Traditional Chinese medicine composition and application thereof

Abstract

The present application relates to the field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition and application thereof. The present application combines the effects of tonifying and removing dampness, resolving phlegm, promoting blood circulation and resolving stasis, focuses on tonifying the lung and supplementing the body's vital qi while resolving stasis, and focuses on regulating the state of the body with deficiency and damage first and the state of accumulation of damp phlegm and stasis as nodules due to deficiency of lung qi and failure of qi to flow and form fluid. The treatment method is tonifying lung qi, resolving dampness and phlegm, promoting blood circulation and resolving stasis, and the drugs are used for both tonifying and attacking, and the formula of insect drugs and shell drugs increases the effects of resolving stasis, resolving phlegm, promoting blood circulation and resolving stasis. The efficacy evaluation of the present application is based on objective lung CT images, and the effectiveness of lung nodules is mainly reflected in the reduction of the size of lung CT nodules, and the present application shows good clinical efficacy.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and particularly to traditional Chinese medicine compositions and their applications. Background Technology

[0002] Pulmonary nodules refer to round or irregular lesions in the lungs with a diameter ≤3cm, without mediastinal lymphadenopathy, and often without respiratory symptoms. Some pulmonary nodules are high-risk cancerous nodules that require surgical removal, while others are intermediate- or low-risk nodules, whose lesion nature is chronic inflammation or adenomatous precancerous lesions, requiring regular follow-up with lung CT scans. Currently, there are no effective treatments in Western medicine.

[0003] Pulmonary nodules are a newly emerging, complex, and difficult-to-diagnose disease, often asymptomatic and detected only through lung CT scans. Several international guidelines for pulmonary nodule research suggest that approximately 14-35.5% of those undergoing lung CT scans will have pulmonary nodules detected. A study conducted by North Sichuan Medical College in my country, involving 10,642 healthy individuals undergoing health checkups, revealed 2,857 cases of pulmonary nodules, a detection rate of 26.8%. Domestic and international guidelines for pulmonary nodules primarily focus on benign / malignant assessment and regular follow-up, with no specific medical treatment offered; surgical removal is performed upon observation of growth or changes. International research suggests that early close monitoring and early surgical intervention for pulmonary nodules can reduce lung cancer mortality by 20%.

[0004] The international medical community has published several guidelines for the diagnosis and treatment of pulmonary nodules. In 2016, my country published the "Guidelines for the Classification, Diagnosis and Treatment of Pulmonary Nodules in China," and in 2018, it supplemented and revised the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules." These guidelines all focus on analyzing the cancer risk of pulmonary nodules and differentiating high, medium, and low-risk cancerous nodules based on their nature (ground-glass opacity, solid, partially solid), size, and presence of malignant features (lobulation, spiculation, vascularization, cavitation, etc.).

[0005] Lung nodule malignancy rate: Lung nodules include benign nodules with chronic inflammation, adenomatous changes, and malignant nodules that have become lung cancer. The US ACCP guidelines state that the malignancy rate for nodules smaller than 5mm is <1%, and for nodules between 5-9mm, it is 2.3-6%. Asian guidelines (Japan) indicate that the malignancy rate for sub-centimeter nodules (<1cm) is >20%. The 2018 Chinese expert consensus on lung nodules points out that the probability of malignant nodules increases significantly with age; the malignancy rate for solitary pulmonary nodules (SPN) in people under 30 years old is 1%–5%, while the malignancy rate increases in people over 70 years old. In a study of 2857 lung nodules at North Sichuan Medical College, micronodules <4mm were predominant, with a detection rate of 74.5%. The detection rate for relatively high-risk nodules ≥8mm was 6.58%. A follow-up study of patients with ≥8mm lung nodules revealed 25 cases of lung cancer among the 86 patients who were effectively revisited, resulting in an overall malignancy detection rate of 2.35‰.

[0006] Lung nodule cancer risk assessment: Domestic and international lung nodule guidelines indicate that lung nodule size and shape, Mayo lung cancer prediction model, etc. can be used to make a comprehensive judgment. According to CT density, it is divided into three categories: solid nodules, part-solid nodules, and pure ground-glass nodules. According to the size and shape (average of the longest and shortest diameters of the largest slice), it can be divided into low, intermediate and high risk nodules. (1) High risk cancer nodules: solid nodules with a diameter ≥15mm or with malignant CT signs of 8-15mm; part-solid nodules with a diameter >8mm. The guidelines recommend puncture biopsy, and surgical treatment or oncology treatment when necessary. (2) Intermediate risk cancer nodules: solid nodules with a diameter of 5-15mm and no obvious malignant CT signs; part-solid nodules with a diameter ≤8mm; pure ground-glass nodules with a diameter ≥5mm. It is recommended that the CT follow-up period be 3-6 months. (3) Low risk cancer nodules: solid nodules with a diameter <5mm; pure ground-glass nodules with a diameter <5mm. It is recommended that the annual CT follow-up period be 3-6 months. Because lung nodules are small, there is currently a lack of blood tests for tumor markers or genetic tests to quickly determine whether they are benign or malignant.

[0007] Pulmonary nodules are a complex and challenging disease. International and domestic guidelines for the diagnosis and treatment of pulmonary nodules recommend surgical resection for nodules with a tendency towards malignancy, while low- and intermediate-risk nodules should be monitored with regular lung CT scans. Surgical resection of high-risk cancerous nodules mostly involves minimally invasive lung cancer or carcinoma in situ, but also adenomatous nodules and chronic inflammatory nodules. Surgical resection is not only invasive and costly, but also results in approximately 10% of surgically resected pulmonary nodules being pathologically benign. Currently, there are few Western medicine treatments available for low- and intermediate-risk nodules. A 6-month randomized controlled trial comparing the efficacy of inhaled corticosteroid fluticasone versus placebo in pulmonary nodules showed no difference between the two (P = 0.094). The fluticasone group showed a 6-month efficacy rate of 16.28% (7 / 43), while the placebo group showed a 6-month efficacy rate of 7.1% (3 / 42).

[0008] Existing patented Chinese medicine formulas vary in quality, and the selected ingredients are mostly phlegm-resolving, blood-stasis-removing, and detoxifying drugs, which have the drawback of damaging the body's vital energy. Although they have certain clinical efficacy in treating pulmonary nodules, the evaluation of clinical efficacy is mainly based on the traditional symptom improvement, ignoring the fact that many patients with pulmonary nodules are asymptomatic or have atypical symptoms.

[0009] Therefore, the invention of the effective traditional Chinese medicine combination, Yifei Sanjie Formula, can effectively intervene and treat pulmonary nodules, reduce the malignant progression of pulmonary nodules, and potentially spare patients from the high costs of surgery, thus offering significant economic benefits. Furthermore, the invention of this effective traditional Chinese medicine combination can effectively intervene and treat pulmonary nodules, alleviate patient fear and anxiety, reduce the incidence of lung cancer, and reduce patient suffering, thus meeting considerable social demand. Summary of the Invention

[0010] In view of this, the traditional Chinese medicine combination of Yifei Sanjie provided by the present invention is an effective drug prescription for treating pulmonary nodules.

[0011] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0012] This invention provides a traditional Chinese medicine composition comprising Codonopsis pilosula, Adenophora stricta, Ganoderma lucidum, deer antler slices, Dioscorea nipponica, Pinellia ternata, Sinapis alba, clam shell, pumice, turtle shell, Eupolyphaga sinensis, bee honeycomb, Curcuma longa, Curcuma longa, Polygonum hydropiper, and Pinus tabuliformis.

[0013] In some specific embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0014]

[0015] In some specific embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0016]

[0017]

[0018] In some specific embodiments of the present invention, the traditional Chinese medicine composition may further include one or more of the following: Arisaema cum Bile, Panax notoginseng powder, Smilax glabra, Ilex cornuta leaf, Curcuma zedoaria, or raw oyster shell.

[0019] In some specific embodiments of the present invention, the pumice is used in place of the raw oyster, and the turmeric is used in place of the curcuma. When there is a lot of phlegm, add Arisaema cum Bile; when there is a lot of blood stasis, add Panax notoginseng powder; when there is a lot of damp heat, add Smilax glabra and Ilex cornuta leaves.

[0020] In some specific embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0021]

[0022]

[0023]

[0024] Based on the above, the present invention also provides the application of the traditional Chinese medicine composition in the treatment of pulmonary nodules.

[0025] In some specific embodiments of the present invention, the pulmonary nodules are low- to intermediate-risk pulmonary nodules;

[0026] Intermediate-risk pulmonary nodules include:

[0027] Solid nodules 5-15 mm in diameter with no obvious malignant CT signs; or

[0028] Partially solid nodules with a diameter ≤8mm; or

[0029] Pure ground glass nodules with a diameter ≥ 5 mm.

[0030] Low-risk pulmonary nodules include:

[0031] Solid nodules with a diameter <5mm; or

[0032] Pure ground glass nodules with a diameter of <5mm.

[0033] The present invention also provides a medicine comprising the aforementioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0034] In addition, the present invention also provides a pharmaceutical composition, including the aforementioned traditional Chinese medicine composition and any other active ingredients.

[0035] This invention combines tonification with phlegm-resolving, blood-activating, and nodule-dispersing effects. While dispersing nodules, it emphasizes nourishing the lungs and replenishing the body's vital energy, focusing on regulating the body's pre-existing deficiency and the resulting stagnation of dampness and phlegm leading to nodules. The treatment principle is to tonify vital energy, resolve dampness and phlegm, activate blood circulation, and disperse nodules. The medications employ both tonifying and purging methods, with the formula incorporating insect-derived and shell-derived herbs to enhance the effects of dispersing nodules, resolving phlegm, activating blood circulation, and removing blood stasis. The efficacy of this invention is evaluated based on objective lung CT imaging. The effectiveness in treating lung nodules is primarily measured by a reduction in nodule size and density, as well as a decrease in the solid component. Clinical studies have shown good efficacy. Attached Figure Description

[0036] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0037] Figure 1 A lung CT scan showing the disappearance of ground-glass nodules in the right lower lung of Mr. Shi after treatment;

[0038] Figure 2 A lung CT scan showing the disappearance of ground-glass nodules in the right lower lung of Mr. Zhang after treatment;

[0039] Figure 3 A lung CT scan showing the disappearance of ground-glass nodules in the right lower lung of Mr. Cui after treatment;

[0040] Figure 4 A lung CT scan showing the disappearance of ground-glass nodules in the upper right lung of Mr. Liu after treatment;

[0041] Figure 5 A lung CT scan showing the disappearance of ground-glass nodules in the left upper lung of Mr. Xu after treatment.

[0042] Figure 6 A lung CT scan showing the disappearance of ground-glass nodules in Mr. Wang's right lower lung after treatment.

[0043] Figure 7 A lung CT scan showing the disappearance of ground-glass nodules in the left lower lung of Mr. Zhang after treatment;

[0044] Figure 8 A lung CT scan showing the disappearance of ground-glass nodules in the upper right lung of Mr. Zhao after treatment;

[0045] Figure 9 A lung CT scan showing that most of the ground-glass nodules in the left lower lung of Mr. Yan have disappeared after treatment.

[0046] Figure 10 A lung CT scan showing that most of the solid nodules in Luo's left upper lung have disappeared after treatment;

[0047] Figure 11 A lung CT scan showing that most of the solid nodules in Mr. Song's left lower lung disappeared after treatment;

[0048] Figure 12 A lung CT scan showing the disappearance of solid nodules in Wang's left lower lung after treatment;

[0049] Figure 13 A lung CT scan showing the disappearance of a solid nodule in the right lower lung of Mr. Huang after treatment;

[0050] Figure 14 A lung CT scan showing the disappearance of solid nodules in the left upper lung of Mr. Pan after treatment;

[0051] Figure 15 A lung CT scan showing that most of the solid nodules in Mr. Chao's left upper lung disappeared after treatment;

[0052] Figure 16 A lung CT scan showing that most of the solid nodules in Zhao's left lower lung have disappeared after treatment;

[0053] Figure 17 A lung CT scan showing the disappearance of mixed ground-glass nodules in the right lower lung of Mr. Wang after treatment.

[0054] Figure 18 A lung CT scan showing the disappearance of mixed ground-glass nodules in the right lower lung of Mr. Meng after treatment;

[0055] Figure 19 A lung CT scan shows that most of the mixed ground-glass nodules in Mr. Shen's left lower lung have disappeared after treatment.

[0056] Figure 20 The image shows a lung CT scan of Mr. Wang's right lower lung where the mixed ground-glass nodules disappeared after treatment. Detailed Implementation

[0057] This invention discloses a traditional Chinese medicine composition and its application. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0058] Pulmonary nodules are a common lung disease with a high incidence rate. Some pulmonary nodules have certain characteristics of malignant transformation and require surgical removal. Pulmonary nodules not only cause physical pain for patients, but also cause anxiety, worry, and fear among the public, especially given the fear of cancer. Pulmonary nodules may not present with respiratory symptoms such as cough or wheezing; some are high-risk cancerous nodules, while many more are low- to intermediate-risk nodules requiring regular follow-up lung CT scans. We have been treating pulmonary nodules for over 10 years, leading the field of traditional Chinese medicine treatment for pulmonary nodules both domestically and internationally. We have treated thousands of patients with pulmonary nodules, including single and multiple nodules, pure ground-glass opacities, solid and partially solid nodules, and post-tumor surgery nodules, with significant therapeutic effects and rich clinical experience. In treatment, we emphasize the patient's physical condition and the characteristics of the lung CT nodules as part of the TCM diagnostic method for analyzing and summarizing the pathogenesis.

[0059] The main pathogenesis of pulmonary nodules: We use the size and shape characteristics of pulmonary nodules on lung CT scans as part of the TCM diagnostic method of observation, providing the main basis for analyzing and summarizing the pathogenesis of pulmonary nodules. Pulmonary nodules appear as nodules on lung CT scans, including pure ground-glass opacities, solid nodules, and partially solid nodules with a mixture of ground-glass and solid components. Based on the characteristics of the nodule shape and substance on lung CT scans, the nodule images reflect the pathological state of dampness, turbidity, phlegm, and blood stasis in TCM. We believe that the main internal factor in nodule formation is deficiency of the body's vital energy (Qi) and insufficient lung Qi, leading to Qi deficiency, dampness obstruction, and the accumulation of phlegm and blood stasis. The lungs govern respiration, the dispersing and descending of Qi, and the regulation of water metabolism. The normal dispersing and descending of lung Qi during inhalation and exhalation propels the circulation of fluids like mist. When the body's vital energy is insufficient and lung Qi is deficient, the resulting deficiency of vital energy, Qi deficiency, dampness obstruction, phlegm, and blood stasis leads to the accumulation of pulmonary nodules. When tangible pathological substances such as dampness, phlegm, and blood stasis obstruct the lungs, the condition progresses. In mild cases, ground-glass nodules appear, while in severe cases, they gradually evolve into mixed solid nodules or compacted nodules. If the accumulated nodules cannot be eliminated for a long time, the phlegm and blood stasis will worsen, leading to nodules with lobulation, spiculation, vascular bundles, vacuoles, etc., or the nodules may rapidly increase in number and deteriorate into cancer.

[0060] Treatment based on the patient's condition: Pulmonary nodules rarely present with respiratory symptoms such as cough and sputum. According to traditional Chinese medicine's diagnostic methods, pulmonary nodules fall into a category where there is no specific syndrome to diagnose in traditional Chinese medicine. We analyzed the pathogenesis of pulmonary nodules based on lung CT images, combined with the patient's tongue, pulse, and constitution at the time of consultation, to determine the appropriate treatment. Analyzing the patient's condition and treating according to the pathogenesis of pulmonary nodules revealed that patients generally suffered from deficiency of vital energy, leading to stagnation of qi and fluids, resulting in dampness, phlegm, and blood stasis—the core of the pathogenesis. Treatment focused on tonifying vital energy, resolving dampness and phlegm, promoting blood circulation, and dispersing nodules, showing good clinical efficacy.

[0061] Based on changes in the size and dimensions of lung nodules on CT scans as indicators for evaluating treatment efficacy, we previously conducted a clinical observation of the efficacy of the "Benefiting the Lungs, Activating Blood Circulation, Resolving Phlegm, and Dispersing Nodules" method in treating 187 patients with lung nodules. The results showed that the overall effective rate was 37.43%. The overall effective rates for low-risk, intermediate-risk, high-risk, multiple, single solid, single partial solid, and single pure ground-glass nodules were 45.24%, 41.94%, 23.08%, 38.57%, 38.71%, 24.39%, and 46.67%, respectively.

[0062] Currently, a randomized controlled trial (RCT) study on the treatment of pulmonary nodules based on the patient's condition (funded by the Beijing Municipal Health Development Fund, project number 2020-2-4202) is underway. This is the first RCT study in Beijing focusing on the treatment of pulmonary nodules with traditional Chinese medicine. Only the research title has been disclosed; the application only lists eight specific drugs without dosage information, and the detailed research content is not publicly available. This project studies the efficacy of traditional Chinese medicine in treating pulmonary nodules. The core formula is adjusted according to the patient's condition, and treatment for intermediate-risk pulmonary nodules is administered for three months as one course of treatment, followed by lung CT scans. Efficacy is evaluated based on nodule size, and the spontaneous remission rate is compared with that of a control group without intervention. The project has observed some therapeutic effects.

[0063] Based on these previous studies, we have developed a traditional Chinese medicine formula for treating pulmonary nodules called Yifei Sanjie Fang, which consists of the following herbs: Codonopsis pilosula, Adenophora stricta, Ganoderma lucidum, deer antler slices, Dioscorea nipponica, Pinellia ternata, Sinapis alba, clam shell, pumice, turtle shell, Eupolyphaga sinensis, bee honeycomb, Curcuma longa, Curcuma longa, Polygonum hydropiper, Pinus tabuliformis, etc.

[0064] This herbal formula is a summary prescription based on the effective treatment of over 2,000 patients with pulmonary nodules in the past decade. It combines the functions of invigorating lung qi, replenishing vital energy, dispelling dampness and phlegm, and promoting blood circulation and resolving nodules. The specific formula has not yet been made public.

[0065] The raw materials and reagents used in the traditional Chinese medicine composition and its application provided by this invention can all be purchased from the market.

[0066] The present invention will be further illustrated below with reference to the embodiments:

[0067] Example 1: Traditional Chinese Medicine Composition

[0068]

[0069]

[0070] Preparation method:

[0071] The above-mentioned Chinese herbal medicine slices are decocted in water as usual. One dose is decocted to obtain 400ml, and 200ml is taken each time, twice a day.

[0072] Alternatively, take the above-mentioned herbal formula granules, which are prepared as two packets of the formula. Take one packet each morning and evening with hot water.

[0073] Example 2 Traditional Chinese Medicine Composition

[0074] Addition, subtraction and proportion:

[0075] When adjusting the prescription, use Curcuma zedoaria instead of Curcuma longa (10-15 parts); use raw oyster shell instead of pumice (20-45 parts); add Arisaema cum Bile (6-10 parts) for excessive phlegm; add Panax notoginseng powder (3-6 parts) for severe blood stasis. Add Smilax glabra (10-15 parts) and Ilex cornuta (10-15 parts) for severe damp-heat.

[0076] Example 3: A randomized controlled clinical observation of the efficacy of Yifei Sanjie Formula in treating 115 patients with intermediate-risk pulmonary solid nodules.

[0077] This embodiment represents a study currently being conducted by the applicant, spanning from 2020 to 2022. It involves a randomized controlled clinical trial targeting intermediate-risk pulmonary nodules. The experimental treatment group and the control group were allocated in a 2:1 ratio. The experimental treatment group received treatment with a modified traditional Chinese medicine formula for benefiting the lungs and dispersing nodules, while the control group received no intervention as a blank control. Both groups underwent a three-month treatment course. Changes in nodule size observed on a follow-up lung CT scan after three months were used as the primary indicator of efficacy.

[0078] From August 2020 to April 2022, a randomized controlled clinical trial was completed on 115 patients with intermediate-risk solid pulmonary nodules, including 77 patients in the experimental group and 38 patients in the blank control group. The research data and results showed that the total effective rate in the experimental group was 51.95%, while the remission rate in the blank control group was 7.89%. This study demonstrates the efficacy of Yifei Sanjie formula in treating intermediate-risk solid pulmonary nodules and provides clinical trial evidence for the Yifei Sanjie formula of this invention.

[0079] I. Materials and Methods

[0080] 1) General information: The cases were sourced from 115 patients with moderately dangerous pulmonary solid nodules who visited the outpatient clinic of Professor Zhang Xiaomei at Dongfang Hospital of Beijing University of Chinese Medicine and the thoracic surgery department of Beijing Shijitan Hospital under the leadership of Director Li Baozhong from August 2020 to April 2022. A random number table was formulated according to the ratio of experimental treatment to control of 2:1. According to the chronological order of enrollment, the patients were randomly divided into an experimental group and a control group. The patients in the experimental group enrolled by Director Li Baozhong of the thoracic surgery department of Beijing Shijitan Hospital went to the outpatient clinic of Zhang Xiaomei at Dongfang Hospital for traditional Chinese medicine prescription treatment. The experimental group was treated with the traditional Chinese medicine Yifei Sanjie Prescription and its modifications for three months. The control group did not receive drug intervention. After three months, the patients in both groups had their chest CT rechecked. There were 47 males and 68 females, with an average age of (56.14 ± 10.601) years. The gender and age distribution of the patients in the two groups are shown in Table 1.

[0081] Table 1 Gender and age distribution of 115 patients with moderately dangerous pulmonary solid nodules

[0082] Gender / Age male female total age experimental group 35 42 77 55.58±10.707 control group 12 26 38 57.26±10.433 total 47 68 115 56.14±10.601

[0083] 2) Diagnostic criteria: Western medicine diagnostic criteria: Refer to the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)" and the "Chinese Guidelines for the Classification, Diagnosis and Treatment of Pulmonary Nodules (2016 Edition)" for the diagnosis and classification of pulmonary nodules. ① Degree of risk: Solid nodules: Moderately dangerous solid nodules with a diameter of 5-15 mm and no obvious malignant CT signs. ② Quantity: A single lesion is solitary, and two or more lesions are defined as multiple. ③ Multiple nodules are classified according to the nodule with the largest area and the highest degree of risk.

[0084] 3) Inclusion criteria: ① Patients with moderately dangerous pulmonary solid nodules who meet the above diagnostic criteria; ② Patients with moderately dangerous pulmonary nodules who need CT follow-up according to the Chinese guidelines and expert consensus on pulmonary nodules. ③ Patients whose pulmonary nodules did not decrease after more than 1 month of CT reexamination of moderately dangerous pulmonary solid nodules.

[0085] 4) Exclusion criteria: ① Patients with severe primary diseases such as cardiovascular and cerebrovascular diseases, liver, kidney, blood, tumors, etc.; ② Patients with active tuberculosis and other infectious diseases; ③ Patients with mental diseases such as mania, schizophrenia, etc. or other reasons who cannot cooperate with the observers; ④ Pregnant or lactating women; ⑤ Patients with missing contact information or incomplete case data.

[0086] 5) Treatment method: Oral treatment with traditional Chinese medicine prescriptions was given in the outpatient clinic. The drugs were traditional Chinese medicine decoction pieces or traditional Chinese medicine formula granules from the pharmacy of Dongfang Hospital of Beijing University of Chinese Medicine. The Yifei Sanjie Prescription was modified and administered once a day by decocting in water or taking it with traditional Chinese medicine granules. The experimental group of traditional Chinese medicine was treated with modifications for 3 months. During this period, follow-up visits were made every 2-4 weeks, and a chest CT was rechecked once after 3 months of treatment. The results were compared with the most recent chest CT results before the initial diagnosis to evaluate the curative effect.

[0087] 6) Efficacy Evaluation Criteria: The size of the nodules on chest CT scans is the primary basis for efficacy evaluation, combined with nodule density and number, for self-comparison before and after treatment. Nodule area of ​​the largest diameter plane in chest CT scans: The area of ​​the largest diameter plane of the lung nodule is calculated as S = π × A × B / 4 (ellipse area formula, where A and B are the major and minor axes of the chest CT report, respectively. If the chest CT report only has diameter D, then A = B = D, which is the area formula for a circle). The area reduction rate before and after treatment is compared, and the number and density of nodules are compared based on the chest CT report and image interpretation. For multiple nodules, the change in the area of ​​the largest nodule is used to statistically evaluate efficacy.

[0088] The therapeutic effects are categorized into the following levels: ① Cured: Chest CT shows nodules disappear; ② Significantly effective: Chest CT shows nodules become smaller, lighter, and fewer, with a reduction in the area of ​​the largest diameter ≥ 50%; ③ Effective: Chest CT shows nodules become smaller, lighter, and fewer, with a reduction in the area (sum of areas) of the largest diameter < 50%; ④ Ineffective: Chest CT shows no change in nodule size, density, or number, or nodule enlargement and progression. The total effective rate in the experimental group or the total remission rate in the control group (%) = (Number of cured cases + Number of significantly effective cases + Number of effective cases) / Total number of cases × 100%.

[0089] II. Results and Conclusions

[0090] 1. Classification of nodules in patients with intermediate-risk solid pulmonary nodules

[0091] The 115 intermediate-risk solid lung nodules included two categories: single solid nodules and multiple solid nodules, with multiple solid nodules being more common. The classification of the number of intermediate-risk solid lung nodules in the two groups is shown in Table 2.

[0092] Table 2 Classification of 115 cases of intermediate-risk solid pulmonary nodules

[0093]

[0094] 2. Time of discovery of intermediate-risk solid pulmonary nodules before initial diagnosis and follow-up chest CT scans.

[0095] The length of the medical history of the 115 patients before the initial diagnosis varied, and most of them had no significant reduction in lung nodule size on previous follow-up CT scans, as shown in Table 3.

[0096] Table 3. Distribution of initial onset time in 115 cases of intermediate-risk solid pulmonary nodules

[0097]

[0098]

[0099] 3. Therapeutic effect

[0100] Among 115 patients with intermediate-risk pulmonary solid nodules, the total effective rate of the Yifei Sanjie Fang experimental treatment group was 51.95%, while the total remission rate of the control group was 7.89%. The total effective rate of the Yifei Sanjie Fang experimental group was significantly better than that of the control group (P<0.001), as shown in Tables 4 and 5.

[0101] Table 4. Observation of the efficacy of 115 cases of solid pulmonary nodules over 3 months

[0102]

[0103] Note: Cure: Nodules disappear; Significant effect: 50% ≤ area reduction rate < 100%; Effective: 0% < area reduction rate < 50%; Stable: No change in area; Progression: Area increases. Total effective rate in the treatment group or total remission rate in the control group = (Cure + Significant effect + Effective) / Total number of cases × 100%. A Z-test was performed to calculate the mean rank, Z-value, and P-value. Z = -4.862, P < 0.01, indicating a significant difference.

[0104] Table 5. Comparison of treatment rates between the two groups in 115 cases of pulmonary solid nodules.

[0105]

[0106] Note: The total effective rate in the experimental group was 51.95%, and the remission rate in the control group was 7.89%. The chi-square test was used to compare the two independent sample groups. P < 0.01, indicating a significant difference.

[0107] The above clinical research data show that the clinical effective rate of the modified Yifei Sanjie formula in the treatment group for intermediate-risk solid pulmonary nodules was 51.95%, while the spontaneous remission rate in the blank control group without treatment intervention was 7.89%. The comparison between the two groups shows that the clinical effective rate of the modified Yifei Sanjie formula in treating intermediate-risk solid pulmonary nodules was significantly higher than the spontaneous remission rate in the control group (P<0.01). The modified Yifei Sanjie formula has good clinical efficacy for solid pulmonary nodules, improving the "nodular" state of patients by tonifying lung qi, eliminating dampness and phlegm, and promoting blood circulation and dispersing nodules, thus reducing local pathological nodules. The modified Yifei Sanjie formula can be used as an effective traditional Chinese medicine formula for treating intermediate-risk solid pulmonary nodules and has positive clinical significance in the treatment of these nodules.

[0108] Example 4: A randomized controlled clinical observation of the efficacy of Yifei Sanjie Formula in treating 97 patients with intermediate-risk pulmonary ground-glass nodules.

[0109] This embodiment represents a study currently being conducted by the applicant, spanning from 2020 to 2022. It involves a randomized controlled clinical trial targeting intermediate-risk pulmonary nodules. The experimental treatment group and the blank control group were allocated in a 2:1 ratio. The experimental treatment group received treatment with a modified traditional Chinese medicine formula for benefiting the lungs and dispersing nodules, while the control group received no drug intervention. Both groups underwent a three-month treatment course. Changes in nodule size observed on follow-up lung CT scans after three months were the primary indicator of efficacy.

[0110] A three-month randomized controlled clinical observation of 97 patients with intermediate-risk pulmonary ground-glass nodules has been completed, including 65 patients in the experimental group and 32 patients in the control group. Statistical analysis of the research data and results showed that the total effective rate in the experimental group treated with traditional Chinese medicine was 46.15%, while the total remission rate in the control group without drug intervention was 12.5%. This demonstrates the efficacy of Yifei Sanjie formula in treating intermediate-risk pulmonary ground-glass nodules and provides clinical trial evidence for the Yifei Sanjie formula of this invention.

[0111] I. Materials and Methods

[0112] 1) General Information: The cases were 97 patients with intermediate-risk pulmonary ground-glass nodules who visited Professor Zhang Xiaomei's clinic at Dongfang Hospital of Beijing University of Chinese Medicine and Director Li Baozhong's Department of Thoracic Surgery at Beijing Shijitan Hospital between August 2020 and April 2022. A random number table was used to randomly divide the patients into the experimental group and the control group according to the order of enrollment. Patients in the experimental group from Shijitan Hospital received traditional Chinese medicine prescriptions at Professor Zhang Xiaomei's clinic at Dongfang Hospital. The experimental group received three months of treatment with the traditional Chinese medicine formula Yifei Sanjie Fang and its modifications, while the control group received no treatment. Both groups underwent follow-up lung CT scans after three months. There were 38 males and 59 females, with a mean age of (53.01±10.02) years. The gender and age distribution of the two groups are shown in Table 6.

[0113] Table 6. Gender and age distribution of 97 cases of intermediate-risk pulmonary ground-glass nodules

[0114] Gender / Age male female total age experimental group 26 39 65 52.74±10.69 control group 12 20 32 53.89±9.45 total 38 59 97 53.01±10.02

[0115] 2) Diagnostic Criteria: Western Medicine Diagnostic Criteria: Referencing the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)" and the "Chinese Guidelines for the Classification, Diagnosis, and Treatment of Pulmonary Nodules (2015 Edition)" for the diagnosis and classification of pulmonary nodules. ① Risk Level: Simple ground-glass nodules are classified as intermediate-risk ground-glass nodules ≥5mm. ② Number: A single lesion is considered isolated; two or more lesions are defined as multiple. ③ For multiple nodules, the nodule with the largest diameter and highest risk is primarily used for efficacy evaluation.

[0116] 3) Inclusion criteria: ① Patients with intermediate-risk pulmonary ground-glass nodules who meet the above diagnostic criteria; ② Patients with intermediate-risk pulmonary nodules requiring CT follow-up according to the Chinese guidelines and expert consensus on pulmonary nodules; ③ Patients whose ground-glass nodules have not decreased in size on follow-up CT scans of the lungs more than 1 month later.

[0117] 4) Exclusion criteria: ① Those with severe primary diseases such as cardiovascular and cerebrovascular diseases, liver diseases, kidney diseases, blood diseases, tumors, etc.; ② Those with active tuberculosis and other infectious diseases; ③ Those with mental diseases such as mania, schizophrenia, etc. or those who cannot cooperate with the observers for other reasons; ④ Pregnant or lactating women; ⑤ Those with missing contact information or incomplete case materials.

[0118] 5) Treatment method: The experimental group was given oral treatment with traditional Chinese medicine prescriptions in the outpatient department. The drugs were traditional Chinese medicine decoction pieces or traditional Chinese medicine formula granules from the pharmacy of Dongfang Hospital of Beijing University of Chinese Medicine. Yifei Sanjie Prescription was mainly used with additions and subtractions. One dose was taken daily. The traditional Chinese medicine was treated with additions and subtractions for 3 months. During this period, follow-up visits were made every 2 - 4 weeks. After 3 months of treatment, chest CT was reexamined once. The results were compared with the chest CT results at the time of enrollment before the initial diagnosis to evaluate the curative effect.

[0119] 6) Curative effect rating criteria: The size of the nodules on chest CT was used as the main basis for curative effect, and in combination with nodule density, quantity, etc., self - comparison before and after was carried out. For the nodule area on the largest diameter plane of the pulmonary nodules in chest CT: Calculate the area S of the nodule on the largest diameter plane as S = π×A×B / 4 (ellipse area formula, A and B are the major axis and minor axis reported in the chest CT report respectively. If only the diameter D is reported in the chest CT report, then A = B = D, which is the circular area formula). Compare the area reduction rate before and after treatment, and compare the quantity and density of the nodules according to the chest CT report and film reading. For multiple nodules, calculate based on the area of the largest diameter.

[0120] The curative effect is divided into the following curative effect levels: ① Cured: The nodules disappeared on chest CT; ② Markedly effective: The nodules on chest CT became smaller, lighter, and fewer, and the area reduction rate of the largest diameter plane (sum of areas) ≥ 50%; ③ Effective: The nodules on chest CT became smaller, lighter, and fewer, and the area reduction rate of the largest diameter plane (sum of areas) < 50%; ④ Ineffective: The size, density, and quantity of the nodules on chest CT were stable without obvious changes or the nodules increased and progressed. The total effective rate of the experimental group or the total remission rate of the control group (%) = (number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0121] II. Results and Conclusions

[0122] 1. Nodule classification of patients with intermediate - risk pulmonary ground - glass nodules

[0123] The 97 cases of intermediate - risk pulmonary ground - glass nodules included two types: single ground - glass nodules and multiple ground - glass nodules. Among them, multiple ground - glass nodules were more common. The classification of the number of intermediate - risk pulmonary ground - glass nodules in the two groups is shown in Table 7.

[0124] Table 7 Classification of 97 cases of intermediate - risk pulmonary ground - glass nodules

[0125]

[0126]

[0127] 2. Time of discovery of intermediate-risk pulmonary ground-glass nodules before initial diagnosis and follow-up chest CT scans.

[0128] The length of the medical history before the initial diagnosis varied among the 97 patients. Most of them had no significant reduction in the size of the lung nodules on previous follow-up CT scans, as shown in Table 8.

[0129] Table 8. Time of initial diagnosis and follow-up CT findings in 97 cases of intermediate-risk pulmonary ground-glass nodules

[0130]

[0131] 3. Therapeutic effect

[0132] After three months of treatment observation, the total effective rate of the Yifei Sanjie formula in the experimental group was 46.15%, while the total remission rate in the control group was 12.50%. The total effective rate of the experimental group was significantly better than that of the control group (P<0.01), as shown in Tables 9 and 10.

[0133] Table 9. Observation of the efficacy of 97 cases of ground-glass nodules over 3 months

[0134]

[0135] Note: Cure: Nodules disappear; Significant effect: 50% ≤ area reduction rate < 100%; Effective: 0% < area reduction rate < 50%; Stable: No change in area; Progression: Area increases. Total effective rate in the treatment group or total remission rate in the control group = (Cure + Significant effect + Effective) / Total number of cases × 100%. A Z-test was performed to calculate the mean rank, Z-value, and P-value. Z = -3.264, P < 0.01, indicating a significant difference.

[0136] Table 10 Comparison of efficacy rates between the two groups in 97 cases of ground-glass nodules

[0137]

[0138]

[0139] Note: The total effective rate in the treatment group was 46.15%, and the total remission rate in the control group was 12.50%. The chi-square test was used to compare the two independent sample groups. P < 0.01, indicating a significant difference.

[0140] The results of the above study show that, for intermediate-risk pulmonary ground-glass nodules, the total clinical effective rate of the experimental group treated with modified Yifei Sanjie formula was 46.15%, while the total remission rate of the blank control group without Chinese medicine intervention was 12.5%. The clinical efficacy of Yifei Sanjie formula in treating intermediate-risk pulmonary ground-glass nodules was significantly higher than that of the blank control group (P<0.01), indicating that Yifei Sanjie formula can be used as an effective formula for the treatment of intermediate-risk pulmonary ground-glass nodules and has positive clinical significance for the treatment of intermediate-risk pulmonary ground-glass nodules.

[0141] Example 5: Case Study of Yifei Sanjie Formula - CT scans of nodules before and after treatment

[0142] Case CT images 1-20 are lung CT scans of effective clinical treatments of various types of pulmonary nodules using the traditional Chinese medicine composition provided by this invention. The images, taken from the same lung CT slice, show the maximum diameter area of ​​the pulmonary nodules. In the upper left or right corner of the lung CT scan, there is patient information in pinyin or Chinese, examination time, hospital, etc., in English.

Claims

1. A traditional Chinese medicine composition for treating intermediate-risk pulmonary nodules, characterized in that, It is prepared from the following components in parts by weight: 10-20 portions of Codonopsis pilosula 10-20 portions of North American ginseng 9-15 portions of Ganoderma lucidum 6-15 portions of deer antler slices 10-20 portions of pangolin 6-9 parts of Pinellia ternata 6-12 portions of white mustard seeds 20-45 pieces of clam shells 20-45 parts of pumice 10-20 parts turtle shell 6-15 parts of ground beetle 3-6 portions of beehives 6-15 parts of turmeric 6-15 parts turmeric 6-10 parts of water safflower seeds 6-10 portions of pine resin.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, It is prepared from the following components in parts by weight: 15 portions of Codonopsis pilosula 15 portions of North American ginseng 10 portions of Ganoderma lucidum 10 portions of deer antler slices 15 portions of pangolin 9 portions of Pinellia ternata 9 portions of white mustard 30 portions of clam shells 30 samples of pumice 15 portions of turtle shell 9 portions of ground beetle 5 portions of beehives 10 portions of turmeric 10 parts turmeric 9 portions of water safflower seeds 10 portions of pine resin.

3. The traditional Chinese medicine composition as described in claim 1 or 2, characterized in that, Based on the aforementioned traditional Chinese medicine composition, one or more of the following ingredients are further added: Arisaema cum Bile, Panax notoginseng powder, Smilax glabra, and Ilex cornuta leaf. For those with excessive phlegm, add 6-10 parts of Arisaema cum Bile; for those with severe blood stasis, add 3-6 parts of Panax notoginseng powder; for those with severe damp-heat, add 10-15 parts of Smilax glabra and 10-15 parts of Ilex cornuta leaf.

4. The traditional Chinese medicine composition as described in claim 3, characterized in that, It is prepared from the following components in parts by weight: 10-20 portions of Codonopsis pilosula 10-20 portions of North American ginseng 9-15 portions of Ganoderma lucidum 6-15 portions of deer antler slices 10-20 portions of pangolin 6-9 parts of Pinellia ternata 6-12 portions of white mustard seeds 20-45 pieces of clam shells 20-45 parts of pumice 10-20 parts turtle shell 6-15 parts of ground beetle 3-6 portions of beehives 6-15 parts of turmeric 6-15 parts turmeric 6-10 parts of water safflower seeds 6-10 portions of pine resin 6-10 parts of Arisaema cum Bile 3-6 parts of Panax notoginseng powder 10-15 parts of Smilax glabra 10-15 parts of holly leaves.

5. The use of the traditional Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for the prevention and / or treatment of intermediate-risk pulmonary nodules.

6. The application as described in claim 5, characterized in that, The lung nodule is a medium-risk lung nodule; Intermediate-risk pulmonary nodules include: Solid nodules 5-15 mm in diameter with no obvious malignant CT signs; or Partially solid nodules with a diameter ≤8mm; or Pure ground glass nodules with a diameter ≥ 5mm.

7. A drug for treating intermediate-risk pulmonary nodules, characterized in that, It is made from the traditional Chinese medicine composition as described in any one of claims 1 to 4 and pharmaceutically acceptable excipients.

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