE staining, and respectively carrying out pathological scoring on the bronchioles and the emphysema degrees of the rats, wherein the scoring standard is as follows: no obvious abnormality is seen, and the value is 0 and marked as "-"; mild lesions, grade i, marked as "+"; moderate lesions, grade ii, marked as "+"; severe lesions, grade iii, "+ + + +", were recorded.
2.3 dose design
According to the data provided by the consignor, the clinically planned dose of the slow-obstructive pulmonary particles is 48g crude drug/day, the rat equivalent dose converted according to the body surface area is 48g crude drug × 0.018/0.2kg ═ 4.32g crude drug/kg, the rat equivalent dose in this test is taken as the dose (4.32g crude drug/kg) of the dose group in the slow-obstructive pulmonary particles, and 0.5 and 2 times of the medium dose are taken as the doses of the low-dose group and the high-dose group of the slow-obstructive pulmonary particles, namely 2.16 and 8.64g crude drug/kg respectively.
The clinical intended dose of the Jinshuibao capsule is 2.97 g/day, the rat equivalent dose converted according to the body surface area is 2.97g 0.018/0.2-0.27 g/kg, and the rat equivalent dose is used as the administration dose of the Jinshuibao capsule group. The specific dose is detailed in Table 1-1.
TABLE 1-1 test groups and dose design
Figure BDA0003534808240000111
Note: (1) the adult weight is measured by 60 kg; (2)1g of dry extract is equivalent to 3.47g of crude drug.
2.4 statistical methods
The test data significant figure rounding was done by rounding and statistical analysis was done as specified by SOP. The software used was counted as SPSS 22.0. The measured data is averaged + -SD
Figure BDA0003534808240000112
Showing that the method of Leven's test is used for checking the normality and the homogeneity of variance. If it has no statistical significance (P)>0.05), statistical analysis was performed using one-way analysis of variance (ANOVA). If ANOVA is statistically significant (P.ltoreq.0.05), a comparative analysis is carried out using LSD test (parametric method). If the variance is not uniform (P.ltoreq.0.05), the test is carried out by Kruskal-Wallis. If the Kruskal-Wallis Test is statistically significant (P.ltoreq.0.05), a comparative analysis is performed using Dunnett's Test (nonparametric method). The statistical results are tested with α ≦ 0.05, where P ≦ 0.05 indicates statistical significance and P ≦ 0.01 indicates that the difference tested was of significant significance.
3 results of the test
3.1 Molding period
3.1.1 pulmonary function index
As shown in the table 1-2, compared with the normal control group, the airway resistance (Penh) of the animals in the model group is obviously increased, the lung compliance (Cpyn) is obviously reduced, and the lipopolysaccharide combined fumigation can cause the abnormality of the lung function index of the rat.
TABLE 1-2 Effect of lipopolysaccharide in combination with smoking on Lung function index in rats: (
Figure BDA0003534808240000121
n＝3)
Figure BDA0003534808240000122
3.1.2 pathological changes in Lung tissue
As shown in figure 1, the number of alveolar septa, alveolar spaces and inflammatory cells of the rats in the normal control group are not obviously abnormal, the pulmonary tissue structure of the rats in the model group is damaged, the number of alveolar septa is obviously reduced, the alveolar spaces are enlarged and are infiltrated by a large number of inflammatory cells, which indicates that the combination of lipopolysaccharide and smoking can induce the emphysema of the rats in a 3.2 test period
3.2.1 Effect on Lung function
As shown in tables 1-3, compared with the normal control group, the FVC, FEV200, PEF, VT and Cypn of the rats in the model control group are obviously reduced (P is less than or equal to 0.05 or P is less than or equal to 0.01); compared with a model control group, the FVC, the FEV200 and the PEF of rats in the Jinshuibao capsule group are obviously increased (P is less than or equal to 0.05), the FVC in the dose group in the slow obstructive pulmonary granules is obviously increased (P is less than or equal to 0.05), the FVC, the FEV200, the PEF and the VT in the high dose group are obviously increased (P is less than or equal to 0.05 or P is less than or equal to 0.01), the PIF and the Cypn have an increasing trend, and the Penh has a decreasing trend but has no statistical difference.
TABLE 1-3 Effect of Chronic obstructive Lung particles on Lung function in COPD rats: (
Figure BDA0003534808240000123
n＝10)
Figure BDA0003534808240000124
Figure BDA0003534808240000131
Note: comparing with normal control group+P≤0.05，++P is less than or equal to 0.01; comparison with model control group*P≤0.05，**P≤0.01。
3.2.2 Effect on leukocytes and five classes
As shown in tables 1-4, the lung counts of model control rats all tended to increase, but were not statistically different, from the normal control rats in WBC, Neu and Lym counts; compared with a model control group, the five categories of white blood cells and white blood cells of the Jinshuibao capsule group, the slow obstructive pulmonary granule low, medium and high dose groups of rats have no statistical difference.
TABLE 1-4 Effect of Slow-obstructive pulmonary particles on white blood cells of alveolar lavage of COPD rats and five classifications: (
Figure BDA0003534808240000132
n＝10)
Figure BDA0003534808240000133
3.2.3 Effect on alveolar lavage fluid cytokines
As shown in tables 1-5, the levels of IL-6, IL-8 and TNF-alpha in the lungs of the rats in the model control group are obviously increased (P is less than or equal to 0.05 or P is less than or equal to 0.01) compared with the normal control group; compared with a model control group, IL-6 in the lung of the rat in the Jinshuibao capsule group is obviously reduced (P is less than or equal to 0.01), the water average of IL-8 and TNF-alpha in the lung of the rat in the slow obstructive pulmonary particles low, medium and high dose groups is obviously reduced (P is less than or equal to 0.05 or P is less than or equal to 0.01), and IL-6 has the tendency of reduction, but has no statistical difference.
TABLE 1-5 Effect of Slow obstructive pulmonary particles on pulmonary alveolar lavage cytokine in COPD rats: (
Figure BDA0003534808240000134
n＝10)
Figure BDA0003534808240000135
Figure BDA0003534808240000141
Note: comparing with normal control group+P≤0.05，++P is less than or equal to 0.01; comparison with model control group*P≤0.05，**P≤0.01。
3.2.4 Effect on blood gas
As shown in tables 1-6, compared with the normal control group, the partial pressure of carbon dioxide in the blood of the rats in the model control group is obviously increased (P is less than or equal to 0.01), and the partial pressure of oxygen is obviously reduced (P is less than or equal to 0.01); compared with the model control group, the oxygen partial pressure in the blood of the rats in the Jinshuibao capsule group is obviously increased (P is less than or equal to 0.01), the carbon dioxide partial pressure in the blood of the rats in the slow obstructive pulmonary particle high-dose group is obviously reduced (P is less than or equal to 0.05), and the oxygen partial pressure is obviously increased (P is less than or equal to 0.01).
TABLE 1-6 Effect of chronic obstructive pulmonary disease particles on blood gas in COPD rats: (
Figure BDA0003534808240000142
n＝10)
Figure BDA0003534808240000143
Note: comparing with normal control group++P is less than or equal to 0.01; comparison with model control group*P≤0.05，**P≤0.01。
4 test summary
The results show that the lipopolysaccharide combined fumigation can cause the increase of the lung function airway resistance of rats, the reduction of lung compliance, the induction of the destruction of the lung tissue structure of the rats, the reduction of the alveolar septa and the enlargement of alveolar cavities, and the suggestion that the lipopolysaccharide combined fumigation can establish a rat emphysema model; the slow lung blocking particles (2.16, 4.32 and 8.64g crude drugs/kg) can obviously reduce the IL-8 and TNF-alpha levels in the lung, wherein the slow lung blocking particles (8.64g crude drugs/kg) can obviously relieve the pulmonary ventilation damage of COPD rats, increase the oxygen partial pressure in blood and reduce the carbon dioxide partial pressure. The slow obstructive pulmonary disease (COPD) particles (8.64g crude drug/kg, equivalent to 2 times of the clinical equivalent dose) are suggested to have obvious therapeutic effect on the rat Chronic Obstructive Pulmonary Disease (COPD) model.
Experiment 2: effect of Chronic obstructive Lung particles on Experimental Rabbit COPD model
Papain acts non-specifically on elastic fibers in alveolar spaces, causing destruction of pulmonary tissue vessel walls and bronchi, causing inflammation, and thus inducing emphysema. Therefore, the invention adopts the experimental rabbit to inject papain through ear vein, and combines with papain inhaled by mouth and nose atomization to establish the experimental rabbit chronic obstructive pulmonary disease model, and the pharmacodynamic effect of the chronic obstructive pulmonary particles on the experimental rabbit chronic obstructive pulmonary disease model is evaluated through lung function index, blood gas analysis and alveolar lavage fluid cytokine detection and trachea and lung histopathological examination.
1. Test materials
1.1 test article: granules for chronic obstructive pulmonary disease, batch number: 200901, content: 1g of dry extract is equivalent to 3.47g of crude drug, and the effective period is as follows: 2022.08.31. the functional indications are as follows: tonify lung, tonify kidney, invigorate spleen, regulate qi, blood and yin and yang. For the stationary phase of Chronic Obstructive Pulmonary Disease (COPD). The symptoms are that the patient takes time to sleep for a long time, the patient is particularly acute when taking the patient, cough, white phlegm, unsmooth expectoration, anorexia, chest distress, discomfort or palpitation, soreness and weakness of waist and knees, clear and long urine. The usage and dosage are as follows: 48g crude drug/day for 1 month. Production unit: new exchange pharmaceutical products of Hunan province, Inc.
1.2 Positive control: jinshuibao capsule, batch number: the specification is as follows based on actual use batch number: 0.33 g/pellet, 9 pellets × 8 plates/box, pot life up to: the practical use is the standard. Indications are as follows: tonifying lung and kidney, replenishing essence and invigorating qi. Can be used for treating deficiency of lung and kidney, deficiency of vital essence and energy, chronic cough, asthma, listlessness, asthenia, insomnia, amnesia, soreness of the lower back and knee joints, menoxenia, sexual impotence, and premature ejaculation; chronic bronchitis is seen in the above syndromes. The usage and dosage are as follows: is administered orally. 3 granules at a time, 3 times a day. Production unit: jiangxi Jinshuibao pharmaceutical Co.
1.3 Primary reagents
Papain, lot number: LE 201103; the validity period is as follows: the year after the opening. Production unit: hefeibomei biotechnology Limited liability company; rat TNF-alpha, IL-6, IL-8 kit, batch number: 092021, production Unit: jiangsu enzyme Immunity Co.
Preparing a 0.8% papain solution: weighing 1.6g of papain, adding the papain into 200mL of 0.9% sodium chloride injection, and preparing a papain solution with the mass concentration of 8 mg/mL; preparing a 0.5% papain solution: 1.0g of papain is weighed and added to 200mL by 0.9% sodium chloride injection to prepare papain solution with the mass concentration of 5 mg/mL.
1.4 Main Instrument
PFT lung function detection system (Shanghai Tawang intelligent science and technology Co., Ltd.), BG-800 type blood gas electrolyte analyzer (Shenzhen Medicong medical electronics Co., Ltd.), BC-5000Vet type five-classification blood cell analyzer for animals (Shenzhen Merrill Co., Ltd.), Spectra Max i3x type multifunctional enzyme-labeled analyzer (Shanghai Merrill), B203LED type biomicroscope (Chongqing Oltte optical instruments Co., Ltd.), RM2235 type paraffin microtome (German Leica), TP1020 type full-automatic dehydrator (German Leica), HI1220 type baking machine (German Leica), HI1210 type spreading machine (German Leica), EG1150H + C type tissue embedding machine (German Leica), DFC 420C type pathology imaging system (German Leica).
2. Experimental methods
2.1 modeling, grouping and administration
90 male rabbits qualified for quarantine are selected as a common grade, 78 of the rabbits are selected as a model group, and are injected by 1 time of 1mL/kg of 0.8% papain through ear marginal vein, and then inhaled by 0.5% papain atomized by an ultrasonic atomizer (more than 90% of particles with the particle size of 5 mu m) for 4 hours/time, and inhaled once a week for 3 times (figure 2). Observations were continued for 40 days after the last inhalation. The remaining 12 animals served as normal controls and were injected and inhaled with 0.9% sodium chloride injection using the same method. Taking 3 animals of the normal control group and the model group to carry out pathological examination of blood gas and lung tissues, and displaying the result that the animals PaO of the normal control group2：120.3±15.8mmHg；PaCO2: 22.6 plus or minus 1.4 mmHg; model group PaO2：103.2±17.0mmHg；PaCO2: 27.8 plus or minus 4.5 mmHg; prompt model animal PaO2Significant reduction in PaCO2Significantly elevated, and pathological results of lung tissue showed necrosis of the bronchioles mucosa, enlargement of alveolar spaces, and a large amount of inflammatory exudation. Selecting 48 model experimental rabbits with the weight of 2.3-3.2 kg, randomly dividing the rabbits into 5 groups according to the weight, wherein the groups are respectively a model control group, a Jinshuibao capsule group (0.14g/kg), a slow-obstructive lung granule low, medium and high dose groups (1.12, 2.24 and 4.48g/kg), and each group comprises 8 animals. The corresponding dose of liquid medicine is administrated to each group of animals by intragastric administration of 5mL/kg, and equal volume of distilled water is administrated to the normal control group and the model control group by intragastric administration for 1 time/day for 28 days continuously.
2.2 index detection
2.2.1 Effect on partial pressure of arterial blood oxygen and partial pressure of carbon dioxide
Blood was collected from the middle ear artery of each group of experimental rabbits after the last administration, and the partial pressure of blood oxygen (PaO) was measured2) Partial pressure of carbon dioxide (PaCO)2)。
2.2.2 Effect on Lung function
After the last administration, each group of experimental rabbits is anesthetized by intravenous injection of propofol emulsion injection of 15mg/kg at the ear margin, an inverted T-shaped opening is formed on the trachea, the trachea is intubated, and indexes such as pulmonary function airway resistance (Penh), lung compliance (Cpyn), tidal Volume (VT), Forced Vital Capacity (FVC), maximum expired air volume (FEV200) expired in 200s of expiration, maximum expiratory flow rate (PEF), maximum inspiratory flow rate (PIF) and the like are detected by a PFT pulmonary function detection system.
2.2.3 Effect on IL-8, TNF-alpha levels in alveolar lavage fluid
The experimental rabbits of each group were exsanguinated and euthanized, 6mL of 0.9% sodium chloride injection was injected into the right lung from the opening of the trachea to perform alveolar lavage, and alveolar lavage fluid was collected, and alveolar lavage fluid white blood cell count and classification were detected by a five-classification animal hemocyte analyzer, and alveolar lavage fluid TNF- α, IL-6, and IL-8 levels were detected by an experimental rabbit ELISA kit.
2.2.4 Effect on Lung histopathology
Taking lungs of each group of experimental rabbits, slicing the lungs, staining the lungs with 10% neutral formalin solution by HE, and respectively carrying out pathological scoring on the bronchioles and the emphysema degrees of the experimental rabbits, wherein the scoring standards are as follows: no obvious abnormality is seen, and the value is 0 and marked as "-"; mild lesions, grade i, marked as "+"; moderate lesions, grade ii, marked as "+"; severe lesions, grade iii, "+ + + +", were recorded.
2.3 dose design
According to the data provided by the consignment, the clinical planned dose of the slow-obstructive pulmonary particles is 48g crude drug/day, the equivalent dose of the experimental rabbit converted according to the body surface area is 48g crude drug multiplied by 0.07/1.5kg to 2.24g crude drug/kg, the equivalent dose of the experimental rabbit is taken as the dose (2.24g crude drug/kg) of the dose group in the slow-obstructive pulmonary particles in the test, and 0.5 and 2 times of the middle dose are respectively taken as the doses of the low-dose group and the high-dose group of the slow-obstructive pulmonary particles, namely 1.12 g crude drug/kg and 4.48g crude drug/kg.
The clinical intended dose of the Jinshuibao capsule is 2.97 g/day, the equivalent dose of the Jinshuibao capsule converted into the rabbit according to the body surface area is 2.97g 0.07/1.5 kg-0.14 g/kg, and the equivalent dose of the experimental rabbit is taken as the administration dose of the Jinshuibao capsule group. The specific dose is shown in Table 2-1.
TABLE 2-1 test groups and dose design
Figure BDA0003534808240000181
Note: (1) the adult weight is measured by 60 kg; (2)1g of dry extract is equivalent to 3.47g of crude drug.
2.4 statistical methods
The test data significant figure rounding was done by rounding and statistical analysis was done as specified by SOP. The software used was counted as SPSS 22.0. The measured data is averaged + -SD
Figure BDA0003534808240000182
Showing that the method of Leven's test is used for checking the normality and the homogeneity of variance. If it has no statistical significance (P)>0.05), statistical analysis was performed using one-way analysis of variance (ANOVA). If ANOVA is statistically significant (P.ltoreq.0.05), a comparative analysis is carried out using LSD test (parametric method). If the variance is not uniform (P.ltoreq.0.05), the test is carried out by Kruskal-Wallis. If the Kruskal-Wallis Test is statistically significant (P.ltoreq.0.05), a comparative analysis is performed using Dunnett's Test (nonparametric method). The statistical results are tested with α ≦ 0.05, where P ≦ 0.05 indicates statistical significance and P ≦ 0.01 indicates that the difference tested was of significant significance.
3 results of the test
3.1 Molding period
3.1.1 general clinical observations
In the model observation period, the experimental rabbits in the model observation period have slight bleeding of mouth and nose, rapid respiration, reduced food intake and autonomous activity, and death of 12 experimental rabbits, lung tissue volume expansion, congestive pulmonary edema and purulent secretion, and severe lung infection (fig. 3).
3.1.2 index of blood gas
As shown in Table 2-2, PaO in blood of model group animals as compared with that of normal control group2A significant decrease in PaCO2The increase is obvious, which indicates that the papain can cause abnormal blood and qi of the experimental rabbits.
TABLE 2-2 Effect of papain on blood gas indices in laboratory rabbits (
Figure BDA0003534808240000191
n＝3)
Figure BDA0003534808240000192
3.1.3 pathological changes in Lung tissue
As shown in FIGS. 4 and 5, the number of alveolar septa and alveolar cavities and inflammatory cells of the rats in the normal control group during the molding period and before administration were not obviously abnormal, the pulmonary tissue structure of the rats in the model group during the molding period and before administration was damaged, the number of alveolar septa was obviously reduced, alveolar cavities were enlarged and infiltrated with a large amount of inflammatory cells, which suggests that papain can induce pulmonary emphysema in the rats, and the model was maintained for a long time.
3.2 test period
3.2.1 Effect on Lung function
As shown in tables 2-3, compared with the normal control group, the FVC, FEV200 and PEF of the experimental rabbits of the model control group are obviously reduced (P is less than or equal to 0.05 or P is less than or equal to 0.01), Penh has an increasing trend, PIF and Cpyn have a decreasing trend, but no statistical difference exists; compared with a model control group, the experiment rabbits FVC, FEV200, PEF, PIF and Cpyn in the Jinshuibao capsule group are all obviously increased (P is less than or equal to 0.05 or P is less than or equal to 0.01), the slow-obstructive pulmonary particles are low, the Cpyn in the medium dose group is obviously increased (P is less than or equal to 0.05), the FEV200, PEF, PIF, VT and Cpyn in the high dose group are all increased, and Penh is reduced but has no statistical difference.
TABLE 2-3 Effect of Chronic obstructive Lung particles on Lung function in COPD test rabbits (
Figure BDA0003534808240000201
n＝8)
Figure BDA0003534808240000202
Note: comparing with normal control group+P is less than or equal to 0.05; comparison with model control group*P≤0.05，**P≤0.01。
3.2.2 Effect on leukocytes and five classes
As shown in tables 2-4, compared with the normal control group, the lung of the experimental rabbit of the model control group has obvious increase of WBC (P is less than or equal to 0.05), and Neu, Lym, Mon and Eos counts all have the trend of increasing, but have no statistical difference; compared with the model control group, WBC in the lung of the test rabbit of the Jinshuibao capsule group is obviously increased (P is less than or equal to 0.05), WBC in the lung of the test rabbit of the slow obstructive pulmonary granule group and the lung of the test rabbit of the high dose group are obviously reduced (P is less than or equal to 0.01), Neu, Lym and Mon counts in the lung of the test rabbit of the medium dose group are obviously reduced (P is less than or equal to 0.05), and Neu, Lym, Mon and Eos counts in the lung of the test rabbit of the high dose group are reduced, but no statistical difference exists.
TABLE 2-4 Effect of Slow-obstructive pulmonary particles on pulmonary alveolar lavage leukocytes and five classifications in COPD Experimental rabbits: (
Figure BDA0003534808240000203
n＝8)
Figure BDA0003534808240000204
Figure BDA0003534808240000211
Note: comparing with normal control group+P is less than or equal to 0.05; comparison with model control group*P≤0.05，**P≤0.01。
3.2.3 Effect on alveolar lavage fluid cytokines
As shown in tables 2-5, compared with the normal control group, the lung levels of IL-6, IL-8 and TNF-alpha of the experimental rabbits in the model control group are obviously increased (P is less than or equal to 0.05 or P is less than or equal to 0.01); compared with a model control group, the water levels of IL-6 and IL-8 in the lung of the experimental rabbits of the Jinshuibao capsule group and the slow obstructive pulmonary particle high-dose group are obviously reduced (P is less than or equal to 0.01).
TABLE 2-5 Effect of Slow obstructive pulmonary particles on alveolar lavage cytokine of COPD Experimental rabbits (
Figure BDA0003534808240000212
n＝8)
Figure BDA0003534808240000213
Note: comparing with normal control group+P≤0.05，++P is less than or equal to 0.01; comparison with model control group**P≤0.01。
3.2.4 Effect on blood gas
As shown in tables 2-6, the partial pressure of carbon dioxide in the blood of the experimental rabbit of the model control group is obviously increased (P is less than or equal to 0.01) compared with that of the normal control group; compared with the model control group, the partial pressure of carbon dioxide in the blood of the experimental rabbit with Jinshuibao capsule group is obviously reduced (P is less than or equal to 0.05), and the partial pressure of carbon dioxide in the blood of the experimental rabbit with low, medium and high dose of slow obstructive pulmonary particles is obviously reduced (P is less than or equal to 0.05 or P is less than or equal to 0.01).
TABLE 2-6 Effect of Slow obstructive Lung particles on blood gas of COPD experimental rabbits (
Figure BDA0003534808240000214
n＝8)
Figure BDA0003534808240000215
Figure BDA0003534808240000221
Note: comparing with normal control group++P is less than or equal to 0.01; comparison with model control group*P≤0.05，**P≤0.01。
4 test summary
The results show that the papain can cause the lung ventilation function of the experimental rabbit to be damaged, can induce the lung tissue structure of the experimental rabbit to be damaged, causes the pulmonary alveolus to be reduced and the pulmonary alveolus to be enlarged, prompts the experimental rabbit to inhale the papain through intravenous injection and mouth-nose atomization to establish an pulmonary emphysema model of the experimental rabbit, and has longer maintenance time; the slow lung blocking particles (1.12 g crude drug/kg and 2.24g crude drug/kg) can obviously increase lung compliance and reduce the partial pressure of carbon dioxide in blood, the slow lung blocking particles (2.24g crude drug/kg) can obviously reduce WBC, Neu, Lym and Mon counts in the lungs of the experimental rabbit, and the slow lung blocking particles (4.48g crude drug/kg) can obviously reduce WBC counts and IL-6 and IL-8 levels in the lungs of the experimental rabbit and reduce the partial pressure of carbon dioxide. The slow obstructive pulmonary particles are suggested to have obvious therapeutic effect on the Chronic Obstructive Pulmonary Disease (COPD) of experimental rabbits.
In conclusion, the traditional Chinese medicine granules prepared by the invention can obviously reduce the levels of leucocytes and cytokines in the lung, can obviously relieve the pulmonary ventilation function impairment of COPD, and can reduce the partial pressure of carbon dioxide in blood and increase the partial pressure of oxygen in blood. Therefore, the traditional Chinese medicine granules have obvious treatment effect on different types of chronic obstructive pulmonary diseases
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (9)

1. The traditional Chinese medicine granule is characterized by being prepared from the following raw materials in parts by weight: 200-300 g of rhodiola rosea, 200-300 g of radix astragali preparata, 100-300 g of radix ophiopogonis, 100-150 g of rhizoma polygonati, 100-200 g of salvia miltiorrhiza, 100-200 g of exocarpium citri rubrum, 150-200 g of semen lepidii (north), 150-200 g of rhizoma pinellinae praeparata, 150-200 g of Japanese ardisia, 50-100 g of herba ephedrae preparata, 100-200 g of schisandra chinensis, 50-100 g of radix sileris and 100-200 g of radix glycyrrhizae preparata.
2. The preparation method of the traditional Chinese medicine granule as claimed in claim 1, which comprises the following steps:
(1) weighing rhodiola rosea, radix astragali preparata, radix ophiopogonis, rhizoma polygonati, salvia miltiorrhiza, exocarpium citri rubrum, semen lepidii (north), rhizoma pinellinae praeparata, Japanese ardisia, herba ephedrae preparata, schisandra chinensis, radix sileris and radix glycyrrhizae preparata respectively according to the formula amount disclosed in claim 1 for later use;
(2) crushing the salvia miltiorrhiza, the schisandra chinensis and the roasted ephedra to 20-80 meshes, carrying out reflux extraction twice by using 65-75% ethanol, and filtering to obtain ethanol extraction filtrate;
(3) decocting the residue after ethanol extraction with radix Rhodiolae, radix astragali Preparata, radix Ophiopogonis, rhizoma Polygonati, exocarpium Citri rubrum, semen Lepidii (North), rhizoma Pinelliae Preparata, herba Ardisiae Japonicae, radix Saposhnikoviae and radix Glycyrrhizae Preparata with water twice, and filtering to obtain water extraction filtrate;
(4) mixing the ethanol extraction filtrate and the water extraction filtrate, concentrating under reduced pressure to obtain fluid extract, and vacuum belt drying and pulverizing to obtain dry extract powder;
(5) adding dextrin and sweetener into the dry paste powder, mixing well, and granulating to obtain the traditional Chinese medicine granules.
3. The preparation method of the traditional Chinese medicine granule as claimed in claim 2, wherein in the step (2), the first extraction time is 2-4 h, and the second extraction time is 1-3 h; and the addition amount of the 70% ethanol is 4-8 times of the mass of the coarse powder.
4. The preparation method of the traditional Chinese medicine granule as claimed in claim 2, wherein in the step (3), the first water decoction time is 2-4 h, and the second water decoction time is 1-3 h; and the water adding amount is 6-10 times of the mass of the medicinal materials.
5. The preparation method of the traditional Chinese medicine granule as claimed in claim 2, wherein in the step (4), the vacuum degree during the reduced pressure concentration is-0.07 to-0.08 Mpa, the temperature is 60 to 65 ℃, and the density of the clear paste measured at 60 ℃ is 1.15 to 1.25, preferably 1.20 to 1.25.
6. The method for preparing Chinese medicinal granules according to claim 2 or 5, wherein the vacuum degree during the vacuum belt drying is-99.0 to-100.0 Kpa, and the temperature in one area is 90 ℃ to 115 ℃; the temperature of the second area is 70-90 ℃; the temperature of the three zones is 30-50 ℃.
7. The method for preparing traditional Chinese medicine granules according to claim 2, wherein in the step (5), 1-20 g of sweetener is added.
8. The use of the Chinese medicinal granule of claim 1 or the Chinese medicinal granule prepared by the method of any one of claims 2 to 7 in the field of medicine.
9. The use of claim 8, further comprising: the Chinese medicinal granule has the effects of tonifying lung and kidney and can be used for preventing and treating chronic obstructive pulmonary disease.
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