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

Abstract

The invention provides a traditional Chinese medicine composition for treating pulmonary fibrosis and a preparation method of the traditional Chinese medicine composition. The preparation method comprises the following steps: accurately weighing and pretreating medicinal materials, decocting and extracting oysters, decocting and extracting water-soluble components with water, extracting fat-soluble components of earthworms with alcohol, mixing and refining, and forming a preparation. A differential extraction process is adopted, the dissolution rate of effective components of mineral medicines and animal medicines is increased, for example, the dissolution rate of calcium salt is increased by 35% by decocting oysters firstly, and the extraction efficiency of liposoluble components of lumbrukinase is remarkably enhanced by alcohol extraction of earthworms. Tannin impurities are removed through chitosan flocculation, and component stability is guaranteed through vacuum concentration. And finally, various dosage forms such as granules, decoction or tablets can be prepared, different clinical requirements are met, and the preparation method has the advantages of scientific process, controllable quality and convenience in application.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compositions, and in particular to a traditional Chinese medicine composition for treating pulmonary fibrosis and a preparation method thereof. Background Art

[0002] Pulmonary fibrosis is a progressive lung disease that poses a serious threat to human health. Its pathological process is complex, severely affecting the patient's respiratory function and quality of life, and the prognosis is poor. In Traditional Chinese Medicine (TCM), some cases of pulmonary fibrosis can be classified as "lung obstruction," of which phlegm and blood stasis obstructing the lungs is a common and key clinical syndrome, characterized by cough, wheezing, chest tightness caused by excessive sputum, dyspnea, especially with movement, a dark purple tongue or ecchymosis, and a greasy tongue coating. Currently, there are two main treatments for pulmonary fibrosis with phlegm and blood stasis obstructing the lungs: Western medicine and traditional Chinese medicine, but both have significant limitations.

[0003] In terms of Western medicine treatment, while commonly used glucocorticoids and immunosuppressants can alleviate lung inflammation for a certain period of time, long-term use can cause numerous side effects. For example, glucocorticoids can easily lead to immunosuppression, increasing the risk of infection and potentially causing adverse reactions such as gastrointestinal ulcers and osteoporosis. Immunosuppressants can affect the body's normal immune surveillance function, and some patients may also experience liver and kidney damage. Furthermore, long-term use of Western medicine can easily lead to drug resistance. As medication duration increases, the drug's efficacy gradually diminishes, significantly increasing the difficulty and risk of subsequent treatment.

[0004] In terms of traditional Chinese medicine treatment, Chinese herbal compound prescriptions have certain advantages in regulating the body's functions and improving symptoms as a whole, but existing Chinese medicine preparations have obvious defects in formulation and preparation process. In terms of formulation, many traditional Chinese medicine formulas for phlegm and blood stasis blocking the lung syndrome fail to fully conform to the complex pathogenesis of "phlegm and blood stasis intertwined, and the lungs fail to descend and ascend", or focus on expectoration while ignoring blood stasis, or focus on blood stasis while neglecting expectoration, making it difficult to achieve the synergistic unity of the two, resulting in the inability of the drug to fully act on multiple pathological links of the disease, effectively improving lung function and delaying disease progression. In terms of preparation process, the traditional water decoction method has a low dissolution rate of the active ingredients of mineral medicinal materials (such as oysters). The structure of oyster mineral medicine is stable, and the effective ingredient of calcium carbonate is difficult to fully release during the water decoction process, which greatly reduces the efficacy of the drug. For the active ingredients (such as lumbrokinase) in animal medicines (such as earthworms), due to the low solubility of such ingredients in water, the water decoction method is difficult to fully extract, which seriously affects the overall efficacy of the drug. In addition, the traditional process has insufficient impurity removal capabilities, and preparations often contain a large amount of tannins and protein impurities, which not only reduce the purity and stability of the drug, but may also cause adverse allergic reactions.

[0005] There are many challenges in solving these problems. The ingredients of traditional Chinese medicine are complex and diverse, and the mechanism of action is still unclear, making it difficult to accurately determine the optimal compatibility ratio and synergistic mode between drugs. When improving the preparation process, it is necessary to take into account the characteristics of traditional Chinese medicine, not only to increase the dissolution rate of the active ingredients of mineral drugs and animal drugs, but also to avoid destroying heat-sensitive components. For example, when using high temperature and high pressure methods to improve the dissolution rate of mineral drug components, the active ingredients in other medicinal materials may be destroyed, and the new process must also comprehensively consider cost, production efficiency and quality control factors, which makes the research and development process complicated and full of difficulties. Therefore, we propose a traditional Chinese medicine composition for the treatment of pulmonary fibrosis and a preparation method thereof. Summary of the Invention

[0006] The purpose of the present invention is to provide a Chinese medicine composition for pulmonary fibrosis with phlegm and blood stasis obstructing the lungs and its preparation method, aiming to solve the problems of existing Western medicines with many side effects and easy drug resistance, and the lack of pertinence of traditional Chinese medicine formulas and preparation process defects leading to limited efficacy. Through scientific and precise drug combinations and optimized and innovative preparation processes, efficient lung-clearing and asthma-relieving, phlegm-removing and blood stasis-removing effects are achieved, and the symptoms of cough, asthma, chest tightness with excessive sputum, and dyspnea in patients with pulmonary fibrosis with phlegm and blood stasis obstructing the lungs are significantly improved, the treatment effect is improved, and at the same time, the safety of the medication is guaranteed, providing a better solution for the traditional Chinese medicine treatment of pulmonary fibrosis.

[0007] The present invention provides the following technical solution: a traditional Chinese medicine composition for treating pulmonary fibrosis, comprising the following ingredients by weight: 30-40 parts of mulberry bark, 30-40 parts of scutellaria baicalensis seeds, 20-30 parts of thunbergia thunbergii bulbs, 10-15 parts of belamcanda vine, 10-15 parts of stir-fried bitter almonds, 10-15 parts of platycodon grandiflorum, 15-25 parts of earthworms, 20-30 parts of salvia miltiorrhiza, 20-30 parts of oysters (fried first), 10-15 parts of stir-fried radish seeds, and 5-10 parts of roasted liquorice.

[0008] A method for preparing a traditional Chinese medicine composition for treating pulmonary fibrosis comprises the following steps: S1: weighing and pre-treating according to proportion: accurate weighing: weighing each medicinal material according to the weight portion of the formula using a 1 / 10,000 electronic scale, with the weighing error controlled within ±0.5%;

[0009] Medicinal material processing: remove impurities and moldy parts from botanicals; crush oysters from minerals into 2-3cm chunks; crush earthworms from animal medicines, stir-fried bitter almonds from seeds, and stir-fried radish seeds into 60 mesh; slice the root and rhizome Salvia miltiorrhiza thinly, and cut the leaf and root Platycodon grandiflorum into small sections;

[0010] S2: Oyster frying and extraction:

[0011] Put the crushed oyster pieces into the extraction tank, add 10 times the amount (v / w) of purified water, soak for 20 minutes, boil over high heat, then reduce the heat to a low boil and fry for 30 minutes. Filter with a 200-mesh sieve while hot, and collect the decoction for later use;

[0012] S3: Water-soluble components decoction extraction:

[0013] Put the bark of Morus alba, the fruit of Lemongrass, the bulb of Thunbergia thunbergii, the dry root of Belamcanda chinensis, the platycodon grandiflorum, the stir-fried seed of Radish, the salvia miltiorrhiza, and the roasted liquorice into a multifunctional extraction tank, add the oyster decoction and 8 times the amount (v / w) of purified water, soak for 1.5 hours, decoct at 100° C. for 2 hours each time, stir every 30 minutes, combine the two decoctions, filter through a 300-mesh stainless steel sieve to remove the medicinal residue, and concentrate the filtrate under reduced pressure to a relative density of 1.05-1.10 (60° C., measured by normal pressure method) to obtain a water-extracted filtrate;

[0014] S4: Alcohol extraction of fat-soluble components of earthworm:

[0015] Add the earthworm powder to a reflux extraction apparatus, add 70% ethanol solution (8 times the weight of the medicinal material), and reflux extract twice in a 75°C water bath for 2 hours each time. Combine the alcohol extracts and recover the ethanol by vacuum distillation (vacuum degree ≥ 0.08 MPa, temperature ≤ 60°C) to obtain an alcohol extract concentrate.

[0016] S5: Mixing, refining and preparation molding:

[0017] Filtrate mixing: transfer the water extraction filtrate and the earthworm alcohol extraction concentrate into a vacuum concentration tank and mix at low speed (50 rpm) for 30 minutes;

[0018] Impurity treatment: add 0.2% (w / v) chitosan solution (dissolved in 1% acetic acid), stir for 30 minutes, let stand for 2 hours, filter and concentrate the filtrate to a relative density of 1.20-1.25 (60°C);

[0019] Dosage form selection: choose to make granules, decoction or tablets.

[0020] As a preferred technical solution of the present invention, in step S1, the botanical medicine includes Morus alba bark, Lepidium tiliaceus seed, Fritillaria thunbergii bulb, Belamcanda chinensis, Platycodon grandiflorum, stir-fried radish seed, Salvia miltiorrhiza, and roasted liquorice root.

[0021] As a preferred technical solution of the present invention, in step S2, frying the oysters first can increase the calcium salt dissolution rate by 35%, and the amino acid components thereof are more soluble in water.

[0022] As a preferred technical solution of the present invention, in step S3, when the water-soluble components are decocted and extracted, the plant cells are soaked for 1.5 hours to allow them to fully absorb water and the effective components to be easily dissolved.

[0023] As a preferred technical solution of the present invention, in step S4, the 70% ethanol solution has moderate polarity, taking into account the extraction of both lumbrokinase protein components and fatty acid components, and the lumbrokinase activity retention rate after alcohol extraction is ≥85%.

[0024] As a preferred technical solution of the present invention, in step S5, the specific method for making tablets is: adding starch and sodium carboxymethyl starch (disintegrant) to the concentrated solution, pressing into tablets, each tablet containing 0.5g of crude drug, with a hardness of 3-5kg and a disintegration time of ≤15 minutes.

[0025] As a preferred technical solution of the present invention, the composition is prepared into granules or decoctions, which are respectively suitable for long-term use and acute use, to meet the needs of diversified clinical medication.

[0026] A method for preparing a granular Chinese medicine composition for treating pulmonary fibrosis, comprising the following steps: S1: pre-treatment of medicinal materials: weighing the medicinal materials in proportion, crushing oysters into 2-3 cm blocks, crushing earthworms, stir-fried bitter almonds, and stir-fried radish seeds to 60 mesh, removing impurities from the remaining medicinal materials and setting aside;

[0027] S2: Oyster pre-fry: Add oyster pieces to the extraction tank, add 10 times the amount of purified water, soak for 20 minutes, then boil over high heat, reduce heat and fry for 30 minutes, filter through a 200-mesh sieve while hot, and collect the decoction;

[0028] S3: Decoction of water-soluble components: Place mulberry bark, scutellaria baicalensis seeds, thunbergia thunbergii bulb, belamcanda Root, platycodon grandiflorum, stir-fried radish seeds, salvia miltiorrhiza, and roasted liquorice in an extraction tank. Add oyster decoction and 8 times the amount of purified water. Soak for 1.5 hours. Decoction at 100°C twice for 2 hours each time. Combine the decoctions and filter through a 300-mesh sieve.

[0029] S4: Alcohol extraction of earthworms: Add 70% ethanol solution (8 times the weight of the medicinal material) to earthworm powder, reflux extract at 75°C twice, each time for 2 hours, and recover ethanol to obtain a concentrated solution;

[0030] S5: Mixing and granulation: Mix the water decoction with the earthworm concentrate, concentrate under reduced pressure to a relative density of 1.10 (60°C), add an appropriate amount of dextrin, dry at 60°C after granulation, and package the whole granules. Each bag contains 20g of crude drug, and the solubility meets the following requirements: take 10g of granules and add 200ml of hot water, and the solubility rate within 5 minutes is ≥90%.

[0031] A method for preparing a Chinese medicine decoction for treating pulmonary fibrosis comprises the following steps:

[0032] S1: Preparation of medicinal materials: weigh the medicinal materials according to the proportion, crush the oysters, and wash and dry the remaining medicinal materials;

[0033] S2: Fry the oysters first: add 10 times the amount of purified water to the oysters, bring to a boil over high heat, then simmer for 30 minutes over low heat;

[0034] S3: Compound decoction: Add mulberry bark, scutellaria baicalensis seeds, thunbergia thunbergii, belamcanda vine, stir-fried bitter almonds, platycodon grandiflorum, stir-fried radish seeds, salvia miltiorrhiza, and roasted liquorice root, add 8 times the amount of purified water, soak for 1 hour, decoct at 100°C twice, each time for 1.5 hours, combine the decoctions, and filter through a 300-mesh sieve;

[0035] S4: Packaging and sterilization: Pack the decoction into sterile bags, 150 ml per bag, and sterilize.

[0036] Compared with the existing technology, the beneficial effects of the present invention are: based on the combination of traditional Chinese medicine theory and modern preparation technology, it has the following clear and traceable advantages and technical effects:

[0037] In the prior art, traditional Chinese medicine formulas for pulmonary fibrosis with phlegm and blood stasis obstructing the lungs are often limited by the principle of "focusing on resolving phlegm and neglecting blood stasis" or "focusing on promoting blood circulation and neglecting lung function", making it difficult to take into account the complex pathogenesis of phlegm, blood stasis, and lung dysfunction. The present invention strictly adheres to the principle of "monarch, minister, assistant, and envoy" compatibility:

[0038] The main medicines are Morus alba bark and Tripterygium wilfordii seeds: one is sweet and cold, the other is bitter and cold, they can clear the lungs and relieve asthma, promote water circulation and reduce swelling, targeting the core pathogenesis of phlegm, fire, water and dampness blocking the lungs, quickly relieving cough, asthma, chest fullness and shortness of breath. The combination of the two can empower the lung qi to descend, and fundamentally improve the disorder of lung qi.

[0039] The auxiliary drugs Fritillaria thunbergii and Belamcanda chinensis: enhance the ability to clear heat and resolve phlegm, and dissolve the phlegm-heat in the lungs; fried bitter almonds and Platycodon grandiflorum have the functions of descending and promoting respectively, and restore the lung's function of promoting and descending. The four drugs are used together to solve the key problems of phlegm blockage and airway obstruction.

[0040] Auxiliary medicines include earthworm, salvia miltiorrhiza, oyster, and stir-fried radish seeds: they respectively work from the perspectives of unblocking meridians and activating blood circulation, softening and dispersing nodules, and eliminating phlegm and relieving stagnation, improving lung meridian obstruction, phlegm and blood stasis, and phlegm and food stagnation in the middle burner, blocking the pathological chain of "phlegm-stasis-stagnation" in pulmonary fibrosis.

[0041] The guiding drug, roasted licorice root, harmonizes all the medicines, protects the spleen and stomach, relieves the irritation of bitter and cold medicines on the gastrointestinal tract, and embodies the wisdom of "attacking and supplementing at the same time".

[0042] This combination scheme forms a three-dimensional effect of "clearing the lungs and relieving asthma, clearing away heat and resolving phlegm, promoting blood circulation and removing blood stasis, softening and dispersing nodules" through the synergy of multiple drugs. Compared with existing single-effect formulas, it covers the core pathogenesis of pulmonary fibrosis and phlegm and blood stasis obstructing the lungs more comprehensively and has clearer clinical indications.

[0043] To address the problem of insufficient extraction of active ingredients from mineral and animal medicines by traditional decoction methods, the present invention adopts a differentiated process to significantly improve the dissolution rate of active ingredients and the quality of the preparation:

[0044] Oyster pre-frying process: After crushing, add 10 times the amount of water and simmer for 30 minutes. This will increase the dissolution rate of calcium carbonate mineral components in the oysters by more than 30% compared with the traditional co-frying method (according to the mineral medicine decoction specifications in the "Chinese Materia Medica Preparation", extending the high-temperature decoction time can destroy the mineral lattice structure). The active ingredients of amino acids and trace elements contained in them are more fully released, enhancing the effects of softening and dispersing nodules and regulating immunity.

[0045] Earthworm alcohol extraction technology: using 70% ethanol reflux extraction, targeting the fat-soluble components of lumbrokinase in earthworms (studies have shown that the solubility of lumbrokinase in ethanol is more than 2 times higher than that in water), the extraction rate is increased by 40% compared with the water decoction method, and high temperature is avoided to destroy the active protein components (activity retention rate ≥85%), fully exerting its medicinal effects of dredging meridians, relieving asthma, and improving pulmonary microcirculation.

[0046] Impurity removal and concentration and purification: After the water extract and the alcohol extract are mixed, they are flocculated with 0.2% chitosan (according to the impurity removal principle of "Chinese Materia Medica Preparation", the positive charge of chitosan combines with the negative charge of tannin impurities and precipitates). The tannin removal rate is ≥60%, which reduces the irritation of the preparation to the gastrointestinal tract. At the same time, the relative density is controlled by decompression and concentration to ensure the stability of the concentration of active ingredients, solving the problems of many impurities and unstable efficacy in traditional processes.

[0047] Protect the spleen and stomach and reduce side effects: the proportion of roasted licorice in the formula is 5-10 parts. Its sweet and mild nature can alleviate the dry and strong nature of the bitter and cold medicines such as Morus alba bark and Tripterygium wilfordii. Experiments have shown (refer to the theory of licorice compatibility in "Chinese Materia Medica") that the combination of roasted licorice and bitter and cold medicines can reduce the incidence of gastrointestinal adverse reactions by 40%. It is suitable for long-term use by patients with pulmonary fibrosis (such patients often have weak spleen and stomach and need to take into account the protection of the body).

[0048] The dosage forms are diverse and can meet clinical needs: they can be prepared into granules, decoctions, and tablets. Granules are easy to dissolve and absorb quickly (the solubility meets the standard: 10g granules are added to 200ml hot water and the dissolution rate is ≥90% within 5 minutes), which is suitable for middle-aged and elderly patients. Decoctions are easy to add or subtract according to symptoms and are suitable for severe acute illnesses. Tablets are easy to carry and meet long-term medication needs, which is more flexible than the single dosage form of existing technology.

[0049] The efficacy of the medicinal materials is clearly supported by classics: Morus alba bark "treats injuries, fatigue, emaciation, metrorrhagia, pulse cessation, and replenishes deficiency and invigorates Qi" (Ben Jing), Trichosanthes kirilowii "treats lung congestion and cough, relieves shortness of breath, and eliminates phlegm and fluid in the chest" (Yao Xing Lun), and Salvia miltiorrhiza "breaks up blood clots, eliminates wind evil and retained heat" (Bielu). The efficacy of each medicinal material is derived from the Chinese Pharmacopoeia and classic herbal works, and the combination conforms to the TCM treatment principles of "treating phlegm and blood stasis together" and "taking both the lungs and spleen into consideration".

[0050] The preparation process parameters are scientific and repeatable: the decoction time (1.5-2 hours), ethanol concentration (70%), and concentrated relative density (1.05-1.10) are all set based on the physical and chemical properties of the active ingredients of the medicinal materials (for example, the boiling point of mulberry glycoside is about 200°C, and decoction at 100°C does not destroy its activity; tanshinone IIA has the highest solubility in 70% ethanol). It has industrial production feasibility and is different from traditional empirical preparation. The technical solution is highly repeatable. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 This is a schematic diagram comparing the Ashcroft fibrosis scores of lung tissues in each group of mice provided by the present invention;

[0052] Figure 2 This is a schematic diagram comparing the hydroxyproline content in lung tissue of each group of mice provided by the present invention;

[0053] Figure 3 This is a schematic diagram comparing the levels of serum inflammatory factors in each group of mice provided by the present invention;

[0054] Figure 4 This is a schematic diagram of the weight change trend of each group of mice provided by the present invention. DETAILED DESCRIPTION

[0055] To make the purpose, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them.

[0056] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the invention claimed for protection, but merely represents some embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. It should be noted that, in the absence of conflict, the embodiments of the present invention and the features and technical solutions in the embodiments can be combined with each other. It should be noted that similar numbers and letters represent similar items in the following drawings. Therefore, once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings.

[0057] Example 1: Preparation of granules of a traditional Chinese medicine composition for treating pulmonary fibrosis: Formula (by weight): 30 parts of mulberry bark, 30 parts of scutellaria baicalensis seeds, 30 parts of thunbergia thunbergii, 12 parts of belamcanda vine, 10 parts of stir-fried bitter almonds, 12 parts of platycodon grandiflorum, 20 parts of earthworms, 30 parts of oysters (fried first), 10 parts of stir-fried radish seeds, 30 parts of salvia miltiorrhiza, and 6 parts of roasted liquorice.

[0058] Preparation steps:

[0059] S1: Medicinal material pretreatment: Weigh each medicinal material in proportion, crush the oyster into 2-3 cm blocks, crush the earthworm, stir-fried bitter almonds, and stir-fried radish seeds into 60 mesh, remove impurities from the remaining medicinal materials and set aside.

[0060] S2: Fry the oysters first: Add the oyster pieces into the extraction tank, add 10 times the amount of purified water, soak for 20 minutes, then boil over high heat, adjust to low heat and fry for 30 minutes, filter with a 200-mesh sieve while hot, and collect the decoction.

[0061] S3: Decoction of Water-Soluble Components: Place Morus alba bark, Lepidium tiliaceus seeds, Fritillaria thunbergii, Belamcanda chinensis, Platycodon grandiflorum, stir-fried Radish seeds, Salvia miltiorrhiza, and roasted Licorice root into an extraction tank. Add oyster decoction and 8 times the amount of purified water. Soak for 1.5 hours. Decoction at 100°C twice, each for 2 hours. Combine the decoctions and filter through a 300-mesh sieve.

[0062] S4: Alcohol extraction of earthworms: Add 70% ethanol solution (8 times the weight of the medicinal material) to the earthworm powder, reflux extract at 75°C twice, each time for 2 hours, and recover the ethanol to obtain a concentrated solution.

[0063] S5: Mixing and Granulation: Combine the decoction with the earthworm concentrate, concentrate under reduced pressure to a relative density of 1.10 (60°C), add an appropriate amount of dextrin, granulate, and dry at 60°C. Package the granules, each containing 20g of the crude drug. Solubility Test: Add 10g of granules to 200ml of hot water; dissolve ≥90% within 5 minutes.

[0064] Example 2: Preparation of a decoction of a Chinese medicine composition for treating pulmonary fibrosis:

[0065] Formula (by weight): 30 parts of mulberry bark, 30 parts of scutellaria baicalensis seeds, 30 parts of thunbergia thunbergii, 12 parts of belamcanda vine, 10 parts of stir-fried bitter almonds, 12 parts of platycodon grandiflorum, 20 parts of earthworms, 30 parts of oysters (fried first), 10 parts of stir-fried radish seeds, 30 parts of salvia miltiorrhiza, and 6 parts of roasted liquorice.

[0066] Preparation steps:

[0067] S1: Preparation of medicinal materials: Weigh the medicinal materials according to the proportion, crush the oysters, and wash and dry the remaining medicinal materials.

[0068] S2: Fry the oysters first: Add 10 times the amount of purified water to the oysters, boil over high heat, then fry over low heat for 30 minutes.

[0069] S3: Decoction of the compound: Add Morus alba bark, Lepidium tiliaceus seeds, Fritillaria thunbergii, Belamcanda chinensis, stir-fried bitter almonds, Platycodon grandiflorum, stir-fried Radish seeds, Salvia miltiorrhiza, and roasted Licorice root, add 8 times the amount of purified water, soak for 1 hour, and decoct at 100°C twice, each for 1.5 hours. Combine the decoctions and filter through a 300-mesh sieve.

[0070] S4: Packaging and sterilization: Pack the decoction into sterile bags, 150 ml per bag, and sterilize.

[0071] Granules are easy to carry and store, making them suitable for long-term use. Decoctions are rapidly absorbed, allowing for flexible dosage adjustments based on the patient's condition, making them suitable for acute episodes. The preparation of these different dosage forms meets diverse clinical needs, and the strict adherence to process parameters during the preparation process ensures drug quality, stability, and effectiveness.

[0072] A traditional Chinese medicine composition for treating pulmonary fibrosis with phlegm and blood stasis obstructing the lungs, Xiefei Pingchuan Decoction, comprises the following ingredients by weight: 30-40 parts of Morus alba bark: This bark has a sweet and cold nature and enters the lungs. It is effective in purging the lungs and relieving asthma, promoting diuresis and reducing swelling, clearing pathogenic heat from the lungs, and relieving lung congestion. It is the primary herbal ingredient and targets the core pathogenesis of phlegm and blood stasis obstructing the lungs, with the mulberry glycosides and flavonoids inhibiting airway inflammation and improving lung ventilation.

[0073] 30-40 parts of scutellaria baicalensis seeds: Bitter and cold, they act as a descending and purging agent, working in conjunction with mulberry bark to enhance lung-draining, asthma-relieving, water-moving, and swelling-reducing properties. They specifically target phlegm and fluid congestion in the lungs, relieving dyspnea, chest fullness, and asthma, acting as the main herb. They contain scutellaria baicalensis glycosides and cardiac glycosides, which enhance myocardial contractility and improve pulmonary circulation congestion.

[0074] 20-30 parts of Fritillaria thunbergii: Bitter and cold, it clears heat and is effective in clearing heat and resolving phlegm, dispersing nodules and eliminating carbuncles. It targets phlegm-heat accumulation in the lungs, dissolving thick phlegm and relieving symptoms of excessive, yellow, and thick phlegm. Fritillaria alkaloids have both antitussive and expectorant properties, alleviating respiratory irritation.

[0075] 10-15 parts of Belamcanda Root: Bitter and cold, it has the effect of clearing away heat and expectoration, dispersing stagnation and reducing swelling, unblocking airway congestion, relieving sore throat and phlegm accumulation in the lungs, and synergizing with Fritillaria thunbergii to enhance the effect of clearing heat and resolving phlegm.

[0076] 10-15 portions of stir-fried bitter almonds: bitter and warm in nature, they can lower the lungs, relieve coughs and asthma, and improve coughs and asthma caused by upward flow of lung qi. After being stir-fried, their medicinal properties become more harmonious, reducing the disadvantages of laxative effects. When combined with Platycodon grandiflorum, they can restore the lungs' function of dispersing and descending.

[0077] 10-15 parts of Platycodon grandiflorum: bitter and pungent in nature, it is good at clearing the lungs and relieving sore throat, removing phlegm and draining pus, carrying medicine upward to the lungs, promoting the discharge of phlegm, and used together with fried bitter almonds to regulate the lung qi and enhance the effect of relieving cough and asthma.

[0078] 15-25 parts of earthworms: salty and cold, it can dredge the meridians. It contains lumbrokinase and amino acid active ingredients, which are good at clearing the lung meridians, relieving asthma and cough, improving pulmonary microcirculation disorders, and reducing the degree of pulmonary interstitial fibrosis. It targets the pathogenesis of blocked meridians in phlegm and blood stasis blocking the lungs.

[0079] 20-30 parts of Salvia miltiorrhiza: bitter and slightly cold, it activates blood circulation, specifically enters the blood, activates blood circulation and removes blood stasis, regulates the lung meridian, improves pulmonary vascular remodeling, and delays the progression of pulmonary fibrosis. Its tanshinone components have antioxidant and anti-fibrotic effects, making it a key drug for treating lung meridian obstruction.

[0080] 20-30 servings of oysters (fried first): salty, astringent and slightly cold, they can soften and disperse lumps when used raw. They are effective for nodules and fibrous tissue hyperplasia formed by phlegm and blood stasis in the lungs. Frying them first can destroy the mineral structure, promote the dissolution of calcium carbonate and amino acids, and enhance the softening and dissipating power.

[0081] 10-15 servings of stir-fried radish seeds: pungent, sweet and neutral in nature, they help digestion and resolve phlegm, lower qi and relieve bloating, are good at eliminating phlegm and food stagnation in the middle burner, reduce the source of phlegm, and help improve chest tightness, abdominal distension, and poor appetite. When used with the main medicine, it embodies the meaning of "cultivating the earth to produce gold."

[0082] 5-10 parts of roasted licorice root: sweet and mild, harmonizing, invigorating the spleen and replenishing qi, alleviating the properties of the medicine, alleviating the stimulation of the bitter and cold medicines in the prescription on the spleen and stomach, protecting the acquired foundation, and coordinating various medicines to attack the evil without harming the body. It is a guiding medicine.

[0083] 2. Preparation Method

[0084] S1: Weighing and pretreatment according to proportion

[0085] Accurate weighing: According to the weight of the formula, use a 1 / 10,000 electronic scale to weigh each medicinal material, and the weighing error should be controlled within ±0.5%.

[0086] Medicinal material processing:

[0087] Remove impurities and moldy parts from herbal medicines (mulberry bark, scutellaria baicalensis seeds) to ensure cleanliness;

[0088] Mineral medicine oysters are crushed into 2-3cm blocks to increase the dissolution area of ​​the active ingredients;

[0089] Animal medicine earthworm, seed medicine fried bitter almond, fried radish seeds are crushed to 60 mesh size for easy alcohol extraction and water decoction;

[0090] Cut the rhizome-based herb Salvia miltiorrhiza into thin slices, and the leaf-based herb Platycodon grandiflorum into small sections to ensure decoction efficiency.

[0091] S2: Oyster frying and extraction

[0092] Operation details: Place the crushed oyster pieces into an extraction tank, add 10 times the amount (v / w) of purified water, and soak for 20 minutes to allow the mineral structure to initially absorb water and expand; bring to a boil over high heat, then reduce the heat to a low boil and simmer for 30 minutes. Filter with a 200-mesh sieve while hot, and collect the decoction for later use.

[0093] Technological advantages: Oysters contain calcium carbonate (accounting for ≥90%) and trace elements. Frying them first can increase the dissolution rate of calcium salts by 35%. Their amino acid components are more soluble in water, enhancing the effects of softening and dispersing nodules and regulating immunity.

[0094] S3: Water-soluble components decoction extraction

[0095] Extraction objects: Morus alba bark, Lepidium tiliaceus seed, Fritillaria thunbergii, Belamcanda chinensis, Platycodon grandiflorum, stir-fried radish seed, Salvia miltiorrhiza, and roasted liquorice root.

[0096] Operation process:

[0097] The medicinal materials were placed in a multifunctional extraction tank, and oyster decoction and 8 times the volume (v / w) of purified water were added. The mixture was soaked for 1.5 hours to allow the plant cells to fully absorb water and the active ingredients to be easily dissolved.

[0098] Decoction at 100°C for 2 times, 2 hours each time, stirring every 30 minutes to ensure even heating.

[0099] The two decoctions were combined, filtered through a 300-mesh stainless steel sieve to remove the residue, and the filtrate was concentrated under reduced pressure to a relative density of 1.05-1.10 (60° C., measured at normal pressure) to obtain a water extract filtrate.

[0100] S4: Alcohol extraction of fat-soluble components of earthworm

[0101] Extraction process:

[0102] Place the earthworm powder in a reflux extraction apparatus, add 70% ethanol solution (8 times the weight of the medicinal material), and reflux extract in a 75°C water bath twice, each time for 2 hours (ethanol has moderate polarity, allowing for the extraction of both lumbrokinase protein components and fatty acid components);

[0103] The alcohol extracts were combined and ethanol was recovered by vacuum distillation (vacuum degree ≥ 0.08 MPa, temperature ≤ 60°C) to avoid high temperature destruction of the active ingredients, thereby obtaining an alcohol extract concentrate with a lumbrokinase activity retention rate of ≥ 85%.

[0104] S5: Mixing, refining and preparation molding:

[0105] Filtrate mixing: transfer the water extraction filtrate and the earthworm alcohol extraction concentrate into a vacuum concentration tank, stir at a low speed (50 rpm) for 30 minutes to fully blend the aqueous phase and alcohol phase components.

[0106] Impurity treatment: Add 0.2% (w / v) chitosan solution (dissolved in 1% acetic acid), stir for 30 minutes, let it stand for 2 hours, use the positive charge of chitosan to adsorb tannins and negatively charged protein impurities, filter and concentrate the filtrate to a relative density of 1.20-1.25 (60°C).

[0107] Dosage form selection:

[0108] Granules: Add soluble dextrin to the concentrate at a ratio of 1:1, dry at 60°C after granulation, and package the whole granules. Each bag contains 20g of crude drug. The solubility meets the standard (10g granules add 200ml of hot water, and the solubility rate within 5 minutes is ≥90%).

[0109] Decoction: Directly pack the filtrate into 100ml bags, containing 30g of crude drug, which can be obtained after sterilization and taken immediately;

[0110] Tablets: Add starch and sodium carboxymethyl starch (disintegrant) to the concentrate and press into tablets. Each tablet contains 0.5g of crude drug, has a hardness of 3-5kg, and a disintegration time of ≤15 minutes.

[0111] Experimental example of a mouse model of treating pulmonary fibrosis with a Chinese medicine composition:

[0112] 1. Experimental Purpose

[0113] To evaluate the intervention effect of the Chinese medicine composition of the present invention on bleomycin-induced pulmonary fibrosis in mice and explore its possible mechanism of action.

[0114] 2. Experimental Materials

[0115] (1) Preparation of medicine: Composition of Chinese medicine composition (by weight):

[0116] 35 parts of Morus alba bark; 35 parts of Lemongrass seeds; 25 parts of Fritillaria thunbergii; 12 parts of Belamcanda chinensis; 12 parts of stir-fried Apricot kernels; 12 parts of Platycodon grandiflorum; 20 parts of Earthworms; 25 parts of Salvia miltiorrhiza; 25 parts of Oyster (fried first); 12 parts of stir-fried Radish seeds; 8 parts of roasted Licorice root;

[0117] (2) Animal Model

[0118] Experimental animals: 40 SPF male C57BL / 6 mice, weighing 20-22 g

[0119] Grouping: Randomly divided into 4 groups (n=10):

[0120] Normal control group (NS group)

[0121] Model control group (PF group)

[0122] High-dose Chinese medicine group (HF group, daily oral administration, dose of 15g / kg·d)

[0123] Low-dose Chinese medicine group (LF group, daily oral administration, dose of 7.5 g / kg·d)

[0124] (3) Reagents and instruments

[0125] Bleomycin A5

[0126] ELISA kits (TGF-β1, IL-6, TNF-α)

[0127] Hydroxyproline Assay Kit

[0128] Fully automatic biochemical analyzer

[0129] Microscope, paraffin sectioner, HE staining and Masson staining reagents

[0130] 3. Experimental Methods

[0131] (1) Establishment of pulmonary fibrosis model

[0132] Day 1: All mice except the normal control group were given bleomycin (5 mg / kg) via tracheal instillation to establish a pulmonary fibrosis model.

[0133] Administration time: starting from the second day after model establishment and continued for 28 days.

[0134] (2) Specimen collection

[0135] On the 29th day, the mice were killed, and the left lung tissue was fixed in 4% paraformaldehyde for pathological examination; the right lung tissue was frozen for hydroxyproline content detection and inflammatory factor ELISA detection.

[0136] (3) Testing indicators

[0137] 1. Pathological Observation

[0138] HE staining and Masson staining were used to observe the structural changes of lung tissue, and the degree of alveolitis and fibrosis was evaluated (Ashcroft score).

[0139] 2. Determination of Hydroxyproline Content

[0140] It reflects the degree of collagen deposition and indirectly reflects the degree of pulmonary fibrosis.

[0141] 3. Serum inflammatory factor levels

[0142] The levels of TGF-β1, IL-6 and TNF-α in serum were determined by ELISA.

[0143] 4. Animal weight changes

[0144] The body weight changes of mice in each group were recorded and their general conditions were evaluated.

[0145] 4. Statistical Processing

[0146] SPSS 26.0 software was used for data analysis. The measurement data were expressed as mean ± standard deviation (x ± s). One-way analysis of variance (ANOVA) was used for comparison between groups. The differences were considered statistically significant when P < 0.05.

[0147] 5. Results

[0148] Group Ashcroft score Hydroxyproline content (μg / g) TGF-β1 (pg / mL) IL-6 (pg / mL) TNF-α (pg / mL)

[0149]

[0150] According to data analysis, the Chinese medicine composition can significantly reduce the degree of pulmonary fibrosis, improve the pathological structure of lung tissue, reduce the release of inflammatory factors, and inhibit collagen deposition.

[0151] VI. Conclusion

[0152] This Chinese medicine composition can effectively alleviate the process of bleomycin-induced pulmonary fibrosis in mice by regulating inflammatory response and anti-fibrosis pathways, and has good application prospects.

[0153] The above embodiments are only used to illustrate the present invention and are not intended to limit the technical solutions described in the present invention. Although this specification has described the present invention in detail with reference to the above embodiments, the present invention is not limited to the above specific implementation methods. Therefore, any modification or replacement of the present invention; and all technical solutions and improvements thereof that do not depart from the spirit and scope of the invention are included in the scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating pulmonary fibrosis, characterized in that: By weight The invention comprises the following ingredients: 30-40 parts of mulberry bark, 30-40 parts of scutellaria baicalensis seeds, 20-30 parts of thunbergia thunbergii bulbs, 10-15 parts of belamcanda vine, 10-15 parts of stir-fried bitter almonds, 10-15 parts of platycodon grandiflorum, 15-25 parts of earthworms, 20-30 parts of salvia miltiorrhiza, 20-30 parts of oysters (fried first), 10-15 parts of stir-fried radish seeds and 5-10 parts of roasted liquorice root.

2. A method for preparing a traditional Chinese medicine composition for treating pulmonary fibrosis, characterized in that: The following steps are involved: S1: Weighing and pretreatment according to proportion: Accurate weighing: according to the weight of the formula, use a 1 / 10,000 electronic scale to weigh each medicinal material, and the weighing error should be controlled within ±0.5%; Medicinal material processing: remove impurities and moldy parts from botanicals; crush oysters from minerals into 2-3cm chunks; crush earthworms from animal medicines, stir-fried bitter almonds from seeds, and stir-fried radish seeds into 60 mesh; slice the root and rhizome Salvia miltiorrhiza thinly, and cut the leaf and root Platycodon grandiflorum into small sections; S2: Oyster frying and extraction: Put the crushed oyster pieces into the extraction tank, add 10 times the amount (v / w) of purified water, soak for 20 minutes, boil over high heat, then reduce the heat to a low boil and fry for 30 minutes. Filter with a 200-mesh sieve while hot, and collect the decoction for later use; S3: Water-soluble components decoction extraction: Put the bark of Morus alba, the fruit of Lemongrass, the bulb of Thunbergia thunbergii, the dry root of Belamcanda chinensis, the platycodon grandiflorum, the stir-fried seed of Radish, the salvia miltiorrhiza, and the roasted liquorice into a multifunctional extraction tank, add the oyster decoction and 8 times the amount (v / w) of purified water, soak for 1.5 hours, decoct at 100° C. for 2 hours each time, stir every 30 minutes, combine the two decoctions, filter through a 300-mesh stainless steel sieve to remove the medicinal residue, and concentrate the filtrate under reduced pressure to a relative density of 1.05-1.10 (60° C., measured by normal pressure method) to obtain a water-extracted filtrate; S4: Alcohol extraction of fat-soluble components of earthworm: Add the earthworm powder to a reflux extraction apparatus, add 70% ethanol solution (8 times the weight of the medicinal material), and reflux extract twice in a 75°C water bath for 2 hours each time. Combine the alcohol extracts and recover the ethanol by vacuum distillation (vacuum degree ≥ 0.08 MPa, temperature ≤ 60°C) to obtain an alcohol extract concentrate. S5: Mixing, refining and preparation molding: Filtrate mixing: transfer the water extraction filtrate and the earthworm alcohol extraction concentrate into a vacuum concentration tank and mix at low speed (50 rpm) for 30 minutes; Impurity treatment: add 0.2% (w / v) chitosan solution (dissolved in 1% acetic acid), stir for 30 minutes, let stand for 2 hours, filter and concentrate the filtrate to a relative density of 1.20-1.25 (60°C); Dosage form selection: choose to make granules, decoction or tablets.

3. The method for preparing a Chinese medicine composition for treating pulmonary fibrosis according to claim 2, wherein: In step S1, the botanical medicine includes mulberry bark, scutellaria baicalensis seeds, thunbergia thunbergii bulb, belamcanda vine, platycodon grandiflorum, stir-fried radish seeds, salvia miltiorrhiza, and roasted liquorice root.

4. A method for preparing a Chinese medicine composition for treating pulmonary fibrosis according to claim 3, characterized in that: In step S2, frying the oysters first can increase the calcium salt dissolution rate by 35%, and the amino acid components thereof are more soluble in water.

5. A method for preparing a Chinese medicine composition for treating pulmonary fibrosis according to claim 4, characterized in that: In step S3, when the water-soluble components are extracted by decoction, the plant cells are soaked for 1.5 hours to allow them to fully absorb water and the effective components to be easily dissolved.

6. A method for preparing a Chinese medicine composition for treating pulmonary fibrosis according to claim 5, characterized in that: In step S4, the 70% ethanol solution has moderate polarity, which allows for the extraction of both lumbrokinase protein components and fatty acid components, and the lumbrokinase activity retention rate after alcohol extraction is ≥85%.

7. A method for preparing a Chinese medicine composition for treating pulmonary fibrosis according to claim 6, characterized in that: In step S5, the specific method for preparing tablets is: adding starch and sodium carboxymethyl starch (disintegrant) to the concentrated solution, pressing into tablets, each tablet containing 0.5g of crude drug, with a hardness of 3-5kg and a disintegration time of ≤15 minutes.

8. The method for preparing a traditional Chinese medicine composition for treating pulmonary fibrosis according to claim 7, characterized in that: The composition can be prepared into granules or decoctions, which are respectively suitable for long-term use and acute use, to meet the needs of diversified clinical medication.

9. A method for preparing the granules of the Chinese medicine composition for treating pulmonary fibrosis according to claim 1, characterized in that: The following steps are involved: S1: Medicinal material pretreatment: Weigh each medicinal material in proportion, crush the oyster into 2-3 cm pieces, crush the earthworm, stir-fried bitter almonds, and stir-fried radish seeds into 60 mesh, remove impurities from the remaining medicinal materials, and set aside; S2: Oyster pre-fry: Add oyster pieces to the extraction tank, add 10 times the amount of purified water, soak for 20 minutes, then boil over high heat, reduce heat and fry for 30 minutes, filter through a 200-mesh sieve while hot, and collect the decoction; S3: Decoction of water-soluble components: Place mulberry bark, scutellaria baicalensis seeds, thunbergia thunbergii bulb, belamcanda Root, platycodon grandiflorum, stir-fried radish seeds, salvia miltiorrhiza, and roasted liquorice in an extraction tank. Add oyster decoction and 8 times the amount of purified water. Soak for 1.5 hours. Decoction at 100°C twice for 2 hours each time. Combine the decoctions and filter through a 300-mesh sieve. S4: Alcohol extraction of earthworms: Add 70% ethanol solution (8 times the weight of the medicinal material) to earthworm powder, reflux extract at 75°C twice, each time for 2 hours, and recover ethanol to obtain a concentrated solution; S5: Mixing and granulation: Mix the water decoction with the earthworm concentrate, concentrate under reduced pressure to a relative density of 1.10 (60°C), add an appropriate amount of dextrin, dry at 60°C after granulation, and package the whole granules. Each bag contains 20g of crude drug, and the solubility meets the following requirements: take 10g of granules and add 200ml of hot water, and the solubility rate within 5 minutes is ≥90%.

10. A method for preparing the Chinese medicine decoction for treating pulmonary fibrosis according to claim 1, characterized in that: The following steps are involved: S1: Preparation of medicinal materials: weigh the medicinal materials according to the proportion, crush the oysters, and wash and dry the remaining medicinal materials; S2: Fry the oysters first: add 10 times the amount of purified water to the oysters, bring to a boil over high heat, then simmer for 30 minutes over low heat; S3: Compound decoction: Add mulberry bark, scutellaria baicalensis seeds, thunbergia thunbergii, belamcanda vine, stir-fried bitter almonds, platycodon grandiflorum, stir-fried radish seeds, salvia miltiorrhiza, and roasted liquorice root, add 8 times the amount of purified water, soak for 1 hour, decoct at 100°C twice, each time for 1.5 hours, combine the decoctions, and filter through a 300-mesh sieve; S4: Packaging and sterilization: Pack the decoction into sterile bags, 150 ml per bag, and sterilize.

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