Traditional Chinese medicine composition for treating lung nodules caused by deficiency of both qi and yin as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating qi-yin deficiency type pulmonary nodule and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 10-30 parts of sun-dried ginseng, 15-45 parts of celandine, 10-40 parts of lily and 10-40 parts of fructus trichosanthis. The traditional Chinese medicine composition disclosed by the invention has an exact curative effect on patients with qi-yin deficiency type pulmonary nodules, and can reduce and stabilize the size of the pulmonary nodules and reduce the malignant risk probability of the patients with the pulmonary nodules; the qi-yin deficiency type clinical symptoms such as fatigue, cough and dry mouth of a patient can be obviously relieved; the release of inflammatory factors of the body is effectively improved, the immune cell microenvironment is regulated, the precancerous soil of a patient is improved, and the clinical application prospect is wide.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine composition for treating qi and yin deficiency type pulmonary nodules, a preparation method and an application thereof. Background Art

[0002] Pulmonary nodules usually refer to focal, round, solid or subsolid lung shadows with increased density and a diameter of ≤3cm. Those with a diameter of <1cm are called "small nodules". According to their pathological properties, they can be divided into benign (inflammatory nodules, tuberculosis, hamartomas, lung abscesses, etc.) and malignant (lung cancer) nodules. Most patients with pulmonary nodules will have two situations. One is excessive anxiety and tension, multiple reexaminations in a short period of time or even direct surgery, which increases unnecessary trauma and is prone to recurrence after surgery, reducing the quality of life. The other is to relax vigilance and fail to monitor regularly. When symptoms are obvious and reexamination is conducted, it has progressed to the middle and late stages of lung cancer, missing the best time for treatment. Therefore, how to intervene in pulmonary nodules early is a hot topic and difficulty in the current medical field.

[0003] Traditional Chinese medicine has unique advantages in shrinking lung nodules and improving precancerous "soil". Although there are no names of "lung nodules" or "lung cancer" in ancient books, they can be classified as "lung accumulation" according to their etiology, pathogenesis and clinical characteristics. The "Nanjing" first pointed out that "lung accumulation is called Xiben, which is located under the right hypochondrium and is as big as a cup". "Yi Zong Must Read" said that "the accumulation is caused by insufficient righteousness, and then evil qi occupies it". Traditional Chinese medicine believes that the lung is a delicate organ that controls the qi of the whole body. With the increase of age, "at the age of forty, the yin qi is halved, and the daily life is declining." The qi of the lung is damaged first, which in turn affects the generation and operation of qi throughout the body. The lung is the upper source of water. If the lung fails to descend, the lung qi deficiency will not be able to promote the blood and body fluid distribution throughout the body. "Suwen·Yin Yang Ying Xiang Da Lun" says "Yang turns into qi, yin forms, and the lung is based on qi and yin." Qi deficiency will damage yin over time, and lung yin is insufficient to moisten the pulse. Yin damages yang, further aggravating qi deficiency. Qi cannot distribute body fluid and qi stagnates and phlegm condenses, which stays in the lungs and forms "lung accumulation"; clinical symptoms include easy fatigue, dry cough or less sputum, dry mouth, poor appetite, red tongue, and thin or weak pulse. Therefore, for this type of lung yin and yang imbalance, qi and yin deficiency are the basis, and the deficiency leads to excess, and the base number of lung nodules is huge, it is very necessary to develop a drug composition that treats both the symptoms and the root cause, has good efficacy, is easy to adhere to, and has few side effects.

[0004] Chinese patent CN116570699A discloses a Chinese medicine composition for treating pulmonary nodules, its preparation and application. The Chinese medicine composition is made of the following components in parts by weight: 15-30 parts of Astragalus, 10 parts of Curcuma, 15-30 parts of Ceropegia, and 15-30 parts of Ranunculaceae. The Chinese medicine combination can invigorate qi and resolve phlegm, dredge meridians, detoxify and disperse nodules, and has a good therapeutic effect on pulmonary nodules.

[0005] Chinese patent CN116920066A discloses a Chinese medicine composition for treating lung nodules and lung cancer, and its preparation and application. The Chinese medicine composition contains the following raw materials: Radix Achyranthis Bidentatae, Radix Bletillae, Radix Rhodiolae, Rhizoma Curcumae, Herba Hedyotis Diffusae, Radix Platycodonis, Radix Achyranthis Bidentatae, Fructus Precipitae, Rhizoma Trichosanthis, Fritillariae Thunbergii, Rhizoma Pinelliae, Radix Trichosanthis. The Chinese medicine composition of the invention has significant efficacy in inhibiting the formation and development of lung nodules, improving lung function, and promoting the disappearance of lung nodules.

[0006] Chinese patent CN 115381915A discloses a Chinese medicine composition for treating pulmonary nodules of phlegm-heat and blood stasis type, its preparation method and application. The Chinese medicine composition is made of the following raw materials: turtle shell, oyster, bupleurum, scutellaria, rhizoma belamcandae, bombyx batryticatus, roasted ginger, cooked rhubarb, red peony root, cinnamon twig, scutellaria baicalensis, pyrrosia, peony bark, trumpet creeper, French pinellia, ginseng, earthworm, honeycomb, peach kernel, white mustard, thunbergia thunbergii, trichosanthes, cat's claw, seaweed, kelp, thorn of honey lonicera, zedoaria and golden buckwheat. The Chinese medicine composition for treating pulmonary nodules of phlegm-heat and blood stasis type of the invention has the effects of clearing away heat and dispersing nodules, resolving phlegm and unblocking collaterals, and invigorating qi and strengthening the body. It is mainly used to treat pulmonary nodules of phlegm-heat and blood stasis type, and can be used as a long-term treatment for small pulmonary nodules of ≤8mm and an auxiliary treatment for pulmonary nodules of 8-30mm.

[0007] The above-mentioned Chinese medicine composition mainly treats phlegm and blood stasis syndrome, promotes blood circulation and dissipates blood stasis, dissipates phlegm and disperses nodules, and is not suitable for long-term use by patients, and is easy to aggravate the damage of qi and yin in the body, and has many medicinal flavors and poor patient compliance. Therefore, it is necessary to develop a Chinese medicine composition and its preparation method that has a therapeutic effect on qi and yin deficiency type lung nodules, has good efficacy and is easy to adhere to the treatment of lung nodules. Summary of the invention

[0008] Based on the deficiencies in the prior art, the present invention aims to provide a Chinese medicine composition for treating qi and yin deficiency type pulmonary nodules, as well as a preparation method and application thereof. The composition starts from the qi and yin deficiency, the root cause of pulmonary nodules, and takes invigorating qi and nourishing yin, dispersing nodules and detoxifying as the treatment principles, taking both the symptoms and the root causes into consideration and the compatibility being precise; the medicine and food have the same origin and the medicinal properties are mild; the composition is simple, the preparation is convenient, and the composition is suitable for patients to take for a long time without adverse reactions.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] On the one hand, the present invention provides a traditional Chinese medicine composition for treating qi and yin deficiency type pulmonary nodules, wherein the traditional Chinese medicine composition is composed of the following components in parts by weight: 10-30 parts of raw sun-dried ginseng, 15-45 parts of celandine, 10-40 parts of lily, and 10-40 parts of whole Trichosanthes.

[0011] Preferably, the Chinese medicine composition is composed of the following components in parts by weight: 10-25 parts of raw sun-dried ginseng, 20-40 parts of celandine, 15-35 parts of lily, and 15-35 parts of whole Trichosanthes.

[0012] More preferably, the 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.

[0013] As some preferred implementation schemes, the mass ratio of the lily to 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 greater 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 greater celandine is 1:2.

[0017] As a preferred embodiment, the 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.

[0018] The above Chinese medicine ingredients:

[0019] Sun-dried ginseng: The dried roots and rhizomes of Panaxginseng CAMey, a plant of the Araliaceae family, are made from 5-7-year-old garden ginseng that has been washed and dried. It is mild in nature, sweet in taste, slightly bitter, and enters the lung, spleen, and heart meridians. It is known as the "king of herbs" and is mainly used to replenish qi and nourish yin. Its qi-replenishing power is stronger than that of white ginseng, and its medicinal properties are more peaceful than those of red ginseng. It is especially suitable for people with insufficient qi and yin, and has the effects of greatly replenishing vital energy, replenishing the lungs and spleen, promoting fluid production and quenching thirst, and nourishing the heart and calming the mind. Clinically, it can not only improve fatigue, dry mouth, and chronic cough caused by deficiency of both lung qi and yin, but also calm the mind and relieve anxiety and insomnia caused by lung nodules. Its main ingredients, ginsenosides and ginseng polysaccharides, can enhance the body's 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 effects of clearing away heat and relieving cough, dispersing stagnation and detoxifying, and relieving pain. It is clinically used for cough and asthma, long-term cough, chest and back pain, chronic bronchitis, etc. and is often effective. Its main ingredients, chelidonine and sanguinarine, have been confirmed by modern pharmacological studies to have significant anti-inflammatory, anti-lung cancer growth and anti-metastasis effects.

[0021] Lily: The underground rhizome of Lilium brownii var.viridulium baker, a plant of the Liliaceae family; it is mild in nature, sweet in taste, and enters the lung and heart meridians; it has strong power to nourish yin and moisten the lungs, clear the heart and calm the mind, and can treat dry cough, dry cough, and chronic cough caused by dry lung or yin deficiency, and can also relieve symptoms such as anxiety, irritability, insomnia, and dreaminess; its main ingredient, colchicine, is widely used to inhibit the mitosis of various tumor cells, promote tumor cell apoptosis, and help dissipate lung nodules.

[0022] Whole Trichosanthes: The dried fruit of Trichosanthes kirilowii Maxim; cold in nature, slightly bitter in taste, and enters the lung, stomach, and large intestine meridians; its Trichosanthes peel has the effects of clearing heat and resolving phlegm, widening the chest and dispersing stagnation, as in the "Illustrated Compendium of Materia Medica": "Trichosanthes treats chest pain and swelling, moistens the lungs and relieves cough, and resolves phlegm and quenches thirst", and is effective in treating dry cough, dry cough, phlegm, chest tightness, and chest pain. Its kernel Trichosanthes seeds can moisten the intestines and promote bowel movements. The lung and large intestine are exterior and interior, and the flow of visceral qi can further promote the descending of lung qi; its main components, Trichosanthes diol and Trichosanthes total saponins, have anti-inflammatory and inhibit lung cancer cell proliferation.

[0023] On the other hand, the present invention also provides a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps:

[0024] The raw sun-dried ginseng, celandine, lily and whole trichosanthes kirilowii in the prescribed amount are soaked in water, the soaked medicinal materials are decocted, then filtered, and the medicinal liquid is retained; the medicinal residues are decocted in water again, then filtered, 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 above the medicinal materials, the soaking time is 30 minutes, and the decoction time is 30-50 minutes.

[0026] In another aspect, the present invention also provides the use of the above-mentioned Chinese medicine composition in the preparation of a medicine for treating Qi and Yin deficiency type pulmonary nodules.

[0027] A medicine for treating qi and yin deficiency type pulmonary nodules, comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0028] "Pharmaceutically acceptable excipients" refer to excipients and additives used in the production of drugs and the preparation of prescriptions. They refer to substances that have been reasonably evaluated for safety and are included in drug preparations in addition to active ingredients. The same pharmaceutical excipient can be used in drug preparations for different routes of administration and has different effects and uses. The pharmaceutical excipients added to the drugs provided by the present invention can play the role of excipient, carrier or stability improvement. In addition, they also have important functions such as solubilization, solubilization or sustained release.

[0029] Typical but non-limiting excipients include: one or more of emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adherents, antioxidants, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids or release retardants.

[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 polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; lubricants include magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide, etc.; suspending agents include polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include starch slurry, polyvinyl pyrrolidone, hydroxypropyl methylcellulose, etc.; sweeteners include sodium saccharin, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, etc.; flavoring agents include sweeteners and various flavors; preservatives include parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroethidine acetate, eucalyptus oil, etc.; matrices include PEG6000, PEG4000, insect wax, etc.

[0031] The pharmaceutical dosage forms of the present invention include tablets, capsules, solutions, granules, pills, powders, pastes 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, which are used to increase the weight or volume of tablets to facilitate tableting, including starch, powdered sugar, dextrin, lactose, compressible starch, microcrystalline cellulose, inorganic salts, and mannitol;

[0035] (2) Wetting agents or binders. Wetting agents refer to excipients that are non-viscous but can induce the viscosity of soft-material drugs, thereby achieving the purpose of granulation and tableting. They include distilled water and ethanol. Binders refer to excipients that give viscosity to non-viscous or insufficiently viscous materials, thereby agglomerating the materials into granules. They include starch slurry, methyl cellulose, hydroxypropyl cellulose, hypromellose, sodium carboxymethyl cellulose, ethyl cellulose, povidone, gelatin, polyethylene glycol, 50%-70% sucrose solution, and sodium alginate solution.

[0036] (3) Disintegrants refer to excipients that promote the rapid breakup of tablets into fine particles in gastrointestinal fluid, including dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked polyvinylpyrrolidone;

[0037] (4) Lubricant, which is a general term for glidants, anti-adherents and lubricants (in a narrow sense). glidants refer to auxiliary materials that reduce friction between particles, thereby improving powder fluidity and reducing weight differences; anti-adherents refer to auxiliary materials that prevent materials from adhering to the surface of the punch and die during tableting to ensure smooth tableting operations and a smooth tablet surface; lubricants (in a narrow sense) refer to auxiliary materials that reduce friction between the tablet and the die wall during tableting and ejection to ensure uniform stress distribution during tableting and prevent tablet cracking; lubricants include: magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycols such as PEG4000, PEG6000, and sodium lauryl sulfate.

[0038] The auxiliary materials may also contain colorants and flavoring agents; colorants refer to auxiliary materials that give the drug color, including pharmaceutical or food grade pigments, including chlorophyll, caramel, amaranth, lemon yellow, carmine, indigo, and their content in the pharmaceutical composition does not exceed 0.05%. Flavoring agents refer to pharmaceutical auxiliary materials used in drugs to improve or shield the bad smell and taste of drugs, making it difficult for patients to perceive the strong bitter taste of drugs (or other peculiar smells such as spicy, irritating, etc.), including sucrose, citrus glycosides, saccharin sodium, protein sugar, sorbitol, and aspartame.

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

[0040] 1. Under the guidance of the theory of "strengthening the body and curing cancer" by national medical masters, the present invention grasps the key of TCM "syndrome" and formulates prescriptions based on the principles of invigorating qi and nourishing yin, detoxifying and dispersing nodules; the whole prescription has simple medicinal flavors and precise compatibility; the medicine and food have the same origin, which is safe and reliable; it is easy to prepare and has high patient compliance.

[0041] 2. This clinical trial and clinical cases have confirmed that the Chinese medicine composition of the present invention has a definite therapeutic effect on patients with qi and yin deficiency type pulmonary nodules, can reduce and stabilize the size of pulmonary nodules, with an effective rate of 80.00% (Example 5), which is much higher than 44.00% of the blank control group; reduces the probability of malignant risk in patients with pulmonary nodules; significantly relieves patients' clinical symptoms of qi and yin deficiency type such as fatigue, cough, and dry mouth; effectively improves the release of inflammatory factors in the body, regulates the immune cell microenvironment, and improves the patient's precancerous "soil", and has broad clinical application prospects.

[0042] 3. The present invention is in line with the root cause of lung nodules, "lung qi and yin deficiency", and takes advantage of the "differentiation of syndromes" of traditional Chinese medicine. It is aimed at this group of people with a wide audience, and is based on replenishing the qi and yin deficiency of the lungs, protecting the acquired spleen and stomach, and calming the mind while taking into account the symptoms of clearing away heat and dispersing nodules. The formula is composed of raw sun-dried ginseng, celandine, lily, and whole trichosanthes. The four medicines all "first return to the lung meridian" and take into account the other meridians of the five internal organs, with strong and special effects; the monarch, minister, assistant and envoy are matched, and the symptoms and root causes are treated, which together play the effects of replenishing the lungs, promoting body fluid, detoxifying and dispersing nodules. The main ingredient of the formula is raw sun-dried ginseng, which can nourish qi and yin, and strengthen the body. Its qi-tonifying power is stronger than that of white ginseng, and its medicinal properties are milder than those of red ginseng. It is especially suitable for those with insufficient lung qi and yin. It has the effects of greatly replenishing vital energy, nourishing the lungs and spleen, promoting the production of body fluids and quenching thirst, nourishing the heart and calming the mind, and it can clear the meridians by replenishing qi and blood; the auxiliary ingredient is white celandine, which can relieve cough and asthma, detoxify and disperse nodules. It complements the raw sun-dried ginseng, and can be used together to eliminate and nourish. It is good at treating cough, shortness of breath, and chest pain caused by deficiency of both qi and yin. At the same time, its heat-clearing and anti-inflammatory effects help to reduce lung inflammation and improve tumor formation Immune environment; adjuvant lily, moistening lungs and relieving cough, clearing heart and calming mind, not only enhances the ability of raw sun-dried ginseng to nourish yin and moisten lungs, relieve restlessness and calm mind, but also neutralizes the ability of celandine to clear heat and detoxify, and has a good therapeutic effect on dry cough, restlessness and insomnia caused by deficiency of both qi and yin; whole trichosanthes as an adjuvant, on the one hand, clears heat and resolves phlegm, relieves chest congestion, enhances the effect of lily in nourishing yin and moistening lungs, relieving cough and resolving phlegm, and at the same time moistens intestines and promotes bowel movements, the lung and large intestine are exterior and interior, further promoting the descending of lung qi, and on the other hand, guiding drugs into meridians, leading all drugs directly to the chest diseased area. The combination of the four drugs achieves the purpose of dispersing congestion and anti-tumor by replenishing the qi and yin of the lungs, which fully embodies the holistic concept of traditional Chinese medicine and the principle of syndrome differentiation and treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is the chest CT image of case 1 before and after treatment;

[0044] Figure 2 This is the chest CT result of case 2 before and after treatment;

[0045] Figure 3 This is the chest CT image of case 3 before and after treatment;

[0046] Figure 4 This is the chest CT image of case 4 before and after treatment;

[0047] Figure 5 These are the chest CT test results of Case 5 before and after treatment. DETAILED DESCRIPTION

[0048] Example 1-5 A Chinese medicine composition for treating pulmonary nodules of Qi and Yin deficiency type and its preparation method

[0049] The Chinese medicine composition is composed of the components in parts by weight as shown in the following table, and the total weight of the medicinal materials in each example is 1000 g:

[0050] Table 0

[0051] Raw sun-dried ginseng (portion) Greater celandine (portion) Lily (portion) Whole Trichosanthes (portion) 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 Chinese medicine composition comprises the following steps:

[0053] Take the raw sun-dried ginseng, celandine, lily and whole trichosanthes kirilowii in the prescribed amount, add water to cover the medicinal materials by 5 cm, soak for 30 minutes, decoct the soaked medicinal materials for 40 minutes, then filter and retain the medicinal liquid; add water to cover the medicinal materials by 5 cm again, decoct for 30 minutes, then filter, combine the two medicinal liquids, and concentrate to 400 mL to obtain the traditional Chinese medicine composition.

[0054] Comparative Example 1:

[0055] The difference from Example 5 is that the raw sun-dried ginseng is replaced by Codonopsis pilosula, and the rest is the same as Example 5.

[0056] Comparative Example 2:

[0057] The difference from Example 5 is that: Greater celandine is omitted, that is, 45 parts of raw sun-dried ginseng, 30 parts of lily bulbs, and 30 parts of whole Trichosanthes kirilowii are used, and the rest is the same as Example 5.

[0058] Comparative Example 3:

[0059] The difference from Example 5 is that: 5 parts of raw sun-dried ginseng, 40 parts of celandine, 50 parts of lily, 10 parts of whole Trichosanthes, and the rest is the same as Example 5.

[0060] Comparative Example 4:

[0061] The difference from Example 5 is that: 40 parts of raw sun-dried ginseng, 5 parts of celandine, 10 parts of lily, 50 parts of whole Trichosanthes, and the rest is the same as Example 5.

[0062] Application Example: Clinical trial of using the Chinese medicine composition prepared in Examples 1-5 and Comparative Examples 1-4 for the treatment of pulmonary nodules of Qi and Yin deficiency type

[0063] 1. Subjects: The cases were patients who visited the Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine for lung nodules from January 2023 to December 2024 (traceable by the doctor's workstation), and a total of 437 cases who met the diagnostic criteria for lung nodules of Qi and Yin deficiency syndrome were included. The patients were non-randomly enrolled according to their willingness to take medication. Both groups of patients signed informed consent forms to voluntarily join this study, and the research plan was approved by the hospital's Medical Ethics Committee.

[0064] 2. Research methods:

[0065] 2.1 Diagnostic criteria:

[0066] Inclusion criteria:

[0067] ① Meet the Western medical diagnosis of pulmonary nodules: refer to the "Guidelines for the Classification, Diagnosis and Treatment of Pulmonary Nodules in China (2020 Edition)" and "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules" (2018 Edition). Imaging diameter ≤ 3cm, focal, round, increased density, solid or subsolid lung shadows, which can be isolated or multiple, without atelectasis, hilar lymphadenopathy and pleural effusion.

[0068] ② Meet the diagnostic criteria of TCM syndrome: refer to the definition of Qi and Yin deficiency syndrome in "Chinese Internal Medicine" and "Chinese Medicine Disease Diagnosis and Efficacy Criteria". Main symptoms: dry cough, little or no sputum; fatigue; shortness of breath; secondary symptoms: dry mouth, thirst; spontaneous sweating, night sweats, fear of wind; dry stool; poor appetite; tongue and pulse: pale red or red tongue, little or peeled coating, thin or weak pulse. With 2 main symptoms, or 1 main symptom, 2 secondary symptoms, or 3 secondary symptoms, combined with tongue and pulse, it can be diagnosed as Qi and Yin deficiency syndrome.

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

[0070] Exclusion criteria: ① According to the guidelines, patients with malignant nodules that may be large or accompanied by other metastatic lesions are recommended for surgery or further systemic examination; ② Patients with severe lung infection, tuberculosis and other diseases; ③ Patients with severe primary diseases of the heart, liver, kidney and hematopoietic system and mental illness; ④ Pregnant women.

[0071] Dropout criteria: ① taking other similar medications without authorization during the trial; ② voluntarily withdrawing from follow-up.

[0072] 2.2 Sample size estimation:

[0073] This study is a non-randomized controlled trial. The efficacy of the longest diameter reduction of pulmonary nodules was used as the main outcome indicator for sample size calculation. The experimental group was the Chinese medicine treatment group, and the control group was the blank control group. According to the literature search and the results of the previous pilot test, the total effective rate of the treatment group was 75%, and the control group was 45%. Considering that this study is a superiority trial, a one-sided test was selected, the type I error α was 0.025, and the type II error β was 0.1; considering that most patients who visit the outpatient clinic of pulmonary nodules in a traditional Chinese medicine hospital are willing to take medicine, the sample size of the experimental group: control group is 7:1. Using PASS21 software to calculate, and considering the dropout during the trial, the sample size was increased by 10%, and the final number of samples included was determined to be 400, with 350 cases in the experimental group and 50 cases in the control group.

[0074] 2.3 Treatment methods:

[0075] Treatment group: Decoction of the pharmaceutical composition prepared in Examples 1-5 and Comparative Examples 1-4, one dose per day, divided into morning and evening after meals, 3 months as one course of treatment, and chest CT reexamination after one course of treatment.

[0076] Control group: No drug treatment, chest CT scan after 3 months. (Refer to the "Chinese Expert Consensus on Diagnosis and Treatment of Pulmonary Nodules" recommendation)

[0077] 2.4 Observation indicators:

[0078] 2.4.1 Main indicators:

[0079] Evaluation of the efficacy of lung nodules: The longest diameter of the nodules in chest CT before and after treatment was measured as a method of determining the efficacy, and divided into three levels: effective, stable, and ineffective. Nodule reduction or complete disappearance is effective, no change is stable, and nodule enlargement or increase is ineffective; effective rate = (effective number of people + stable number of people) / total number of people. Among them, further grouping and statistics are made according to nodule size <1cm and 1-3cm.

[0080] 2.4.2 Secondary indicators:

[0081] ① TCM syndrome scoring: refer to the definition of qi and yin deficiency syndrome in "Chinese Internal Medicine" and "Chinese Medicine Disease Diagnosis and Efficacy Standards", and divide clinical symptoms into primary and secondary symptoms according to TCM diagnostic standards. According to the degree, it is divided into none, mild, moderate, and severe. The primary symptoms are recorded as 0, 2, 4, and 6 points respectively, and the secondary symptoms are recorded as 0, 1, 2, and 3 points respectively, and the total score is recorded.

[0082] ②Mayo model predicts the probability of malignancy of pulmonary nodules: malignancy probability = e x / (1+e x ). X = -6.8272 + (0.0391 × age) + (0.7917 × smoking history) + (1.3388 × history of tumors in other parts of the body) + (0.1274 × nodule diameter) + (1.0407 × spicule sign) + (0.7838 × nodule location). Where e is the natural logarithm; age is calculated numerically; if there is a history of smoking, it is 1, otherwise it is 0; if there is a history of extrathoracic tumors within 5 years, it is 1, otherwise it is 0; nodule diameter is calculated in millimeters; if there are spicules on the edge of the nodule, it is 1, otherwise it is 0; if the lung nodule is located in the upper lobe, it is 1, otherwise it is 0.

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

[0084] 2.5 Statistical methods: When the total sample size of enumeration data was n≥40 and T≥5, the Pearson χ2 test was used; when n≥40 and 1≤T<5, the continuity-corrected χ2 test was used; when T<1 or n<40, the Fisher exact test was used; for measurement data: normality test was performed, and if the data were in accordance with normal distribution, the mean ± standard deviation (X±S) was used for statistical description. The independent sample t test was used for mutual comparison between the two groups, and the paired t test was used for self-comparison before and after treatment within the group. If the data were not in accordance with normal distribution, the median (interquartile range) was used for statistical description. The independent sample rank sum test was used for mutual comparison between the two groups, and the related sample rank sum test was used for comparison before and after treatment within the group; P<0.05 was used as the standard for bilateral significant difference (the Bonferroni method was used for self-comparison before and after treatment within the group, and the α value was adjusted according to the number of comparisons).

[0085] 3. Test results:

[0086] 3.1 General data comparison:

[0087] Finally, a total of 398 effective cases were included, including 348 cases in the treatment group (including Examples 1-5, 40 people in each group; Comparative Examples 1-4, 37 people in each group), and 50 cases in the blank control group. The average age of the patients in the treatment group was 57.5 years old, 61% were female, and 213 cases (61.2%) had nodules less than 1 cm; the average age of the blank control group was 60.5 years old, 55% were female, and 32 cases (64.0%) had nodules less than 1 cm. Before treatment, there was no statistical difference in the baseline comparison between the two groups of patients, and they were comparable.

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

[0089] Before treatment, there was no difference in the distribution of nodule size ratio among the groups, which was comparable. After treatment, the patient's lung nodules shrank or completely disappeared, which was effective, no changes in nodules were stable, and nodules enlarged or increased, which was ineffective. Effective rate = (effective number of people + stable number of people) / total number of people. The total effective rate of the blank control group was 44.00%; the comparison groups 1-4 in the treatment group were all higher than the blank control group, among which the total effective rate of comparison group 1 was 48.65%, the total effective rate of comparison group 2 was 51.35%, and the total effective rate of comparison groups 3 and 4 was 54.05% (*, P<0.05). The treatment groups of Example 1-5 were significantly higher than those of Comparative Example 1-4 and the blank control group (**, P<0.01; #, P<0.05), among which, the total effective rate of Example 1 and Example 3 was 70.00%, the total effective rate of Example 2 and Example 4 was 72.50%, and the total effective rate of Example 5 reached 80.00% (**, P<0.01; ##, P<0.01). Further subgroup analysis according to the size of lung nodules showed that the efficacy of each group in the treatment group for lung nodules less than 1 cm was better than that for lung nodules of 1-3 cm. See Table 1 below for details.

[0090] Table 1 Comparison of clinical efficacy of pulmonary nodules

[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 Assessment of the probability of malignancy of pulmonary nodules

[0094] The classic Mayo model score was used to predict the probability of malignant risk of pulmonary nodules; before treatment, there was no statistical difference in the scores of each group. After treatment, the Mayo model malignant score of the blank control group did not decrease compared with that before treatment (P>0.05); in the comparative example 1-4 groups in the treatment group, the Mayo model malignant score decreased after treatment compared with that before treatment, but the difference was not statistically significant (P>0.05); in the example 1-5 groups in the treatment group, the Mayo model malignant risk probability of pulmonary nodules decreased significantly after treatment compared with that before treatment, and the difference was statistically significant (P<0.05), among which the improvement in the example 5 group was particularly significant (P<0.01), as shown in Table 2 below.

[0095] Table 2 Comparison of malignant probability of pulmonary nodules before and after treatment ( point)

[0096] Group Number of cases 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 37 0.041±0.003 0.040±0.007 1.652 0.323 Comparative Example 2 37 0.043±0.004 0.041±0.006 -1.123 0.194 Comparative Example 3 37 0.042±0.003 0.038±0.005 -1.586 0.137 Comparative Example 4 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 the baseline of each group; after treatment, the intra-group comparison showed that the TCM syndrome score and the main clinical symptom score of qi and yin deficiency in the blank control group were not statistically different from those before treatment (P>0.05); in the treatment group, the total score of TCM syndrome in the comparison examples 1-4 groups was improved compared with that before treatment, and the comparison examples 3 and 4 groups were statistically different from those before treatment (P<0.05); in the treatment group, the total score of TCM syndrome in the embodiment 1-5 groups and the main clinical symptoms of qi and yin deficiency (fatigue, cough, dry mouth, constipation) were significantly improved compared with those before treatment (P<0.05), and the improvement of the embodiment 5 group was the most obvious. After treatment, the inter-group comparison showed that the comparison examples 1-4 groups were compared with the blank control group in the treatment group, and there was no statistical difference; in the treatment group, the total score of TCM syndrome and the main clinical symptoms of qi and yin deficiency in the embodiment 1-5 groups were significantly lower than those in the blank control group (P<0.05), and the improvement of the symptoms in the embodiment 5 groups was particularly obvious (P<0.01), as shown in Table 3 below.

[0100] Table 3 Comparison of total TCM syndrome scores and clinical symptoms before and after treatment ( point)

[0101]

[0102]

[0103] Note: Intra-group comparison with pre-treatment, *, P<0.05, **, P<0.01; inter-group comparison with blank control group after treatment, #, P<0.05, ##, P<0.01.

[0104] 3.5 Comparison of inflammatory immune indicators:

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

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

[0107]

[0108]

[0109] Note: Intra-group comparison with pre-treatment, *, P<0.05; inter-group comparison with blank control group after treatment, #, P<0.05.

[0110] Conclusion: The pharmaceutical composition is used to treat pulmonary nodules of qi and yin deficiency type, can effectively reduce and stabilize the size of nodules, reduce the risk of malignancy in patients with pulmonary nodules, improve clinical symptoms of TCM syndromes such as cough, dry mouth, fatigue and weakness, play an anti-inflammatory, immune-regulating, and improve the patient's precancerous "soil". Among them, in the treatment group, comparative example 1 is better than the blank control group, comparative examples 1-2 have equivalent efficacy, comparative examples 3-4 have equivalent efficacy but are better than comparative examples 1-2; in the treatment group, examples 1-5 are better than comparative examples 1-4, examples 1-4 have equivalent efficacy, and example 5 has the best efficacy.

[0111] Typical cases:

[0112] Case 1:

[0113] Wu Moumou, female, 37 years old. On July 15, 2024, a chest CT scan at an external hospital revealed: a subpleural nodule in the left lower lobe of the lung, with a long diameter of about 14 mm, and visible lobulation and pleural indentation signs. She then came to the outpatient clinic for treatment, with symptoms of coughing, which was obvious at night, less sputum and white color, chest tightness and pain, dry mouth, dry stool, red tongue with white fur, and thin pulse. According to Chinese medicine syndrome differentiation, it was a deficiency of both qi and yin. The Chinese medicine composition embodiment 5 of the present invention (15 parts of raw sun-dried ginseng, 30 parts of celandine, 30 parts of lily, and 30 parts of whole Trichosanthes) was decocted and taken orally in the morning and evening for more than 3 months. The cough was relieved after the follow-up visit, with occasional dry cough, no chest tightness or pain, no dry mouth or constipation symptoms. On October 26, 2024, a chest CT scan showed: a nodule shadow was seen under the pleura of the left lower lobe of the lung, with a long diameter of about 7 mm, ground glass-like edges, and punctate solid shadows inside. No abnormal density foci were found in the remaining two lungs. Advise to continue taking the Chinese medicine composition of the present invention and then have a review after half a year.

[0114] Case 2:

[0115] Ms. Fan, female, 41 years old. Because of the cough after a cold for more than a month, she went to an external hospital for a chest CT on July 30, 2024, which showed: multiple ground glass nodules in both lungs, with a maximum diameter of about 7mm, small nodules and fibrous foci in both lungs; symptoms of coughing, dry cough without sputum, fatigue, dry mouth, insomnia, pale red tongue, thin white fur, and fine pulse. According to Chinese medicine syndrome differentiation, it is a deficiency of both qi and yin. The Chinese medicine composition embodiment 4 of the present invention (20 parts of raw sun-dried ginseng, 40 parts of celandine, 30 parts of lily, and 20 parts of whole Trichosanthes) is decocted and taken orally in the morning and evening for more than a month. After more than one month, she was reexamined due to anxiety. During the follow-up visit, the symptoms of cough and fatigue were relieved compared with the previous ones, with occasional dry cough, dry mouth, and insomnia slightly relieved. On September 10, 2024, the chest CT reexamination in the external hospital showed: multiple ground glass nodules in both lungs were similar to the previous ones, with a maximum diameter of about 7mm; the Chinese medicine composition of the present invention was continued for half a year and then reexamined.

[0116] Case 3:

[0117] Wu Moumou, male, 60 years old. Due to repeated paroxysmal cough for more than half a year, chest CT scan at an external hospital on January 15, 2024 showed: multiple ground glass nodules in both lungs, the largest nodule was located in the right upper lung, with a diameter of about 20mm, and normal images of both lung hilums. The patient refused puncture, surgery and other operations. Symptoms included occasional dry cough, dry mouth, difficult bowel movements, red tongue and thin pulse. Chinese medicine diagnosis was qi and yin deficiency type. The Chinese medicine composition embodiment 3 of the present invention (30 parts of raw sun-dried ginseng, 45 parts of celandine, 10 parts of lily, and 10 parts of whole Trichosanthes) was decocted and taken orally in the morning and evening for more than 3 months before reexamination. Dry mouth, tongue and pulse symptoms were relieved compared with the previous visit, and there was still a dry cough. Chest CT scan on April 10, 2024 showed: ground glass nodules in the right upper lobe of the lung, about 17*16mm in size, and mild enhancement was visible in the solid part. The patient was asked to continue taking the Chinese medicine composition of the present invention for reexamination after 3 months.

[0118] Case 4:

[0119] Wang, male, 71 years old. The patient had chronic emphysema in the past, but shortness of breath was not taken seriously. On August 19, 2024, the chest CT of the external hospital showed: a mass in the middle lobe of the right lung, about 30*20mm in size, chronic emphysema; symptoms of cough and shortness of breath, white sputum that is difficult to cough, chest pain when coughing, obvious dry mouth, red tongue, thin pulse, the patient refused puncture and surgery; Chinese medicine syndrome differentiation is qi and yin deficiency type, and the Chinese medicine composition embodiment 2 of the present invention (raw sun-dried ginseng 10 parts, celandine 20 parts, lily 20 parts, whole trichosanthes 10 parts) is decocted, and 1 dose is taken orally in the morning and evening for more than 3 months before reexamination. During the follow-up visit, the symptoms of cough, shortness of breath and dry mouth were significantly relieved compared with the previous ones, and sometimes white sputum was difficult to cough up, and the tongue was light red; the chest CT reexamination on November 20, 2024 showed: irregular nodules in the middle lobe of the right lung, which were smaller than before, about 14*10mm in size, and chronic emphysema. The patient was asked to continue taking the Chinese medicine composition of the present invention for a reexamination after 3 months.

[0120] Case 5:

[0121] Xie, female, 61 years old. The patient had early adenocarcinoma of the right lower lobe of the lung more than 5 years after surgery, and left breast cancer more than 10 years after surgery. On January 11, 2024, the chest CT of the routine physical examination in the external hospital showed: multiple ground glass nodules were found in the right upper lobe, right lower lobe, and left upper lobe. The larger one was located in the apical segment of the right upper lobe of the lung, with a size of about 5x5mm and unclear boundaries. It was recommended to re-examine; the patient felt tired and weak, dry mouth, dry stool, irritability, no cough and sputum, red tongue, and thin pulse; TCM syndrome was Qi and Yin deficiency type, and the Chinese medicine composition embodiment 1 of the present invention (raw sun-dried ginseng 15 parts, celandine 15 parts, lily 40 parts, whole Trichosanthes 40 parts) was decocted, and 1 dose was taken orally in the morning and evening for more than 3 months before re-examination. During the follow-up visit, the symptoms of fatigue and dry stool were significantly relieved compared with before, and the tongue was pale red; the chest CT scan on April 20, 2024 showed that the number of multiple ground glass nodules was reduced to 1 under the thin layer of pleura in the upper field of the right lung, with a diameter of about 3mm. The patient was asked to continue taking the Chinese medicine composition of the present invention and then re-examined after half a year.

Claims

1. A Chinese medicine composition for treating pulmonary nodules of Qi and Yin deficiency type, characterized in that: The traditional Chinese medicine composition consists of the following components in parts by weight: 10-30 parts of raw sun-dried ginseng, 15-45 parts of celandine, 10-40 parts of lily and 10-40 parts of whole trichosanthes.

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

3. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition consists 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.

4. The Chinese medicine composition according to claim 1, characterized in that: The mass ratio of the lily and the whole Trichosanthes kirilowii is 1-3:

1.

5. The Chinese medicine composition according to claim 1, characterized in that: The mass ratio of the raw sun-dried ginseng to the greater celandine is 1:1-4.

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

1.

7. The Chinese medicine composition according to claim 5, characterized in that: The mass ratio of the raw sun-dried ginseng to greater celandine is 1:

2.

8. The Chinese medicine composition according to claim 6 or 7, characterized in that: The traditional Chinese medicine composition consists 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.

9. The method for preparing the Chinese medicine composition according to any one of claims 1 to 8, characterized in that: The steps include: Take the raw sun-dried ginseng, celandine, lily and whole Trichosanthes kirilowii in the prescribed amount, soak them in water, decoct the soaked medicinal materials, filter them and keep the medicinal liquid; The medicinal residue is boiled again with water, then filtered, and the two medicinal liquids are combined and concentrated to obtain the traditional Chinese medicine composition.

10. Use of the Chinese medicine composition according to any one of claims 1 to 8 in the preparation of a medicine for treating pulmonary nodules of qi and yin deficiency type.

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