Use of a traditional Chinese medicine composition in treating radiation pneumonia

Abstract

This invention belongs to the field of traditional Chinese medicine application technology and provides an application of a traditional Chinese medicine composition in the treatment of radiation-induced pneumonia. The traditional Chinese medicine composition is made from bamboo sap and *Trifolium repens*; the mass ratio of bamboo sap to *Trifolium repens* is (1-10):(1-10). Radiation-induced pneumonia refers to lung inflammation caused by radiotherapy for malignant tumors of the chest. The traditional Chinese medicine composition provided by this invention has the effects of clearing heat and detoxifying, resolving phlegm and dissipating nodules. It has a simple composition and high safety, providing a new option for the treatment of radiation-induced pneumonia.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine application technology, and relates to the application of a traditional Chinese medicine composition containing bamboo sap and *Trifolium repens* in the treatment of radiation-induced pneumonia. Background Technology

[0002] Radiation-induced lung injury is the most serious complication after radiotherapy for thoracic tumors, including the exudative pneumonitis in the early acute phase and extensive pulmonary fibrosis in the later chronic phase. Extensive pulmonary fibrosis in the chronic phase, in particular, is the leading cause of non-primary disease death in patients undergoing radiotherapy for thoracic tumors. Therefore, the treatment of acute radiation pneumonitis and preventing its progression to the chronic phase are crucial for its management. The main pathological feature of acute radiation pneumonitis is the infiltration of inflammatory cells in the alveoli and pulmonary interstitium. Current chemotherapy mainly focuses on glucocorticoids, anti-infectives, and symptomatic supportive care, which only improves symptoms. Long-term or high-dose use can lead to side effects such as decreased immunity, secondary infections, and osteoporosis. Furthermore, long-term high-dose use of glucocorticoids can inhibit fibroblast apoptosis, promote collagen deposition, weaken the lung tissue's repair capacity, leading to alveolar structural damage, and induce lung infections or other lung diseases (such as tuberculosis), indirectly aggravating lung injury and potentially accelerating the progression to pulmonary fibrosis.

[0003] Bamboo sap is the liquid naturally extracted from the stems of several species of the same genus, including Phyllostachys edulis and Phyllostachys bambusoides, after heating. It is sweet and cold in nature, and enters the heart, lung, and stomach meridians. It has the function of clearing heat and resolving phlegm, and is used for cough with excessive phlegm due to lung heat, asthma, and chest tightness. Current research shows that fresh bamboo sap can significantly prolong the latency period of cough induced by citric acid and ammonia, and reduce the frequency of coughs. Fresh bamboo sap can exert its antitussive effect by inhibiting the release of inflammatory substances such as histamine or promoting the secretion of certain protective substances; bamboo sap can significantly inhibit capillary permeability in mice, exhibiting good anti-inflammatory effects; bamboo sap has a strong inhibitory effect on various putrefactive bacteria, with more pronounced inhibitory effects on Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Aspergillus niger; bamboo sap can inhibit the proliferation of SMMC-7721, K562, and A375 cells in vitro, and can inhibit the in vivo growth of transplanted liver cancer H22 and transplanted sarcoma S180 in mice; it prolongs the survival time of tumor-bearing mice, demonstrating a certain anti-tumor effect.

[0004] *Trifolium repens* is the fresh or dried tuberous root of *Trifolium repens*, a plant in the Vitaceae family. It is slightly bitter and neutral in nature. It enters the liver and lung meridians; it has the functions of clearing heat and detoxifying, reducing swelling and relieving pain, and resolving phlegm and dissipating nodules. Pharmacological and clinical studies have shown that *Trifolium repens* can weaken the transmembrane signal transduction of LPS by inhibiting the expression of TLR4 and D-2 in lung tissue; it can also inhibit the phosphorylation of NF-κB, JNK, and P38.MAPK in lung tissue, thereby preventing the transfer of LPS inflammatory signals to the cell nucleus and reducing the activation of pro-inflammatory cytokine genes. Furthermore, *Trifolium repens* can also inhibit the phosphorylation and activation of NF-κB and JNK by inhibiting the expression of CD14, TLR4, MD-2, and MyD88 in macrophages and the formation of the TLR4 / MD-2 receptor complex, increasing the level of anti-inflammatory factors. It continuously reduces the cascade transduction of LPS inflammatory signals from the extracellular, cell membrane, to the cell nucleus, demonstrating the anti-inflammatory effect of *Trifolium repens*. Trifoliate orange exerts its anti-tumor effects through mechanisms such as inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell angiogenesis, and reversing tumor cell drug resistance.

[0005] There are no reports on the efficacy of bamboo sap and trifoliate orange, alone or in combination, for radiation-induced lung injury and radiation-induced pneumonia. Summary of the Invention

[0006] In order to provide a new option for the treatment of radiation pneumonia, especially in the acute phase, the present invention provides a traditional Chinese medicine composition that has a significant therapeutic effect on radiation pneumonia. This composition can be used alone or in combination with other drugs to treat radiation pneumonia.

[0007] To achieve the above objectives, the present invention adopts the following technical solution.

[0008] The application of a traditional Chinese medicine composition in the preparation of a drug for radiation-induced pneumonia, characterized in that the traditional Chinese medicine composition is made from bamboo sap and *Trifolium repens*.

[0009] The mass ratio of bamboo sap to *Trifolium repens* is (1-10):(1-10) based on the Chinese medicinal materials or prepared slices of Chinese medicinal herbs; preferably (6-10):(6-10); in some embodiments, the mass ratio of bamboo sap to *Trifolium repens* is 9:6.

[0010] The bamboo sap can be in its original liquid state, or it can be concentrated and dried into a concentrate or dry extract.

[0011] The *Trifolium repens* is either pulverized powder or *Trifolium repens* extract.

[0012] The *Trifolium repens* extract is prepared by the following method: adding *Trifolium repens* to 8-10 times its mass of water or 30% v / v-95% v / v ethanol solution for extraction, and then concentrating or drying the extract to obtain the extract.

[0013] Preferably, the extraction method described above is at least one of the following: immersion method, percolation method, or heating reflux method.

[0014] More preferably, the preparation of the *Trifolium repens* extract includes the following steps: Take *Trifolium repens*, decoct it twice with water, adding 10 times the amount of water for the first decoction and 8 times the amount of water for the second decoction. Each decoction is decocted for 1 hour. Combine the decoctions and concentrate them into a clear extract, or concentrate and dry the decoction into a dry extract; or... Take *Trifolium repens* and extract it with 30% v / v-95% v / v ethanol. Extraction methods include maceration, percolation, and reflux. The ethanol in the extract is recovered and concentrated to a clear extract, or the ethanol in the extract is recovered, concentrated, and dried to a dry extract.

[0015] In some embodiments, the preparation of *Trifolium repens* extract includes the following steps: Take *Trifolium repens*, add 75% v / v ethanol and heat under reflux for two extractions. Add 10 times the volume of 75% v / v ethanol for the first extraction and 8 times the volume of 75% ethanol for the second extraction. Extract for 1 hour each time. Combine the extracts, recover the ethanol from the extracts, and concentrate to a clear extract or recover the ethanol from the extracts, concentrate, and dry to a dry extract.

[0016] Radiation-induced pneumonia refers to lung inflammation caused by radiotherapy for malignant tumors in the chest. The traditional Chinese medicine composition provided by this invention is particularly suitable for the treatment of acute radiation-induced pneumonia.

[0017] The present invention has the following advantages: The traditional Chinese medicine composition provided by this invention is prepared from bamboo sap and three-leaf green, and has the effects of clearing heat and detoxifying, resolving phlegm and dissipating nodules. It has a simple composition and high safety, and provides a new option for the treatment of radiation pneumonia. Detailed Implementation

[0018] The present invention will be further described below with reference to the embodiments, but the present invention is not limited to the following embodiments.

[0019] Example 1: Preparation of a composition of bamboo sap and *Trifolium repens* Take 60g of *Trifolium repens*, add water and decoct twice. Add 10 times the amount of water for the first decoction and 8 times the amount of water for the second decoction. Decoction for 1 hour each time. Combine the decoctions and concentrate them into a clear paste. Add 90g of bamboo sap to the San Ye Qing Qing Gao, mix well, dry at low temperature, grind finely, add an appropriate amount of dextrin to 95g, mix well, and obtain composition 1.

[0020] Example 2: Preparation of a composition of bamboo sap and *Trifolium repens* Take 60g of Clematis armandii, add 75% ethanol and heat under reflux to extract twice. Add 10 times the amount of 75% ethanol for the first extraction and 8 times the amount of 75% ethanol for the second extraction. Extract for 1 hour each time. Combine the extracts, recover the ethanol and concentrate to a clear extract. Add 90g of bamboo sap to the San Ye Qing Qing Gao, mix well, dry at low temperature, grind finely, add an appropriate amount of dextrin to 95g, mix well, and obtain composition 2.

[0021] Example 3: Treatment of a radiation-induced pneumonia model rat with a combination of bamboo sap and *Trifolium repens*. 1. Preparation of the medicinal solution Take the composition of Examples 1 and 2, dissolve it in water, and prepare a medicinal solution containing 0.95g of Chinese medicine per 1mL.

[0022] Take bamboo sap, add water, and make a medicinal solution containing 0.90g of bamboo sap in 1mL.

[0023] Take 60g of Clematis armandii, add 75% ethanol and heat under reflux to extract twice. Add 10 times the amount of ethanol for the first extraction and 8 times the amount of water for the second extraction. Extract for 1 hour each time. Combine the extracts, recover the ethanol, concentrate, add water, and prepare a 1mL solution containing 0.60g of Clematis armandii.

[0024] 2. Animal Model Construction and Grouping Seventy-two male SPF-grade Wistar rats, aged 5-6 weeks and weighing 130-160g, were acclimatized for 3 days. Sixty rats were randomly selected for modeling: the rats were placed in a supine position and covered with a semi-circular lead bucket with a hole in the middle, exposing only a 2 cm × 2 cm area of ​​the chest (from the midpoint between the two axillae of the rat's forelimb to the xiphoid process of the sternum). The rats were irradiated with 40 Gy X-rays for 14 min per irradiation, with a 1-day interval between irradiations, for a total of 8 weeks.

[0025] Rats that received no treatment served as the normal control group. The rats used for modeling were randomly divided into four groups: bamboo sap group, *Trifolium repens* group, combination 1 group, and combination 2 group. During irradiation, the rats were administered drugs via gavage 2-3 hours before irradiation. The dosages were: bamboo sap group (9g crude drug / kg), *Trifolium repens* group (6g crude drug / kg), combination 1 group (15g crude drug / kg), and combination 2 group (15g crude drug / kg). The modeling groups were administered only an equal volume of physiological saline via gavage.

[0026] 3. Functional testing On the second day after modeling, inspiratory time (Ti), expiratory time (Te), maximum inspiratory volume (PIF), maximum expiratory volume (PEF), tidal volume (TV), expiratory volume (EV), and expiratory volume per minute (MV) were measured using a small animal pulmonary function analyzer. See table. Table 1. Effects of the combination of bamboo sap and *Trifolium repens* on lung function and cytokines in rats with radiation-induced pneumonia. Note: Δ Compared with the normal control group P <0.01; Comparison with model group P <0.05.

[0027] As shown in Table 1, there were significant differences in all indicators between the model group and the normal control group. P <0.01 indicates successful model establishment. Significant differences were observed between each drug treatment group and the modeling group. P The value <0.05 indicates that the invented traditional Chinese medicine composition has the effect of preventing and treating radiation-induced pneumonia. Bamboo sap and *Trifolium repens* alone also have a certain effect in preventing and treating radiation-induced pneumonia, but the effect is more significant when they are combined.

[0028] Example 4: Preparation of a composition of bamboo sap and three-leaf green. Take 60g of *Trifolium repens*, add water and decoct twice. Add 10 times the amount of water for the first decoction and 8 times the amount of water for the second decoction. Decoction for 1 hour each time. Combine the decoctions and concentrate them into a clear paste. Add 90g of bamboo sap to the San Ye Qing Qing Gao, mix well, dry at low temperature, grind finely, add an appropriate amount of dextrin to 95g, mix well, and obtain the composition.

[0029] Example 5: Preparation of a composition of bamboo sap and *Trifolium repens* Take 60g of Clematis armandii, add 30% ethanol and heat under reflux to extract twice. Add 10 times the amount of 75% ethanol for the first extraction and 8 times the amount of 30% ethanol for the second extraction. Extract for 1 hour each time. Combine the extracts, recover the ethanol and concentrate to a clear extract. Add 90g of bamboo sap to the San Ye Qing Qing Gao, mix well, dry at low temperature, grind finely, add an appropriate amount of dextrin to 95g, mix well, and obtain the composition.

[0030] Example 6 Preparation of a composition of bamboo sap and three-leaf green leaves Take 60g of Clematis armandii, add 90% ethanol and heat under reflux to extract twice. Add 10 times the amount of 75% ethanol for the first extraction and 8 times the amount of 90% ethanol for the second extraction. Extract for 1 hour each time. Combine the extracts, recover the ethanol and concentrate to a clear extract. Add 90g of bamboo sap to the San Ye Qing Qing Gao, mix well, dry at low temperature, grind finely, add an appropriate amount of dextrin to 95g, mix well, and obtain the composition.

[0031] Animal experiments using a radiation-induced pneumonia model confirmed that the composition prepared in the above examples significantly improved the therapeutic effect compared to taking Tripterygium wilfordii or bamboo sap alone.

[0032] The above description is merely an embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of this application should be included within the scope of the claims of this application.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for treating radiation pneumonitis, characterized in that, The traditional Chinese medicine composition is made from bamboo sap and three-leaf green.

2. Use according to claim 1, characterized in that, The mass ratio of bamboo sap to *Trifolium repens* is (1-10):(1-10); (6-10):(6-10) or 9:

6.

3. Use according to claim 1, characterized in that, The bamboo sap is the original liquid; it is concentrated and dried to form a concentrate or dry extract.

4. Use according to claim 1, characterized in that, The *Trifolium repens* is either *Trifolium repens* powder or *Trifolium repens* extract.

5. The application according to claim 4, characterized in that, The *Trifolium repens* extract is prepared by the following method: adding *Trifolium repens* to 8-10 times its mass of water or 30% v / v-95% v / v ethanol solution for extraction, and then concentrating or drying the extract to obtain the extract.

6. The application according to claim 5, characterized in that, The extraction method is at least one of the following: immersion method, percolation method, or heating reflux method.

Images