Traditional Chinese medicine composition for treating qi depression syndrome ground vitreous nodules of lung and traditional Chinese medicine preparation and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating qi depression syndrome ground vitreous nodules of lung as well as a traditional Chinese medicine preparation and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 9-12 parts of ginger processed cortex magnoliae officinalis, 15-20 parts of poria cocos, 6-9 parts of pericarpium citri reticulatae, 12-15 parts of perilla leaves, 10-15 parts of selfheal and 15-20 parts of oldenlandia diffusa. The invention further discloses a preparation of the traditional Chinese medicine composition. The traditional Chinese medicine composition and the preparation thereof can effectively reduce the maximum diameter of the ground vitreous nodules, reduce the number of the ground vitreous nodules or / and reduce the development risk of the ground vitreous nodules, can effectively improve the clinical symptoms of patients, regulate the mental mood of the patients, stabilize the psychological state of the patients and improve the curative effect of the patients. And further prevention and treatment of lung cancer can be facilitated.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and more specifically, to a traditional Chinese medicine composition for treating ground-glass nodules of the lungs due to qi stagnation syndrome, and a traditional Chinese medicine preparation and application thereof. Background Art

[0002] Lung cancer, as a chronic malignant disease that seriously threatens human health, not only threatens individual life safety, but also imposes a serious burden on family, social and public health resources. Therefore, early identification and intervention of lung cancer precancerous lesions is a key challenge that needs to be overcome in the current medical research and public health fields. Lung cancer precancerous lesions mainly include atypical adenomatous hyperplasia and adenocarcinoma in situ. Ground-glass nodules are the main imaging signs of lung cancer precancerous lesions. Due to their increasing incidence, lack of effective intervention methods and long follow-up time, the disease is in a stage of "easy to diagnose and difficult to treat".

[0003] Previous studies have found that many patients are overly concerned about the possibility of their lung nodules becoming cancerous. If they also have respiratory system symptoms, this further increases their psychological burden and may even lead to psychiatric symptoms such as anxiety and depression. Over time, abnormal emotional states and the development of lung nodules form a vicious cycle, increasing the tendency of lung nodules to become cancerous. This disease state belongs to the "Qi Yu Syndrome" of traditional Chinese medicine.

[0004] The theories of "differentiation of syndromes and treatment" and "preventive treatment" are the foundation of traditional Chinese medicine and are also effective countermeasures for controlling the progression of diseases. "Differential diagnosis of syndromes and treatment" includes two links: "differentiation of syndromes" and "treatment", which ensures the accurate identification of different syndromes of patients with ground-glass nodules in the lungs and determines the corresponding treatment principles, while "preventive treatment" fully reflects the importance of early prevention and treatment of lung cancer. Therefore, under the guidance of the theories of "differentiation of syndromes and treatment" and "preventive treatment", the development of drugs for ground-glass nodules in the lungs with qi stagnation syndrome is of great significance for preventing the occurrence of lung cancer, reducing the harm of precancerous lesions of lung cancer, improving the overall health level of the people, and laying a solid foundation for public health. Summary of the invention

[0005] In view of the above technical problems, one object of the present invention is to provide a new Chinese medicine composition, which can effectively reduce the maximum diameter of ground-glass nodules in the lungs, reduce the number of ground-glass nodules in the lungs and / or reduce the risk of progression of ground-glass nodules in the lungs, and can effectively improve the patient's clinical symptoms, regulate the patient's mental emotions, stabilize the patient's psychological state, change "passive follow-up" to "effective intervention", and help further move the threshold of lung cancer prevention and treatment forward.

[0006] Another object of the present invention is to provide various Chinese medicine preparations prepared using the above-mentioned Chinese medicine composition.

[0007] Another object of the present invention is to provide the use of the above-mentioned Chinese medicine composition and Chinese medicine preparation in the preparation of medicines for treating ground-glass nodules of the lung due to qi stagnation syndrome.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] In a first aspect, a traditional Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome is provided. The raw materials of the traditional Chinese medicine composition include, by weight: 9-12 parts of ginger magnolia bark, 15-20 parts of poria cocos, 6-9 parts of tangerine peel, 12-15 parts of perilla leaf, 10-15 parts of selfheal, and 15-20 parts of oldenlandia diffusa.

[0010] The Chinese medicine composition of the present invention regulates qi, promotes qi circulation, relieves depression, detoxifies, resolves phlegm and disperses nodules. It is mainly used to treat ground-glass nodules in the lungs due to qi stagnation syndrome. It treats qi stagnation, which is blocked in the lungs, affects water metabolism, generates phlegm and toxins, and eventually forms ground-glass nodules in the lungs; or because of emotional frustration, it disturbs the rise and fall of qi, and causes various symptoms of qi disorder.

[0011] In the prescription of the present invention, ginger and magnolia bark are used as the main medicine, which is mainly bitter, dry, pungent and dispersing, warm and can dispel cold, and is good at promoting qi to regulate qi. Ginger has a warming effect, which makes the medicinal properties tend to rise. Poria, tangerine peel, and perilla leaf are all ministerial medicines. Poria strengthens the spleen and infiltrates dampness and calms the heart, so that dampness is removed without phlegm. Tangerine peel strengthens the spleen and regulates qi and resolves phlegm, and strengthens the spleen and stomach to take care of the pivot of qi ascending and descending. The method of regulating qi is enhanced by using perilla leaf in combination with aromatic liver-soothing and qi-promoting, which helps ginger and magnolia bark to reach the qi stagnation in the chest. White flower oldenlandia diffusa and Prunella vulgaris detoxify and disperse knots, which are adjuvants. The whole prescription has harmonious and complementary drug compatibility, and treats phlegm and qi at the same time, playing the merits of regulating qi, promoting qi, relieving depression, detoxifying, resolving phlegm and dispersing knots.

[0012] In the present invention, exemplarily, the raw materials of the traditional Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome include, by weight: 10 parts of ginger magnolia bark, 15 parts of poria cocos, 9 parts of tangerine peel, 15 parts of perilla leaf, 15 parts of selfheal, and 15 parts of oldenlandia diffusa.

[0013] Exemplarily, the raw materials of the traditional Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome include, by weight: 9 parts of ginger magnolia bark, 20 parts of poria cocos, 6 parts of tangerine peel, 15 parts of perilla leaf, 10 parts of selfheal, and 20 parts of oldenlandia diffusa.

[0014] Exemplarily, the raw materials of the traditional Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome include, by weight: 12 parts of ginger magnolia bark, 15 parts of poria cocos, 9 parts of tangerine peel, 12 parts of perilla leaf, 15 parts of selfheal, and 15 parts of oldenlandia diffusa.

[0015] The basic formula of each raw material medicine of the above-mentioned Chinese medicine composition of the present invention can be adjusted according to clinical symptoms on the basis of the above-mentioned Chinese medicine composition during specific implementation, so as to further enhance the adaptability of the composition of the present invention and improve the therapeutic effect. These adjustments made based on the basic formula of the present invention are also within the protection scope of this application.

[0016] Exemplarily, for those with phlegm-dampness, one or more of Platycodon grandiflorum and Cat's Claw can be added. The recommended dosage of Platycodon grandiflorum is 10-12 parts, and the dosage of Cat's Claw is 15-20 parts.

[0017] Exemplarily, for patients with blood stasis, one or more of Curcuma and Ligusticum chuanxiong are added, and the recommended dosage of Curcuma is 10-12 parts, and the dosage of Ligusticum chuanxiong is 10-12 parts.

[0018] In a second aspect, the present invention provides a traditional Chinese medicine preparation for treating ground-glass nodules in the lungs due to qi stagnation syndrome, the raw materials of which include the above-mentioned traditional Chinese medicine composition.

[0019] According to actual needs, the Chinese medicine preparation may also include pharmaceutically acceptable adjuvants. According to conventional pharmaceutical preparation processes, various preparations such as decoctions, tablets, granules, pills, powders, capsules or powders may be prepared.

[0020] In a third aspect, the present invention also provides the use of the above-mentioned Chinese medicine composition and Chinese medicine preparation in the preparation of a medicine for treating ground-glass nodules in the lung caused by qi stagnation syndrome.

[0021] Furthermore, the drug can reduce the maximum diameter of ground-glass nodules in the lungs, reduce the number of ground-glass nodules in the lungs, and / or reduce the risk of progression of ground-glass nodules in the lungs.

[0022] Furthermore, the drug can improve the patient's symptoms of sighing, chest or lower abdominal distension and pain, bitter taste in the mouth, depression, belching and / or insomnia, and can significantly improve the patient's anxious and depressed psychological state.

[0023] In addition, unless otherwise specified, the raw materials of the Chinese medicine composition of the present invention can be obtained commercially, and any range recorded in the present invention, including the end values ​​and any numerical value between the end values ​​and any sub-range of the Chinese medicine composition formed by the end values ​​or any numerical value between the end values, can achieve the purpose of treating ground glass nodules in the lungs caused by qi stagnation syndrome.

[0024] The beneficial effects of the present invention are as follows:

[0025] The Chinese medicine composition of the present invention is combined with the clinical characteristics of patients with ground-glass nodules of the lung due to qi stagnation syndrome, and is based on the classic prescription Siqi Decoction. Siqi Decoction comes from "Sanyin Jiyi Bingzheng Fanglun", and is composed of ginger pinellia, magnolia bark, tuckahoe, and perilla leaf, and has the functions of descending adverse and resolving phlegm, promoting qi and relieving depression. On this basis, the Chinese medicine composition of the present invention removes the toxic pinellia, adds tangerine peel, white flower oldenlandia diffusa, and selfhealing three flavors, enhances the effects of promoting qi and relieving depression, and dissipating nodules. It has been verified through clinical trials that it has a very good therapeutic effect for patients with ground-glass nodules of the lung due to qi stagnation syndrome, and is safer and suitable for clinical promotion and application. DETAILED DESCRIPTION

[0026] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0027] Example 1

[0028] A Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome:

[0029] Raw material medicine formula: 12g of Magnolia officinalis, 15g of Poria cocos, 9g of dried tangerine peel, 12g of Perilla leaf, 15g of Prunella vulgaris, and 15g of Oldenlandia diffusa.

[0030] Take the above raw materials according to the formula, add water and boil, heat to boiling, keep boiling for 1 hour, filter; continue to add water to boil the residue, heat to boiling, keep boiling for 0.5 to 1 hour, filter, and combine the two filtrates. Then reduce the pressure and concentrate the filtrate into a clear paste with a certain specific gravity.

[0031] Example 2

[0032] A Chinese medicine preparation for treating ground-glass nodules of the lung due to qi stagnation syndrome:

[0033] Raw material medicine formula: 9g of Magnolia officinalis, 20g of Poria cocos, 6g of dried tangerine peel, 15g of Perilla leaf, 10g of Prunella vulgaris, and 20g of Oldenlandia diffusa.

[0034] Take the above raw materials according to the formula, add water and boil, heat to boiling, keep boiling for 1 hour, filter; continue to add water to boil the residue, heat to boiling, keep boiling for 0.5 to 1 hour, filter, and combine the two filtrates. Then reduce the pressure and concentrate the filtrate into a clear paste with a certain specific gravity, spray dry, sieve to obtain dry paste powder, and use dry granulation to make granules.

[0035] Example 3 Clinical Trial

[0036] 1 Clinical Data

[0037] 1.1 Research subjects

[0038] The research cases in this clinical trial are patients with ground-glass nodules (<15mm) in the lungs and qi stagnation syndrome who visited the cancer prevention clinic of the Oncology Department of Guang'anmen Hospital, China Academy of Chinese Medical Sciences between September 2023 and March 2024.

[0039] 1.2 Diagnostic criteria

[0040] 1.2.1 Western medicine diagnostic criteria

[0041] The diagnostic criteria for pulmonary nodules were formulated based on the relevant contents of the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)": focal, round, increased density lung shadows with a diameter of ≤3 cm on imaging, without atelectasis, hilar lymphadenopathy, and pleural effusion.

[0042] 1.2.2 TCM syndrome diagnostic criteria

[0043] The "Qi Yu Syndrome" standard is set based on the "Guidelines for Clinical Research of New Chinese Medicines", "Chinese Medicine Diagnosis" published by China Traditional Chinese Medicine Press, and "Chinese Medicine Internal Medicine" published by China Traditional Chinese Medicine Press, and combined with clinical comprehensiveness:

[0044] Main symptoms: depression, tension, anxiety, sighing, abdominal distension

[0045] Secondary symptoms: chest, flank or lower abdominal distension and pain, bitter taste in the mouth, insomnia, belching, breast pain in women

[0046] Tongue and pulse: red tongue, thin white fur, stringy pulse

[0047] If the patient meets 2 main symptoms and ≥1 secondary symptom, or ≥1 main symptom and ≥2 secondary symptoms, combined with the tongue and pulse, the patient can be diagnosed with Qi stagnation syndrome.

[0048] 1.3 Inclusion criteria

[0049] ① Unlimited gender, age 18-75 years old; ② Pulmonary ground-glass nodules <15 mm, TCM syndrome of qi stagnation; ③ Patients who have not undergone surgery; ④ Volunteer to participate in this study and sign the informed consent.

[0050] 1.4 Exclusion criteria

[0051] ① The total number of lung nodules is ≥ 10; ② Patients with a history of malignant tumors; ③ Patients taking oral antibiotics; ④ Patients with severe cardiovascular or hematopoietic diseases, or lesions of important organs such as the liver and kidney; ⑤ Patients who are allergic to the Chinese medicine they take; ⑥ Pregnant women, patients with mental illness or those in breastfeeding period; ⑦ Patients participating in other clinical trials.

[0052] 1.5 Shedding and rejection criteria

[0053] ① Patients who experience serious adverse events and stop the trial; ② Patients who refuse to accept follow-up; ③ Patients who cannot be contacted for various reasons; ④ Patients whose information is incomplete and affects the final evaluation; ⑤ Subjects request to withdraw from the study.

[0054] 2 Research content and methods

[0055] This study has been registered with the International Traditional Medicine Clinical Registry and reviewed by the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences. A pragmatic randomized controlled design was adopted to collect patients with pulmonary ground glass nodules who met the inclusion criteria from September 2023 to March 2024 and fill in the case report form. This study adopted the randomized controlled trial (PRPP) method based on patient preference in a pragmatic randomized controlled trial (pRCT), asking patients for their preferences. If they had preferences, they were grouped according to their wishes; if they had no preferences, they were numbered according to the order of their visits and divided into the treatment group and the control group using a random number table. A total of 86 patients were included in this study, and the changes in the maximum diameter and number of nodules in the two groups of patients at 24 weeks were observed. The changes in nodules before and after treatment were evaluated, and the changes in the TCM syndrome scores, psychological state scores, and adverse drug reactions of the patients were observed every 12 weeks.

[0056] 2.1 Treatment options

[0057] Treatment group: Chinese medicine granules made of ginger magnolia bark, Poria cocos, dried orange peel, perilla leaf, white flower oldenlandia diffusa, and selfhealing herb (prescription: ginger magnolia bark 10g, Poria cocos 15g, dried orange peel 9g, perilla leaf 15g, selfhealing herb 15g, white flower oldenlandia diffusa 15g), taken twice a day, in the morning and evening after meals. At the same time, lifestyle guidance was given, such as daily life, exercise, diet, etc., and regular follow-up and reexamination of low-dose spiral CT of the chest were performed.

[0058] Control group: Lifestyle guidance was given, such as daily life, exercise, diet, etc., and regular follow-up and reexamination of low-dose spiral CT of the chest were performed.

[0059] 2.2 Observation indicators

[0060] 2.2.1 Main efficacy indicators

[0061] Before and after treatment, the maximum diameter and number of lung nodules in the two groups of patients were measured by CT scan in the same hospital as the main efficacy indicators, and the clinical efficacy was determined based on the changes in target nodules in the "Screening and Prevention Program for Early Lung Cancer with Traditional Chinese Medicine" formulated by the Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences:

[0062] Markedly effective: The target nodules were completely absorbed and no longer visible on chest CT scan.

[0063] Effective: The target nodule is partially absorbed, the target nodule is visible upon reexamination, there is no indication of target nodule progression, and one of the following conditions is met: (1) the average diameter of the target nodule is reduced by ≥30% compared with that before treatment; (2) the CT value of the target nodule is reduced; (3) the solid component of the target nodule is reduced.

[0064] Stable: The target nodule is stable and the target nodule does not meet the indications of progression or complete absorption or partial absorption.

[0065] Progression: Target nodules progress if one of the following conditions is met: (1) the average diameter of the target nodules increases by ≥30% compared with the previous value; (2) the CT value of the target nodules increases; (3) the average diameter of the solid components of the target nodules increases by >1.5 mm; (4) the target nodules show malignant signs such as lobulation, spiculation, pleural indentation, and vascular bundle signs;

[0066] Effective rate = (number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0067] Stability rate = (number of stable cases) / total number of cases × 100%.

[0068] Progression rate = (number of progressed cases) / total number of cases × 100%.

[0069] Note: The average diameter of a nodule refers to the sum of the maximum long diameter of the solid part of the nodule and the longest short diameter perpendicular to the maximum long diameter (maximum short diameter) divided by 2.

[0070] 2.2.2 Secondary efficacy indicators

[0071] 2.2.2.1 TCM syndrome scoring: The TCM syndrome scoring scale was formulated with reference to the Guiding Principles for Clinical Research of New Chinese Medicines. The main symptoms such as emotional depression, tension and anxiety, sighing, and abdominal distension were divided into 4 levels according to the severity of the symptoms, and recorded as severe (6 points), moderate (4 points), mild (2 points), and none (0 points). The secondary symptoms such as chest and flank or lower abdominal distension and pain, bitter taste in the mouth, insomnia, heat, and breast pain in women were divided into 4 levels according to the severity of the symptoms, and recorded as severe (3 points), moderate (2 points), mild (1 point), and none (0 points). The changes in the TCM syndrome scores of the two groups of patients before and after treatment were observed and recorded.

[0072] 2.2.2.2 Evaluation of psychological status: The Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the anxiety status of patients, and the criteria were: total score ≥29 points, which may be severe anxiety; ≥21 points, which definitely has obvious anxiety; ≥14 points, which definitely has anxiety; >7 points, which may have anxiety; <7 points, which has no anxiety symptoms. The Hamilton Depression Rating Scale (HAMD) was used to evaluate the depression status of patients, and the criteria were: total score >35 points, which is severe depression; >20 points, which definitely has depression; total score ≥8 points, which may have depression; total score <8 points, which is normal.

[0073] 2.2.3 Safety indicators

[0074] Record in detail any adverse reactions related to treatment, such as abnormal liver and kidney function, gastrointestinal reactions, etc.

[0075] 2.2.4 Follow-up time and method

[0076] Follow-up will be conducted through outpatient follow-up, online platform, telephone inquiries, etc. The follow-up period starts from the patient's enrollment. Clinical symptoms, psychological status scores, blood routine, liver and kidney function, etc. will be followed up every 12 weeks. CT imaging evaluation will be performed after the 24th week. The study will be terminated if nodule deterioration or surgery is found. The follow-up deadline is September 30, 2024.

[0077] 2.3 Statistical methods

[0078] SPSS 27.0 software was used for statistical analysis, and the mean ± standard deviation was used. Describe the measurement data, and use frequency and percentage to describe the count data. The inter-group comparison of measurement data was performed using the grouped t test (normality, equal variance) or Wilcoxon rank sum test (non-normality, unequal variance), and the intra-group comparison was performed using the paired t test (normality) or Wilcoxon signed rank sum test (non-normality); the count data were tested using the chi-square test or Fisher's exact probability method. All statistical analysis tests used two-sided hypothesis tests, and the hypothesis test level was set at α = 0.05, that is, P < 0.05 was considered to be statistically significant.

[0079] 3 Results

[0080] 3.1 Case completion status

[0081] A total of 86 patients with pulmonary ground-glass nodules were enrolled in this study, with 43 cases in the treatment group and 43 cases in the control group. Among them, 2 cases dropped out of the treatment group (discontinuing medication during treatment), and 3 cases dropped out of the control group (1 patient did not cooperate with the test, and 2 patients withdrew on their own). Finally, 41 cases in the treatment group and 40 cases in the control group, a total of 81 patients completed the treatment and follow-up, as shown in Table 1.

[0082] Table 1 Subjects' completion of the study

[0083]

[0084] 3.2 Comparison of baseline data

[0085] 3.2.1 Demographic data

[0086] A total of 81 subjects were included in this study, including 41 in the treatment group and 40 in the control group. There was no significant difference in the baseline data between the two groups (P>0.05), and they were comparable (see Table 2).

[0087] Table 2 Demographic data of the two groups of subjects

[0088]

[0089]

[0090] 3.2.2 Imaging data

[0091] A total of 81 patients with pulmonary ground glass nodules were included in this study. Among the subjects included in the study, pure ground glass nodules (43 cases, 53.09%) were greater than mixed ground glass nodules (38 cases, 46.91%), and the average nodule size of the subjects was 6.56±1.34mm. There was no significant difference in the baseline data between the two groups of subjects (P>0.05), and they were comparable (see Table 3).

[0092] Table 3 Imaging data of the two groups of subjects

[0093]

[0094] 3.2.3 TCM symptom data

[0095] The TCM syndrome scoring scale of this study included 4 main symptoms and 5 secondary symptoms. The top three symptoms in the treatment group were belching (85.37%), emotional depression (78.05%), and insomnia (73.17%), while the top three symptoms in the control group were belching (82.5%), insomnia (77.5%), and emotional depression (75%). Among the 81 subjects, the top three symptoms in terms of frequency were belching (83.95%), emotional depression (76.54%), and insomnia (75.31%).

[0096] Except for the item "chest, flank or lower abdominal distension and pain", the other baseline data of the two groups of subjects showed no statistically significant difference (P>0.05), and were comparable (see Table 4).

[0097] Table 4 TCM symptom data of the two groups of subjects

[0098] Treatment Group Control group total <![CDATA[t / χ 2 ]]> P Depression (%) 32(78.05) 30(75) 62(76.54) 0.32 0.75 Tension and anxiety (%) 24(58.54) 28(70) 52(64.2) -1.070 0.288 Sigh of joy (%) 23(56.1) 18(45) 41(50.62) 0.993 0.324 Abdominal distension (%) 22(53.66) 23(57.5) 45(55.56) 0.103 0.918 Distension and pain in the chest, flank or lower abdomen (%) 19(46.34) 28(70) 47(58.02) -2.194 0.031 Bitter taste in mouth (%) 22(53.66) 20(50) 44(54.32) 0.103 0.918 Insomnia (%) 30(73.17) 31(77.5) 61(75.31) -0.447 0.656 Belching (%) 35(85.37) 33(82.5) 68(83.95) 0.347 0.729 Breast pain in women (%) 13(52) 13(59.09) 26(55.32) -0.479 0.635

[0099] 3.2.4 Psychological status data

[0100] A total of 81 subjects were included in this study, and neither group had severe anxiety or severe depression. The largest number of subjects had a score of ≥14 and <21 on the Hamilton Anxiety Rating Scale (HAMA) (50 cases, 61.73%), and the largest number of subjects had a score of ≥8 and <20 on the Hamilton Depression Rating Scale (HAMD) (66 cases, 81.48%). The HAMA anxiety scale data of the two groups showed a statistically significant difference (P < 0.05), while the HAMD depression scale data showed no statistically significant difference (P > 0.05), which was comparable (see Table 5 and Table 6).

[0101] Table 5 HAMA anxiety scale data of the two groups of subjects

[0102]

[0103] Table 6 HAMD depression scale data of the two groups of subjects

[0104]

[0105] 3.3 Efficacy analysis

[0106] 3.3.1 Primary efficacy analysis

[0107] (1) Changes in the maximum diameter of ground-glass nodules before and after treatment

[0108] As shown in Table 7, compared with the control group, the Chinese medicinal preparation of the present invention can significantly reduce the maximum diameter of the nodules in the treatment group.

[0109] Comparison between the treatment group and the control group: The baseline distribution of the maximum diameter of ground-glass nodules in the two groups was statistically significant (P < 0.05). After 24 weeks of treatment, the maximum diameter of ground-glass nodules in the control group increased significantly compared with the treatment group (P < 0.05), and the difference in the maximum diameter of ground-glass nodules in the treatment group before and after treatment was significantly better than that in the control group (P < 0.05).

[0110] Intra-group comparison between the treatment group and the control group: After 24 weeks, the maximum diameter of ground-glass nodules in the treatment group was significantly reduced (P < 0.05), while the maximum diameter of ground-glass nodules in the control group was significantly increased, and the difference was statistically significant (P < 0.05).

[0111] Table 7 Comparison of the maximum diameter of nodules in the two groups of patients before and after treatment (mm)

[0112]

[0113]

[0114] Note: Compared with the group before treatment, * P<0.05; compared with the control group,△ P<0.05.

[0115] (2) Changes in the number of ground-glass nodules before and after treatment

[0116] As shown in Table 8, compared with the control group, the Chinese medicinal preparation of the present invention can significantly reduce the number of nodules in the treatment group.

[0117] Comparison between the treatment group and the control group: There was a statistically significant difference in the baseline distribution of the number of ground-glass nodules in the two groups before treatment (P < 0.05). After 24 weeks of treatment, the number of nodules in the control group was significantly higher than that in the treatment group, and the difference was statistically significant (P < 0.05), and the difference in the number of nodules before and after treatment in the treatment group was significantly better than that in the control group (P < 0.05).

[0118] Intra-group comparison between the treatment group and the control group: there was no significant difference in the number of ground-glass nodules in the treatment group before and after treatment (P>0.05), while the number of ground-glass nodules in the control group increased significantly, with no significant difference before and after treatment (P>0.05).

[0119] Table 8 Comparison of the number of nodules in the two groups of patients before and after treatment

[0120] Group Treatment Group Control group t P Before treatment 2.24±1.16 <![CDATA[2.83±1.26 △ ]]> -2.164 0.033 After treatment 2.22±1.17 <![CDATA[2.87±1.32 △ ]]> -2.360 0.021 Difference -0.03±0.16 <![CDATA[0.05±0.23 △ ]]> -1.754 0.083

[0121] Note: Compared with the group before treatment, * P<0.05; compared with the control group, △ P<0.05.

[0122] (3) Comparison of overall efficacy between the two groups

[0123] As shown in Tables 9 and 10, compared with the control group, the Chinese medicine preparation of the present invention can significantly reduce the diameter of nodules, stabilize the state of nodules, and reduce the risk of nodule progression in the treatment group.

[0124] In the treatment group, 13 patients had their diameter reduced by more than 30% compared with the previous value, and in the control group, 1 patient had their diameter reduced by more than 30% compared with the previous value. In addition, none of the 41 patients in the treatment group had their disease progress, and in the control group, 14 patients had their disease progress.

[0125] Table 9 Comparison of imaging features between the two groups of patients after treatment

[0126] Table 10 Comparison of the efficacy of the two groups of patients before and after treatment

[0127] Group n Significant effect efficient Stablize progress Treatment Group 41 0 13 28 0 Control group 40 0 1 25 14

[0128] As shown in Table 11, compared with the control group, the Chinese medicine preparation of the present invention can significantly improve the effective rate of nodule treatment, enhance the stability rate of nodules, and significantly inhibit the progression rate of nodules in the treatment group.

[0129] The comparison between the two groups of subjects showed that the effective rate of the treatment group was 31.71%, the stable rate was 68.29%, and the progressive rate was 0; the effective rate of the control group was 2.5%, the stable rate was 62.5%, and the progressive rate was 35%. The data of the two groups were tested by rank sum test, Z = -4.673, P < 0.01, and the difference was statistically significant (P < 0.05).

[0130] Table 11 Comparison of effective rate, stabilization rate and progression rate between the two groups of patients before and after treatment

[0131] Group n Effectiveness (%) Stability Progress rate Treatment Group 41 31.71* 68.29 0 Control group 40 2.5 62.5 35

[0132] Note: Compared with the control group, *P<0.05.

[0133] 3.3.2 Secondary efficacy analysis

[0134] 3.3.2.1 Comparison of TCM syndrome scores

[0135] As shown in Table 12, compared with the control group, Siqi Changzhi Drink could significantly improve the clinical symptoms and quality of life of the patients in the treatment group.

[0136] After 12 weeks of treatment, the symptoms of euphoria and sighing in the treatment group were significantly improved (P < 0.05), and the total score of the TCM syndrome scale, euphoria and sighing, chest or lower abdominal distension and pain, and bitter taste in the mouth were significantly improved in the treatment group than in the control group (P < 0.05).

[0137] After 24 weeks of treatment, the total score of the TCM Syndrome Scale, emotional depression, sighing, and belching symptoms of the treatment group were significantly improved compared with before (P < 0.05), and the total score of the TCM Syndrome Scale, emotional depression, sighing, chest or lower abdominal distension and pain, bitter taste in the mouth, insomnia, and belching symptoms were significantly better than those in the control group (P < 0.05). Although there was no statistical difference in the changes of other symptoms, they showed an overall stable and alleviated trend.

[0138] The total score of the TCM Syndrome Scale of patients in the control group tended to increase, and the difference in scores between female patients before and after treatment was statistically significant (P < 0.05). Although there was no statistical difference in the changes of other symptoms, they showed a stable and slowly increasing trend overall.

[0139] Table 12 Comparison of TCM syndrome scores between the two groups before and after treatment

[0140]

[0141] Note: Compared with before treatment,* P<0.05; compared with 12 weeks of treatment, △ P<0.05; compared with the control group, ** P<0.05.

[0142] 3.3.2.2 Psychological status scores before and after treatment

[0143] As shown in Table 13, compared with the control group, the Chinese medicine preparation of the present invention can significantly improve the psychological state of the patients and regulate mood swings in the treatment group.

[0144] After 12 weeks of treatment, the HAMA and HAMD scores of the treatment group were significantly improved (P<0.05), while the HAMA and HAMD scores of the control group were significantly increased (P<0.05).

[0145] After 24 weeks of treatment, the HAMA score of the treatment group was significantly improved (P<0.05), while the HAMA and HAMD scores of the control group were increased (P>0.05).

[0146] Table 13 Comparison of psychological status scores between the two groups before and after treatment

[0147]

[0148] Note: Compared with before treatment, *P<0.05; compared with 12 weeks of treatment, △P<0.05.

[0149] 3.4 Adverse events in the two groups of patients during the experiment

[0150] As shown in Table 14, during the treatment, one patient in the treatment group had abnormal liver function (AST elevation), and no adverse events occurred in the control group. The incidence of adverse reactions between the treatment group and the control group was compared, and the difference was not statistically significant (P>0.05) by Fisher's exact probability test.

[0151] Table 14 Comparison of the incidence of adverse reactions between the two groups

[0152]

[0153] Note: Fisher's exact probability method, no statistics.

[0154] Experimental Example 4 Typical Case

[0155] Case 1

[0156] Huang, female, 41 years old. On December 13, 2023, the chest CT examination showed multiple mixed ground glass nodules in the right lung, the larger of which was located in the lower lobe of the right lung, with a diameter of about 5.2mm. She came to the clinic on December 14, 2023. The current symptoms are: intermittent cough, poor emotional control, more thoughts, and easy sighing. Appetite is good, sleep is normal, bowel movements are once a day, formed, and urination is normal. The tongue is dark red, the tongue coating is white, there are saliva lines on both sides of the tongue, and the pulse is stringy. The HAMA score is 23 points and the HAMD score is 17 points.

[0157] Take granules of the present invention (prescription: 10g of ginger and magnolia bark, 15g of Poria cocos, 9g of dried orange peel, 15g of perilla leaf, 15g of selfheal, 15g of oldenlandia diffusa), 1 dose per day, take warm after meals in the morning and evening.

[0158] On June 29, 2024, the patient returned for a follow-up visit and complained that his cough was less severe than before, his mood was more relaxed, and his mood was more comfortable. His tongue was pale red, his fur was white, the salivary lines on both sides disappeared, and his pulse was floating. His HAMA score was 5 points and his HAMD score was 6 points.

[0159] Re-examination of chest CT showed: multiple mixed ground-glass nodules in the right lower lobe, the larger one was located in the right lower lobe, with a diameter of about 4.3mm, which was smaller than the ground-glass nodules at the initial diagnosis.

[0160] Case 2

[0161] Liu, male, 53 years old. Chest CT scan on January 21, 2024 showed pure ground glass nodules in the left lung, the largest of which was located in the upper lobe of the left lung, with a maximum diameter of about 6.8 mm. He came to the clinic on January 25, 2024. His current symptoms were: depression and anxiety. Poor appetite, poor sleep, easy awakening, bowel movement once every 3 days, and normal urination. Dark red tongue, greasy white fur, and slippery pulse. HAMA score was 21 points, and HAMD score was 17 points.

[0162] Take granules of the present invention (prescription: 9g of ginger and magnolia bark, 20g of Poria cocos, 6g of dried orange peel, 15g of perilla leaf, 10g of selfheal, 20g of oldenlandia diffusa), 1 dose per day, take warm after meals in the morning and evening.

[0163] On August 2, 2024, the patient reported a significant improvement in mood, a stable state of mind, good appetite, and improved sleep. The tongue was red, the coating was white, and the pulse was stringy. The HAMA score was 5 points and the HAMD score was 9 points. The chest CT scan showed: ground-glass nodules in the left upper lobe, the largest of which was about 4.3 mm in diameter, which was smaller than the ground-glass nodules at the initial diagnosis.

[0164] Case 3

[0165] Ms. Hu, female, 61 years old. On October 2, 2023, a chest CT scan showed a pure ground glass nodule in the middle lobe of the right lung, with a diameter of about 8.1 mm. She came to the clinic on October 9, 2023. The current symptoms are: occasional cough, sighing, normal appetite, poor sleep, difficulty falling asleep, loose stools once every 2 days, and 3 nocturia. The tongue is dark red, the coating is white, and the pulse is deep. The HAMA score is 18 points and the HAMD score is 13 points.

[0166] Take granules of the present invention (prescription: 10g of ginger and magnolia bark, 15g of Poria cocos, 9g of dried orange peel, 15g of perilla leaf, 15g of selfheal, 15g of oldenlandia diffusa), 1 dose per day, take warm after meals in the morning and evening.

[0167] On April 15, 2024, the patient was re-examined and reported that his cough was significantly relieved, his sighing frequency was reduced, and his sleep was OK. His tongue was red, his fur was white, and his pulse was deep. His HAMA score was 5 and his HAMD score was 7. A chest CT scan showed that there was a ground-glass nodule in the middle lobe of the right lung, with a diameter of about 6.2 mm, which was smaller than the ground-glass nodule at the initial visit.

[0168] Case 4

[0169] Liang, female, 49 years old. On October 28, 2023, a chest CT scan showed multiple mixed ground-glass nodules in the right lung, the largest of which was located in the upper lobe of the right lung, with a diameter of about 6.4 mm. She came to the clinic on October 28, 2023. The current symptoms are: occasional emotional outbursts, bitter taste in the mouth in the morning, good appetite, normal sleep, unformed bowel movements once a day, and normal urination. Red tongue, white and greasy coating, and rapid pulse. HAMA score is 16 points, and HAMD score is 15 points.

[0170] Take granules of the present invention (prescription: 12g of ginger and magnolia bark, 15g of Poria cocos, 9g of dried orange peel, 12g of perilla leaf, 15g of selfheal, 15g of oldenlandia diffusa), 1 dose per day, take warm after meals in the morning and evening.

[0171] On May 2, 2024, the patient reported that his mood control was good and the bitter taste in his mouth had disappeared. His tongue was red, his fur was thin and white, and his pulse was fine. His HAMA score was 7 and his HAMD score was 7. A chest CT scan showed that there were multiple ground-glass nodules in the right lung, the largest of which was located in the upper lobe of the right lung, with a diameter of about 3.8 mm, which was smaller than the ground-glass nodules at the initial visit.

[0172] Case 5

[0173] Wang, male, 69 years old. Chest CT scan on February 19, 2024 showed multiple mixed ground-glass nodules in the right lung, the largest of which was located in the middle lobe of the right lung, with a diameter of about 8.4 mm. He came to the clinic on February 23, 2024. The current symptoms are: nervousness and anxiety, good appetite, shallow sleep, sticky stool once a day, and normal urine. Dark red tongue, white fur, slow pulse. HAMA score of 12 points, HAMD score of 15 points. History of previous occupational exposure.

[0174] Take granules of the present invention (prescription: 10g of ginger and magnolia bark, 15g of Poria cocos, 9g of dried orange peel, 15g of perilla leaf, 15g of selfheal, 15g of oldenlandia diffusa), 1 dose per day, take warm after meals in the morning and evening.

[0175] On May 2, 2024, the patient reported that his anxiety and tension had disappeared and his stools were formed. His tongue was red, his fur was white, and his pulse was deep. His HAMA score was 8 and his HAMD score was 6. A chest CT scan showed that there were multiple ground-glass nodules in the right lung, the largest of which was located in the middle lobe of the right lung, with a diameter of about 5.6 mm, which was smaller than the ground-glass nodules at the initial visit.

[0176] In summary, for patients with ground-glass nodules in the lungs that are symptoms of qi stagnation, the Chinese medicine composition of the present invention and its preparation can effectively reduce the size of lung nodules, significantly inhibit the risk of nodule progression, improve the patient's clinical symptoms, regulate the patient's mental emotions, stabilize the patient's psychological state, and change "passive follow-up" to "effective intervention", which will help to further move the threshold of lung cancer prevention and treatment forward.

[0177] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating ground-glass nodules of the lung due to qi stagnation syndrome, characterized in that: In parts by weight, the raw materials of the traditional Chinese medicine composition include: 9-12 parts of ginger magnolia bark, 15-20 parts of tuckahoe, 6-9 parts of tangerine peel, 12-15 parts of perilla leaf, 10-15 parts of selfheal, and 15-20 parts of oldenlandia diffusa.

2. The Chinese medicine composition according to claim 1, characterized in that: In terms of weight, the raw materials of the Chinese medicine composition include: 10 parts of ginger magnolia bark, 15 parts of tuckahoe, 9 parts of tangerine peel, 15 parts of perilla leaf, 15 parts of selfheal, and 15 parts of oldenlandia diffusa; Alternatively, the raw materials of the Chinese medicine composition include, by weight: 9 parts of ginger magnolia bark, 20 parts of tuckahoe, 6 parts of tangerine peel, 15 parts of perilla leaf, 10 parts of selfheal, and 20 parts of oldenlandia diffusa; Or, 12 parts of Rhizoma Zingiberis, 15 parts of Poria, 9 parts of Perilla frutescens, 12 parts of Folium Perillae, 15 parts of Spica Prunellae, and 15 parts of Hedyotis diffusa.

3. The Chinese medicine composition according to claim 1, characterized in that In parts by weight, the raw materials of the traditional Chinese medicine composition also include one or more of the following: 10-12 parts of Platycodon grandiflorum and 15-20 parts of Cat's Claw.

4. The Chinese medicine composition according to claim 1, characterized in that: In parts by weight, the raw materials of the traditional Chinese medicine composition also include one or more of the following: 10-12 parts of Curcuma and 10-12 parts of Ligusticum chuanxiong.

5. A Chinese medicine preparation for treating ground-glass nodules of the lung due to qi stagnation syndrome, characterized in that: The raw materials of the traditional Chinese medicine preparation include the traditional Chinese medicine composition according to any one of claims 1-4.

6. The Chinese medicine preparation according to claim 5, characterized in that: The raw materials of the traditional Chinese medicine preparation also include pharmaceutically acceptable excipients.

7. The Chinese medicine preparation according to claim 5, characterized in that: The dosage form of the traditional Chinese medicine preparation includes decoction, tablet, granule, pill, powder, capsule or powder.

8. Use of the Chinese medicine composition according to any one of claims 1 to 4 or the Chinese medicine preparation according to any one of claims 5 to 7 in the preparation of a drug for treating ground-glass nodules of the lung due to qi stagnation syndrome.

9. The use according to claim 8, characterized in that: The drug can reduce the maximum diameter of ground-glass nodules in the lungs, reduce the number of ground-glass nodules in the lungs, or / and reduce the risk of progression of ground-glass nodules in the lungs.

10. The use according to claim 8, characterized in that: The medicine can improve the patient's symptoms of sighing, chest or lower abdominal distension and pain, bitter taste in the mouth, depression, belching and / or insomnia, and can improve the patient's anxious and depressed psychological state.

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