Traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules and preparation method of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules and a preparation method of the traditional Chinese medicine composition. The composition is prepared from 30 parts of coix seeds, 15 parts of astragalus membranaceus, 30 parts of pyrrosia lingua, 10 parts of raw rhizoma atractylodis macrocephalae, 10 parts of fried hawthorn, 10 parts of folium isatidis, 30 parts of oysters, 15 parts of caulis spatholobi, 30 parts of oldenlandia diffusa, 10 parts of fructus lycii, 10 parts of glossy privet fruits, 15 parts of radix glehniae, 3 parts of gecko, 6 parts of liquorice, 15 parts of codonopsis pilosula, 6 parts of cassia twigs, 30 parts of salvia chinensis, 15 parts of Chinese waxgourd seeds, 10 parts of verbena and 10 parts of asparagus cochinchinensis. During preparation, the medicinal materials are selected and crushed, and refined honey is added to prepare pills. Clinical research shows that after the preparation is taken for 6 months, the maximum diameter of pulmonary nodules of a patient is remarkably reduced, the malignant probability of mei-ovum is reduced from 16.60% to 8.33%, the integral of traditional Chinese medicine syndromes is reduced from 10.91 to 6.91, and the serum CEA is reduced from 2.0 ng / mL to 1.51 ng / mL. The traditional Chinese medicine composition has the effects of tonifying qi and yin, reducing phlegm, removing toxins and eliminating diseases aiming at the lung nodule precancerous lesion with the syndrome of vital qi deficiency and phlegm stagnation, and is definite in curative effect and high in safety.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules and its preparation method. Background Technology

[0002] Lung cancer is one of the most common cancers in my country and the leading cause of cancer death. Early-stage lung cancer often presents as asymptomatic pulmonary nodules, which are round or irregular lesions with a diameter of 3 cm or less in the lung. On imaging, they appear as shadows with increased density, and can be single or multiple, with clear or indistinct borders. With the widespread use of high-resolution CT, the detection rate of pulmonary nodules has increased significantly; studies show that the incidence rate in East Asian populations is approximately 35.5%. Although most nodules are benign, the malignancy risk of some types (such as mixed ground-glass nodules) can reach 63%. The diameter of pulmonary nodules is closely related to the probability of malignancy: the malignancy rate of pulmonary nodules <5 mm is less than 1%, the malignancy rate of pulmonary nodules with a diameter of 5 mm-10 mm is approximately 6%-8%, and the malignancy rate of pulmonary nodules with a diameter of 20 mm is as high as 64%-82%. Therefore, early identification and appropriate intervention of pulmonary nodules have become crucial aspects of early prevention and treatment of lung cancer.

[0003] In modern medicine, the management of pulmonary nodules remains controversial. The main treatment methods include surgical resection, anti-infection treatment, and regular follow-up observation. For pulmonary nodules discovered incidentally during physical examinations without obvious clinical symptoms, if the risk of malignancy is low, a strategy of regular follow-up observation is usually adopted. For nodules suspected of being inflammatory, anti-infective drug treatment is given. For nodules highly suspected of being malignant or confirmed as malignant by puncture biopsy, surgical resection is usually performed. Some patients in the middle and late stages may also require further intervention with radiotherapy, chemotherapy, and targeted therapy. Clinically, there are many cases of overdiagnosis and over-surgery, which not only increases the physical and mental burden and medical costs on patients but may also damage their lung function.

[0004] There is no corresponding name for pulmonary nodules in ancient Chinese medicine texts. Currently, most TCM practitioners believe that based on the clinical symptoms of pulmonary nodules, they can be classified under categories such as "cough" and "accumulation." TCM believes that the pathogenesis of pulmonary nodules is mainly due to the interaction of "deficiency," "phlegm," "blood stasis," and "toxins," which obstruct the flow of Qi. In recent years, TCM treatment of pulmonary nodules has received widespread attention, and the number of related patent applications has increased year by year. Studies have shown that among the published patents for TCM treatment of pulmonary nodules, the top five most frequently used herbs are licorice root, astragalus root, prepared pinellia tuber, turmeric, and oldenlandia diffusa. These herbs are mainly sweet and warm in nature, primarily affecting the lung, liver, and spleen meridians, and their effects are mainly clearing heat, drying dampness and resolving phlegm, and promoting diuresis and reducing swelling.

[0005] Several patents have been published for traditional Chinese medicine compositions used to treat pulmonary nodules. For example, patent CN114699502A discloses a composition for dispersing nodules, resolving phlegm, and promoting blood circulation, composed of turtle shell, oyster shell, bupleurum, scutellaria, belamcanda, silkworm, prepared ginger, cinnamon twig, lepidium seed, pyrrosia, prepared pinellia, ginseng, bee honeycomb, white mustard seed, fritillaria thunbergii, cat's claw herb, gleditsia sinensis thorn, turmeric, buckwheat, and prepared licorice root, primarily used to treat pulmonary nodules of the phlegm-blood stasis type. Another example is patent CN113197992A, which discloses a composition for treating pulmonary nodules, composed of bupleurum, chuanxiong, turmeric, green tangerine peel, angelica, white peony root, tangerine peel, belamcanda, prepared pinellia, trichosanthes fruit, oyster shell, kelp, seaweed, prunella vulgaris, salvia miltiorrhiza, ground beetle, and cat's claw herb, which has the effects of soothing the liver, relieving depression, softening and dispersing nodules. In addition, there are compositions targeting pulmonary nodules caused by phlegm and blood stasis (such as tangerine peel, prepared pinellia, poria, peach kernel, cat's claw herb, turmeric, coix seed, and scutellaria barbata), as well as compositions for resolving phlegm, promoting blood circulation, and dispersing nodules (such as turtle shell, oyster shell, scutellaria, prepared pinellia, ginseng, white mustard seed, fritillaria thunbergii, cat's claw herb, gleditsia sinensis thorn, turmeric, and buckwheat). However, the aforementioned existing patents mainly focus on the syndrome of phlegm and blood stasis or phlegm and blood stasis obstruction. Their formulations are either primarily focused on attacking pathogenic factors (such as softening and dispersing nodules, promoting blood circulation and removing blood stasis), or supplemented with a small amount of tonifying herbs. They rarely address the core pathogenesis of "deficiency of vital energy and phlegm accumulation" through a comprehensive and systematic combination of tonifying and eliminating pathogenic factors. In particular, for precancerous lesions of pulmonary nodules with deficiency of both qi and yin as the root cause and phlegm and toxin accumulation as the manifestation, existing patents are insufficient in balancing the needs of tonifying qi and nourishing yin with resolving phlegm and detoxifying. Furthermore, most patents lack systematic clinical research data to support their efficacy, and their actual efficacy needs further verification.

[0006] Traditional Chinese medicine (TCM) has a long history and rich theoretical foundation, offering more flexible approaches to treating pulmonary nodules. It also has advantages in reducing patients' psychological burden and regulating their constitution. Through extensive clinical observation, we believe the core pathogenesis of pulmonary nodules is prolonged lung disease leading to deficiency of both the lung and spleen, qi deficiency and yin weakness, resulting in the internal generation of phlegm, which accumulates and eventually becomes toxic, summarized as "deficiency of vital energy and phlegm accumulation." Therefore, there is an urgent need to develop an effective TCM composition for the most common type of pulmonary nodules, namely, deficiency of vital energy and phlegm accumulation. Summary of the Invention

[0007] The present invention aims to provide a traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules and its preparation method, so as to solve the technical problem of the lack of effective traditional Chinese medicine preparations for intervening in precancerous lesions of pulmonary nodules of the type of deficiency and phlegm accumulation in the prior art.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] A traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules, made from the following raw materials in parts by weight:

[0010] Coix seed 30 parts, Astragalus membranaceus 15 parts, Pyrrosia lingua 30 parts, Atractylodes macrocephala 10 parts, Crataegus pinnatifida 10 parts, Isatis indigotica 10 parts, Oyster shell 30 parts, Spatholobus suberectus 15 parts, Hedyotis diffusa 30 parts, Lycium barbarum 10 parts, Ligustrum lucidum 10 parts, Adenophora stricta 15 parts, Gynostemma pentaphyllum 3 parts, Glycyrrhiza uralensis 6 parts, Codonopsis pilosula 15 parts, Cinnamomum cassia 6 parts, Lysimachia christinae 30 parts, Benincasa hispida 15 parts, Verbena officinalis 10 parts, Asparagus cochinchinensis 10 parts.

[0011] The present invention also provides a method for preparing a traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules, comprising the following steps: after cleaning and selecting the above-mentioned parts by weight of medicinal materials, pulverizing them separately, mixing them evenly, making them into pills with refined honey as an excipient, and packaging them after drying and passing quality inspection.

[0012] Compared with the prior art, the present invention has the following main advantages:

[0013] This invention's formula is applicable to treating precancerous lesions of pulmonary nodules of the deficiency-phlegm-accumulation type, where the deficiency is primarily qi and yin deficiency. Astragalus and Codonopsis are the principal herbs, tonifying the qi of the lungs and spleen. Adenophora, Asparagus, Atractylodes macrocephala, Lycium barbarum, and Ligustrum lucidum are the assistant herbs; Atractylodes macrocephala strengthens the spleen, dries dampness, and tonifies qi; Adenophora and Asparagus nourish the yin of the lungs and spleen; and Lycium barbarum and Ligustrum lucidum also nourish the yin of the liver and kidneys. The lungs are the receptacle for phlegm, and the spleen is the source of phlegm production. The formula uses coix seed to strengthen the spleen and resolve dampness, winter melon seed to moisten the lungs and resolve phlegm, and pyrrosia lingua to promote diuresis and eliminate dampness. With the spleen and lungs harmonized, phlegm and dampness are eliminated. Verbena officinalis, Hedyotis diffusa, and Isatis tinctoria clear heat and detoxify, while oyster shell softens hardness and dissipates nodules. Combined with the insect-derived herb Tianlong, the formula enhances its detoxifying and nodule-dispersing effects. Spatholobus suberectus, Hedyotis diffusa, and stir-fried hawthorn invigorate blood and remove blood stasis, promoting the flow of qi and blood and facilitating the dissipation of accumulated toxins. Cinnamomum cassia harmonizes yin and yang, preventing the cold and cooling herbs from harming the spleen and stomach. Finally, licorice root is used as the guiding herb to harmonize the other herbs in the formula. The combined effects of these herbs are to tonify qi and nourish yin, resolve phlegm, detoxify, and eliminate masses.

[0014] 1. Significantly reduces the maximum diameter of pulmonary nodules: Clinical studies have shown that after taking the traditional Chinese medicine composition of this invention, the maximum diameter of patients' pulmonary nodules can be significantly reduced, indicating that this invention can effectively inhibit the growth of pulmonary nodules and even promote the shrinkage of nodules.

[0015] 2. Effectively reduces the probability of malignancy in pulmonary nodules: Calculated using the Mayo Clinic model prediction formula, the probability of malignancy in patients' pulmonary nodules decreased from 16.60% before treatment to 8.33%, indicating that the present invention can significantly reduce the risk of pulmonary nodule cancer and is of great significance for the early prevention and treatment of lung cancer.

[0016] 3. Significantly improved TCM syndrome scores: The patient's TCM syndrome score decreased from 10.91 before treatment to 6.91 after treatment, indicating that the present invention can significantly improve clinical symptoms such as cough, sputum, chest tightness, fatigue, and shortness of breath, and improve the patient's quality of life.

[0017] 4. Reduced tumor marker CEA levels: The patient's serum CEA level decreased from 2 ng / mL before treatment to 1.51 ng / mL after treatment, indicating that the present invention has a benign regulatory effect on tumor-related indicators.

[0018] 5. High safety and no adverse reactions: During the clinical observation period, no abnormalities were found in the patients' blood routine and liver and kidney functions. No adverse reactions occurred during the use of this invention, indicating that the traditional Chinese medicine composition has good safety. Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments. All selected Chinese medicinal materials were obtained from commercial channels such as the market and meet the standards of the 2025 edition of the Chinese Pharmacopoeia. Unless otherwise specified, all parts are by weight.

[0020] 1. The formula includes the following components:

[0021] Coix seed 30 parts, Astragalus membranaceus 15 parts, Pyrrosia lingua 30 parts, Atractylodes macrocephala 10 parts, Crataegus pinnatifida 10 parts, Isatis indigotica 10 parts, Oyster shell 30 parts, Spatholobus suberectus 15 parts, Hedyotis diffusa 30 parts, Lycium barbarum 10 parts, Ligustrum lucidum 10 parts, Adenophora stricta 15 parts, Gynostemma pentaphyllum 3 parts, Glycyrrhiza uralensis 6 parts, Codonopsis pilosula 15 parts, Cinnamomum cassia 6 parts, Lysimachia christinae 30 parts, Benincasa hispida 15 parts, Verbena officinalis 10 parts, Asparagus cochinchinensis 10 parts.

[0022] 2. The specific preparation method is as follows:

[0023] After the above-mentioned weight proportions of medicinal materials are cleaned and selected, they are crushed separately, passed through an 80-mesh sieve, mixed evenly, and made into pills with refined honey as an excipient. Each pill weighs about 9g, and is dried at 60℃ until the moisture content is ≤9%. After passing the quality inspection, they are packaged.

[0024] 3. Clinical observation trial

[0025] 3.1 Research Subjects

[0026] This study selected patients aged 18-75 years, regardless of gender, who visited Wenzhou Municipal Hospital of Traditional Chinese Medicine between December 2022 and January 2026, underwent chest CT scans, were diagnosed with pulmonary nodules, and met the inclusion criteria.

[0027] 3.2 Diagnostic criteria

[0028] 3.2.1 Western Medicine Diagnostic Criteria

[0029] According to the diagnostic criteria of the "Chinese Guidelines for Classification, Diagnosis and Treatment of Pulmonary Nodules (2016 Edition)", pulmonary nodules are round or irregular lesions with a diameter of less than or equal to 3 cm in the lungs. The imaging manifestations are shadows with increased density. They can be single or multiple, and the lesions can be clear or unclear.

[0030] 3.2.2 Diagnostic Criteria for Traditional Chinese Medicine Syndromes

[0031] Based on the descriptions of phlegm syndrome in "Traditional Chinese Medicine Diagnostics", "Traditional Chinese Medicine Clinical Diagnosis and Treatment Terminology - Syndrome Section" and "Traditional Chinese Medicine Phlegm Syndrome Diagnostic Criteria (2016 Edition Guidelines)", and combined with clinical diagnosis and treatment experience, the diagnostic criteria for deficiency of vital energy and phlegm accumulation syndrome are formulated as follows: the main symptoms are cough, expectoration, and chest tightness; the secondary symptoms are fatigue, shortness of breath, poor appetite, dry mouth, and bitter taste; the tongue and pulse are pale or light red, with a white and greasy or thick and greasy coating, and a soft or weak pulse.

[0032] 3.3 Discharge Standards

[0033] 3.3.1 Inclusion Criteria

[0034] ① Age between 18 and 75 years old, gender not limited; ② Meets the Western medicine diagnostic criteria for precancerous lesions of pulmonary nodules; ③ Meets the diagnostic criteria for deficiency of vital energy and phlegm accumulation syndrome in traditional Chinese medicine; ④ Good compliance and signed informed consent form; ⑤ If basic information is incomplete, it can be obtained and supplemented through follow-up.

[0035] 3.3.2 Exclusion Criteria

[0036] ① Those who do not meet the diagnostic criteria for precancerous lesions of pulmonary nodules; ② Those with serious underlying diseases of the heart, lungs, liver, kidneys, etc.; ③ Those who have recently had pneumonia or lung diseases caused by rheumatic immune diseases; patients with hemoptysis or blood in sputum and patients with pulmonary tuberculosis; those with other uncontrolled tumors; ④ Pregnant or lactating women; ⑤ Patients with mental abnormalities or confusion; ⑥ Patients allergic to traditional Chinese medicine; ⑦ Those whose medical records are incomplete and cannot be supplemented through follow-up; ⑧ Those with poor compliance.

[0037] 3.4 Treatment methods

[0038] All 11 patients included in the study took the traditional Chinese medicine pills prepared in Example 1 of this invention, twice daily, one pill (approximately 9g) each time, taken with warm water. The observation period was 6 months.

[0039] 3.5 Observation Indicators

[0040] 3.5.1 Therapeutic Indicators

[0041] ①Tumor markers: Serum CEA and NSE levels were measured before and after treatment using laboratory biochemical methods.

[0042] ② Imaging parameters: The maximum diameter of the nodules was determined using chest CT. If there were multiple nodules in the lungs, the maximum diameter of the largest nodule or the maximum diameter of the nodule with the highest probability of malignancy was recorded.

[0043] ③ Probability of malignancy of lung nodules: The probability of malignancy of lung nodules was calculated by referring to the Mayo Clinic model prediction formula recommended in the guidelines.

[0044] ④ TCM syndrome scoring for pulmonary nodules: A quantification table of primary and secondary symptoms was developed based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" (2002 edition). Primary symptoms (cough, sputum, chest tightness) were categorized as none, mild, moderate, and severe, scored as 0, 2, 4, and 6 points respectively. Secondary symptoms (fatigue, shortness of breath, appetite, bowel movements, bitter taste in the mouth, dry mouth, sleep disturbances, etc.) were categorized as none, mild, moderate, and severe, scored as 0, 1, 2, and 3 points respectively. Tongue and pulse descriptions were provided but not included in the syndrome scoring. Records were made before and after treatment.

[0045] 3.5.2 Safety Indicators

[0046] ① General condition: body temperature, heart rate, respiration, blood pressure; ② Liver and kidney function, blood routine before and after treatment; ③ Record whether the patient has any adverse reactions after taking the medication.

[0047] 3.6 Statistical Analysis

[0048] SPSS 25.0 statistical software was used. Quantitative data were first tested for normality. Data conforming to a normal distribution were expressed as mean ± standard deviation and compared within groups using paired samples t-tests. Data not conforming to a normal distribution were expressed as median (interquartile range) and compared within groups using Wilcoxon rank-sum tests. A p-value < 0.05 was considered statistically significant.

[0049] 3.7 Research Results

[0050] 3.7.1 Case Completion Status

[0051] This study included 11 patients with precancerous pulmonary nodules who met the criteria. Of these, 10 patients completed NSE (tumor marker) testing, and the remaining 11 patients completed testing for all other indicators. All patients completed 6 months of treatment and follow-up, with no dropouts.

[0052] 3.7.2 Comparison of the probability of malignancy of pulmonary nodules before and after treatment

[0053] Normality test analysis of the difference in the Mayo Caucus probabilities of pulmonary nodules before and after treatment showed a non-normal distribution (P < 0.05). Rank-sum Wilcoxon test analysis confirmed a statistically significant difference in the malignancy probability of Mayo Caucus nodules before and after treatment (P < 0.05). See Table 1.

[0054] Table 1. Malignancy probability of Mayo Clinic nodules before and after treatment.

[0055]

[0056] 3.7.3 Comparison of the maximum diameter of pulmonary nodules before and after treatment

[0057] Normality test analysis of the difference in the maximum diameter of pulmonary nodules before and after treatment showed a non-normal distribution (P < 0.05). Rank-sum Wilcoxon analysis confirmed a statistically significant difference in the maximum diameter of pulmonary nodules before and after treatment (P < 0.05). See Table 2.

[0058] Table 2 Maximum diameter of pulmonary nodules before and after treatment.

[0059]

[0060] 3.7.4 Comparison of TCM syndrome scores before and after treatment

[0061] Normality test analysis of the difference in TCM syndrome scores before and after treatment showed that the difference was normally distributed (P>0.05). Paired-samples t-test analysis showed a statistically significant difference in TCM syndrome scores of pulmonary nodules before and after treatment (P<0.01). See Table 3.

[0062] Table 3. TCM syndrome scores before and after treatment

[0063]

[0064] 3.7.5 Comparison of tumor markers before and after treatment

[0065] Normality test analysis of the difference in tumor marker NSE before and after treatment showed that the values ​​were normally distributed (P>0.05). Paired-samples t-test analysis showed no statistically significant difference in tumor marker NSE before and after treatment (P>0.05). See Table 4.

[0066] Table 4 NSE before and after treatment

[0067]

[0068] Normality test analysis of the difference in tumor marker CEA before and after treatment showed a non-normal distribution (P < 0.05). Rank-sum Wilcoxon test analysis confirmed a statistically significant difference in CEA levels before and after treatment (P < 0.05). See Table 5.

[0069] Table 5 CEA levels before and after treatment

[0070]

[0071] 3.7.6 Safety Evaluation

[0072] The 11 patients included in the trial showed no abnormalities in blood routine tests or liver and kidney function before and after treatment, and no adverse reactions occurred during the administration of the traditional Chinese medicine composition of this invention. This indicates that the traditional Chinese medicine composition has good safety.

[0073] 3.8 Conclusion

[0074] Based on the above clinical research results, the traditional Chinese medicine composition of the present invention can significantly reduce the maximum diameter of pulmonary nodules, reduce the probability of malignancy of pulmonary nodules, improve the TCM syndrome score, and reduce the level of tumor marker CEA. Moreover, it has good safety and no adverse reactions occurred, indicating that the traditional Chinese medicine composition has a definite therapeutic effect on precancerous lesions of pulmonary nodules of the deficiency-phlegm accumulation type.

Claims

1. A traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: Coix seed 30 parts, Astragalus membranaceus 15 parts, Pyrrosia lingua 30 parts, Atractylodes macrocephala 10 parts, Crataegus pinnatifida 10 parts, Isatis indigotica 10 parts, Oyster shell 30 parts, Spatholobus suberectus 15 parts, Hedyotis diffusa 30 parts, Lycium barbarum 10 parts, Ligustrum lucidum 10 parts, Adenophora stricta 15 parts, Gynostemma pentaphyllum 3 parts, Glycyrrhiza uralensis 6 parts, Codonopsis pilosula 15 parts, Cinnamomum cassia 6 parts, Lysimachia christinae 30 parts, Benincasa hispida 15 parts, Verbena officinalis 10 parts, Asparagus cochinchinensis 10 parts.

2. The traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules according to claim 1, characterized in that, The dosage form of the traditional Chinese medicine composition is pills.

3. A method for preparing a traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules as described in claim 1 or 2, characterized in that, Includes the following steps: The medicinal materials in the specified weight proportions are cleaned, crushed, and mixed evenly. They are then made into pills using refined honey as an excipient, dried, and packaged after passing quality inspection.

4. The use of the traditional Chinese medicine composition for treating precancerous lesions of pulmonary nodules according to claim 1 or 2 in the preparation of a medicine for treating precancerous lesions of pulmonary nodules of the type of deficiency of vital energy and phlegm accumulation.

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