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

Abstract

The invention discloses a traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine, the traditional Chinese medicine composition comprises the following raw materials: pseudo-ginseng, ligusticum wallichii, astragalus membranaceus, American ginseng, lance asiabell root, sculellaria barbata, rhodiola rosea, fructus perillae, vinegar-processed curcuma zedoary, vinegar-processed turtle shell, semen lepidii and honey-fried licorice root; the invention further discloses a preparation method and application of the traditional Chinese medicine composition. Pseudo-ginseng and ligusticum wallichii are used as monarch drugs, have the effects of promoting blood circulation and qi circulation, dissipating blood stasis and relieving pain, and play roles through anti-inflammatory, anti-oxidation, immunoreaction regulation, anti-fibrosis and other mechanisms; the main active component panax notoginseng saponins of panax notoginseng can inhibit an NF-kB signal channel, regulate a TGF-beta1 / p38MAPK signal channel and the like to prevent and treat pulmonary fibrosis, and ligustrazine can resist platelet aggregation, inhibit pulmonary vascular structure reconstruction, reduce the content of lung tissue collagen and regulate inflammatory response, so that pulmonary fibrosis is prevented and treated.

Description

Technical Field

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

[0002] Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible chronic lung fibrosis disease. It is an interstitial lung disease with dry cough, progressive dyspnea and progressive deterioration of lung function as clinical characteristics. It belongs to the category of "lung paralysis" and "pulmonary atrophy" in traditional medicine. In recent years, due to viral infection and environmental changes, the number of patients suffering from IPF has continued to increase. The global incidence and prevalence of IPF have been increasing year by year, and it is more common in elderly men. At the same time, IPF patients have a poor prognosis, with a five-year survival rate of 20% to 40%, and a mortality rate higher than that of most tumors. Most patients' lung function deteriorates over time, and some patients with stable conditions may still experience acute respiratory exacerbations, and have multiple complications such as gastroesophageal reflux, which affects the patient's quality of life and physical and mental health.

[0003] The cause of IPF is unknown, and the pathogenesis has not been fully elucidated, but there is sufficient evidence to show that it is related to immune inflammatory damage. The characteristics of immune inflammatory response shown in different specimens are not consistent. Peripheral blood reflects more prominent immune abnormalities, while bronchoalveolar lavage fluid shows mainly inflammatory response. The abnormalities of local lung tissues are different, so this difference needs to be taken into account when evaluating various research data. Alveolar epithelial cell damage and abnormal repair are the main mechanisms leading to pulmonary fibrosis. After the injury occurs, the normal re-epithelialization process cannot be completed during the repair process, leading to alveolar-capillary damage. This process induces the production of cytokines, and fibroblasts express cytokine receptors on their surface. Under the action of cytokines, they gather at the site of injury and proliferate.

[0004] At present, IPF is mostly treated clinically with medication, lung transplantation, palliative care and other methods. Two anti-fibrosis drugs are recommended for drug treatment: pirfenidone and nintedanib. However, these two drugs have side effects such as gastrointestinal reactions and photosensitivity, and are ineffective in some patients. In addition, mainstream treatment drugs are expensive, with a high disease burden and poor compliance. In addition, lung transplantation, as the preferred method for moderate to severe disease, still has many limitations, such as insufficient donors, poor prognosis, and high costs.

[0005] In view of this, the inventor conducted in-depth research on this demand, and thus the present case was produced. Summary of the invention

[0006] The present invention is based on the holistic concept of traditional Chinese medicine, focuses on the pathogenesis, and expounds on the pathological factors of deficiency, blood stasis and phlegm, and provides a Chinese medicine composition for treating idiopathic pulmonary fibrosis, and its preparation method and application, to improve IPF physical weakness, weak qi and inability to circulate blood and blood stasis, or exogenous pathogenic obstruction, or seven emotions disorder and poor qi and blood stasis in the lung network and lung paralysis, long-term illness and mutual damage of yin and yang, and "long-term illness and poor circulation of qi and blood, blood stasis must be present in the blood network". The Chinese medicine composition follows the guidance of the Chinese medicine classic "Huangdi Neijing" that "the treatment of the disease must be sought from the root", and has the effect of multi-component, multi-target and multi-pathway treatment in the treatment of IPF.

[0007] A traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis comprises the following raw materials, measured by weight: 5-15 parts of Panax notoginseng, 5-15 parts of Chuanxiong, 25-35 parts of Astragalus, 10-20 parts of American ginseng, 5-15 parts of Conch shells, 15-25 parts of Scutellaria barbata, 3-9 parts of Rhodiola rosea, 5-15 parts of Curcuma zedoaria, 25-35 parts of Carapace of Trionycis vinegar, 5-15 parts of Perilla seeds, 10-20 parts of Lepidium melongena seeds, and 3-9 parts of roasted Licorice root.

[0008] Preferably, the following raw materials are included by weight: 7-13 parts of Panax notoginseng, 7-13 parts of Chuanxiong, 27-33 parts of Astragalus, 12-18 parts of American ginseng, 7-13 parts of Conch shells, 17-23 parts of Scutellaria barbata, 4-8 parts of Rhodiola rosea, 7-13 parts of pickled Curcuma, 27-33 parts of pickled turtle shell, 7-13 parts of Perilla seed, 12-18 parts of Lepidium melongena, and 4-8 parts of roasted Licorice root.

[0009] Preferably, the following raw materials are included by weight: 9-11 parts of Panax notoginseng, 9-11 parts of Chuanxiong, 29-31 parts of Astragalus, 14-16 parts of American ginseng, 9-11 parts of Conch shells, 19-21 parts of Scutellaria barbata, 5-7 parts of Rhodiola rosea, 9-11 parts of pickled Curcuma, 29-31 parts of pickled turtle shell, 9-11 parts of Perilla seed, 14-16 parts of Lepidium melongena, and 5-7 parts of roasted Licorice root.

[0010] Preferably, the following raw materials are included by weight: 10 parts of Panax notoginseng, 10 parts of Chuanxiong, 30 parts of Astragalus, 15 parts of American ginseng, 10 parts of Conch shells, 20 parts of Scutellaria barbata, 6 parts of Rhodiola rosea, 10 parts of pickled Curcuma, 30 parts of pickled turtle shell, 10 parts of Perilla seed, 15 parts of Lemongrass seed, and 6 parts of roasted Licorice root.

[0011] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis in preparing a medicine for treating idiopathic pulmonary fibrosis.

[0012] The present invention also provides a medicine for treating idiopathic pulmonary fibrosis, comprising the above-mentioned traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis and pharmaceutically acceptable adjuvants.

[0013] Preferably, the dosage form of the drug is a Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

[0014] Preferably, the medicine is a Chinese medicine decoction, and its preparation method is as follows:

[0015] Step 1, weighing the raw materials according to the weight ratio, cleaning, drying, cutting, crushing, sieving, and mixing evenly;

[0016] Step 2, adding water to the raw material drug and refluxing to extract twice, collecting volatile oil at the same time, combining the two extracts, and then centrifuging the extracts to obtain the supernatant;

[0017] Step 3: Concentrate the supernatant in step 2 under reduced pressure, transfer and dispense into clean containers, add volatile oil, make up to volume, mix well, dispense, and store at low temperature.

[0018] Preferably, the water-adding reflux extraction in step 2 is performed twice, the first time 7 to 9 times the amount of water is added, the extraction is performed for 1 to 2 hours, and the volatile oil is collected at the same time; the second time 5 to 7 times the amount of water is added, the extraction is performed for 0.5 to 1.5 hours, and the volatile oil is collected at the same time; the centrifugal speed is 2000 to 4000 r / min, and the time is 4 to 6 min.

[0019] Preferably, the temperature of the reduced pressure concentration in step 3 is 58 to 60°C; and the temperature of the low temperature storage is -15 to -25°C.

[0020] The beneficial effects produced by the technical solution of the present invention are as follows:

[0021] The Chinese medicine composition provided by the present invention uses Panax notoginseng and Chuanxiong as the main drugs, which can promote blood circulation and qi, dissipate blood stasis and relieve pain. The two play a role through anti-inflammatory, anti-oxidation, immune response regulation and anti-fibrosis mechanisms. Panax notoginseng total saponins, the main active ingredient of Panax notoginseng, can inhibit NF-κB signaling pathway, regulate TGF-β1 / p38MAPK signaling pathway and prevent and treat pulmonary fibrosis; Chuanxiongzine can resist platelet aggregation, inhibit pulmonary vascular structure reconstruction, reduce the collagen content of lung tissue, and regulate inflammatory response, thereby preventing and treating pulmonary fibrosis. Astragalus and American ginseng are compatible, which can nourish qi and yin; Mountain conch and Scutellaria barbata are compatible to nourish the middle qi, promote blood circulation and remove blood stasis, moisten the lungs and detoxify; Rhodiola rosea is compatible with Astragalus and American ginseng to replenish deficiency, regulate qi and nourish blood, and work together with Mountain conch and Scutellaria barbata to promote blood circulation, clear lungs and relieve pain, and they are all ministerial drugs. Curcuma zedoaria can promote qi and dissolve blood, eliminate stagnation and relieve pain. When used together with turtle shell, it can nourish yin and suppress yang, soften and disperse nodules. The two medicines can enhance the effect of promoting blood circulation and removing blood stasis. Perilla seeds are pungent and warm, good at lowering lung qi, resolving phlegm and saliva, relieving asthma and relieving cough. Lemongrass seeds are bitter and cold, good at purging lung heat, relieving asthma and relieving cough. The two medicines are mutually cold and warm, and they are adjuvants. Roasted licorice root nourishes the spleen and replenishes qi, and harmonizes all the medicines. It is a guiding medicine. All the medicines are used together to treat both the symptoms and the root causes, and to attack and supplement at the same time, so as to achieve the effects of promoting blood circulation and unblocking collaterals, replenishing qi and nourishing yin, dispersing nodules and resolving phlegm.

[0022] In addition, the Chinese medicine composition provided by the present invention adopts natural Chinese medicine for treatment, has multiple curative effects, and has significant curative effects, and has the effect of improving the disease in multiple ways and multiple targets. The low, medium and high dose groups of animal experimental prescriptions can improve the weight, lung coefficient, survival rate and other aspects of IPF mice, and at the same time, the disease progression of IPF mice is delayed by improving the dual angles of pulmonary inflammatory infiltration and collagen deposition, and anti-inflammatory and anti-fibrosis effects are exerted. Compared with the current anti-fibrosis drug pirfenidone, it can reduce the number of deaths and has significant curative effects. Moreover, based on the formula, various convenient preparation forms such as granule formulas or soups can be provided for clinical application, which is easy to popularize and promote, and the patient acceptance is high, which can improve the compliance of the patient's drug use. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 The survival curves of the mice in each group in the embodiment;

[0025] Figure 2 The weight change diagram of each group of mice in the embodiment;

[0026] Figure 3 The lung coefficient diagram of each group of mice in the embodiment;

[0027] Figure 4 The lung tissue of each group of mice in the embodiment is shown in FIG.

[0028] Figure 5 HE staining images of liver tissues of mice in each group in the example (400×);

[0029] Figure 6 HE staining images of kidney tissues of mice in each group in the example (400×);

[0030] Figure 7 HE staining images of lung tissues of mice in each group in the example (200×, 400×);

[0031] Figure 8 Masson staining images of lung tissues of mice in each group in the example (200×, 400×);

[0032] Fig. 9 Figure 2 is a graph of hydroxyproline levels in lung tissue and serum of each group of mice in the example;

[0033] Fig.10The inflammatory factor levels in the serum of each group of mice in the embodiment;

[0034] Fig.11 The mRNA level diagram of lung tissue fibrosis related indicators of each group of mice in the embodiment;

[0035] Fig.12 The protein level diagram of lung tissue fibrosis related indicators of each group of mice in the embodiment;

[0036] Fig.13 Statistical graphs of protein levels of lung tissue fibrosis-related indicators of each group of mice in the example. DETAILED DESCRIPTION

[0037] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Therefore, the following detailed description of the embodiments provided by the present invention is not intended to limit the scope of the claimed invention, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] This embodiment fully analyzes the related problems of IPF, such as physical weakness, weak qi and inability to circulate blood, blood stasis, or obstruction by exogenous pathogens, or imbalance of qi and poor qi movement, which leads to obstruction of lung collaterals and lung paralysis, and mutual damage of yin and yang due to long-term illness, and "long-term illness leads to poor circulation of qi and blood, and blood stasis must occur in the blood vessels". A Chinese medicine composition for the treatment of idiopathic pulmonary fibrosis, a preparation method and application thereof are provided, including the following raw materials: Panax notoginseng, Chuanxiong, Astragalus, American ginseng, Conch, Scutellaria barbata, Rhodiola rosea, Curcuma zedoaria, Carapax tricolor, Perilla seed, Lepidium membranaceus seed, and Radix Glycyrrhizae uralensis.

[0039] Panax notoginseng: It is the dried root and rhizome of Panax notoginseng of the Araliaceae family. It tastes sweet and slightly bitter, is warm in nature, and enters the liver and stomach meridians. It has the effects of dispersing blood stasis and stopping bleeding, reducing swelling and relieving pain. Panax notoginseng mainly contains tetracyclic triterpenoid components such as ginsenoside, notoginsenoside, and aescin. In addition, it also contains substances such as notoginseng, quercetin, and polysaccharides. It has the effects of dispersing blood stasis and stopping bleeding, reducing swelling and relieving pain.

[0040] Chuanxiong: It is the dried rhizome of the plant Chuanxiong of the Umbelliferae family. It tastes bitter and pungent, is warm in nature, and enters the liver meridian, gallbladder meridian, and pericardium meridian. It has the effects of promoting blood circulation and qi, dispelling wind and relieving pain. The chemical components of Chuanxiong are mainly phthalides, terpenes, enols, ligustrazine, 1-acetyl-β-carboline, adenosine, niacin, protocatechuic acid, ferulic acid, polysaccharides, etc. It has a wide range of pharmacological activities on the nervous, respiratory, and cardiovascular and cerebrovascular systems, and plays a pharmacological role in protecting nerves, anti-inflammation, anti-oxidation, and anti-coagulation.

[0041] Astragalus: It is the dried root of Astragalus mongolica or Astragalus membranaceus, a plant of the Leguminosae family. It is sweet in taste, slightly warm in nature, and enters the lung and spleen meridians. It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. The main active ingredients of Astragalus include total astragalosides, astragaloside IV, astragaloside polysaccharides, astragaloside glycoproteins, astragaloside flavonoids, amino acids, etc. Modern pharmacological studies have shown that Astragalus can improve immunity, coordinate the function of the oxidative stress system, regulate blood lipids, and have anti-fibrosis, antibacterial and antiviral effects.

[0042] American ginseng: It is the dried root of American ginseng, a plant of the Araliaceae family. It tastes sweet and slightly bitter, is cool in nature, and enters the heart, lung, and kidney meridians. It has the effects of replenishing qi and nourishing yin, clearing away heat and promoting body fluid, and is used for qi deficiency and yin deficiency, deficiency heat and fatigue, cough, asthma, sputum and blood, internal heat and thirst, dry mouth and throat, etc. American ginseng contains a variety of triterpenoid saponins such as ginsenoside Rb1, Rc, Rd, R, Rq1, as well as polysaccharides, flavonoids, volatile oils, proteins, amino acids, nucleic acids, peptides, sterols, starch, vitamins, fatty acids, organic acids, minerals, etc.

[0043] Mountain snail: It is the root of the plant milkwort of Campanulaceae. It tastes sweet and spicy, is neutral in nature, and enters the spleen and lung meridians. It has the effects of nourishing qi and yin, detoxifying and reducing swelling, draining pus, and promoting lactation. Mountain snail mainly contains chemical components such as triterpenoid saponins, alkaloids, and phenylpropanol glycosides. Modern pharmacological studies have shown that mountain snail has pharmacological effects such as antioxidant, sedative, analgesic, anticonvulsant, anti-inflammatory, lipid-lowering, anti-thrombotic, and immunomodulatory.

[0044] Scutellaria barbata: It is the dried whole herb of Scutellaria barbata, a plant of the Labiatae family. It tastes pungent and bitter, is cold in nature, and enters the lung, liver, and kidney meridians. It has the effects of clearing away heat and detoxifying, dispersing blood stasis and stopping bleeding, and diuresis and swelling. Its chemical components include flavonoids, flavanones, flavonoid glycosides and chalcones, diterpenes and their lactones, polysaccharide components, volatile oils, trace elements, etc. Modern pharmacology has confirmed that it has anti-cancer, antibacterial, anti-inflammatory, antiviral, antioxidant, and immunomodulatory effects.

[0045] Rhodiola rosea: It is the dried root and rhizome of the Crassulaceae plant Rhodiola rosea. It tastes sweet, bitter, and flat. It enters the lung and heart meridians. It has the effects of invigorating qi and activating blood circulation, unblocking meridians and relieving asthma. It is often used for qi deficiency and blood stasis, chest pain, heart pain, hemiplegia caused by stroke, fatigue and asthma. Rhodiola rosea mainly contains salidroside, salidroside aglycone, diphenylmethyl hexahydropyridine, B-sitosterol and other ingredients, which have the effects of invigorating qi and activating blood circulation, unblocking meridians and relieving asthma.

[0046] Vinegar Curcuma: It is the dried rhizome of Curcuma zedoaria, Curcuma guangxiensis, and Curcuma wenjin, plants of the genus Curcuma in the ginger family. It tastes pungent and bitter, is warm in nature, and enters the liver and spleen meridians. It has the effects of promoting qi and removing blood, eliminating accumulation and relieving pain. Modern phytochemical research shows that the chemical components of Curcuma zedoaria mainly contain volatile oils and curcumin, polysaccharides, sterols, phenolic acids, alkaloids, etc. Modern pharmacological research shows that Curcuma zedoaria has multiple pharmacological effects such as anti-tumor, anti-thrombotic, blood lipid regulating, anti-fibrosis of liver, kidney and lung tissues, anti-inflammatory and analgesic, antibacterial and antiviral, hypoglycemic, and antioxidant.

[0047] Vinegar-soaked turtle shell: It is the carapace of the turtle of the family Testudinidae. It tastes salty, is slightly cold in nature, and enters the liver and kidney meridians. It can nourish yin and suppress yang, reduce fever and eliminate steaming, soften and disperse lumps. It is used for fever due to yin deficiency, bone steaming and fever due to fatigue, hyperactivity of yang due to yin deficiency, dizziness, internal movement of wind, spasms in the hands and feet, amenorrhea, masses, and chronic malaria. Turtle shell mainly contains animal glue, keratin, iodine and vitamin D, which can inhibit the proliferation of connective tissue of the liver and spleen, increase the level of plasma protein, and have anti-tumor effects.

[0048] Perilla seeds: the dried mature fruit of Perilla frutescens of the Lamiaceae family. It is pungent, warm in nature, non-toxic, and has the effects of lowering qi and eliminating phlegm, relieving asthma, and moistening the intestines. It is clinically used to treat diseases such as phlegm-stagnation and qi reversal, cough and asthma, and constipation caused by dry intestines. Its chemical components mainly include volatile oils, flavonoid compounds, phenolic acid compounds, triterpenes and sterol compounds, glycoside compounds, fatty acid compounds, alkaloid compounds, etc. Modern pharmacological studies have shown that Perilla seeds have the effects of relieving cough, relieving asthma, anti-aging, anti-oxidation, anti-allergy, and lowering blood lipids.

[0049] Lepidium sativum seeds: The dried mature seeds of Artemisia sophora japonica or Lepidium sativum, a plant of the cruciferous family. It is pungent in taste and cold in nature. It has the effects of purging the lungs and relieving asthma, promoting diuresis and reducing swelling. The main chemical components of Lepidium sativum seeds include glucosinolates, isothiocyanates, flavonoids, phenylpropanoids, etc. Its extract has good pharmacological activity in improving cardiovascular function, relieving cough, removing phlegm, relieving asthma, and diuresis.

[0050] Licorice root: It is the dried root and rhizome of the leguminous plants licorice, licorice glabra or licorice inflated fruit. It tastes sweet and is neutral in nature. It enters the heart, lung, spleen and stomach meridians. It has the effects of clearing away heat and detoxification, removing phlegm and relieving cough, tonifying the spleen and lungs, and relieving pain. The chemical components of licorice root mainly include triterpenoid saponins, flavonoids, polysaccharides, coumarins and alkaloids. Its pharmacological effects include anti-tumor, anti-depression, anti-inflammatory, anti-arrhythmic, liver protection, antioxidant and immunomodulatory.

[0051] As a preferred embodiment, the invention comprises the following raw materials in parts by weight: 5-15 parts of Panax notoginseng, 5-15 parts of Chuanxiong, 25-35 parts of Astragalus, 10-20 parts of American ginseng, 5-15 parts of Conch shells, 15-25 parts of Scutellaria barbata, 3-9 parts of Rhodiola rosea, 5-15 parts of Curcuma zedoaria, 25-35 parts of Carapace of Turtle in vinegar, 5-15 parts of Perilla seed, 10-20 parts of Lepidium melongena, and 3-9 parts of roasted Licorice root.

[0052] As a preferred embodiment, the invention comprises the following raw materials in parts by weight: 7-13 parts of Panax notoginseng, 7-13 parts of Chuanxiong, 27-33 parts of Astragalus, 12-18 parts of American ginseng, 7-13 parts of Conch shells, 17-23 parts of Scutellaria barbata, 4-8 parts of Rhodiola rosea, 7-13 parts of Curcuma zedoaria, 27-33 parts of Carapace of turtle in vinegar, 7-13 parts of Perilla seed, 12-18 parts of Lepidium melongena, and 4-8 parts of roasted Licorice root.

[0053] As a preferred embodiment, the invention comprises the following raw materials in parts by weight: 9-11 parts of Panax notoginseng, 9-11 parts of Chuanxiong, 29-31 parts of Astragalus, 14-16 parts of American ginseng, 9-11 parts of Conch shells, 19-21 parts of Scutellaria barbata, 5-7 parts of Rhodiola rosea, 9-11 parts of Curcuma zedoaria, 29-31 parts of Carapace of Turtle in vinegar, 9-11 parts of Perilla seed, 14-16 parts of Lepidium melongena, and 5-7 parts of Radix Glycyrrhizae Radix.

[0054] As a preferred embodiment, the invention comprises the following raw materials by weight: 10 parts of Panax notoginseng, 10 parts of Chuanxiong, 30 parts of Astragalus, 15 parts of American ginseng, 10 parts of Conch shells, 20 parts of Scutellaria barbata, 6 parts of Rhodiola rosea, 10 parts of pickled Curcuma zedoaria, 30 parts of pickled turtle shell, 10 parts of Perilla seed, 15 parts of Lemongrass seed, and 6 parts of roasted Licorice root.

[0055] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis in preparing a medicine for treating idiopathic pulmonary fibrosis.

[0056] The present invention also provides a medicine for treating idiopathic pulmonary fibrosis, comprising the above-mentioned traditional Chinese medicine composition for treating idiopathic pulmonary fibrosis and pharmaceutically acceptable adjuvants.

[0057] As a preferred embodiment, the dosage form of the drug is a Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

[0058] As a preferred embodiment, the medicine is a Chinese medicine decoction, and its preparation method is as follows:

[0059] Step 1, weighing the raw materials according to the weight ratio, cleaning, drying, cutting, crushing, sieving, and mixing evenly;

[0060] Step 2, adding water to the raw material drug and refluxing to extract twice, collecting volatile oil at the same time, combining the two extracts, and then centrifuging the extracts to obtain the supernatant;

[0061] Step 3: Concentrate the supernatant in step 2 under reduced pressure, transfer and dispense into clean containers, add volatile oil, make up to volume, mix well, dispense, and store at low temperature.

[0062] As a preferred embodiment, the water reflux extraction in step 2 is performed twice, the first time 7 to 9 times the amount of water is added, the extraction is performed for 1 to 2 hours, and the volatile oil is collected at the same time; the second time 5 to 7 times the amount of water is added, the extraction is performed for 0.5 to 1.5 hours, and the volatile oil is collected at the same time; the centrifugal speed is 2000 to 4000 r / min, and the time is 4 to 6 min.

[0063] As a preferred embodiment, the temperature of the reduced pressure concentration in the step three is 58 to 60°C; the temperature of the low temperature storage is -15 to -25°C.

[0064] The present invention is further described in detail below in conjunction with specific embodiments:

[0065] Example 1

[0066] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 5 parts of Panax notoginseng, 5 parts of Chuanxiong, 25 parts of Astragalus, 10 parts of American ginseng, 5 parts of Conch, 15 parts of Scutellaria barbata, 3 parts of Rhodiola rosea, 5 parts of Curcuma zedoariae, 25 parts of Carapax trichosanthis, 5 parts of Perilla seeds, 10 parts of Lemongrass seeds, and 3 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 1 is a Chinese medicine decoction, and its preparation method is as follows:

[0067] Step 1, weighing the raw materials according to the weight ratio, cleaning, drying, cutting, crushing, sieving, and mixing evenly;

[0068] Step 2: The API was extracted twice by reflux with water. For the first extraction, 8 times the amount of water was added and the extraction was performed for 1.5 hours, and the volatile oil was collected at the same time. For the second extraction, 6 times the amount of water was added and the extraction was performed for 1 hour, and the volatile oil was collected at the same time. The extracts were combined and centrifuged to obtain the supernatant at a speed of 3000 r / min for 5 minutes.

[0069] Step 3: Concentrate the supernatant in step 2 under reduced pressure at 60°C to an appropriate volume, transfer and dispense into clean containers, add volatile oil, make up to volume, mix well, dispense, and store at -20°C.

[0070] Example 2

[0071] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 7 parts of Panax notoginseng, 7 parts of Chuanxiong, 27 parts of Astragalus, 12 parts of American ginseng, 7 parts of Conch, 17 parts of Scutellaria barbata, 4 parts of Rhodiola rosea, 7 parts of Curcuma zedoariae, 27 parts of Carapax trichosanthis, 7 parts of Perilla seeds, 12 parts of Lemon seeds, and 4 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 2 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0072] Example 3

[0073] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 9 parts of Panax notoginseng, 9 parts of Chuanxiong, 29 parts of Astragalus, 14 parts of American ginseng, 9 parts of Conch, 19 parts of Scutellaria barbata, 5 parts of Rhodiola rosea, 9 parts of Curcuma zedoariae, 29 parts of Carapax trichosanthis, 9 parts of Perilla seeds, 14 parts of Lemon seeds, and 5 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 3 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0074] Example 4

[0075] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 10 parts of Panax notoginseng, 10 parts of Chuanxiong, 30 parts of Astragalus, 15 parts of American ginseng, 10 parts of Conch, 20 parts of Scutellaria barbata, 6 parts of Rhodiola rosea, 10 parts of Curcuma zedoariae, 30 parts of Carapax trichosanthis, 10 parts of Perilla seeds, 15 parts of Lemongrass seeds, and 6 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 4 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0076] Example 5

[0077] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 11 parts of Panax notoginseng, 11 parts of Chuanxiong, 31 parts of Astragalus, 16 parts of American ginseng, 11 parts of Conch, 21 parts of Scutellaria barbata, 7 parts of Rhodiola rosea, 11 parts of Curcuma zedoariae, 31 parts of Carapax trichosanthis, 11 parts of Perilla seeds, 16 parts of Lemon seeds, and 7 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 5 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0078] Example 6

[0079] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 13 parts of Panax notoginseng, 13 parts of Chuanxiong, 33 parts of Astragalus, 18 parts of American ginseng, 13 parts of Conch, 23 parts of Scutellaria barbata, 8 parts of Rhodiola rosea, 13 parts of Curcuma zedoariae, 33 parts of Carapax trichosanthis, 13 parts of Perilla seeds, 18 parts of Lemon seeds, and 8 parts of Radix Glycyrrhizae Preparata. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 6 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0080] Example 7

[0081] A medicine for treating idiopathic pulmonary fibrosis, wherein the raw materials of Chinese medicine formula are grabbed according to the following mass parts: 15 parts of Panax notoginseng, 15 parts of Chuanxiong, 35 parts of Astragalus, 20 parts of American ginseng, 15 parts of Conch, 25 parts of Scutellaria barbata, 9 parts of Rhodiola rosea, 15 parts of Curcuma zedoariae, 35 parts of Carapax trichosanthis, 15 parts of Perilla seeds, 20 parts of Lemon seeds, and 9 parts of Radix Glycyrrhizae. The medicine for treating idiopathic pulmonary fibrosis in this embodiment 7 is a Chinese medicine decoction, and its preparation method is the same as that in embodiment 1.

[0082] In order to verify the effect of the Chinese medicine composition provided by the present invention on pulmonary fibrosis, the following experiments were conducted:

[0083] Experiment 1: The drug prepared in the preferred embodiment 4 was used to conduct an experiment to identify the effect of the dosage used in the present invention on the drug efficacy:

[0084] 1. Experimental Animals

[0085] 90 SPF-grade healthy male C57BL / 6J mice, 8-10 weeks old, weighing 20-25 g, were purchased from Guangdong Weitonglihua Experimental Animal Technology Co., Ltd. (Animal Production License No. SCXK (Guangdong) 2022-0063) and raised in the SPF-grade Animal Experiment Center of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The experimental environment: constant temperature of 20-25 ° C, relative humidity of 40-60%, light cycle of 12 hours, free access to food and water, and the experiment began after 1 week of adaptive feeding.

[0086] 2. Experimental drugs and equipment

[0087] Bleomycin sulfate (purchased from Shanghai MacLean Biochemical Technology Co., Ltd., B802467); pirfenidone (purchased from Shanghai TCI Chemical Industry Development Co., Ltd., P1871); small animal laryngoscope (purchased from Shanghai Yuyan Scientific Instrument Co., Ltd., SR310-M), digital pathology section scanning system (3D HISTEC, Pannoramic MIDI).

[0088] 3. Modeling and experimental grouping

[0089] 3.1 Experimental Grouping

[0090] After 1 week of adaptive feeding, 90 mice were randomly divided into 6 groups, 15 mice in each group, namely:

[0091] ①Control group,

[0092] ②Model group,

[0093] ③ Positive drug group (pirfenidone group),

[0094] ④ Example 4 low dose group,

[0095] 5. The medium dose group of the drug in Example 4,

[0096] 6. high dose group of the drug of Example 4;

[0097] 3.2 Model construction

[0098] Except for the control group, the rest of the mice were treated with a one-time intratracheal instillation of 3.5 mg / kg bleomycin to establish an IPF mouse model. The control group was instilled with normal saline. The instillation method was: the mouse was hung vertically, the mouse tongue was gently pulled with forceps, and the laryngoscope was inserted to see the glottic fissure. The drug solution was slowly instilled with the mouse's breathing rhythm, and the liquid was seen entering the trachea with breathing. After the instillation was completed, the mouse was immediately rotated upright to evenly distribute the drug solution in both lungs, and the mouse was continued to be fed after waking up.

[0099] 3.3 Administration

[0100] From the first day after modeling, each group of mice was given 2uL / g of the corresponding solution according to the weight of the mice, once a day. Among them, the low-dose group, medium-dose group and high-dose group of the drug in Example 4 were given 0.5, 1, and 2 times the clinical dose of the drug prepared in Example 4, that is, according to the weight of the mice, 11.18g / kg, 22.36g / kg, and 44.72g / kg of the mouse weight were given daily, respectively, and the mice were gavaged continuously for 21 days. The mice in the positive drug group were given pirfenidone 100mg / kg, and they were gavaged continuously for 21 days. The control group and the model group were given an equal amount of normal saline, and they were gavaged continuously for 21 days.

[0101] 4. Observation indicators

[0102] 4.1 Observe the general condition of mice: Observe the general condition and survival status of mice during the experiment, record their weight and mortality, and calculate the daily weight changes and survival rate of mice.

[0103] 4.2 Detection of mouse lung coefficient: Weigh the whole lung weight of the mouse and calculate the lung coefficient. Lung coefficient = whole lung weight / body weight on the 21st day × 100%.

[0104] 4.3 Observation of mouse lung tissue and histopathological changes: Observe the gross appearance of mouse lung tissue, and evaluate the degree of lung inflammatory infiltration and collagen deposition by HE staining and Masson staining; evaluate the hepato-renal toxicity of the drug by HE staining of liver and kidney tissues.

[0105] 4.4 Detection of hydroxyproline content in mice: The hydroxyproline content in mouse lung tissue and serum was detected by alkaline hydrolysis method.

[0106] 4.5 Detection of inflammatory factor-related indicators in mouse serum: ELISA method was used to detect the levels of IL-6, IL-8, TNF-α, and TGF-β in mouse serum.

[0107] 4.6 Detection of fibrosis-related mRNA levels in mouse lung tissue: RNA was extracted from mouse lung tissue by Trizol method, and the concentration and purity were determined. RT-PCR was used to detect the mRNA expression levels of α-SMA, Col1a1, Col3a1, E-cadherin, Fibronectin, Vim, Tnc and TGF-β in mouse lung tissue.

[0108] 4.7 Detection of fibrosis-related protein levels in mouse lung tissue: The BCA method was used to extract mouse lung tissue proteins, and western blot was used to observe the protein levels of α-SMA, Collagen I, Fibronectin and E-cadherin in lung tissue.

[0109] 5. Statistical methods

[0110] Statistical analysis was performed using GraphadPrism 8.4.3 software, and all data in the experiments were expressed as mean ± standard error. One-way analysis of variance was used for multiple groups, and Dunnett's method or Dunnett's T3 method was used for pairwise comparisons between groups according to the homogeneity of variance; Kruskal Wallis nonparametric test was used for non-normal distribution, and Dunns method was used for pairwise comparisons between groups. P < 0.05 was considered statistically significant.

[0111] 6. Results Analysis

[0112] (1) By Figures 1-2 It can be seen that as the experiment progressed, a total of 5 mice died in the model group and a total of 4 mice died in the positive drug group. After treatment, the low, medium and high doses of the drug in Example 4 can reduce the number of deaths of IPF mice (2, 1 and 1 deaths, respectively). Moreover, the weight loss of mice in the positive drug group and the low, medium and high dose groups of the drug in Example 4 was improved, and recovered earlier than the model group.

[0113] (2) By Figure 3 (Compared with the control group, ### P<0.001; compared with the model group, * P < 0.05), it can be seen that after treatment, the lung coefficients of mice in the positive drug group and the low, medium and high dose groups of the drug in Example 4 were significantly improved, and the effect of the drug dose group in Example 4 was more obvious than that of the positive drug group, and the difference was statistically significant (P < 0.05).

[0114] (3) By Figures 4 to 8 It can be seen that compared with the positive drug group, the dark red congestion of the lung tissue of mice treated with the low, medium and high dose groups of the drug in Example 4 was significantly improved, especially the drug effect of the medium and high dose groups was better. Figure 4; The pathological results of the liver and kidney tissues of each group of mice after HE staining showed that the low, medium and high dose groups of the drug in Example 4 had no hepatotoxicity to the mice (P>0.05). Figure 5 (Compared with the control group, ns P>0.05; compared with the model group, ns P>0.05) and Figure 6 (Compared with the control group, ns P>0.05; compared with the model group, ns P>0.05); The pathological results of lung tissues of mice in each group after HE staining and Masson staining showed that compared with the positive drug group, the low, medium and high dose groups of Example 4 were able to effectively improve alveolitis (P<0.0001) and collagen deposition (P<0.0001) after drug treatment. Figure 7 (Compared with the control group, #### P<0.0001; compared with the model group, **** P<0.0001) and Figure 8 (Compared with the control group, #### P<0.0001; compared with the model group, **** P<0.0001).

[0115] (4) By Fig. 9 It can be seen that compared with the positive drug group, the hydroxyproline content in the lung tissue (P < 0.0001) and serum (P < 0.0001) of the mice treated with the low, medium and high dose groups of the drug in Example 4 was reduced, and the difference was statistically significant. Fig. 9 (Compared with the control group, #### P<0.0001; compared with the model group, * P<0.05, ** P<0.01, **** P<0.0001).

[0116] (5) By Fig.10 It can be seen that the inflammatory factors IL-6 (P < 0.05), IL-8 (P < 0.01), TNF-α (P < 0.05) and TGF-β (P < 0.0001) in the serum of mice treated with the low, medium and high dose groups of the drug in Example 4 were all reduced. Fig.10 (Compared with the control group, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01).

[0117] (6) By Fig.10It can be seen that the mRNA levels of fibrosis-related markers α-SMA, Col1a1, Col3a1, E-cadherin, Fibronectin, VIM, TNC and TGF-β in the lung tissue of mice treated with the low, medium and high dose groups of the drug in Example 4 were improved (P < 0.05). Fig.10 (Compared with the control group, ## P<0.01, ### P < 0.001, #### P<0.0001; compared with the model group, * P<0.05, ** P<0.01, *** P < 0.001, **** P<0.0001).

[0118] (7) By Fig.11 It can be seen that the mRNA levels of fibrosis-related markers α-SMA (P < 0.0001), Col1a1 (P < 0.01), Col3a1 (P < 0.01), E-cadherin (P < 0.05), Fibronectin (P < 0.0001), Vin (P < 0.0001), Tnc (P < 0.0001) and TGF-β (P < 0.05) in the lung tissue of mice treated with the low, medium and high dose groups of the drug in Example 4 were improved. Fig.11 (Compared with the control group, ## P<0.01, ### P<0.0001; compared with the model group, * P<0.05, ** P<0.01, *** P < 0.001, **** P<0.0001).

[0119] (8) By Figures 12-13 It can be seen that the protein levels of fibrosis-related markers α-SMA (P < 0.0001), Collagen I (P < 0.0001), Fibronectin (P < 0.01) and E-cadherin (P < 0.001) in the lung tissue of mice treated with the low, medium and high dose groups of the drug in Example 4 were all improved (P < 0.01). Fig.12 and Fig.13 (Compared with the control group, ### P < 0.001, #### P<0.0001; compared with the model group, ** P<0.01, *** P < 0.001, **** P<0.0001).

[0120] In summary, this study and invention fully demonstrates that the formula can improve the degree of alveolitis and collagen deposition in IPF based on animal experiments, and is slightly better than pirfenidone.

[0121] Typical cases:

[0122] Case 1:

[0123] Patient Tan, female, 70 years old, had repeated coughs for more than 3 months. Came to our hospital for treatment in September 2024, with clinical manifestations of cough and sputum, sticky sputum, weakness and slight edema in the lower limbs, general appetite and sleep, normal bowel movements, pale red tongue, thin white fur, and stringy pulse. Chinese medicine diagnosis: lung bi-Qi deficiency and blood stasis type. Orally take the Chinese medicine decoction containing Example 4 provided by the present invention, 1 dose per day, decocted twice, decocted in water to 250-300mL each time, warmed after meals, and treated for 4 weeks. After taking the medicine, the patient's cough and sputum symptoms improved. It shows that this prescription can relieve symptoms such as cough in patients with idiopathic pulmonary fibrosis, and has a better effect on patients with Qi deficiency and blood stasis.

[0124] Case 2:

[0125] Patient Luo, female, 48 years old, had repeated dry cough for more than 2 years. Came to our hospital for treatment in April 2024, clinical manifestations were cough, less sputum, white and sticky, severe cough during the day, occasional cough at night, slightly dry mouth, no shortness of breath, slightly dizzy, fatigue, poor appetite and sleep, two bowel movements, pale tongue with white greasy coating, and stringy and smooth pulse. Chinese medicine diagnosis: lung bi-Qi deficiency and blood stasis type. Oral Chinese medicine decoction containing Example 4 provided by the present invention, 1 dose per day, decocted twice, decocted in water to 250-300mL each time, warmed after meals, and treated for 3 weeks. After taking the medicine, the patient coughed and expectorated, and the symptoms of fatigue improved. It shows that this prescription can relieve symptoms such as cough and sputum in patients with idiopathic pulmonary fibrosis, and has a better effect on patients with Qi deficiency and blood stasis.

[0126] Case 3:

[0127] Patient Zhong, male, 71 years old, had repeated coughs for more than 1 year. He came to our hospital for treatment in September 2024. The clinical manifestations were repeated coughs, phlegm in the throat that was difficult to cough up, chest tightness and shortness of breath, occasional headaches and dizziness, fatigue, good appetite, regular bowel movements, pale red tongue with white greasy fur, and deep and astringent pulse. Chinese medicine diagnosis: lung arthralgia-Qi deficiency and blood stasis type. Orally take the Chinese medicine decoction containing Example 4 provided by the present invention, 1 dose per day, decocted twice, decocted in water to 250-300mL each time, warm after meals, and treat for 3 weeks. After taking the medicine, the patient coughed and expectorated, and the symptoms of fatigue improved. This shows that this prescription can relieve symptoms such as cough, sputum, fatigue, etc. in patients with idiopathic pulmonary fibrosis, and has a better effect on patients with Qi deficiency and blood stasis.

[0128] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating idiopathic pulmonary fibrosis, characterized in that: The invention comprises the following raw materials by weight: 5-15 parts of Panax notoginseng, 5-15 parts of Chuanxiong, 25-35 parts of Astragalus, 10-20 parts of American ginseng, 5-15 parts of Conch shells, 15-25 parts of Scutellaria barbata, 3-9 parts of Rhodiola rosea, 5-15 parts of Curcuma zedoariae with vinegar, 25-35 parts of turtle shell with vinegar, 5-15 parts of Perilla seed, 10-20 parts of Lepidium membranaceus seed and 3-9 parts of roasted Licorice root.

2. The Chinese medicine composition for treating idiopathic pulmonary fibrosis according to claim 1, characterized in that: The invention comprises the following raw materials by weight: 7-13 parts of Panax notoginseng, 7-13 parts of Chuanxiong, 27-33 parts of Astragalus, 12-18 parts of American ginseng, 7-13 parts of Conch shells, 17-23 parts of Scutellaria barbata, 4-8 parts of Rhodiola rosea, 7-13 parts of Curcuma zedoariae with vinegar, 27-33 parts of turtle shell with vinegar, 7-13 parts of Perilla seed, 12-18 parts of Lepidium membranaceus seed and 4-8 parts of roasted Licorice root.

3. The Chinese medicine composition for treating idiopathic pulmonary fibrosis according to claim 1, characterized in that: The invention comprises the following raw materials by weight: 9-11 parts of Panax notoginseng, 9-11 parts of Chuanxiong, 29-31 parts of Astragalus, 14-16 parts of American ginseng, 9-11 parts of Conch shells, 19-21 parts of Scutellaria barbata, 5-7 parts of Rhodiola rosea, 9-11 parts of Curcuma zedoaria, 29-31 parts of Carapace of Turtle in vinegar, 9-11 parts of Perilla seed, 14-16 parts of Lepidium officinale seed and 5-7 parts of roasted Licorice root.

4. Use of the Chinese medicinal composition for treating idiopathic pulmonary fibrosis according to any one of claims 1 to 3 in the preparation of a medicament for treating idiopathic pulmonary fibrosis.

5. A drug for treating idiopathic pulmonary fibrosis, characterized in that: The invention comprises the Chinese medicine composition for treating idiopathic pulmonary fibrosis according to any one of claims 1 to 3 and pharmaceutically acceptable excipients.

6. The drug for treating idiopathic pulmonary fibrosis according to claim 5, characterized in that: The dosage form of the medicine is Chinese medicine decoction, decoction, granules, pills, capsules, tablets, tea, suspension, powder or oral solution.

7. The method for preparing the drug for treating idiopathic pulmonary fibrosis according to claim 5 or 6, characterized in that: The medicine is a Chinese medicine decoction, and its preparation method is as follows: Step 1, weighing the raw materials according to the weight ratio, cleaning, drying, cutting, crushing, sieving, and mixing evenly; Step 2, adding water to the raw material drug and refluxing to extract twice, collecting volatile oil at the same time, combining the two extracts, and then centrifuging the extracts to obtain the supernatant; Step 3: Concentrate the supernatant in step 2 under reduced pressure, transfer and dispense into clean containers, add volatile oil, make up to volume, mix well, dispense, and store at low temperature.

8. The method for preparing a drug for treating idiopathic pulmonary fibrosis according to claim 7, characterized in that: In the step 2, water is added for reflux extraction twice, 7 to 9 times the amount of water is added for the first time, and the extraction is performed for 1 to 2 hours, while the volatile oil is collected; 5 to 7 times the amount of water is added for the second time, and the extraction is performed for 0.5 to 1.5 hours, while the volatile oil is collected; the centrifugal speed is 2000 to 4000 r / min, and the time is 4 to 6 minutes.

9. The method for preparing a drug for treating idiopathic pulmonary fibrosis according to claim 7, characterized in that: The temperature of the reduced pressure concentration in step 3 is 58 to 60°C; the temperature of the low temperature storage is -15 to -25°C.

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