Traditional Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis as well as preparation and application thereof

Abstract

The invention provides a traditional Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis as well as a preparation and application thereof, and belongs to the technical field of biological medicines. The traditional Chinese medicine monomer composition comprises the following components: schisandrin B and platycodin D. The traditional Chinese medicine monomer composition can obviously reduce fiber cell and collagen deposition, relieve inflammatory cell infiltration, obviously reduce the lung coefficient, alveolar inflammation score and pulmonary fibrosis score, and recover the normal physiological structure of rat lung tissue. The traditional Chinese medicine monomer composition provided by the invention can reduce the expression contents of KL-6, MMP-7, SP-A and SP-D and lung tissue HYP in serum, and has the effects of relieving collagen deposition and alveolar epithelium injury, maintaining alveolar homeostasis and improving pulmonary fibrosis. Therefore, the traditional Chinese medicine composition provided by the invention is definite and reliable in curative effect and can be used for preparing medicines for preventing and / or treating pulmonary fibrosis.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a traditional Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, and a preparation and application thereof. Background Art

[0002] Pulmonary fibrosis is a common end-stage pathological change in various interstitial lung diseases. It is characterized by abnormal fibroblast proliferation, extracellular matrix deposition, inflammatory damage, and structural and functional impairment of lung tissue. Patients present with exertional dyspnea and decreased lung function. As the disease progresses, it can lead to respiratory failure and even death. Patients with pulmonary fibrosis have a poor prognosis, with a short median survival after diagnosis in untreated patients. Currently, two marketed antifibrotic drugs—nintedanib, a multi-target intracellular tyrosine kinase receptor antagonist, and pirfenidone, a novel oral pyridone derivative—have been widely recognized for their efficacy and safety. However, existing antifibrotic drugs can slow but not halt or reverse the progression of fibrosis. These drugs also have adverse effects that can make them intolerable to patients, resulting in a high mortality rate. There is an urgent need for therapeutic agents with improved antifibrotic efficacy, better tolerance, and more clearly targeted therapies. In recent years, combination therapy, which targets multiple inflammatory targets to enhance pharmacological activity and minimize side effects, has become an effective strategy for alleviating inflammation. Compared to the complexity of compound prescriptions, the composition, content, and target of monomeric combination drugs are clearly controllable, meeting the requirements of "clarity and reproducibility" in modern drug development. Currently, there are no reports on the application of the Chinese herbal monomeric combination of schisandrin B and platycodonoside D in the prevention and treatment of pulmonary fibrosis. Summary of the Invention

[0003] In view of this, the object of the present invention is to provide a Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, and its preparation and use.

[0004] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0005] The present invention provides a traditional Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, comprising the following components: schisandrin B and platycoside D.

[0006] Preferably, the active ingredients of the traditional Chinese medicine monomer composition consist of schisandrin B and platycoside D.

[0007] Preferably, the mass ratio of schisandrin B to platycoside D is 1-4:1-4.

[0008] Preferably, the mass ratio of schisandrin B to platycoside D is 1:2 or 1:4.

[0009] The present invention provides a traditional Chinese medicine monomer composition preparation for preventing and / or treating pulmonary fibrosis, comprising the above-mentioned traditional Chinese medicine monomer composition.

[0010] Preferably, the traditional Chinese medicine monomer composition preparation further comprises sodium carboxymethyl cellulose solution.

[0011] Preferably, the mass percentage concentration of the sodium carboxymethyl cellulose solution is 0.5-1.5%; the mass volume ratio of schisandrin B, platycoside D and sodium carboxymethyl cellulose solution is (10-40) mg: (10-40) mg: 10 mL.

[0012] The present invention provides an application of the above-mentioned traditional Chinese medicine monomer composition or traditional Chinese medicine monomer composition preparation in the preparation of a product for preventing and / or treating pulmonary fibrosis.

[0013] The present invention provides a use of the above-mentioned traditional Chinese medicine monomer composition or traditional Chinese medicine monomer composition preparation in the preparation of a product for preventing and / or treating inflammation caused by pulmonary fibrosis.

[0014] Preferably, the inflammation comprises alveolitis.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention provides a Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, and its preparation and application. The Chinese medicine monomer composition of the present invention can significantly reduce fibroblast and collagen deposition, reduce inflammatory cell infiltration, significantly reduce lung coefficient, alveolitis score and pulmonary fibrosis score, and restore the normal physiological structure of rat lung tissue. The Chinese medicine monomer composition provided by the present invention can reduce the expression levels of KL-6, MMP-7, SP-A and SP-D in serum and HYP in lung tissue, has the effect of reducing collagen deposition and alveolar epithelial damage, maintaining alveolar homeostasis, and improving pulmonary fibrosis. At the same time, the Chinese medicine monomer composition of the present invention has a synergistic effect in preventing and / or treating pulmonary fibrosis. Therefore, the Chinese medicine composition provided by the present invention has a reliable efficacy and can be used to prepare a medicine for preventing and / or treating pulmonary fibrosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 HE and Masson staining images of lung tissue sections in different groups (×200). DETAILED DESCRIPTION

[0018] The present invention provides a traditional Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, comprising the following components: schisandrin B and platycoside D.

[0019] In the present invention, it is found that compared with a single drug (schisandrin B or platycoside D), the combination of schisandrin B and platycoside D is more effective in preventing and / or treating pulmonary fibrosis and has a synergistic effect. Moreover, schisandrin B and platycoside D are combined according to different mass ratios. The mass ratio of schisandrin B to platycoside D is preferably 1 to 4: 1 to 4, more preferably 1: 2 to 4. Compared with the combination of schisandrin B and platycoside D with other different mass ratios, it has better effects of reducing collagen deposition and alveolar epithelial damage, reducing lung coefficient, alveolitis score and pulmonary fibrosis score, and maintaining alveolar homeostasis. It is further preferred that the mass ratio of schisandrin B to platycoside D is 1: 2 or 1: 4. The present invention has found that when the mass ratio of schisandrin B to platycoside D is 1: 2, the mass ratio of schisandrin B to platycoside D is 1: 2, which has a synergistic effect. As a preferred embodiment, the active ingredients of the Chinese medicine monomer composition are composed of schisandrin B and platycoside D. Further, the Chinese medicine monomer composition is composed of schisandrin B and platycoside D in a mass ratio of 1:2. In the present invention, the pulmonary fibrosis is bleomycin-induced pulmonary fibrosis.

[0020] The present invention provides a traditional Chinese medicine monomer composition preparation for preventing and / or treating pulmonary fibrosis, comprising the above-mentioned traditional Chinese medicine monomer composition.

[0021] In the present invention, the Chinese medicine monomer composition preparation further includes a sodium carboxymethylcellulose solution. The mass percentage concentration of the sodium carboxymethylcellulose solution is 0.5-1.5%, preferably 0.7-1.2%, and more preferably 1%. Taking the preparation method of a CMC-Na solution with a mass percentage concentration of 1% as an example, the preparation of a CMC-Na solution with a mass percentage concentration of 1% is as follows: 1g of CMC-Na is mixed with 100mL of water to obtain a CMC-Na solution with a mass percentage concentration of 1%; the mass volume ratio of schisandrin B, platycoside D and sodium carboxymethylcellulose solution is preferably (10-40)mg:(10-40)mg:10mL, more preferably 10mg:(20-40)mg:10mL, and further preferably 10mg:20mg:10mL or 10mg:40mg:10mL.

[0022] The present invention provides an application of the above-mentioned traditional Chinese medicine monomer composition or traditional Chinese medicine monomer composition preparation in the preparation of a product for preventing and / or treating pulmonary fibrosis.

[0023] The present invention provides a use of the above-mentioned traditional Chinese medicine monomer composition or traditional Chinese medicine monomer composition preparation in the preparation of a product for preventing and / or treating inflammation caused by pulmonary fibrosis.

[0024] In the present invention, the product comprises a reagent or a drug. The drug further comprises pharmaceutically acceptable excipients, wherein the excipients include one or more of a filler, a disintegrant, a binder, a lubricant, and a flavoring agent. The drug may be in the form of a granule, a decoction, a tablet, a capsule, or a pill. The drug may be administered orally, by subcutaneous injection, intraperitoneal injection, intravenous injection, or intramuscular injection. In the present invention, the inflammation includes alveolitis. In the present invention, the weight ratio of the Chinese medicine monomer composition to the product is 40-80%.

[0025] The Chinese medicine monomer composition provided by the present invention can reduce the expression levels of KL-6, MMP-7, SP-A, and SP-D in serum, as well as HYP in lung tissue, thereby alleviating collagen deposition and alveolar epithelial damage, maintaining alveolar homeostasis, and improving pulmonary fibrosis. Therefore, the Chinese medicine composition provided by the present invention has reliable efficacy and can be used to prepare a drug for the prevention and treatment of pulmonary fibrosis. This invention provides a theoretical basis for the development of drugs for pulmonary fibrosis.

[0026] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0027] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0028] The sources of the drugs and kits used in the examples of the present invention are:

[0029] Schisandrin B (≥98%): Jiangsu Yongjian Pharmaceutical Technology Co., Ltd., batch number B01842;

[0030] Platycoside D (≥98%): Jiangsu Yongjian Pharmaceutical Technology Co., Ltd., batch number B01765;

[0031] Bleomycin: Solebao Biotechnology Co., Ltd., batch number Z8020;

[0032] KL-6 (sialylated sugar chain antigen) was purchased from Shanghai ELISA Biotechnology Co., Ltd., batch number: ml002982;

[0033] MMP-7 (matrix metalloproteinase-7) was purchased from Shanghai ELISA Biotechnology Co., Ltd., batch number: ml002982;

[0034] SP-D (pulmonary surfactant protein-D) was purchased from Shanghai ELISA Biotechnology Co., Ltd., batch number: ml037116;

[0035] SP-A (pulmonary surfactant protein-A) was purchased from Shanghai ELISA Biotechnology Co., Ltd., batch number: ml002982;

[0036] HYP (hydroxyproline) Shanghai ELISA Biotechnology Co., Ltd., batch number: ml092985.

[0037] Preparation of a CMC-Na solution with a mass percentage concentration of 1%: Mix 1 g of CMC-Na with 100 mL of water to obtain a CMC-Na solution with a mass percentage concentration of 1%.

[0038] Example 1

[0039] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0040] 10 mg of schisandrin B and 10 mg of platycoside D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0041] Example 2

[0042] A method for preparing a Chinese medicine monomer composition for treating pulmonary fibrosis, comprising the following steps:

[0043] 10 mg of schisandrin B and 20 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0044] Example 3

[0045] A method for preparing a Chinese medicine monomer composition for treating pulmonary fibrosis, comprising the following steps:

[0046] 10 mg of schisandrin B and 40 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0047] Example 4

[0048] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0049] 20 mg of schisandrin B and 10 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0050] Example 5

[0051] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0052] 20 mg of schisandrin B and 20 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0053] Example 6

[0054] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0055] 20 mg of schisandrin B and 40 mg of platycoside D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0056] Example 7

[0057] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0058] 40 mg of schisandrin B and 10 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0059] Example 8

[0060] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0061] 40 mg of schisandrin B and 20 mg of platycodon saponin D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0062] Example 9

[0063] A method for preparing a Chinese medicine monomer composition comprises the following steps:

[0064] 40 mg of schisandrin B and 40 mg of platycoside D were mixed, and 10 mL of a CMC-Na solution with a mass percentage concentration of 1% was added to dissolve the mixture to obtain a traditional Chinese medicine monomer composition.

[0065] Example 10

[0066] The therapeutic effect of the Chinese medicine monomer composition described in Examples 1 to 9 on rats with bleomycin-induced pulmonary fibrosis model was evaluated

[0067] 1. Experimental Animals

[0068] A total of 110 male Sprague Dawley rats (SPF), weighing 190–210 g, were purchased from Liaoning Changsheng Biotechnology Co., Ltd. and housed at the Experimental Animal Center of Heilongjiang University of Chinese Medicine under license number SYXK(Liao)2020-0001. The use of animals in this study was approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine, approval number 2024121303.

[0069] 2. Methods

[0070] 2.1 Preparation of rat pulmonary fibrosis model

[0071] The rat pulmonary fibrosis model was established by intratracheal injection of bleomycin. Rats in each group were fasted for more than 12 hours before surgery and intraperitoneally injected with 40 mg kg of 3% sodium pentobarbital. -1 After anesthesia, the rat was placed on its back with its head and limbs fixed on a mouse board. After depilation of the neck, the surgical site was disinfected with iodine. The skin in the middle of the neck was cut longitudinally, and the subcutaneous tissue and muscles were bluntly separated, avoiding the salivary glands. The trachea was exposed and a 1 mL syringe was gently inserted into the trachea. The needle core was pulled out and cotton wool was placed on the outer opening of the syringe tube. If the cotton wool swayed with breathing, it indicated that the syringe was successfully inserted into the trachea. 5 mg kg was rapidly injected with this syringe. -1 Bleomycin: The sham-operated group was injected with the same volume of normal saline and 0.2 mL of air was injected with a syringe. After the syringe was pulled out, the rats were stood upright and rocked left and right to allow the drug solution to reach the lungs evenly. The skin was sutured and the rats were raised normally after waking up naturally.

[0072] 2.2 Specific drug administration conditions for experimental animals

[0073] There were 8 SD rats in each of the sham operation group, model group and drug-treated groups.

[0074] SD rats in the sham operation group and the model group were gavaged with 1 mL / 100 g normal saline for 28 consecutive days;

[0075] In experimental groups 1 to 9, SD rats were gavaged with the Chinese medicine monomer composition described in Examples 1 to 9, respectively, at a daily gavage volume of 1 mL / 100 g, for 28 consecutive days.

[0076] The drugs in experimental groups 1 to 9 of this example correspond to the Chinese medicine monomer compositions prepared in Examples 1 to 9, respectively.

[0077] Schisandrin B solution: 10 mg of schisandrin B was added into 10 mL of 1% CMC-Na solution to dissolve the solution to obtain schisandrin B solution.

[0078] Platycoside D solution: 20 mg of platycoside D was added into 10 mL of 1% CMC-Na solution to dissolve the solution.

[0079] Schisandrin B group: SD rats were gavaged with Schisandrin B solution at a daily gavage volume of 1 mL / 100 g for 28 consecutive days.

[0080] Platycoside D group: SD rats were gavaged with Platycoside D solution at a daily gavage volume of 1 mL / 100 g for 28 consecutive days.

[0081] 2.3. Lung coefficient determination

[0082] After 28 days of administration, the blood on the surface of lung tissues of the sham operation group, model group and experimental groups 1 to 9 was aspirated, the lung mass was weighed and the lung coefficient of each group of rats was calculated: organ coefficient = organ mass / body mass × 100%.

[0083] 2.4 Pathological observation of lung tissue

[0084] Twenty-eight days after administration, lung tissues were collected from rats in the sham-operated group, model group, and experimental group 2. After fixation with 4% paraformaldehyde, the tissues were trimmed, dehydrated, and embedded in paraffin to form 5-μm sections. The sections were then dewaxed with xylene, rehydrated, stained with H&E or Masson staining, dehydrated, and mounted. The sections were then examined under a microscope for histopathological changes.

[0085] 2.5. Evaluation of the degree of alveolar inflammation

[0086] Evaluation of alveolar inflammation: 28 days after administration, the samples of the sham operation group, model group, and experimental groups 1 to 9 were fixed with 4% paraformaldehyde. After being well fixed, they were trimmed, dehydrated, embedded, sliced, stained with HE, and sealed in strict accordance with the SOP procedures of this pathological experiment. Finally, qualified samples were examined under a microscope.

[0087] The degree of alveolar inflammation in each group of rats was evaluated according to the modified scoring criteria. The specific scoring criteria are shown in Table 1:

[0088] Table 1 Scoring criteria for alveolar inflammation in rats

[0089]

[0090] Note: Rats with a score of 0 indicate that the model preparation failed.

[0091] 2.6 Pulmonary fibrosis degree detection

[0092] Evaluation of alveolar fibrosis: 28 days after administration, samples 1 to 9 in the sham operation group, model group, and experimental group were fixed with 4% paraformaldehyde. After good fixation, they were trimmed, dehydrated, embedded, sliced, Masson stained, and sealed in strict accordance with the SOP procedures of this pathological experiment. Finally, qualified samples were examined under a microscope.

[0093] The degree of pulmonary fibrosis in rats in each group was evaluated according to the scoring criteria. The specific scoring criteria are shown in Table 2:

[0094] Table 2 Scoring criteria for the degree of pulmonary fibrosis in rats

[0095]

[0096] 2.7 Detection of serum KL-6, MMP-7, SP-D, and SP-A and lung tissue HYP expression levels

[0097] After 28 days of administration, the levels of MMP-7, KL-6, SP-A, SP-D in the serum and HYP in the lung tissue of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA).

[0098] 2.8 Statistical analysis

[0099] Data were analyzed using SPSS 26.0 statistical software. Measurement data were expressed as mean ± standard deviation (mean ± SD). Pairwise comparisons between groups were performed using one-way analysis of variance. Equal variances were tested using the LSD test, while unequal variances were tested using the Tamhane's T2 (M) test. P < 0.05 was considered statistically significant, and P < 0.01 was considered statistically significant.

[0100] 3 Results

[0101] 3.1 Effect on rat lung coefficient

[0102] The results in Table 3 show that compared with the sham operation group, the lung coefficient of the rats in the model group was significantly increased (P<0.01), preliminarily judging that the model preparation was successful; compared with the model group, the lung coefficient of each experimental group was significantly decreased after 28 days of administration (P<0.05), indicating that the present invention has the effect of reducing the lung coefficient.

[0103] Table 3 Effects on lung organ coefficients in rats with pulmonary fibrosis ( n=8)

[0104]

[0105] Note: Compared with the sham operation group, ##P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0106] 3.2 Pathological observation of rat lung tissue

[0107] Figure 1 HE and Masson staining of lung tissue sections (×200). HE staining shows that the lung tissue in the sham group was intact, with clear lung structure, no inflammatory cell infiltration within the alveoli, and no congestion or edema. In the model group, lung tissue showed extensive consolidation, extensive connective tissue hyperplasia, numerous granulocyte infiltration of the alveolar walls, and compensatory alveolar dilatation. Irregular arrangement of mucosal epithelial cells was observed in a few bronchioles, and edema with loose, pale cytoplasm was observed in a few bronchioles. Eosinophilic material and desquamated epithelial cells were rarely observed within the bronchioles. The interstitium, which includes connective tissue and blood vessels, showed scattered perivascular infiltration of small numbers of lymphocytes. In experimental group 2 (also referred to as experimental group 2), the overall lung tissue structure was mildly abnormal, with clear alveolar structure and no significant alveolar atrophy or dilatation. Mild thickening of the alveolar walls and a small number of inflammatory cell infiltrates were observed.

[0108] Masson staining revealed intact lung tissue and clear lung architecture in the sham-operated group, with no alveolar wall thickening or collapse, and only a small amount of fiber within the pulmonary septa. In the model group, fibrotic areas of lung tissue showed extensive proliferation of fibrocytes and collagen fiber deposition, thickening of the alveolar walls, and significant overall structural abnormalities. In experimental group 2 (also referred to as experimental group 2), alveolar wall thickening was occasionally observed in the lung tissue, with reduced fibrocyte and collagen deposition and significantly reduced inflammatory cell infiltration.

[0109] It can be seen that the use of the Chinese medicine monomer composition of the present invention can reduce the deposition of fibrocytes and collagen and the infiltration of inflammatory cells, thereby achieving the purpose of effectively improving pulmonary fibrosis.

[0110] 3.3 Alveolitis and pulmonary fibrosis grading scores in each group

[0111] The results in Table 4 show that compared with the sham operation group, the alveolitis score and pulmonary fibrosis score of the rats in the model group were significantly increased (P<0.01); compared with the model group, the alveolitis score and pulmonary fibrosis score of each experimental group decreased to varying degrees after 28 days of administration (P<0.05, P<0.01), indicating that the present invention has the effect of improving alveolitis and pulmonary fibrosis.

[0112] Table 4 Comparison of pathological scores among the groups ( n=8)

[0113] Group Alveolitis score Pulmonary fibrosis score Sham operation group 0.40±0.55 0.20±0.45 Model Group <![CDATA[2.60±0.55 ## ]]> <![CDATA[4.40±0.55 ## ]]> Experimental Group 1 1.60±0.55 3.00±0.71* Experimental Group 2 1.20±0.45** 2.60±0.55** Experimental Group 3 1.40±0.55* 3.00±1.00* Experimental Group 4 1.80±0.84 2.80±0.84** Experimental Group 5 1.60±0.55 3.00±0.71* Experimental Group 6 1.80±0.45 3.20±0.84 Experimental Group 7 1.40±0.55* 3.60±0.55 Experimental Group 8 1.60±0.55 3.80±0.45 Experimental Group 9 1.20±0.45** 3.20±0.45

[0114] Note: Compared with the sham operation group, ## P<0.01; compared with the model group, *P<0.05, **P<0.01.

[0115] A comprehensive score was calculated by comparing the lung coefficient, alveolitis score, and pulmonary fibrosis score of each experimental group after 4 weeks of administration. The score ratio was lung coefficient: alveolitis score: pulmonary fibrosis score = 2:4:4. The comprehensive score was calculated as comprehensive score = (lung coefficient × 0.2 + alveolitis score × 0.4 + pulmonary fibrosis score × 0.4) × 10. The specific results are shown in Table 5 below.

[0116] Table 5 Comprehensive scores of Chinese medicine monomer compositions

[0117] Group Overall score Sham operation group 10.88 Model Group 46.32 Experimental Group 1 32.68 Experimental Group 2 27.94 Experimental Group 3 29.3 Experimental Group 4 31.62 Experimental Group 5 30.36 Experimental Group 6 32.06 Experimental Group 7 35.22 Experimental Group 8 35.28 Experimental Group 9 29.42

[0118] It can be seen from Table 5 that the comprehensive score of experimental group 2 is the lowest, that is, the optimal ratio screened out is a mass ratio of schisandrin B to platycoside D of 1:2, that is, the Chinese medicine monomer composition prepared by Example 2 of the present invention has the best effect in treating pulmonary fibrosis.

[0119] Furthermore, the optimal combination group (the Chinese medicine monomer composition of Example 2) and the monomer group (schisandrin B group or platycoside D group) were compared with the model group:

[0120] The changes in the expression levels of KL-6, MMP-7, SP-A, SP-D in serum and HYP in lung tissue of rats in each group after administration are shown in Table 6.

[0121] Table 6 Expression levels of KL-6, MMP-7, SP-A, SP-D in serum and HYP in lung tissue of rats ( n=8)

[0122]

[0123]

[0124] Note: Compared with the sham operation group, # P<0.05, ## P<0.01, ### P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0125] As can be seen from Table 6, compared with the sham operation group, the expression levels of KL-6, MMP-7, SP-A, SP-D in serum and HYP in lung tissue of rats in the model group were significantly increased; compared with the model group, after 28 days of administration, the expression levels of KL-6, MMP-7, SP-A, SP-D in serum and HYP in lung tissue of rats in each drug group were significantly decreased (P<0.05, P<0.01, P<0.001), and the effect of the Chinese medicine monomer composition of Example 2 of the present invention was better than that of the single drug group (schisandrin B group or platycoside D group).

[0126] Furthermore, the Bliss independence model was used to calculate the expected combined effect using the formula: expected effect (Eexpected) = E1 + E2 - E1 × E2, where E1 and E2 are the individual effect values of the Schisandrin B group and the Platycodonoside D group, respectively, and Ecombined is the actual effect value of the combined medication (the Chinese medicine monomer composition of Example 2). CI value = Eexpected / Ecombined, with the following criteria: CI < 1: synergistic effect; CI = 1: additive effect; CI > 1: antagonistic effect.

[0127] Table 7 Comprehensive analysis of the synergistic effect of multiple indicators

[0128] index <![CDATA[KL-6 / U·mL -1 ]]> <![CDATA[MMP-7 / μg·L -1 ]]> <![CDATA[SP-A / ng·L -1 ]]> <![CDATA[SP-D / ng·L -1 ]]> <![CDATA[HYP / μg·mg -1 ]]> Δ Model 1327.4 3.16 9.05 15.82 17.04 E1 0.232 0.427 0.320 0.225 0.143 E2 0.273 0.421 0.315 0.284 0.205 E-United 0.591 0.699 0.558 0.463 0.333 E-expected 0.442 0.668 0.534 0.445 0.319 CI value 0.748 0.956 0.957 0.961 0.958 Synergistic effect judgment Collaboration Collaboration Collaboration Collaboration Collaboration

[0129] As can be seen from Table 7, the Chinese medicine monomer composition of Example 2 of the present invention showed a synergistic effect on lung injury-related indicators, suggesting that the combined use of schisandrin B and platycoside D in a mass ratio of 1:2 may have a synergistic effect in the treatment of pulmonary fibrosis.

[0130] In summary, the Chinese medicine monomer composition of the present invention can reduce the volume of pulmonary fibrosis and the expression levels of serum KL-6, MMP-7, SP-A, SP-D and lung tissue HYP; HE staining and Masson staining showed that the degree of alveolar inflammation and pulmonary fibrosis was significantly improved, indicating that the Chinese medicine monomer composition of the present invention has synergistic anti-inflammatory and anti-pulmonary fibrosis effects.

[0131] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A Chinese medicine monomer composition for preventing and / or treating pulmonary fibrosis, characterized in that: Includes the following ingredients: schisandrin B and platycoside D.

2. The Chinese medicine monomer composition according to claim 1, characterized in that The active ingredients of the traditional Chinese medicine monomer composition consist of schisandrin B and platycodonoside D.

3. The Chinese medicine monomer composition according to claim 1 or 2, characterized in that: The mass ratio of schisandrin B to platycoside D is 1-4:1-4.

4. The Chinese medicine monomer composition according to claim 1 or 2, characterized in that: The mass ratio of schisandrin B to platycoside D is 1:2 or 1:

4.

5. A Chinese medicine monomer composition preparation for preventing and / or treating pulmonary fibrosis, characterized in that: The invention comprises the Chinese medicine monomer composition according to any one of claims 1 to 4.

6. The Chinese medicine monomer composition preparation according to claim 5, characterized in that: The traditional Chinese medicine monomer composition preparation also includes sodium carboxymethyl cellulose solution.

7. The Chinese medicine monomer composition preparation according to claim 5, characterized in that: The mass percentage concentration of the sodium carboxymethyl cellulose solution is 0.5-1.5%; the mass volume ratio of schisandrin B, platycoside D and sodium carboxymethyl cellulose solution is (10-40) mg: (10-40) mg: 10 mL.

8. Use of the traditional Chinese medicine monomer composition according to any one of claims 1 to 4 or the traditional Chinese medicine monomer composition preparation according to any one of claims 5 to 7 in the preparation of a product for preventing and / or treating pulmonary fibrosis.

9. Use of the Chinese medicine monomer composition according to any one of claims 1 to 4 or the Chinese medicine monomer composition preparation according to any one of claims 5 to 7 in the preparation of a product for preventing and / or treating inflammation caused by pulmonary fibrosis.

10. The use according to claim 9, characterized in that The inflammation includes alveolitis.

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