CN115845021A - Traditional Chinese medicine composition for preventing and treating pulmonary fibrosis and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for preventing and treating pulmonary fibrosis. The traditional Chinese medicine composition comprises the raw medicinal materials of the pubescent angelica root, the astragalus root, the wild buckwheat rhizome, the ginseng, the astilbe chinensis, the snakegourd peel, the schisandra fruit, the dried ginger, the liquorice and the like, has the effects of clearing away heat and toxic materials, reducing phlegm, tonifying qi, activating blood circulation and dissipating stagnation, is clinically used for treating the pulmonary fibrosis, has a remarkable curative effect, and provides a new choice for clinically improving or treating the pulmonary fibrosis.

Description

Traditional Chinese medicine composition for preventing and treating pulmonary fibrosis and preparation method thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating pulmonary fibrosis and a preparation method thereof.

Background

Pulmonary Fibrosis (PF) is a chronic inflammatory interstitial lung disease of unknown origin, characterized by diffuse alveolitis, alveolar disorganization and ultimately pulmonary fibrosis, and pulmonary function examinations often show restricted ventilation dysfunction and diffuse dysfunction. Of the diffuse interstitial lung diseases, idiopathic pulmonary interstitial fibrosis (IPF) is the most prevalent and has a very poor prognosis. Clinically, patients with pulmonary fibrosis have nonspecific symptoms such as cough and dyspnea, gradually worsen, progress to the terminal stage and have respiratory failure, and generally die in about 3-8 years after symptoms appear. The disease course is progressively worsened from the symptom onset to the end-stage respiratory failure or death of pulmonary fibrosis, the average survival period after the diagnosis of IPF is 2-4 years, the five-year survival rate is 30% -50%, and the IPF is considered as a common disease and a refractory disease of respiratory diseases.

In recent years, with the intensive research on the basic theory, pathogenesis and clinical treatment of pulmonary fibrosis, it is recognized that cytokines play an important role in the development of the pulmonary fibrosis, and they constitute a complex network system and chain reaction system of extracellular signaling molecules, resulting in immune-mediated chronic inflammation characterized by inflammatory cell infiltration, fibroblast proliferation and interstitial connective tissue deposition. Pulmonary injury is manifested early in the form of alveolitis, which is thought to be due to cytokine release of large amounts of inflammatory mediators, resulting in damage to the capillary endothelium of the alveolar wall and increased permeability. There are many cell growth factors in alveolar inflammatory effusion, and their action concentration, kind of cytokine expression, time difference of high expression and degree of activation of their corresponding receptors play an important role in repair of alveolar epithelium or generation and development of pulmonary fibrosis, so the cytokines play an important role in generation and development of PF, and these cytokine media can affect activation, proliferation and collagen deposition of fibroblasts in disease process. Among them, TNF-alpha and TGF-beta are most important in the occurrence and development of pulmonary fibrosis.

In recent years, various traditional Chinese medicine compound preparations are applied to intervention and treatment of pulmonary fibrosis by more and more researchers, and part of research results have played an important guiding role in clinical treatment of fibrosis. The pulmonary fibrosis is called as 'lung impediment' or 'lung atrophy' in traditional Chinese medicine, the position of the lung in all visceral organs is highest, the lung is called as 'lung canopy' in traditional Chinese medicine, and the lung is the only organ communicated with the outside in five internal organs, so that the lung is most susceptible to diseases caused by various pathogenic factors of the outside, and the functions of dispersing, descending, regulating respiration and regulating water channels are influenced. The most main pathogenic factors are qi stagnation, phlegm coagulation and blood stasis, which can interact with each other to cause diseases. The main pathogenesis of the lung fibrosis is that the lung collaterals are blocked due to the deficiency of vital qi, mainly the weakness of qi and blood of the three organs of lung, spleen and kidney, and the pulmonary fibrosis caused by the pathogenesis is called as lung obstruction, and mainly causes pathogenic excess, wherein the qi and blood are not regulated, and the stagnation of collaterals is the most common; the other is caused by qi and blood deficiency and collaterals weakness, called lung atrophy, mainly due to deficiency of the original qi. The "lung impediment" is usually caused by exogenous pathogens, internal injury, and eating disorder, which lead to fluid retention and accumulation of phlegm; consumptive lung disease usually occurs in the chronic persistent period of the disease, and is mainly caused by long-term phlegm coagulation, which leads to unsmooth qi movement, qi and blood stagnation, intermingled phlegm and blood stasis, complicated disease conditions, and increasingly deficient and disordered qi and blood functions of viscera. Therefore, the traditional Chinese medicine strengthens the functions of tonifying qi, removing blood stasis and reducing phlegm in the treatment of pulmonary fibrosis, enables body fluid to be normally transported and metabolized by tonifying lung qi so as to block the generation of turbid phlegm, eliminates excessive pathogens by removing blood stasis and reducing phlegm, and achieves the effect of strengthening body resistance by pathogens.

Disclosure of Invention

Aiming at the defects of the prior art for treating pulmonary fibrosis, the invention aims to provide a traditional Chinese medicine composition for preventing and treating pulmonary fibrosis.

A traditional Chinese medicine composition for preventing and treating pulmonary fibrosis comprises the following traditional Chinese medicine components in parts by weight:

10-15 parts of veronica pubescens flower and 15-25 parts of wild buckwheat rhizome

8-12 parts of astilbe chinensis and 8-12 parts of snakegourd fruit.

Further, the composition comprises the following components in parts by weight:

further, the composition comprises the following components in parts by weight:

the Glycyrrhrizae radix is radix Glycyrrhizae Preparata.

An oral pharmaceutical preparation prepared from a traditional Chinese medicine composition for preventing and treating pulmonary fibrosis is one of oral liquid, granules, microcapsules, capsules, pills or tablets.

The invention also discloses a preparation method of the oral medicinal preparation of the traditional Chinese medicine composition, which comprises the following steps:

(1) Taking the raw medicinal materials according to the prescription amount, wherein the pubescent angelica is moistened thoroughly after impurity removal, cut into short sections and dried for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, astilbe chinensis, and Zingiberis rhizoma, moistening thoroughly, slicing into thick slices or slices, and drying; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with honey to yellow or deep yellow, and cooling;

(2) Decocting the above medicinal materials with 6-10 times of water for 2-3 times, mixing decoctions, filtering, and concentrating the filtrate to obtain extract with relative density of 1.20-1.35 (80 deg.C) at 50-60 deg.C;

(3) And (3) taking the extract obtained in the step (2), directly or after concentrating, adding corresponding pharmaceutically acceptable auxiliary materials, and preparing the oral medicinal preparation by a conventional process.

The traditional Chinese medicine composition provided by the invention is applied to preparation of medicines for preventing and treating pulmonary fibrosis.

The chuanchunhua in the prescription is a monarch drug and has the effects of clearing away heat and toxic materials, dispelling wind and relieving cough, eliminating phlegm and resolving masses and the like. The golden buckwheat rhizome is pungent and cool, the snakegourd fruit is sweet, cold and moist, the new women falls and is bitter and cool, the three medicines enter lung channels, and the three medicines play roles of clearing heat and resolving masses, eliminating phlegm and expelling pus, and activating blood and dissipating stasis together and are used as ministerial medicines. Astragalus root, radix astragali, radix Glycyrrhizae Preparata and Ginseng radix, together with radix Glycyrrhizae Preparata and Ginseng radix, invigorates the qi of spleen, lung and kidney to enrich the source of generation; the shizandra berry and the dried ginger are commonly used in compatibility of medicines in the book of Shang Han (golden Cabinet), one is scattered and the other is absorbed, so that the lung qi can be kept inside, cold evil can be emitted, and drinking evil can be warmed, and are used as adjuvant and guiding medicines together; gan Jiang is pungent and warm in property, stays in the stomach and can restrict the cold-bitter property of herbs to impair the stomach, so it is used as adjuvant drug. The whole formula combines cold and warm properties, and combines pathogen dissipation and root resistance strengthening, so that the formula is a good prescription for treating pulmonary fibrosis.

The traditional Chinese medicine composition is prepared into a traditional Chinese medicine extract by extracting and purifying the traditional Chinese medicine raw materials, and the traditional Chinese medicine extract is used as a raw material, added with acceptable auxiliary materials and prepared into various clinically applicable formulations according to the conventional technology of pharmaceutics. The preparation can be granule, oral liquid, capsule, tablet, pill, pellet, microcapsule, soft capsule, powder, mixture, syrup, etc.

The pharmaceutically acceptable excipients are common excipients or excipients well known in the art for preparing oral preparations, and include, but are not limited to, fillers or diluents, lubricants or glidants or anti-adherents, disintegrants, dispersants, flavoring agents, wetting agents or binders, and the like. Such fillers include, but are not limited to, lactose, sugar powder, saccharin, xylitol, mannitol, cyclodextrins, starch and derivatives thereof, cellulose and derivatives thereof, inorganic calcium salts, sorbitol, or glycine; the lubricant includes but is not limited to aerosil, magnesium stearate, talcum powder, aluminium hydroxide, boric acid, hydrogenated vegetable oil, polyethylene glycol; disintegrants include, but are not limited to, starch and its derivatives, polyvinylpyrrolidone or microcrystalline cellulose; such binders include, but are not limited to, syrup, acacia, gelatin, sorbitol, tragacanth, cellulose and its derivatives, gelatin slurry, syrup, starch slurry, polyvinylpyrrolidone; the flavoring agents include but are not limited to steviosin, aspartame, and the like; such wetting agents include, but are not limited to, sodium lauryl sulfate, water, alcohols, and the like.

The traditional Chinese medicine composition disclosed by the invention is applied to preparation of a medicine for preventing and treating pulmonary fibrosis. The composition has the effects of clearing away heat and toxic materials, reducing phlegm, tonifying qi, activating blood circulation and resolving masses, and has a remarkable clinical curative effect.

Detailed Description

In order to verify the curative effect of the traditional Chinese medicine composition, the inventor carries out a great deal of pharmacodynamic and clinical experimental research, and it should be noted that the medicine selected by the pharmacodynamic experiment of the medicine is the medicine obtained by the representative formula and the preparation method thereof, and the experiments and results related to the medicines obtained by other formulas and the preparation method thereof are not exhaustive because of space limitations.

At present, the pathogenesis of pulmonary fibrosis is not completely elucidated, but the pathogenesis has a common rule, including inflammation of alveoli, pulmonary interstitium, small pulmonary blood vessels and the like, although the degree is not the same, pulmonary fibrosis is gradually formed in the development process aiming at inflammatory injury and repair. Certain inflammatory changes predominate in pulmonary fibrosis, and if the etiology can be removed early or effectively treated, the pathology will have the opportunity to reverse; if the inflammatory phase is not effectively treated so that inflammation persists, it leads to structural destruction of lung tissue and proliferation of fibrous tissue, eventually leading to irreversible pulmonary fibrosis. Research finds that the cytokines and the cytokine network play an important role in causing the occurrence and the development of the pulmonary fibrosis. Including TGF-beta 1, TNF-alpha, etc., secreted by injured alveolar epithelial cells, are involved in the injury and subsequent repair of lung tissue.

A variety of cells in the lung are capable of secreting TGF-beta 1, including alveolar macrophages, endothelial cells, epithelial cells, fibroblasts, and the like, and alveolar macrophages are probably the primary cells secreting TGF-beta 1. TGF-beta 1 has chemotactic effect on alveolar macrophages, neutrophils, fibroplast and the like, and can promote the expression of platelet-derived growth factor (PDGF), TNF-alpha, interleukin-1 (1L-1) and the like, wherein the PDGF is related cytokines for promoting pulmonary fibrosis, the PDGF can promote the proliferation and the fibroplasia of lung fibroplast, and IL-1 is a potential mitogen of fibroplast.

TNF-alpha is a small molecule protein, mainly secreted by macrophages and monocytes, and when lung tissue is fibrotic, not only activated monocytes and macrophages are released, but also cells of alveolar epithelium are expressed. It has wide biological activity, and has functions of participating in inflammatory reaction and immune response, etc. and has cytotoxic, cytolytic and proliferation inhibiting effects on tumor cell, and also has effect on the growth and differentiation of various normal cells. In the test, TGF-beta 1 and TNF-alpha are used as indexes to investigate the influence of the composition on the expression levels of the two in the lung tissues of the bleomycin rat.

Experimental example 1 Experimental study on Effect of TGF-beta 1 and TNF-alpha on pulmonary fibrosis rat pulmonary tissues

1.1 test animals and materials

Clean grade healthy male Wistar rats, 96, weighing 200 ± 20g, were provided by lumnan pharmaceutical group, ltd, animal license number SYXK (lu) 20180008. The test was started after 1 week of acclimatizing feeding under conventional conditions in an environment of 20 + -2 deg.C at room temperature.

Bleomycin hydrochloride for injection, produced by Nippon chemical Co., ltd.; chloral hydrate, produced by Sanyi pharmaceutical Co., ltd; prednisone acetate tablet 5mg, produced by Rongsheng pharmaceutical Co., ltd; TGF-beta 1 immunohistochemical kit, TNF-alpha immunohistochemical kit, TGF-beta 1 primary antibody, TNF-alpha primary antibody and the like, produced by Wuhan Dr's bioengineering Co., ltd.

1.2 animal modeling and grouping

Rats are randomly divided into 8 groups, each group comprises 12 rats, namely a normal group, a model group, a positive control group, a composition control group and a vernal flower group. Except for the normal group, rats in other groups are subjected to the method of intratracheal instillation of bleomycin to establish a rat pulmonary fibrosis model.

After the rats are anesthetized by a method of injecting 10% chloral hydrate (2 ml/kg) into the abdominal cavity, the rat plates fix four limbs, the head is lifted by 45 degrees and fixed, the throat parts of the rats are irradiated by a light source, the tongue is pulled at the left side, foreign bodies in the oral cavity are cleaned, and the larynx and the glottis are fully exposed. A No. 16 indwelling needle hose is held by the right hand (the needle head is cut off and is cut short to be initially wedge-shaped), about 0.2ml of normal saline is injected into the hose and inserted into an trachea, the bubble in the hose moves up and down, the correct insertion of the trachea is proved to observe the respiratory activity of a rat, a clean hose is used for instilling a bleomycin solution (1.5 ml/kg) into the trachea of the rat at the moment of air suction of the rat, the hose is taken out after the bleomycin solution is successfully instilled, the rat is vertically rotated left and right, and the drugs are enabled to be uniformly distributed in lung tissues so as to copy a pulmonary fibrosis model of the rat. The rats in the normal group were instilled with the same volume of physiological saline in the same manner.

Compared with the normal rats, the rats after molding have the symptoms of weight loss, reduced food intake, depilation, reduced activity, dyspnea and the like, which indicates the success of molding.

1.3 methods of testing and administration

Except the normal group and the model group, the other groups are administered by intragastric administration from the day of the model building, each group is continuously administered until the test specimen is obtained, and the administration volume of each group of rats is 20 ml/(kg. D). The normal group and the model group were administered with an equal volume of physiological saline, and the gavage was performed once a day until the end of the test.

Positive control group: prednisone acetate 6 mg/(kg. D);

control group: 3.96g crude drug/(kg. D) of the control composition;

and (3) a Xiaochunhua group: 4.50g of the composition of the pubescent angelica, the wild buckwheat rhizome, the astilbe chinensis and the snakegourd fruit/(kg. D);

the low dose group was tested: 3.825g of crude drug/(kg. D) of the composition of the invention;

dose groups in the experiment: the composition of the invention is 7.65g of crude drugs/(kg. D);

trial high dose group: the composition of the invention is 15.30g of crude drugs/(kg. D);

the preparation method of the control group comprises the following steps:

375g of astragalus root, 150g of schisandra fruit, 225g of trichosanthes fruit

Ginseng 150g dried ginger 75g licorice 125g

1) Taking the raw material medicines according to the prescription amount, wherein the astragalus, the ginseng and the dried ginger are thoroughly moistened after impurity removal, and are cut into thick slices or thin slices and dried for later use; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with honey to yellow or deep yellow, and cooling;

2) Decocting the 6 medicinal materials with 6-10 times of water for 2-3 times, mixing decoctions, filtering, and concentrating the filtrate to appropriate amount for use.

The preparation method of the veronicastrum pubescens composition comprises the following steps:

300g of spring flower, astilbe chinensis, 225g of wild buckwheat rhizome, 500g of snakegourd fruit, 225g

1) Taking the raw medicinal materials according to the prescription amount, wherein the pubescent angelica is moistened after impurity removal, cut into short segments and dried for later use; removing impurities from rhizoma Fagopyri Dibotryis and astilbe chinensis, moistening thoroughly, cutting into thick slices or thin slices, and drying; flattening fructus Trichosanthis, and shredding or blocking;

2) Decocting the 4 medicinal materials with 6-10 times of water for 2-3 times, mixing decoctions, filtering, and concentrating the filtrate to appropriate amount for use.

The preparation method of the composition comprises the following steps:

1) Taking the raw medicinal materials according to the prescription amount, wherein the pubescent angelica is moistened after impurity removal, cut into short segments and dried for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, astilbe chinensis, and Zingiberis rhizoma, moistening thoroughly, cutting into thick slices or thin slices, and drying; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with honey to yellow or deep yellow, and cooling;

2) Decocting the above 9 medicinal materials with 6-10 times of water for 2-3 times, mixing decoctions, filtering, and concentrating the filtrate to obtain extract with relative density of 1.20-1.35 (80 deg.C) at 50-60 deg.C;

3) Adding a proper amount of sucrose powder and dextrin into the extract obtained in the step (2), preparing 1000g, and drying to obtain the granules.

2. Test procedure

2.1 general case observations

The color change of the skin and hair, the skin change of the abdominal injection part and the excrement condition of the rat are observed.

2.2 Observation of Pathology in groups of rats under light microscope

Animals were sacrificed 1 each day 14 and 28, respectively. Pentobarbital sodium intraperitoneal injection, anesthesia and abdominal exsanguination are carried out to kill rats, the thoracic cavity is opened to strip the lung, bronchoalveolar lavage fluid is collected from the left lung lobe through a bronchus, the collected bronchoalveolar lavage fluid is centrifuged by a centrifuge at 3000r/min for 10min, and then supernatant is taken and placed in a refrigerator at the temperature of 20 ℃ below zero for storage and examination. The right lung lobes are perfused with 10% formalin solution for ligation, and soaked in 10% formalin solution for fixation and preservation to prepare pathological specimens. And (5) carrying out HE staining and immunohistochemical staining on the pathological section, and observing under a microscope.

HE dyeing step:

(1) placing the slices in an oven at 70 deg.C, baking, and dissolving wax for 30min;

(2) taking out the hot product and putting the product in xylene for dewaxing for 2 multiplied by 10min;

(3) washing xylene with anhydrous ethanol for 2 × 1min;

(4) 95%,80%,70% alcohol for 1min respectively, washing with tap water for 1min;

(5) staining with hematoxylin for 5min, washing with tap water for 1min;

(6) differentiating with 1% hydrochloric acid alcohol for 20s, washing with tap water for 1min;

(7) returning blue to 1% diluted ammonia water for 30s, washing with tap water for 1min;

(8) staining with eosin for 1min, washing with tap water for 30s;

(9) dehydrating with 70% alcohol for 20s, dehydrating with 80% alcohol for 30s, and dehydrating with 95% alcohol for 2 × 1min;

transparent in xylene for 3X 2min, air drying, and sealing with neutral gum. Each histopathological morphological change was observed under a light microscope.

Immunohistochemistry step:

(1) after lung tissues are fixed by paraformaldehyde, dehydrating by conventional gradient alcohol, dipping in wax, embedding, and slicing by conventional paraffin;

(2) slicing 4 μm thick paraffin into xylene solution for 5min × 3 times, sequentially deparaffinizing with gradient alcohol, hydrating, and washing with PBS (pH7.2-7.6) for 5min × 3 times;

(3) immersing in freshly prepared 3% hydrogen peroxide deionized water, incubating at room temperature for 10min to inactivate endogenous peroxidase, and washing with distilled water for 2min × 3 times;

(4) microwave antigen retrieval: placing the slices in a container containing 0.01M citrate buffer solution, heating in a microwave oven to maintain the temperature of the liquid in the container at 100 deg.C for 15min, naturally cooling, cooling with thick PBS (pH7.2-7.6), and washing for 1-2 times;

(5) adding 5% BSA blocking solution dropwise, cooling at room temperature for 20min, and discarding the excess solution;

(6) adding rabbit anti-mouse antibody dropwise, wherein the dilution of TGF-beta 1 antibody is 1:200,TNF-. Alpha.antibody dilution 1:200 2h at 20 ℃, and washing with PBS (pH7.2-7.6) for 2min × 3 times;

(7) adding biotinylated goat anti-mouse IgG dropwise, washing for 2min and 3 times, wherein the washing time is 2min and 3 times, and the washing time is 2min and 7.6 times;

(8) dropping reagent SABC,20min, washing with PBS (pH7.2-7.6) for 5min × 4 times;

(9) DAB color development: using DAB color reagent box, 1ml distilled water is added into 1 drop of A, B, C reagent in the reagent box, and the mixture is added into the slice after mixing evenly. Developing at room temperature, and controlling reaction time under a mirror, wherein the reaction time is generally 5-30min;

performing mild counterstaining on the red skin, taking out 2 times with 95% ethanol for 1min, dehydrating with 100% ethanol for 1min × 2 times, clearing with xylene for 5min × 3 times, sealing, and observing under microscope.

2.3 TGF-beta 1 and TNF-alpha scoring method

Observing under a light microscope, taking the positive result that the TGF-beta 1 takes the positive result that dark yellow particles appear in cytoplasm of alveolar epithelial cells, bronchial mucosa epithelial cells, fibroblasts, vascular endothelial cells, bronchioles walls and vascular wall smooth muscle cells, and the positive reaction is that the cytoplasm is colored dark brown; TNF-alpha is positive to the presence of tan particles in the cytoplasm of alveolar macrophages, lymphocytes, neutrophils, capillary endothelial cells, alveolar epithelial cells, bronchiolar subepithelial tissues, lung interstitium and vascular smooth muscle cells, and positive to the presence of tan staining of the cytoplasm. Negative controls are partial sections with PBS replacing the primary antibody.

The immunohistochemical staining was judged using a brescalier semi-quantitative scoring system: randomly selecting 5 visual fields from each section under the visual field of 400 times, scoring the staining intensity according to colorless (0), faint yellow (1), brown (2) and brown (3), obtaining the staining breadth according to the percentage of the number of positive cells to the total cells, multiplying the staining intensity by the staining breadth, and taking the average value of the 5 visual fields as the quantitative result of the immunohistochemical staining of the whole section. The formula is as follows: is = [ (0 × F0) + (1 × F1) + (2 × F2) + (3 × F3) ].

2.4 statistical methods

The result is analyzed by SPSS22.0 statistical software in mean + -standard deviation

And (4) showing. And (3) performing normality test and variance analysis on each group of data, and if the data accord with normal distribution and homogeneity of variance, adopting One-Way analysis of variance (One-Way ANOVA) and taking P less than 0.05 as a significance difference level.

3 results of the experiment

3.1 general conditions in groups of rats

The rats in the normal group have good mental status, bright fur, sensitive response, difficult capture and normal food and water intake. Weight gain, breathing as usual. The rats in the model group are listened, have less activity, have slow reaction, have less eating and drinking water than the rats in the normal group, have unobvious weight increase, have different respiratory acceleration degrees, have cyanotic lips, and have progressive worsening of symptoms and partial depilation with increasing days. The condition of rats in each treatment group is obviously better than that of the model group, and the middle and high dose groups and the positive control group of the composition are closer to the normal group.

3.2 Observation of groups of rats under light microscope

Under the microscope, the normal group of rats can see clear and complete lung tissues and alveolar structures, normal alveolar walls and alveolar septal forms, normal alveolar form volumes, no congestion, inflammation, exudation and other manifestations. A large amount of inflammatory cells are exuded in the alveolar cavities of the rats of the model group at day 14, fibroblasts are proliferated, alveolar spaces are thickened to some extent, most of alveolar structures are damaged, and the alveolar cavities are reduced; on day 28, the alveolar spaces thickened, fibroblasts increased, alveolar spaces were significantly reduced, and collagen fibers were formed. Compared with the rats in the model group, the rats in each treatment group have the same rule, but the pulmonary alveolitis and the pulmonary fibrosis are lower than those in the model group, and the pathological changes of the medium-high dose group and the positive control group of the composition are closer to those of the normal group.

3.3 expression of TGF-. Beta.1 and TNF-. Alpha.in groups of rat Lung tissues on day 14

The expression of TGF-beta 1 and TNF-alpha in the lung tissue of rats in the model group and each treatment group is obviously higher than that of a normal control group at the 14 th day, and the significant difference is realized (P is less than 0.05); the expression of TGF-beta 1 and TNF-alpha in the lung tissue of rats in each treatment group at 14 days is obviously lower than that of a model group, and the significant difference is realized (p is less than 0.05); the positive control group and the composition of the invention, the high dose group rat lung tissue expression level of TGF-beta 1 and TNF-alpha is obviously lower than that of the composition control group, and has significant difference (P < 0.05). Compared with a positive control group, the high-dose group of the composition has no obvious difference. The results are shown in Table 1.

TABLE 1 expression of TGF-. Beta.1 and TNF-. Alpha.in groups of rat lung tissue on day 14

Note: "+" indicates p <0.05 compared to normal group; ". Indicates p <0.05 compared to the model group;

"#" indicates p <0.05 compared to the composition control group; ". Indicates p <0.05 compared with the group of Jatropha curcas.

3.3 expression of TGF-. Beta.1 and TNF-. Alpha.in groups of rat Lung tissues on day 28

The expression of TGF-beta 1 and TNF-alpha in the lung tissue of rats in the model group and each treatment group is obviously higher than that of a normal control group at the 28 th day, and the significant difference is realized (P is less than 0.05); the positive control group and the composition of the invention are low, medium and high dose groups, the expression of TGF-beta 1 and TNF-alpha in the lung tissue of the rat is obviously lower than that of the model group at the 28 th day, and the significant difference is realized (p is less than 0.05); the expression level of TGF-beta 1 of lung tissues of rats in a positive control group and a high-dose group in the composition is obviously lower than that of the composition control group, and the difference is significant (P < 0.05). Compared with a positive control group, the middle and high dose groups of the composition have no significant difference. The results are shown in Table 2.

TABLE 2 expression of TGF-. Beta.1 and TNF-. Alpha.in groups of rat Lung tissues on day 28

/>

Note: "+" indicates p <0.05 compared to normal group; ". Indicates p <0.05 compared to the model group;

"#" indicates p <0.05 compared to the composition control group; ". Indicates p <0.05 compared with the group of Jatropha curcas.

The results show that the composition can inhibit the expression of TGF-beta 1 and TNF-alpha in pulmonary tissues of rats with pulmonary fibrosis, and achieves the effect of preventing pulmonary fibrosis.

Experimental example 2 clinical observations of the composition of the invention on patients with pulmonary fibrosis

2.1 general data

58 patients with pulmonary fibrosis who have a diagnosis in respiratory department in hospital of people in Zhejiang province were randomly selected as study subjects, and the lung-blocking syndrome due to qi deficiency and phlegm stasis was identified by the traditional Chinese medical clinician, and the main symptoms were: shortness of breath, dyspnea, cough with weakness, especially with movement, or clear and thin expectoration, bloody sputum, blood-stained blood, dark red or stabbing pain in chest, cyanosis of lips and nails, pale and dark tongue with ecchymosis, and thready and weak or unsmooth pulse. Dividing patients into a control group and an observation group, wherein 29 cases respectively comprise 18 cases of men and 11 cases of women in the control group, and the average age is 66.13 +/-5.99 years; the groups were observed to be 17 men and 12 women, with a mean age of 65.45 ± 6.97 years. Before treatment, gender, age and course of disease of the two groups are statistically treated, and the two groups have no significant difference. The control group and the observation group exclude pulmonary primary diseases such as tuberculosis, fungi, tumors and the like.

2.2 test methods

The control group was orally administered with N-acetylcysteine capsule (manufactured by Guangdong people Kangyao Co., ltd., approval No.: national Standard H20000519, standard: 0.2 g/capsule) 3 times a day, 600mg each time.

The observation group adopts the composition of the invention to be combined with the N-acetylcysteine capsule for oral treatment, and the oral administration method and the dosage of the N-acetamide cysteine capsule are the same as those of the control group.

2.3 Observation index

2.3.1 patient chief symptoms score comparison: scoring the symptoms of dyspnea, shortness of breath, cough, chest pain, etc. before and after treatment of two groups of patients according to 0 point, 2 points, 4 points and 6 points of non-, mild-, moderate-and severe-degree, respectively, and calculating total score;

2.3.2 pulmonary function index: adopt the pulmonary function appearance to detect lung and ventilate and close and disperse the function, include: forced expiratory volume (FEV 1), forced Vital Capacity (FVC) and carbon monoxide Dispersion (DLCO) at 1 second.

2.4 results

2.4.1 after treatment the score for the chief complaints was significantly reduced in both groups compared to that before treatment (P < 0.05), and the reduction was more significant in the observed group compared to the thick-treated control group (P < 0.05).

Note: Δ P <0.05 compared to pre-treatment; it is <0.05 compared to the control group.

2.4.2: compared with the lung function indexes of two groups of patients, the levels of the lung function indexes such as FVC, FEV1, DLCO and the like of the two groups of patients before treatment have no statistical significance (P > 0.05), the lung function indexes of FVC, FEV1 and DLCO of the two groups of patients after treatment are all improved compared with the levels before treatment, the difference has statistical significance (P < 0.05), and the observation groups are compared with the control group of patients, and the difference has statistical significance (P < 0.05).

In conclusion, the composition has good treatment effect on the main symptoms and the improvement of the lung function caused by the pulmonary fibrosis.

Claims (6)

1. A traditional Chinese medicine composition for preventing and treating pulmonary fibrosis is characterized by comprising the following traditional Chinese medicine components in parts by weight:

10-15 parts of veronica pubescens flower and 15-25 parts of wild buckwheat rhizome

8-12 parts of astilbe chinensis and 8-12 parts of snakegourd fruit.

2. The traditional Chinese medicine composition according to claim 1, wherein the composition comprises the following components in parts by weight:

10-15 parts of veronicastrum pubescens flower, 10-20 parts of astragalus membranaceus, 15-25 parts of wild buckwheat rhizome

5-8 parts of ginseng, 8-12 parts of astilbe chinensis and 8-12 parts of trichosanthes kirilowii maxim

5-8 parts of schisandra chinensis, 2-4 parts of dried ginger and 3-8 parts of liquorice.

3. The traditional Chinese medicine composition according to claim 2, wherein the composition comprises the following components in parts by weight:

12 parts of veronicastrum pubescens, 15 parts of astragalus mongholicus and 20 parts of wild buckwheat rhizome

6 parts by weight of ginseng, 9 parts by weight of astilbe chinensis and 9 parts by weight of snakegourd fruit

6 parts of schisandra chinensis, 3 parts of dried ginger and 5 parts of liquorice.

4. An oral pharmaceutical preparation prepared from the traditional Chinese medicine composition of any one of claims 1 to 3, which is one of oral liquid, granules, microcapsules, capsules, pills or tablets.

5. The method for preparing an oral pharmaceutical preparation of a Chinese medicinal composition according to claim 4, comprising the steps of:

(1) Taking the raw medicinal materials according to the prescription amount, wherein the pubescent angelica is moistened thoroughly after impurity removal, cut into short sections and dried for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, astilbe chinensis, and Zingiberis rhizoma, moistening thoroughly, slicing into thick slices or slices, and drying; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with honey to yellow or deep yellow, and cooling;

(2) Decocting the above materials with 6-10 times of water for 2-3 times, mixing decoctions, filtering, and concentrating the filtrate to obtain extract with relative density of 1.20-1.35 (80 deg.C) at 50-60 deg.C;

(3) And (3) taking the extract obtained in the step (2), directly or after concentrating, adding corresponding pharmaceutically acceptable auxiliary materials, and preparing the oral medicinal preparation by a conventional process.

6. The use of the Chinese medicinal composition of claim 1 in the preparation of a medicament for the prevention and treatment of pulmonary fibrosis.