CN115845021B - A Chinese medicinal composition for preventing and treating pulmonary fibrosis, and its preparation method - 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 raw medicinal materials such as small spring flowers, astragalus mongholicus, wild buckwheat rhizome, ginseng, astilbe chinensis, snakegourd peel, schisandra chinensis, dried ginger, liquorice and the like, has the effects of clearing heat, detoxicating, resolving phlegm, tonifying qi, activating blood and resolving masses, is clinically used for treating pulmonary fibrosis, has remarkable curative effect, and provides a new choice for clinically improving or treating the pulmonary fibrosis.

Description

A Chinese medicinal composition for preventing and treating pulmonary fibrosis, and its preparation method

Technical Field

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

Background

Pulmonary fibrosis (pulmonary fibrosis, PF) is a chronic inflammatory interstitial lung disease of unknown cause characterized by diffuse alveolitis, alveolar structural disturbances and ultimately pulmonary fibrosis, and lung function tests often manifest as restricted ventilation dysfunction and diffuse dysfunction. Of diffuse interstitial lung diseases, idiopathic pulmonary interstitial fibrosis (idiopathic pulmonary fibrosis, IPF) is the highest in incidence and has very poor prognosis. Clinically, patients with pulmonary fibrosis have nonspecific symptoms such as cough and dyspnea, gradually worsen, and progress to the final stage and combine to have respiratory failure, and generally die about 3-8 years after symptoms. Respiratory failure or death from the onset of symptoms to the end stage of pulmonary fibrosis, progressive deterioration of the course of disease, an average survival time of 2-4 years after diagnosis of IPF, and five-year survival rate of 30% -50%, have been considered common and refractory diseases of respiratory diseases.

In recent years, with intensive research into the underlying theory of pulmonary fibrosis, pathogenesis, and clinical treatments, it was recognized that cytokines play an important role in the development of their development, they constitute a complex network system of extracellular signaling molecules and chain reaction systems, leading to immune-mediated chronic inflammation characterized by inflammatory cell infiltration, fibroblast proliferation, and deposition of interstitial connective tissue. Early lung injury is manifested by alveolitis, a change in which is most probably due to the release of a large amount of inflammatory mediators by cytokines, resulting in injury to the capillary endothelium of the alveolar wall and an increase in permeability. The alveolar inflammatory exudates have various cell growth factors, the action concentration, the type of cytokine expression, the time difference of high expression and the activation degree of corresponding receptors, and have important roles in the development of alveolar epithelial repair or pulmonary fibrosis, so that the cytokines play an important role in the development of PF, and the cytokine mediators can influence the activation, proliferation and collagen deposition of fibroblasts in the disease process. Of these, TNF- α, TGF- β are most important in the development and progression of pulmonary fibrosis.

In recent years, various traditional Chinese medicine compounds are increasingly applied to the intervention and treatment of pulmonary fibrosis by researchers, and part of research results have played an important guiding role in the clinical treatment of the fibrosis. The lung fibrosis is called as "lung arthralgia" or "consumptive lung" in the traditional Chinese medicine, the lung is the highest in all viscera, the traditional Chinese medicine is called as "lung is the waffle", and the lung is the only organ communicated with the outside in the five viscera, so that the lung is most susceptible to pathogenic qi of the outside to cause diseases, and the functions of dispersing, descending, regulating respiration and dredging and regulating water passages are affected. Its main pathogenic factors are qi stagnation, phlegm coagulation and blood stasis, which can interact to cause diseases together. The first main pathogenesis is that the qi is deficient, and the qi and blood deficiency of the lung, spleen and kidney mainly causes the obstruction of the collaterals of the lung, and the pulmonary fibrosis caused by the pathogenesis is called as 'pulmonary arthralgia', and is mainly caused by pathogenic excess, wherein the qi and blood are not regulated, and the obstruction of collaterals and blood stasis is most common; the other is due to qi and blood deficiency and deficiency of collaterals, which is called "consumptive lung disease", mainly indicated for deficiency of this nature. The lung obstruction is usually caused by exogenous pathogenic factors, internal injury and eating disorder in the acute stage of the disease, and the excessive body fluid is not transformed and accumulated to be phlegm; the 'consumptive lung disease' is mainly caused by chronic migration and delay of diseases, and mainly caused by long-term phlegm coagulation, the qi movement is unsmooth, qi and blood are blocked, phlegm and blood stasis are combined, the disease condition is complicated, and the qi and blood functions of viscera are increasingly damaged and disregulated. Therefore, in the treatment of pulmonary fibrosis, the traditional Chinese medicine emphasizes the effects of invigorating qi, removing blood stasis and resolving phlegm, and by invigorating lung qi, body fluid is normally transported, transformed and metabolized, so that the generation of turbid phlegm is blocked, and by removing blood stasis and resolving phlegm, the effect of eliminating excessive evil is achieved, and the effect of strengthening body resistance by evil is achieved.

Disclosure of Invention

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

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

10-15 parts of small spring 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 radix Glycyrrhizae 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 pharmaceutical preparation of the traditional Chinese medicine composition, which comprises the following steps:

(1) Taking the raw medicinal materials with the prescription amount, thoroughly moistening the small spring flowers after removing impurities, cutting into short sections, and drying for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, herba astilbe chinensis and Zingiberis rhizoma, moistening thoroughly, cutting into thick slices or slices, and drying for use; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with Mel to yellow or deep yellow, and cooling;

(2) Decocting the above materials in 6-10 times of water for 2-3 times, mixing decoctions, filtering, concentrating the filtrate to obtain extract with relative density of 1.20-1.35 (80deg.C) at 50-60deg.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 pharmaceutical preparation by using a conventional process.

The invention provides an application of a traditional Chinese medicine composition in preparing medicines for preventing and treating pulmonary fibrosis.

The Chinese spring flower in the formula is taken as a monarch drug and has the effects of clearing heat and detoxicating, dispelling wind and relieving cough, eliminating phlegm and resolving masses and the like. The wild buckwheat rhizome is pungent and cool, the snakegourd fruit is sweet and cold in nature and moist, the astilbe chinensis is bitter and cool, all three herbs enter lung meridian and play roles of clearing heat and resolving masses, eliminating phlegm and expelling pus, and activating blood and removing stasis together, and are ministerial drugs. Astragalus root, radix astragali has the effects of invigorating qi, consolidating superficial resistance, expelling toxin, expelling pus, preventing patients from feeling the exogenous evils again, and is cooperated with radix Glycyrrhizae Preparata and Ginseng radix to invigorate qi of spleen, lung and kidney to promote the generation of qi; the shizandra berry and the dried ginger are commonly used in the aspects of typhoid fever and golden-kui, and have the functions of dispersing and collecting, dispersing and taking, so that lung qi is kept internally, cold evil is dispersed, and pathogenic drink is warmed, and the shizandra berry and the dried ginger are used as adjuvant and guiding drugs; dry Jiang Xinwen, which can restrict the disadvantage of stomach hurt due to bitter and cold, is an adjuvant drug. All Fang Hanwen is combined with the combination of eliminating pathogenic factors and consolidating constitution, and 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 material, and various clinically applicable formulations are prepared by adding acceptable auxiliary materials into the traditional Chinese medicine extract serving as a raw material according to the conventional technology of pharmaceutics. The dosage forms can be granule, oral liquid, capsule, tablet, pill, micropill, microcapsule, soft capsule, powder, mixture, syrup, etc.

The pharmaceutically acceptable excipients are commonly used excipients or auxiliaries well known in the art for preparing oral formulations, including but 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, powdered sugar, saccharine, xylitol, mannitol, cyclodextrin, starches and derivatives thereof, cellulose and derivatives thereof, inorganic calcium salts, sorbitol, or glycine; the lubricant comprises, but is not limited to, aerosil, magnesium stearate, talcum powder, aluminum hydroxide, boric acid, hydrogenated vegetable oil and polyethylene glycol; disintegrants include, but are not limited to, starch and its derivatives, polyvinylpyrrolidone or microcrystalline cellulose; the binder includes, but is not limited to, syrup, acacia, gelatin, sorbitol, tragacanth, cellulose and derivatives thereof, gelatin syrup, starch slurry, polyvinylpyrrolidone; the flavoring agents include, but are not limited to, steviosin, proteoglycan, aspartame; such wetting agents include, but are not limited to, sodium lauryl sulfate, water, alcohols, and the like.

The invention relates to application of a traditional Chinese medicine composition in preparing medicines for preventing and treating pulmonary fibrosis. The composition has the effects of clearing heat, detoxicating, resolving phlegm, tonifying qi, activating blood and resolving masses, and has obvious clinical curative effect.

Detailed Description

In order to verify the curative effect of the traditional Chinese medicine composition, the inventor develops a great deal of pharmacodynamics and clinical experiment research, and needs to say that medicines selected in the pharmacodynamics experiment of the medicine are representative formulas and medicines obtained by the preparation method of the medicine, and experiments and results related to other formulas and medicines obtained by the preparation method of the medicine are not exhaustive because of space limitation.

At present, the pathogenesis of pulmonary fibrosis is not completely elucidated, but has common rules, including the occurrence of inflammation of alveoli, pulmonary interstitium, pulmonary small blood vessels and the like, and the pulmonary fibrosis is gradually formed in the development process of injury and repair against inflammation although the degree is not the same. Certain pulmonary fibrosis, which is predominantly inflammatory, has the opportunity to reverse if the etiology is removed early or effective treatment is obtained; if the inflammatory phase is not effectively treated so that inflammation continues, it may lead to destruction of the lung tissue structure and proliferation of fibrous tissue, eventually leading to irreversible lung fibrosis. It has been found that cytokines and cytokine networks play an important role in causing the development and progression of pulmonary fibrosis. TGF-beta 1, TNF-alpha, etc., secreted by damaged alveolar epithelial cells, among others, are involved in the damage of lung tissue and subsequent repair processes.

Various cells within the lung are capable of secreting TGF- β1, including alveolar macrophages, endothelial cells, epithelial cells, fibroblasts, etc., which may be the primary cells secreting TGF- β1. TGF-beta 1 has chemotactic effects on alveolar macrophages, neutrophils, fibroblastist and the like, and can promote the expression of Platelet Derived Growth Factors (PDGF), TNF-alpha, interleukin-1 (1L-1) and the like, which are relevant cytokines for promoting pulmonary fibrosis, PDGF can promote pulmonary fibroblastist proliferation and fibroplasia, and IL-1 is a potential mitogen of fibroblastist.

TNF-alpha is a small molecule protein secreted mainly by macrophages and monocytes, and when fibrosis occurs in lung tissue, not only are mononuclear-macrophages and neutrophils released by activation, but also alveolar epithelial cells are expressed. It has wide biological activity, and has the functions of cytotoxicity, cytolysis, inhibiting proliferation, etc. of tumor cell, and may have also influence on the growth and differentiation of various normal cells. The test uses TGF-beta 1 and TNF-alpha as indexes to examine the influence of the composition on the expression level of the composition in the lung tissue of the bleomycin rat.

Experimental example 1 Experimental study of the effects of TGF-beta 1 and TNF-alpha on pulmonary fibrosis rat pulmonary tissue

1.1 test animals and materials

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

Bleomycin hydrochloride for injection, manufactured by japan chemical pharmaceutical co; chloral hydrate, produced by the third beneficial pharmaceutical company of the national pharmaceutical group; prednisone acetate 5mg, produced by Guogong pharmaceutical Co., ltd; TGF-beta 1 immunohistochemical kit, TNF-alpha immunohistochemical kit, TGF-beta 1 primary antibody, TNF-alpha primary antibody and the like, manufactured by the biological engineering Co., ltd.

1.2 animal modeling and grouping

Rats were randomly divided into 8 groups of 12 animals each, which were normal, model, positive control, composition control, and spring of small day, respectively, with low, medium, and high doses of the composition of the present invention. Except for the normal group, rats in each group were subjected to a pulmonary fibrosis model by intratracheal instillation of bleomycin.

After the rats are anesthetized by the method of injecting 10% chloral hydrate (2 ml/kg) into the abdominal cavity, the limbs are fixed by the rat plates, the heads are lifted by 45 degrees to be fixed, the throat of the rats are irradiated by a light source, the tongue is pulled at the left side, and foreign matters in the oral cavity are cleaned, so that the throat and glottis are fully exposed. The right hand holds a 16-gauge indwelling needle hose (the needle is cut off, the cutting is in a wedge shape), about 0.2ml of physiological saline is injected into the hose, the hose is inserted into the trachea, and when bubbles in the hose move up and down, the correct insertion into the trachea is proved to observe the respiratory activity of a rat, a clean hose is used for instilling bleomycin solution (1.5 ml/kg) into the trachea of the rat at the moment of inspiration of the rat, after successful instillation, the hose is taken out, and the rat plate is vertically rotated left and right, so that the medicine is uniformly distributed in lung tissues to replicate a rat lung fibrosis model. Normal rats were instilled with the same volume of physiological saline by the same method.

Compared with normal rats, the rats after molding have the symptoms of weight reduction, eating reduction, unhairing, activity reduction, dyspnea and the like, which indicates that the molding is successful.

1.3 assays and methods of administration

The other groups except the normal group and the model group were subjected to gastric lavage from the next day of molding, and each group was continuously subjected to gastric lavage until the test specimens were obtained, and the administration volume of each group of rats was 20 ml/(kg.d). The normal and model groups were dosed with equal volumes of physiological saline, and the stomach was irrigated once a day to the end of the trial.

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

control group: control composition 3.96g crude drug/(kg.d);

group of flowers: spring, wild buckwheat rhizome, astilbe and snakegourd fruit composition 4.50g crude drug/(kg.d);

test low dose group: 3.825g of the composition of the invention is crude drug/(kg.d);

dose group in trial: 7.65g of the composition of the invention is crude drug/(kg.d);

test high dose group: 15.30g of the composition of the invention is crude drug/(kg.d);

control group preparation method:

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

Ginseng 150g dried ginger 75g licorice 125g

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

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

The preparation method of the small spring flower composition comprises the following steps:

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

1) Taking the raw medicinal materials with the prescription amount, thoroughly moistening the small spring flowers after removing impurities, cutting into short sections, and drying for later use; removing impurities from rhizoma Fagopyri Dibotryis and astilbe chinensis, moistening thoroughly, cutting into thick slices or thin slices, and drying for use; flattening fructus Trichosanthis, and shredding or blocking;

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

The preparation method of the composition comprises the following steps:

1) Taking the raw medicinal materials with the prescription amount, thoroughly moistening the small spring flowers after removing impurities, cutting into short sections, and drying for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, herba astilbe chinensis and Zingiberis rhizoma, moistening thoroughly, cutting into thick slices or slices, and drying for use; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with Mel to yellow or deep yellow, and cooling;

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

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

2. Test procedure

2.1 general Condition observations

The change in the color of the rat coat, the change in the skin at the injection site of the abdomen and the condition of the stool were observed.

2.2 pathological observation under the Lung tissue of rats of each group

Animals were sacrificed on day 14 and day 28, respectively. After the rats are killed by intraperitoneal injection of sodium pentobarbital and anesthesia, the thoracic cavity is opened to strip the lung, the left lung lobe is used for collecting bronchoalveolar lavage fluid through bronchus, the obtained bronchoalveolar lavage fluid is centrifuged for 10min by a centrifuge at 3000r/min, and the supernatant is taken and stored in a refrigerator at-20 ℃ for standby detection. The right lung lobe is infused with 10% formalin solution for ligation, and the right lung lobe is soaked in 10% formalin solution for fixation and preservation to obtain pathological specimens. Pathological sections were stained with HE and immunohistochemical staining, and observed under a microscope.

HE staining step:

(1) slicing, and baking at 70deg.C for 30min;

(2) taking out the mixture when the mixture is hot, putting the mixture into dimethylbenzene, and dewaxing the mixture for 2X 10min;

(3) washing off xylene with absolute ethanol for 2X 1min;

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

(5) hematoxylin is dyed for 5min, and washing is carried out for 1min;

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

(7) returning 1% dilute ammonia water to blue for 30s, and washing for 1min;

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

(9) dehydration of 70% alcohol for 20s, dehydration of 80% alcohol for 30s, dehydration of 95% alcohol for 2X 1min;

and (3) transparent to xylene for 3X 2min, air drying, and sealing with neutral resin. Each histopathological morphology change was observed under a light microscope.

An immunohistochemical step:

(1) fixing lung tissue with paraformaldehyde, conventional gradient alcohol dehydrating, waxing, embedding and conventional paraffin slicing;

(2) 4 μm thick paraffin sections were added with xylene solution 5min x 3 times, then sequentially subjected to gradient alcohol dewaxing, finally hydrated, and washed 5min x 3 times with PBS (pH 7.2-7.6);

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

(4) microwave repairing antigen: placing the slices into a container containing 0.01M citrate buffer solution, heating in a microwave oven, maintaining the temperature of the liquid in the container at 100deg.C for 15min, naturally cooling, cooling to thick PBS (pH 7.2-7.6), and washing for 1-2 times;

(5) dropwise adding 5% BSA blocking solution, and at room temperature for 20min, removing excessive liquid without washing;

(6) rabbit anti-murine antibody was added dropwise with TGF- β1 antibody dilution of 1:200, tnf-a antibody dilution of 1:200 Washing with PBS (pH 7.2-7.6) for 2min X3 times at 20deg.C for 2 h;

(7) dripping biotinylated goat anti-mouse IgG,20min, and washing with PBS (pH 7.2-7.6) for 2min×3 times;

(8) dripping SABC as a test agent, 20min, and washing with PBS (pH 7.2-7.6) for 5min×4 times;

(9) DAB color development: 1ml of distilled water was taken using a DAB chromogenic kit, 1 drop of each of A, B, C reagents in the kit was added, and the mixture was added to the sections after mixing uniformly. Developing color at room temperature, controlling reaction time under a mirror, and generally controlling the reaction time to be 5-30min;

is lightly counterstained with hematoxylin, dehydrated for 2 times by 1min with 95% ethanol and 1min multiplied by 2 times with 100% ethanol, and then transparent for 5min multiplied by 3 times with dimethylbenzene, and then is sealed and observed under a microscope.

2.3 TGF-beta 1 and TNF-alpha scoring methods

When observed under a light microscope, TGF-beta 1 takes alveolar epithelial cells, bronchial mucosa epithelial cells, fibroblasts, vascular endothelial cells, bronchioles walls and vascular wall smooth muscle cells as positive reaction, wherein brown yellow particles appear in cytoplasm; TNF-alpha is positive by brown yellow particles in cytoplasm of alveolar macrophages, lymphocytes, neutrophils, capillary endothelial cells, alveolar epithelial cells, bronchiolar epithelial tissues and pulmonary interstitium and vascular smooth muscle cells, and the cytoplasmic staining is brown and positive reaction. The negative control was a partial slice with PBS instead of primary antibody.

The determination was made for immunohistochemical staining using bresalaier's semi-quantitative scoring system: each slice randomly selects 5 visual fields under 400 times of visual fields, the staining intensity is scored according to colorless (0), light yellow (1), brown yellow (2) and brown (3), the staining breadth is obtained according to the percentage of positive cell number to total cells, the staining intensity is multiplied by the staining breadth, and the average value of the 5 visual fields is used as the immunohistochemical staining quantitative result of the whole slice. The formula is as follows: is= [ (0×f0) + (1×f1) + (2×f2) + (3×f3) ].

2.4 statistical methods

Analysis was performed using SPSS22.0 statistical software, with results as mean.+ -. Standard deviationAnd (3) representing. The data of each group are firstly subjected to normal examination and variance analysis, if the normal distribution and the variance alignment are met, single-factor variance analysis (One-Way ANOVA) is adopted, and P is less than 0.05 and is taken as the significance difference level.

3 results of experiments

3.1 general cases of rats in groups

The normal group rats have good mental state, bright fur, sensitive response, difficult capture and normal eating and drinking. Weight gain and breathing are normal. The rats in the model group are low in spirit, less in activity, slow in response, less in eating and drinking than the rats in the normal group, less in weight growth, and with different degrees of breathing acceleration, lip cyanosis, progressive aggravation of symptoms and partial dehairing with the increase of days. The rats in each treatment group were significantly better than in the model group, and the high dose group and the positive control group were closer to the normal group in the composition of the present invention.

3.2 observation of Lung tissue of rats in each group under light microscope

The normal group rats have clear and complete lung tissue and alveolus structure, normal alveolus wall and alveolus interval morphology, normal alveolus morphology and volume, and no congestion, inflammation, exudation and other manifestations. A large amount of inflammatory cells can be oozed out of the alveolar space of the rats in the model group on day 14, fibroblasts proliferate, the alveolar space is thickened, most of alveolar structures are destroyed, and the alveolar space is reduced; on day 28 the alveolar space thickened, fibroblasts increased, alveolar spaces significantly contracted, and collagen fibers formed. The rats in each treatment group have the same rule compared with rats in the model group, but the pulmonary alveolitis and pulmonary fibrosis degree are lighter than those in the model group, and the pathological changes of the composition, the high-dose group and the positive control group are closer to those of the normal group.

3.3 expression of TGF-. Beta.1 and TNF-. Alpha.in Lung tissue of rats of each group 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 in the normal control group on the 14 th day, and the expression has obvious difference (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 was significantly lower on day 14 than in the model group, with significant differences (p < 0.05); the expression levels of TGF-beta 1 and TNF-alpha in the lung tissue of rats in the positive control group and the composition of the invention in the high dose group are obviously lower than those in the composition control group, and have obvious difference (P < 0.05). The high dose group of the composition of the invention has no significant difference compared with the positive control group. The results are shown in Table 1.

TABLE 1 expression of TGF- β1 and TNF- α in rat lung tissue of groups on day 14

Note that: ". Times." indicates that p <0.05 compared to the normal group; "Δj" indicates that p <0.05 compared to the model group;

"#" indicates p <0.05 compared to the composition control group; "" indicates that p <0.05 was compared with the group of flowers of small spring.

3.3 expression of TGF-. Beta.1 and TNF-. Alpha.in Lung tissue of rats of each group 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 in the normal control group on day 28, and has obvious difference (P is less than 0.05); the expression of TGF-beta 1 and TNF-alpha in the lung tissue of rats in the positive control group and the low, medium and high dose groups of the composition of the invention is obviously lower than that in the model group on day 28, and has obvious difference (p is less than 0.05); the expression level of TGF-beta 1 in the lung tissue of rats in the positive control group and the high-dose group in the composition is obviously lower than that in the control group of the composition, and has obvious difference (P is less than 0.05). There was no significant difference between the high dose group and the positive control group in the composition of the present invention. The results are shown in Table 2.

TABLE 2 expression of TGF- β1 and TNF- α in rat lung tissue of groups on day 28

Note that: ". Times." indicates that p <0.05 compared to the normal group; "Δj" indicates that p <0.05 compared to the model group;

"#" indicates p <0.05 compared to the composition control group; "" indicates that p <0.05 was compared with the group of flowers of small spring.

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

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

2.1 general data

58 cases of pulmonary fibrosis patients in the respiratory department of the Zhejiang people hospital are randomly selected as study objects, and the syndrome differentiation of the traditional Chinese medicine clinics is that the lung fibrosis is caused by qi deficiency and phlegm stasis, and the main symptoms are as follows: shortness of breath, dyspnea, cough with weakness, especially movement, or clear and thin expectoration, bloody sputum, bloody or dark red blood, or chest tinge, cyanosis of the lips and nails, pale and dark tongue or ecchymosis, and thready and weak or astringent pulse. Patients were divided into 29 control groups and observation groups, respectively, 18 men and 11 women of the control group, and the average age was 66.13.+ -. 5.99 years; group 17 men and 12 women were observed, with average age 65.45 + -6.97 years. The gender, age and course of disease before treatment of the two groups are treated statistically without significant differences. The control group and the observation group both exclude pulmonary primary diseases such as tuberculosis, fungi, tumor and the like.

2.2 test methods

The control group was orally administered with N-acetylcysteine capsule (approved paper number: national standard H20000519, specification: 0.2 g/granule, manufactured by Guangdong Kangdong pharmaceutical Co., ltd.) 3 times daily, 600mg each time.

The observation group adopts the combination of the composition and the N-acetylcysteine capsule for oral treatment, and the oral administration method and the dosage of the N-acetamidincysteine capsule are the same as those of the control group.

2.3 observations index

2.3.1 patient cardinal symptom score comparison: marking symptoms such as dyspnea, shortness of breath, cough, chest pain and the like before and after treatment of the two groups of patients according to the score of 0, 2, 4 and 6 of the non-mild, moderate and severe degree respectively, and calculating total scores;

2.3.2 pulmonary function index: adopt pulmonary function appearance to detect pulmonary ventilation and close dispersion 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 the total sign of the chief complaints was significantly reduced in both groups after treatment compared to that before treatment (P < 0.05), and the observed group was significantly reduced (P < 0.05) compared to the thick control group.

Note that: Δp <0.05 compared to pre-treatment; compared with the control group, P <0.05.

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

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

Claims (5)

1. The traditional Chinese medicine composition for preventing and treating pulmonary fibrosis is characterized by being prepared from the following traditional Chinese medicine components in parts by weight:

10-15 parts of small spring flower, 10-20 parts of astragalus mongholicus, and 15-25 parts of wild buckwheat rhizome

5-8 parts of ginseng, 8-12 parts of astilbe chinensis, 8-12 parts of snakegourd fruit

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

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

12 parts of small spring flower, 15 parts of astragalus membranaceus and 20 parts of wild buckwheat rhizome

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

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

3. An oral pharmaceutical formulation made from the traditional Chinese medicine composition according to any one of claims 1-2, wherein the oral pharmaceutical formulation is one of an oral liquid, a granule, a microcapsule, a capsule, a pill or a tablet.

4. A method for preparing an oral pharmaceutical preparation of a traditional Chinese medicine composition according to claim 3, characterized by comprising the steps of:

(1) Taking the raw medicinal materials with the prescription amount, thoroughly moistening the small spring flowers after removing impurities, cutting into short sections, and drying for later use; removing impurities from radix astragali, rhizoma Fagopyri Dibotryis, ginseng radix, herba astilbe chinensis and Zingiberis rhizoma, moistening thoroughly, cutting into thick slices or slices, and drying for use; flattening fructus Trichosanthis, and shredding or blocking; removing impurities from fructus Schisandrae chinensis, and mashing; parching Glycyrrhrizae radix with Mel to yellow or deep yellow, and cooling;

(2) Decocting the above materials in 6-10 times of water for 2-3 times, mixing decoctions, filtering, concentrating the filtrate to obtain extract with relative density of 1.20-1.35 at 50-60deg.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 pharmaceutical preparation by using a conventional process.

5. The use of the Chinese medicinal composition according to claim 1 in the preparation of medicaments for preventing and treating pulmonary fibrosis.