A traditional Chinese medicine composition for treating lung nodules of qi-yin deficiency type, a preparation method and application thereof

Abstract

The application provides a traditional Chinese medicine composition for treating lung nodules of qi-yin deficiency type, a preparation method and application, and belongs to the technical field of traditional Chinese medicine preparations. The traditional Chinese medicine composition is composed of the following components in parts by weight: raw dried ginseng 10-30 parts, white swertia 15-45 parts, lily 10-40 parts, and whole gualou 10-40 parts. The traditional Chinese medicine composition has a definite curative effect on lung nodule patients of qi-yin deficiency type, can reduce and stabilize the size of lung nodules, reduce the risk probability of lung nodule patients, significantly relieve the clinical symptoms of qi-yin deficiency type such as fatigue, cough, dry mouth and the like of patients, effectively improve the release of inflammatory factors of the body, regulate the microenvironment of immune cells, improve the precancerous'soil' of patients, and has a wide clinical application prospect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine composition for treating lung nodules of qi-yin deficiency type, a preparation method and application. BACKGROUND

[0002] Lung nodules refer to local, round, and density-increased solid or sub-solid lung shadows with a diameter of less than 3 cm. Those with a diameter of less than 1 cm are called "small nodules". According to the pathological nature, lung nodules can be divided into benign (inflammatory nodules, pulmonary tuberculosis, hamartoma, lung abscess, etc.) and malignant (lung cancer) nodules. Most patients with lung nodules will have two situations. One is excessive anxiety and tension, and multiple reexaminations in a short time or even direct surgery, which increases unnecessary trauma and is prone to recurrence after surgery, and reduces the quality of life. The other is relaxation and non-periodic monitoring, and when the symptoms are obvious, the lung cancer has progressed to the middle and late stages, and the best treatment time is missed. Therefore, how to intervene in lung nodules in the early stage is a hot and difficult point in the current medical field.

[0003] Traditional Chinese medicine has unique advantages in reducing lung nodules and improving the "soil" of precancer. Although there is no "lung nodule" or "lung cancer" in ancient books, according to the etiology and pathogenesis and clinical characteristics, it can be classified into the "lung accumulation" category. The earliest "lung accumulation" is pointed out in the Difficult Classic, which is "the accumulation of the lung, called Xieben, on the right side of the chest, covering a large cup". The accumulation is caused by deficiency of vital qi and invasion of pathogenic qi. Traditional Chinese medicine believes that the lung is a delicate organ and is the master of the body's qi. With age, "at the age of forty, the yin qi is half, and the living is declining", the lung qi is damaged first, and then the generation and operation of the body's qi are affected. The lung is the source of water, and the lung loses its descending function. If the lung qi is deficient, the blood and body fluid in the body cannot be transported. The Classic of Internal Classic says "yang transforms qi, and yin forms shape. The lung is based on qi and yin". If the lung qi is deficient for a long time, it will damage the yin, and the lung yin will not be able to moisten the pulse. The damage of yin to yang further aggravates the deficiency of qi, and the accumulation of qi and phlegm occurs when the qi does not transport the body fluid. The accumulation of qi and phlegm in the lung forms "lung accumulation". The clinical symptoms are easy fatigue, dry cough or little phlegm, dry mouth, poor appetite, red tongue, and thin or fine pulse. Therefore, for this group of lung yin and yang imbalance, qi and yin deficiency, and real and virtual, it is necessary to develop a medicine composition with good curative effect, easy to adhere to, and small side effects.

[0004] A traditional Chinese medicine composition for treating lung nodules, its preparation and application are disclosed in Chinese patent CN116570699A. The traditional Chinese medicine composition is made from the following components in parts by weight: 15-30 parts of radix astragali, 10 parts of curcuma zedoaria, 15-30 parts of berberis wilsonii, and 15-30 parts of cat's claw. The traditional Chinese medicine composition has the effects of tonifying qi, reducing phlegm, dredging collaterals, and detoxifying and resolving nodules, and has good therapeutic effect on lung nodules.

[0005] A Chinese patent CN116920066A discloses a traditional Chinese medicine composition for treating lung nodules and lung cancer, a preparation thereof and an application thereof. The traditional Chinese medicine composition comprises the following raw medicinal materials: Semen Euryales, Solanum lyratum, Rhodiola, Curcuma, Oldenlandia, Platycodon, Radix Achyranthis Bidentatae, Radix Trichosanthis, Radix Tripterylii Wilfordii, Fritillaria Thunbergii, Pinellia, Radix Paeoniae Alba, and the like. The traditional Chinese medicine composition has remarkable effects in inhibiting the generation and development of lung nodules, improving lung function, and promoting the dispersion of lung nodules.

[0006] A Chinese patent CN115381915A discloses a traditional Chinese medicine composition for treating lung nodules of phlegm-heat and blood-stasis type, a preparation method and an application thereof. The traditional Chinese medicine composition is made of the following raw materials: Carapax Trionycis, Ostrea, Radix Bupleuri, Radix Scutellariae, Belamcanda chinensis, Bombyx Batryticatus, Zingiber Officinale, Radix et Rhizoma Rhei, Radix Paeoniae Rubra, Ramulus Cinnamomi, Semen Lepidii, Radix Pyrrosiae, Radix Paeoniae Alba, Lonicera Japonica, Rhizoma Pinelliae, Radix et Rhizoma Ginseng, Ground Beetle, Honeycomb, Semen Persicae, Semen Raphani, Fritillaria Thunbergii, Radix Tripterylii Wilfordii, Sea Algae, Laminaria, Sickle Sallow, Curcuma and Fagopyrum Dibotrys. The traditional Chinese medicine composition has the effects of clearing heat and resolving stasis, resolving phlegm and dredging collaterals, and tonifying qi and strengthening the body resistance, and is used for treating lung nodules of phlegm-heat and blood-stasis type, and can be used for long-term treatment of lung nodules less than 8mm in diameter and auxiliary treatment of lung nodules of 8-30mm in diameter.

[0007] The above-mentioned traditional Chinese medicine composition is mainly used for treating blood stasis and resolving phlegm and stasis, and is not suitable for long-term use by patients, which may aggravate the damage of qi and yin in the body, and the patient compliance is poor due to too many medicinal materials. Therefore, it is necessary to develop a traditional Chinese medicine composition for treating lung nodules of qi and yin deficiency type, which has good curative effect and is easy to adhere to the treatment of lung nodules, and a preparation method thereof. SUMMARY

[0008] Based on the deficiencies in the prior art, the present application aims to provide a traditional Chinese medicine composition for treating lung nodules of qi and yin deficiency type, a preparation method and an application thereof. The composition is based on the root cause of lung nodules, that is, qi and yin deficiency, and is used for tonifying qi and nourishing yin, resolving stasis and detoxification, and has the advantages of balancing the root and branch, proper combination, homology of medicine and food, mild medicinal properties, simple composition, easy preparation, long-term use by patients and no adverse reactions.

[0009] In order to achieve the above-mentioned purposes, the present application adopts the following technical solutions:

[0010] In one aspect, the present application provides a traditional Chinese medicine composition for treating lung nodules of qi and yin deficiency type. The traditional Chinese medicine composition is composed of the following components by weight: Radix et Rhizoma Ginseng 10-30 parts, Chelidonium majus 15-45 parts, Lilium 10-40 parts, and Fructus Trichosanthis 10-40 parts.

[0011] Preferably, the traditional Chinese medicine composition is composed of the following components by weight: Radix et Rhizoma Ginseng 10-25 parts, Chelidonium majus 20-40 parts, Lilium 15-35 parts, and Fructus Trichosanthis 15-35 parts.

[0012] More preferably, the traditional Chinese medicine composition is composed of the following components in parts by weight: 15-20 parts of raw sun-dried ginseng, 25-35 parts of celandine, 20-30 parts of lily, and 20-30 parts of whole Trichosanthes kirilowii.

[0013] As some preferred embodiments, the mass ratio of the lily and the whole Trichosanthes kirilowii is 1-3:1; preferably 1:1.

[0014] As other preferred embodiments, the mass ratio of the raw sun-dried ginseng to greater celandine is 1:1-4, preferably 1:2.

[0015] As some further preferred embodiments, the mass ratio of the lily to the whole Trichosanthes kirilowii is 1-3:1, and the mass ratio of the raw sun-dried ginseng to the celandine is 1:1-4.

[0016] As a preferred embodiment, the mass ratio of the lily to the whole Trichosanthes kirilowii is 1:1, and the mass ratio of the raw sun-dried ginseng to the celandine is 1:2.

[0017] As a preferred embodiment, the traditional Chinese medicine composition is composed of the following components in parts by weight: 15 parts of raw sun-dried ginseng, 30 parts of celandine, 30 parts of lily, and 30 parts of whole Trichosanthes kirilowii.

[0018] The above-mentioned Chinese herbal ingredients:

[0019] Sun-dried ginseng: Made from the dried roots and rhizomes of Panax ginseng (Camey), a plant of the Araliaceae family, 5-7 years old, is washed and sun-dried. It has a neutral nature, sweet and slightly bitter flavor, and enters the lung, spleen, and heart meridians. Known as the "King of Herbs," it primarily nourishes qi and yin, boasting a stronger qi-tonifying effect than white ginseng, yet possesses a milder medicinal property than red ginseng. It is particularly suitable for those with qi and yin deficiency, boasting benefits such as tonifying vital energy, tonifying the lungs and spleen, promoting fluid production and quenching thirst, and nourishing the heart and calming the mind. Clinically, it can improve fatigue, dry mouth, and chronic cough caused by lung qi and yin deficiency, as well as calm the mind and alleviate anxiety and insomnia associated with lung nodules. Its key components, ginsenosides and ginseng polysaccharides, can enhance immunity and inhibit the growth of lung cancer cells.

[0020] Greater celandine: The whole herb with flowers belongs to the Papaveraceae family. It is warm in nature, bitter in taste, and enters the lung and stomach meridians. It has strong analgesic and heat-clearing, cough-relieving, stagnation-dispersing, detoxifying effects, and is clinically effective in treating cough, asthma, persistent cough, associated chest and back pain, and chronic bronchitis. Its main ingredients, chelidonine and sanguinarine, have been shown by modern pharmacological studies to have significant anti-inflammatory and anti-lung cancer growth and metastasis effects.

[0021] Lily: the underground rhizome of Lilium brownii var. viridulium baker; it is flat in nature and sweet in taste, and belongs to the lung and heart channels; it can nourish yin and moisten the lungs, and has strong effects of clearing the heart and soothing the nerves; it can treat dry cough, dry cough, and prolonged cough, and can also relieve anxiety, insomnia, and other symptoms; its main component, colchicine, can inhibit mitosis of various tumor cells and promote apoptosis of tumor cells, which can help to dissipate pulmonary nodules.

[0022] Whole Gualou: the dried fruit of Trichosanthes kirilowii Maxim; it is cold in nature and slightly bitter in taste, and belongs to the lung, stomach, and large intestine channels; Gualoupi has the effects of clearing heat and reducing phlegm, and can also relieve chest congestion and resolve nodules; as the Bencao Tujing says: "Gualou is used for treating chest congestion, swelling, and toxicity, and can moisten the lungs, stop coughing, and reduce phlegm and thirst"; it is effective in treating dry cough, dry cough, and phlegm that is not easy to expel, and can also relieve chest congestion and chest pain; the fruit kernel, Gualouzi, can moisten the intestines and promote defecation; the lung and large intestine are interrelated, and the function of the bowel can further promote the descending of lung qi; the main components of Gualouren glycol and Gualouren total saponins have anti-inflammatory and inhibitory effects on lung cancer cell proliferation.

[0023] In another aspect, the present application also provides a preparation method of the above-mentioned traditional Chinese medicine composition, comprising the following steps:

[0024] Take the prescription amount of raw dried ginseng, white swallowwort, lily, and whole Gualou and soak them in water, then decoct the soaked medicinal materials, filter, and reserve the medicinal liquid; the dregs are decocted again with water, then filtered, and the two medicinal liquids are combined and concentrated to obtain the traditional Chinese medicine composition.

[0025] The amount of water added is 3-5 cm higher than the medicinal materials, the soaking time is 30 minutes, and the decocting time is 30-50 minutes.

[0026] In another aspect, the present application also provides the use of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating lung nodules of qi and yin deficiency.

[0027] A drug for treating lung nodules of qi and yin deficiency, which comprises the above-mentioned traditional Chinese medicine composition and a pharmaceutically acceptable excipient.

[0028] "Pharmaceutically acceptable excipient" refers to excipients and additives used in the production of drugs and the dispensing of prescriptions, which are substances other than active ingredients that have been reasonably evaluated in terms of safety and are included in drug formulations. The same pharmaceutical excipient can be used in drug formulations for different administration routes, and has different functions and uses. The pharmaceutical excipients added in the drug provided by the present application can act as excipients, serve as carriers, or improve stability, in addition to having important functions such as solubilization, solubilization, and controlled release.

[0029] Typical, but non-limiting, excipients include one or more of emulsifiers, colorants, binders, disintegrants, fillers, lubricants, humectants, tonicity adjusting agents, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, aromatics, anti-caking agents, antioxidants, chelating agents, penetration enhancers, pH adjusting agents, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickening agents, complexing agents, moisturizers, absorbents, diluents, flocculating and deflocculating agents, filter aids or release retarders.

[0030] Fillers include starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; disintegrants include starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; lubricants include magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide, etc.; suspending agents include polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose, etc.; binders include starch paste, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, etc.; sweeteners include sodium saccharin, aspartame, sucrose, cyclamate, glycyrrhizic acid, etc.; flavoring agents include sweeteners and various flavors; preservatives include nipagin, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chlorhexidine acetate, eucalyptus oil, etc.; bases include PEG 6000, PEG 4000, insect wax, etc.

[0031] The pharmaceutical dosage form of the present application includes tablets, capsules, solutions, granules, pills, powders, ointments or pills.

[0032] Preferably, the pharmaceutical dosage form is a tablet

[0033] Pharmaceutical excipients used in the preparation of tablets include, but are not limited to:

[0034] (1) fillers or diluents, i.e. used to increase the weight or volume of the tablet, so as to facilitate tabletting, including starch, sugar, dextrin, lactose, compressible starch, microcrystalline cellulose, inorganic salts, mannitol;

[0035] (2) wetting agents or binders, wetting agents refer to excipients that are not sticky themselves, but can induce the stickiness of the soft material drug, so as to achieve the purpose of granulation and tabletting, including distilled water, ethanol; binders refer to excipients that give stickiness to materials that are not sticky or not sticky enough, so that the materials coalesce into granules, including starch paste, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, povidone, gelatin, polyethylene glycol, 50%-70% sucrose solution, sodium alginate solution;

[0036] (3) Disintegrants, which are excipients that promote the rapid disintegration of tablets in the gastrointestinal fluid into small particles, including dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked povidone;

[0037] (4) Lubricants, which are collectively referred to as glidants, anti-adherents and lubricants (in a narrow sense). The glidants are excipients that reduce the friction between particles, thereby improving the flowability of the powder and reducing the weight difference. The anti-adherents are excipients that prevent the material from adhering to the surface of the punch and die during tabletting, so as to ensure the smooth operation of tabletting and the smooth surface of the tablets. The lubricants (in a narrow sense) are excipients that reduce the friction between the tablets and the die wall during tabletting and tablet ejection, so as to ensure uniform stress distribution during tabletting and prevent tablet cracking. The lubricants include magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol such as PEG4000 and PEG6000, and sodium lauryl sulfate.

[0038] The excipients can also contain colorants and flavoring agents. The colorants are excipients that impart color to the drug, including pharmaceutical-grade or food-grade pigments, including chlorophyll, caramel, amaranth red, lemon yellow, cochineal red, and indigo, and the content of the colorants in the pharmaceutical composition is not more than 0.05%. The flavoring agents are pharmaceutical excipients used to improve or mask the unpleasant odor and taste of the drug, so that the patient cannot easily perceive the strong bitter taste (or other odors such as pungent, irritating, etc.) of the drug, including sucrose, sweet orange glycoside, sodium saccharin, protein sugar, sorbitol, and aspartame.

[0039] Compared with the prior art, the present application has the following beneficial effects:

[0040] 1. The present application is guided by the theory of "cancer treatment by strengthening the body resistance" of the national medical master, and grasps the key of TCM "syndrome" to treat lung nodules with qi and yin deficiency. The treatment principle is to tonify qi and nourish yin, resolve toxicity and disperse knots. The medicine has simple flavors, appropriate compatibility, and is safe and reliable. The preparation is convenient, and the patient has high compliance.

[0041] 2. The clinical trials and clinical cases confirm that the traditional Chinese medicine composition of the present application has a definite effect on patients with lung nodules with qi and yin deficiency, can reduce and stabilize the size of lung nodules, and the effective rate reaches 80.00% (Example 5), which is much higher than that of the blank control group of 44.00%; reduces the risk probability of lung nodule patients; significantly relieves the clinical symptoms of patients with qi and yin deficiency, such as fatigue, dry mouth, and cough; effectively improves the release of inflammatory factors in the body, regulates the microenvironment of immune cells, and improves the "soil" of patients with precancer, which has a broad clinical application prospect.

[0042] 3.The present invention is in line with the root cause of pulmonary nodule "deficiency of lung qi and yin", from the TCM "differential diagnosis" advantage, for this group of wider audience, to supplement the lung qi and yin deficiency, protect the acquired spleen and stomach, calm the heart and nourish the spirit, at the same time, take into account the clearing heat and resolving mass. The composition of raw and dried ginseng, white podophyllum, lily and whole gualou, all of which "first return to the lung meridian", and take into account other meridians of five internal organs, strong and efficient; The monarch, minister, assistant and messenger are matched, which means supplementing and dredging, treating both the symptoms and the root cause, and supplementing the lung and producing saliva, detoxifying and resolving mass. In the formula, raw and dried ginseng supplements qi and nourishes yin, supports the healthy and solid foundation, and its qi supplementing effect is stronger than that of white ginseng, and the drug nature is milder than that of red ginseng, especially suitable for people with lung qi and yin deficiency, which has the effect of greatly supplementing primordial qi, benefiting the lung and spleen, producing saliva to stop thirst, nourishing the heart and calming the spirit, and dredging the meridians by filling qi and blood; White podophyllum relieves cough and asthma, detoxifies and resolves mass, and is matched with raw and dried ginseng, which is a combination of tonifying and supplementing, and is good at treating cough, shortness of breath and chest pain caused by qi and yin deficiency, and its heat-clearing and anti-inflammatory effect helps to reduce lung inflammation and improve tumor immune environment; Lily, as an assistant medicine, moistens the lung to stop coughing, clears the heart and calms the spirit, which not only enhances the yin-nourishing and lung-moistening effect of raw and dried ginseng, but also neutralizes the heat-clearing and detoxifying effect of white podophyllum, and has a good therapeutic effect on dry cough and insomnia caused by qi and yin deficiency; As an assistant medicine, whole gualou clears heat and reduces phlegm, widens the chest and resolves mass, enhances the yin-nourishing and lung-moistening effect of lily, and stops coughing and phlegm, at the same time, it moistens the intestines and promotes defecation, the lung and large intestine are internally related, which further promotes the descending of lung qi, and leads the medicine into the meridian and directly to the chest. The four drugs are used together to supplement the lung qi and yin, achieve the purpose of resolving mass and resisting tumor, and fully reflect the principles of TCM holistic concept and syndrome differentiation. BRIEF DESCRIPTION OF DRAWINGS

[0043] Figure 1 The chest CT images before and after the treatment of case 1;

[0044] Figure 2 The chest CT detection results before and after the treatment of case 2;

[0045] Figure 3 The chest CT images before and after the treatment of case 3;

[0046] Figure 4 The chest CT images before and after the treatment of case 4;

[0047] Figure 5 The chest CT detection results before and after the treatment of case 5. DETAILED DESCRIPTION

[0048] Embodiment 1-5 A kind of traditional Chinese medicine composition for treating qi and yin deficiency type pulmonary nodule and preparation method

[0049] The traditional Chinese medicine composition is composed of the components in Table 0 by weight, and the total weight of medicinal materials in each embodiment is 1000g:

[0050] Table 0

[0051] Radix ginseng rubra (parts) Chelidonium majus (parts) Lilium brownii (parts) Fructus trichosanthis (parts) Example 1 15 15 40 40 Example 2 10 20 20 10 Example 3 30 45 10 10 Example 4 20 40 30 20 Example 5 15 30 30 30

[0052] The preparation method of the traditional Chinese medicine composition is as follows:

[0053] Take the prescription amount of raw sun-dried ginseng, white swallowwort, lily and whole gualou, soak the medicinal materials in water by 5 cm for 30 minutes, decoct the soaked medicinal materials for 40 minutes, then filter, reserve the medicinal liquid; add water to the medicinal residues by 5 cm again, decoct for 30 minutes, then filter, combine the two medicinal liquids, concentrate to 400 mL, and the traditional Chinese medicine composition is obtained.

[0054] Comparative Example 1:

[0055] The difference from Example 5 is that raw sun-dried ginseng is replaced by dangshen, and the others are the same as Example 5.

[0056] Comparative Example 2:

[0057] The difference from Example 5 is that white swallowwort is omitted, i.e. raw sun-dried ginseng 45 parts, lily 30 parts, whole gualou 30 parts, and the others are the same as Example 5.

[0058] Comparative Example 3:

[0059] The difference from Example 5 is that raw sun-dried ginseng 5 parts, white swallowwort 40 parts, lily 50 parts, whole gualou 10 parts, and the others are the same as Example 5.

[0060] Comparative Example 4:

[0061] The difference from Example 5 is that raw sun-dried ginseng 40 parts, white swallowwort 5 parts, lily 10 parts, whole gualou 50 parts, and the others are the same as Example 5.

[0062] Application Example: The traditional Chinese medicine compositions prepared in Examples 1-5 and Comparative Examples 1-4 are used for clinical trials for treating lung nodules of qi-yin deficiency type

[0063] 1. Test subjects: The cases come from patients who visited the Oncology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2023 to December 2024 due to lung nodules (doctor workstation can be traced), a total of 437 cases were included in accordance with the diagnostic criteria for lung nodules of qi-yin deficiency type. According to the patient's willingness to take medicine, two groups of patients were non-randomly enrolled, and all patients signed the informed consent and voluntarily joined the study. The research program was approved by the hospital medical ethics committee.

[0064] 2. Research method:

[0065] 2.1 Diagnostic criteria:

[0066] Inclusion criteria:

[0067] ① In line with the western medicine diagnosis of pulmonary nodules: refer to the "Chinese pulmonary nodule classification, diagnosis and treatment guidelines (2020 edition)", "pulmonary nodule diagnosis and treatment Chinese expert consensus" (2018 edition). The image diameter of the local, circular, density increased solid or sub-solid lung shadow is less than or equal to 3 cm, which can be isolated or multiple, without atelectasis, hilar lymph node enlargement and pleural effusion.

[0068] ② In line with the diagnostic criteria of TCM syndrome type: refer to the definition of qi-yin deficiency syndrome in "Chinese internal medicine" and "diagnosis and treatment criteria of TCM syndromes". Main symptoms: dry cough, little sputum or no sputum; fatigue; shortness of breath; secondary symptoms: dry mouth, thirst; self sweating, night sweating, fear of wind; dry stool; poor appetite; tongue and pulse: pale red or red tongue, little or peeled tongue, thin or weak pulse. With 2 main symptoms, or 1 main symptom, 2 secondary symptoms, or 3 secondary symptoms, combined with tongue and pulse, can be diagnosed as qi-yin deficiency syndrome.

[0069] ③ The patient's age is between 18 and 80 years old.

[0070] Exclusion criteria: ① According to the guidelines, the nodules may be malignant or accompanied by other metastases, suggesting surgery or further systemic examination; ② Patients with serious lung infection, tuberculosis and other diseases; ③ Patients with serious heart, liver, kidney and hematopoietic system diseases and mental illness; ④ Pregnant women.

[0071] Dropout criteria: ① During the trial, other similar drugs were taken without authorization; ② Self-exit and loss of follow-up.

[0072] 2.2 Sample size estimation:

[0073] This study is a non-randomized controlled trial, with the efficacy of reducing the longest diameter of pulmonary nodules as the main outcome measure. The treatment group is the traditional Chinese medicine treatment group, and the control group is the blank control group. According to the literature search and the results of the previous pre-test, the total effective rate of the treatment group is 75%, and that of the control group is 45%. Considering that this study is an efficient test, a one-sided test is selected, with a type I error of 0.025 and a type II error of 0.1. Considering that many patients in the lung nodules clinic of the hospital have the willingness to take medicine, the sample size of the treatment group to the control group is 7:1. Using PASS21 software to calculate, and considering the dropouts in the trial process, increasing the sample size by 10%, the final number of samples is 400, with 350 in the treatment group and 50 in the control group.

[0074] 2.3 Treatment method:

[0075] Treatment group: the drug composition prepared by examples 1-5 and comparative examples 1-4 is taken as a dose every day, taken orally before breakfast and dinner, 3 months as a course of treatment, and chest CT is rechecked after 1 course of observation.

[0076] Control group: no drug treatment, recheck chest CT after 3 months. (Refer to the recommended "Chinese expert consensus on the diagnosis and treatment of pulmonary nodules")

[0077] 2.4 Observation index:

[0078] 2.4.1 Main index:

[0079] Pulmonary nodule efficacy evaluation: measure the longest diameter of the nodule in chest CT before and after treatment as the efficacy evaluation method, divided into effective, stable and ineffective three levels. Nodule shrinkage or complete dispersion is effective, nodule has no change is stable, and nodule enlargement or increase is ineffective; Effective rate = (effective number + stable number) / total number. Among them, further grouping statistics according to the size of the nodule <1cm and 1-3cm.

[0080] 2.4.2 Secondary index:

[0081] ① TCM syndrome score: according to the definition of qi-yin deficiency syndrome in "Internal Medicine of Traditional Chinese Medicine" and "Diagnosis and Treatment Criteria of TCM Syndromes", the clinical symptoms are divided into main symptoms and secondary symptoms according to the diagnostic criteria of traditional Chinese medicine. According to the degree, it is divided into no, mild, moderate and severe, and the main symptoms are recorded as 0, 2, 4 and 6 points, and the secondary symptoms are recorded as 0, 1, 2 and 3 points, respectively. Record the total score.

[0082] ② Mayo model to predict the probability of malignant pulmonary nodules: probability of malignancy = e x / (1+e x ). X = -6.8272 + (0.0391 x age) + (0.7917 x smoking history) + (1.3388 x history of tumor in other parts) + (0.1274 x nodule diameter) + (1.0407 x burr sign) + (0.7838 x nodule location). Where e is the natural logarithm; Age is calculated by number; If there is a history of smoking, it is 1, otherwise it is 0; If there is a history of extrathoracic tumor within 5 years, it is 1, otherwise it is 0; Nodule diameter is calculated in millimeters; If there is burr on the edge of the nodule, it is 1, otherwise it is 0; If the pulmonary nodule is located in the upper lobe, it is 1, otherwise it is 0.

[0083] ③ Inflammatory immune microenvironment index: fasting peripheral venous blood samples were collected from patients in both groups before and after treatment, and enzyme-linked immunosorbent assay was used to detect the levels of serum tumor necrosis factor (TNF-α), IL-6 and IL-12; Flow cytometry was used to detect the changes of T lymphocyte subsets in peripheral blood of the subjects, including CD3+, CD4+, CD8+ and NK cell percentage.

[0084] 2.5 Statistical methods: For count data, when n≥40 and T≥5, Pearson χ2test was used; when n≥40 and 1≤T<5, continuity-corrected χ2test was used; when T<1 or n<40, Fisher's exact test was used. For measurement data, normality test was performed. When the data were normally distributed, mean ± standard deviation (X±S) was used for statistical description. Independent sample t test was used for comparison between two groups, and paired t test was used for comparison before and after treatment. When the data were not normally distributed, median (interquartile range) was used for statistical description. Independent sample rank sum test was used for comparison between two groups, and correlation sample rank sum test was used for comparison before and after treatment. P<0.05 was considered as the standard of significant difference for two-sided test (Bonferroni method was used for comparison before and after treatment in the same group, and the value of α was corrected according to the number of comparisons).

[0085] 3. Test results:

[0086] 3.1 Comparison of general information:

[0087] Finally, a total of 398 valid cases were included, including 348 cases in the treatment group (including examples 1-5, 40 people in each group; and comparative examples 1-4, 37 people in each group) and 50 cases in the blank control group. The average age of patients in the treatment group was 57.5 years old, and females accounted for 61%. There were 213 cases (61.2%) with nodules less than 1 cm. The average age of patients in the blank control group was 60.5 years old, and females accounted for 55%. There were 32 cases (64.0%) with nodules less than 1 cm. There was no statistical difference in the baseline of each item before treatment between the two groups, and they were comparable.

[0088] 3.2 Main index - clinical efficacy of pulmonary nodules:

[0089] Before treatment, the proportion of each group according to the size of the nodule was not different, and was comparable. After treatment, the patient's lung nodule was reduced or completely disappeared, which was effective, the nodule was stable, the nodule was increased or increased, which was ineffective, the effective rate = (effective number + stable number) / total number. The total effective rate of the blank control group was 44.00%; the total effective rate of the treatment group was higher than that of the blank control group, wherein the total effective rate of the comparative example 1 group was 48.65%, the total effective rate of the comparative example 2 group was 51.35%, the total effective rate of the comparative example 3 group and the comparative example 4 group was 54.05% (*, P < 0.05). The total effective rate of the treatment group was significantly higher than that of the comparative example 1-4 group and the blank control group (**, P < 0.01; #, P < 0.05), wherein the total effective rate of the example 1 group and the example 3 group was 70.00%, the total effective rate of the example 2 group and the example 4 group was 72.50%, and the total effective rate of the example 5 group reached 80.00% (**, P < 0.01; ##, P < 0.01). Further analysis according to the subgroup of lung nodule size showed that the curative effect of each group in the treatment group on lung nodule less than 1 cm was better than that on 1-3 cm lung nodule. See Table 1 below for details.

[0090] Table 1 Comparison of clinical curative effect of lung nodule

[0091]

[0092] Note: compared with the blank control group, *, P < 0.05, **, P < 0.01; compared with the comparative example 4 group, #, P < 0.05, ##, P < 0.01.

[0093] 3.3 Lung nodule malignant risk probability evaluation

[0094] The classic Mayo model integral was used to predict the lung nodule malignant risk probability; before treatment, the integral of each group had no statistical difference. After treatment, the Mayo model malignant integral of the blank control group was not reduced compared with before treatment (P > 0.05); in the treatment group, the Mayo model malignant integral of the comparative example 1-4 group was decreased after treatment, but the difference was not statistically significant (P > 0.05); in the treatment group, the Mayo model lung nodule malignant risk probability of the example 1-5 group was significantly decreased after treatment, and the difference was statistically significant (P < 0.05), among which the improvement of the example 5 group was particularly significant (P < 0.01), see Table 2 below for details.

[0095] Table 2 Comparison of lung nodule malignant probability before and after treatment

[0096] Group Example number Before treatment After treatment Z P Blank control group 50 0.041±0.004 0.045±0.005 1.783 0.557 Comparative example 1 group 37 0.041±0.003 0.040±0.007 1.652 0.323 Comparative example 2 group 37 0.043±0.004 0.041±0.006 -1.123 0.194 Comparative example 3 group 37 0.042±0.003 0.038±0.005 -1.586 0.137 Comparative example 4 group 37 0.039±0.004 0.037±0.007 -1.179 0.171 Example 1 group 40 0.041±0.003 0.030±0.004* -2.818 0.034 Example 2 group 40 0.039±0.003 0.028±0.005* -3.329 0.041 Example 3 group 40 0.043±0.003 0.032±0.004* -2.952 0.022 Example 4 group 40 0.044±0.002 0.031±0.005* -3.671 0.017 Example 5 group 40 0.042±0.003 0.026±0.005** -4.113 0.003

[0097] Note: compared with before treatment, *, P < 0.05, **, P < 0.01.

[0098] ​3.4 Comparison of total TCM syndrome score and main clinical symptoms

[0099] Before treatment, there was no difference in baseline among groups; after treatment, there was no statistical difference in TCM syndrome score and main clinical symptoms score of qi-yin deficiency in the blank control group compared with before treatment (P>0.05); in the treatment group, the total TCM syndrome score of the comparative examples 1-4 was improved compared with before treatment, and the comparative examples 3 and 4 had statistical difference (P<0.05); in the treatment group, the total TCM syndrome score and main clinical symptoms (spiritual fatigue, cough, dry mouth, constipation) of the examples 1-5 were significantly improved compared with before treatment (P<0.05), and the improvement of the example 5 was the most obvious. After treatment, there was no statistical difference between the comparative examples 1-4 and the blank control group in the treatment group; in the treatment group, the total TCM syndrome score and main clinical symptoms of qi-yin deficiency of the examples 1-5 were significantly lower than those of the blank control group (P<0.05), and the symptom improvement of the example 5 was particularly obvious (P<0.01), as shown in Table 3 below.

[0100] Table 3 Comparison of total TCM syndrome score and clinical symptoms before and after treatment

[0101]

[0102]

[0103] Note: *, P<0.05, **, P<0.01 for group comparison before and after treatment; #, P<0.05, ##, P<0.01 for group comparison after treatment.

[0104] 3.5 Comparison of inflammatory and immune indexes

[0105] Before treatment, there was no statistical difference in peripheral blood inflammatory factors and immune indexes among groups, which were comparable. After treatment, there was no difference in inflammatory factors and immune indexes of the blank control group compared with before treatment (P>0.05); in the treatment group, the inflammatory factors TNF-α and IL-6 of the comparative examples 1-4 were reduced to different degrees compared with before treatment, but there was no statistical difference, and the level of T lymphocyte subsets did not change significantly; in the treatment group, the TNF-α, IL-6 and IL-12 of the examples 1-5 were reduced compared with before treatment, the change of inflammatory factor IL-6 was significant (P<0.05), and the level of CD3+ and CD4+ subsets of T lymphocytes was significantly higher than that before treatment (P<0.05). After treatment, there was no statistical difference between the comparative examples 1-4 and the blank control group in the treatment group; in the treatment group, the improvement of IL-6 and CD3+ T lymphocyte subsets of the examples 1-5 was better than that of the blank control group (P<0.05), as shown in Table 4 below.

[0106] Table 4 Comparison of peripheral blood inflammatory and immune indexes before and after treatment​

[0107]

[0108]

[0109] Note: *P < 0.05 compared with before treatment within the group; #P < 0.05 compared between the groups after treatment.

[0110] Conclusion: The pharmaceutical composition is used for treating lung nodules of qi and yin deficiency type, can effectively reduce and stabilize the size of the nodules, reduce the risk probability of lung nodule patients, improve the clinical symptoms of cough, dry mouth, fatigue and weakness, and play the role of anti-inflammatory, immune regulation, and improvement of the patient's precancerous "soil". Among them, the comparative example 1 in the treatment group is better than the blank control group, the comparative examples 1-2 have equivalent curative effects, the comparative examples 3-4 have equivalent curative effects but are better than the comparative examples 1-2; the examples 1-5 in the treatment group are better than the comparative examples 1-4, the examples 1-4 have equivalent curative effects, and the example 5 has the best curative effect.

[0111] Typical cases:

[0112] Case 1:

[0113] Wu, female, 37 years old. On July 15, 2024, a chest CT was found in a physical examination in an external hospital: a subpleural nodule in the left lower lobe of the lung, about 14 mm in length, with lobulation, pleural indentation, and other signs. She came to the clinic for treatment, with symptoms of coughing, more at night, little white sputum, chest tightness and pain, dry mouth, constipation, red tongue, white fur, and thin pulse. The TCM syndrome was qi and yin deficiency, and she was given the herbal composition of example 5 of the present invention (15 parts of raw ginseng, 30 parts of white swallowwort, 30 parts of lily, and 30 parts of whole snakegourd) for decoction, 1 dose in the morning and evening, for more than 3 months. On reexamination, the cough was relieved, and there were occasional dry cough, no chest tightness and pain, no dry mouth, and no constipation. On October 26, 2024, a chest CT showed a nodule shadow in the left lower lobe of the lung, about 7 mm in length, with a ground-glass edge and a few solid shadows inside, and no abnormal density was found in the other two lungs. She was advised to continue taking the herbal composition of the present invention for half a year and then reexamine.

[0114] Case 2:

[0115] Fan, female, 41 years old. Cough for more than 1 month after cold, 2024-7-30 to the hospital for chest CT showed: multiple ground glass nodules in both lungs, the largest diameter was about 7mm, multiple small nodules and fibrosis in both lungs; symptoms: cough when, dry cough without sputum, fatigue, dry mouth, insomnia, tongue pale red, thin white fur, pulse number. TCM syndrome is deficiency of both qi and yin, the application example 4 of the invention (20 parts of raw radix ginseng, 40 parts of radix chelidonii, 30 parts of flos lonicerae japonicae, 20 parts of pericarpium trichosanthis) is decocted, and 1 dose is taken orally in the morning and evening for more than 1 month. After reexamination due to anxiety, the symptoms of cough and fatigue are relieved, and there is occasional dry cough, dry mouth and insomnia. On September 10, 2024, the chest CT reexamination showed that the multiple ground glass nodules in both lungs were similar to those before, with a maximum diameter of about 7mm; the patient was advised to continue taking the invention for 6 months.

[0116] Case 3:

[0117] Wu, male, 60 years old. Recurrent paroxysmal cough for more than half a year, 2024-1-15 chest CT showed: multiple ground glass nodules in both lungs, the largest nodule was about 20mm in diameter in the right upper lung, and the bilateral pulmonary hilar images were normal. The patient refused to puncture, operation and other operations, symptoms: occasional dry cough, dry mouth, constipation, tongue red pulse, TCM syndrome is deficiency of both qi and yin, the application example 3 of the invention (30 parts of raw radix ginseng, 45 parts of radix chelidonii, 10 parts of flos lonicerae japonicae, 10 parts of pericarpium trichosanthis) is decocted, and 1 dose is taken orally in the morning and evening for more than 3 months. After reexamination, the symptoms of dry mouth and tongue pulse were relieved, and there was still dry cough. On April 10, 2024, the chest CT reexamination showed that the ground glass nodule in the right upper lobe was about 17*16mm in size, and the solid part showed mild enhancement. The patient was advised to continue taking the invention for 3 months.

[0118] Case 4:

[0119] Wang, male, 71 years old. The patient ignored the previous chronic pulmonary emphysema. On August 19, 2024, the chest CT showed: right middle lobe of lung was occupied, about 30*20mm in size, chronic pulmonary emphysema; symptoms: cough and shortness of breath, white sputum was difficult to expectorate, cough induced chest pain, dry mouth was obvious, tongue was reddish, pulse was thin, the patient refused to puncture, operation and other operations; TCM syndrome is deficiency of both qi and yin, the application example 2 of the invention (10 parts of raw radix ginseng, 20 parts of radix chelidonii, 20 parts of flos lonicerae japonicae, 10 parts of pericarpium trichosanthis) is decocted, and 1 dose is taken orally in the morning and evening for more than 3 months. After reexamination, the symptoms of cough and shortness of breath, dry mouth were obviously relieved, there was white sputum difficult to expectorate occasionally, tongue was pale red; on November 20, 2024, the chest CT reexamination showed that the irregular nodule in the right middle lobe of lung was smaller than before, about 14*10mm in size, chronic pulmonary emphysema. The patient was advised to continue taking the invention for 3 months.

[0120] Case 5:

[0121] Xie, female, 61 years old. The patient was diagnosed with early adenocarcinoma of the right lower lobe more than 5 years ago and left breast cancer more than 10 years ago. On January 11, 2024, a routine physical examination at an external hospital showed multiple ground glass nodules in the right upper lobe, right lower lobe, and left upper lobe of the lung. The larger one was located in the apical segment of the right upper lobe, with a size of about 5x5 mm and unclear boundaries, suggesting a recheck. The patient felt fatigue, dry mouth, dry stool, irritability, no cough or sputum, red tongue, and thin and stringy pulse. The TCM syndrome was deficiency of both qi and yin. Example 1 of the Chinese medicine composition of the present invention (15 parts of raw ginseng, 15 parts of white swallowwort, 40 parts of lily, and 40 parts of whole snakegourd fruit) was decocted and taken orally, one dose in the morning and one in the evening, for more than 3 months. After reexamination, the symptoms of fatigue and dry stool were significantly improved, and the tongue was pale red. On April 20, 2024, a chest CT examination showed that the number of multiple ground glass nodules was reduced to one in the right upper lobe, with a diameter of about 3 mm. The patient was advised to continue taking the Chinese medicine composition of the present invention for half a year and then reexamine.

Claims

1. A traditional Chinese medicine composition for treating lung nodules of qi-yin deficiency type, characterized in that: The traditional Chinese medicine composition is composed of the following components in parts by weight: raw dried ginseng 10-30 parts, white poppy 15-45 parts, lily 10-40 parts, and whole snakegourd 10-40 parts; ​ The mass ratio of the lily and the whole snakegourd is 1-3:1; The mass ratio of the raw dried ginseng and the white poppy is 1:1-4.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is composed of the following components in parts by weight: raw dried ginseng 10-25 parts, white poppy 20-40 parts, lily 15-35 parts, and whole snakegourd 15-35 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is composed of the following components in parts by weight: raw dried ginseng 15-20 parts, white poppy 25-35 parts, lily 20-30 parts, and whole snakegourd 20-30 parts.

4. The traditional Chinese medicine composition according to claim 1, characterized in that: The mass ratio of the lily and the whole snakegourd is 1:

1.

5. The traditional Chinese medicine composition according to claim 1, characterized in that: The mass ratio of the raw dried ginseng and the white poppy is 1:

2.

6. The traditional Chinese medicine composition according to claim 4 or 5, characterized in that: The traditional Chinese medicine composition is composed of the following components in parts by weight: raw dried ginseng 15 parts, white poppy 30 parts, lily 30 parts, and whole snakegourd 30 parts.

7. The method for preparing the traditional Chinese medicine composition according to any one of claims 1-6, characterized in that: The method comprises the following steps: The raw dried ginseng, the white poppy, the lily, and the whole snakegourd are soaked in water in a formula amount, and the soaked medicinal materials are decocted, filtered, and the medicinal liquid is reserved; The medicinal residues are decocted again with water, filtered, and the medicinal liquids of the two times are combined and concentrated to obtain the traditional Chinese medicine composition.

8. Use of the traditional Chinese medicine composition of any one of claims 1-6 in the preparation of a medicine for treating lung nodules of qi-yin deficiency type.

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