A medicinal composition for benefiting qi, activating blood and resolving stasis, preparation and application thereof

Abstract

This invention relates to the field of traditional Chinese medicine technology. It discloses a pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving lumps, its preparation, and its application. The pharmaceutical composition comprises 10-30 parts of *Codonopsis pilosula*, 5-20 parts of *Trifolium repens*, 10-20 parts of *Panax ginseng*, 5-15 parts of *Zingiber officinale*, and 5-15 parts of *Desmodium triquetrum*. Capsules or pills are prepared by mixing the alcohol and water extracts of the pharmaceutical composition with pharmaceutically acceptable excipients required for preparation. Experimental verification shows that the composition of this invention has good effects in invigorating qi, promoting blood circulation, and resolving lumps. It has achieved significant therapeutic effects in dispersing pulmonary nodules in patients with qi deficiency and blood stasis, and has no toxic side effects, making it safe and reliable. It has broad application prospects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation, as well as its preparation and application. Background Technology

[0002] The statements in this section provide only background information relevant to the disclosure of this application and may not constitute prior art.

[0003] With the application of high-resolution CT, the detection rate of pulmonary nodules has gradually increased. Pulmonary nodules refer to focal, round or oval, solid or subsolid pulmonary shadows with increased density, ≤3 cm in diameter, as seen on imaging. They can be solitary or multiple, without atelectasis, hilar lymphadenopathy, or pleural effusion. The detection rate of pulmonary nodules in the population undergoing chest CT examinations ranges from 20% to 50%. Although most pulmonary nodules are benign, especially smaller ones, some can develop into precancerous lesions or early-stage lung cancer. Early-stage lung cancer or precancerous lesions primarily appear as pulmonary nodules on imaging, making pulmonary nodules a crucial window for early diagnosis and treatment of lung cancer.

[0004] Currently, modern medicine manages pulmonary nodules by performing positron emission tomography / computed tomography (PET / CT) and biopsy to determine their benign or malignant nature, or by surgically removing high-risk nodules. In addition, most patients with pulmonary nodules receive only expectant management through regular imaging follow-ups or indiscriminate antibiotic intervention. Traditional Chinese medicine (TCM), with its advantages of syndrome differentiation and treatment, holistic regulation, and comprehensive management, can participate in the construction and improvement of the pulmonary nodule diagnosis and treatment system in a full-cycle and multi-dimensional manner. Therefore, it is essential to explore the basic treatment methods of TCM intervention for pulmonary nodules, further leverage the "prevention of disease" advantages of TCM, and develop a drug that treats both the symptoms and the root cause of pulmonary nodules. Summary of the Invention

[0005] The purpose of this invention is to address the current lack of intervention methods and drugs for pulmonary nodules in modern medicine by providing a drug composition, preparation and application of invigorating qi, promoting blood circulation and dispersing nodules, thus solving the problem of no intervention drugs for pulmonary nodules, giving full play to the advantages of traditional Chinese medicine in "prevention of disease", treating both the symptoms and the root cause, dispersing pulmonary nodules and preventing further evolution of nodules.

[0006] The technical solution of the present invention is as follows:

[0007] The present invention provides a pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation, which, by weight, consists of the following components: 10-30 parts of Codonopsis pilosula, 5-20 parts of Clematis armandii, 10-20 parts of Panax ginseng, 5-15 parts of Zingiber officinale, and 5-15 parts of Panax quinquefolius.

[0008] According to a preferred embodiment, the product is composed of the following components by weight: 12-28 parts of Codonopsis pilosula, 7-18 parts of Clematis armandii, 12-18 parts of Panax quinquefolius, 7-18 parts of Zingiber officinale, and 7-18 parts of Panax quinquefolius.

[0009] According to a preferred embodiment, the product is composed of the following components by weight: 15-25 parts of Codonopsis pilosula, 8-16 parts of Clematis armandii, 13-18 parts of Panax ginseng, 10-15 parts of Zingiber officinale, and 10-15 parts of Panax quinquefolius.

[0010] Traditional Chinese medicine (TCM) does not have a specific disease name for pulmonary nodules. Based on clinical manifestations, TCM categorizes them under "pulmonary accumulation," "phlegm nodules," and "cough." The *Medical Essentials* states, "The formation of accumulations is due to insufficient vital energy, which allows pathogenic factors to take hold." Deficiency of vital energy is the root cause of pulmonary nodules. Insufficient congenital endowment or prolonged illness depletes lung qi, leading to a decline in the body's ability to resist external pathogens, qi imbalance, and weakened vital energy. This easily results in abnormal lung fluid metabolism, stagnation of dampness and the formation of phlegm, which obstructs qi and blood flow. Blood stasis leads to blood stasis, and since the lungs are rich in blood vessels, prolonged phlegm and blood stasis in the lung vessels manifest as nodules. In the pharmaceutical composition of this application, *Codonopsis pilosula* is sweet and slightly bitter, warm in nature, and non-toxic. It enters the lung, spleen, and kidney meridians and is listed in the *Guizhou Province Standards for the Quality of Traditional Chinese and Ethnic Medicines (2003 Edition)*. It has the effects of tonifying the middle energizer and replenishing qi, moistening the lungs and promoting fluid production, stopping bleeding, and promoting lactation. *Trifolium repens* is bitter and pungent, neutral in nature, and has the effects of dispersing nodules and reducing swelling, clearing heat and detoxifying, and dispelling wind and resolving phlegm. The two are used together as the principal drug to tonify the middle energizer and replenish qi, disperse nodules and reduce swelling. The assistant drug, *Panax ginseng*, was first mentioned in *Diannan Materia Medica* by Lan Mao, which states that "Panax ginseng is bitter, sweet, and neutral in nature, and slightly warm in nature; it circulates through the twelve meridians." As a unique ethnic medicine of Yunnan, it is included in the *Yunnan Provincial Drug Standards* and the *Chinese Pharmacopoeia* (1977 edition). The *Yunnan Ethnic Medicine Records* states that the Bai and Yi ethnic groups believe that small red ginseng is sweet and neutral in nature, possessing the functions of softening hard masses, replenishing blood, promoting blood circulation, removing blood stasis, and calming the mind. Combined with the principal herb, it enhances the effects of promoting blood circulation, removing blood stasis, and dispersing nodules. The adjuvant herb, black ginger, is bitter and pungent, warm in nature, and non-toxic. It enters the lung and spleen meridians, promoting qi circulation, breaking up blood stasis, stimulating appetite, and relieving pain; it is considered a "key medicine for breaking up blood stasis." It is used in conjunction with the principal and assistant herbs to break up blood stasis, promote qi circulation, and assist in dispersing nodules. The guiding herb, *Wan Zhang Shen*, is slightly sweet and bitter, cool in nature, and enters the lung and liver meridians. It has the effects of strengthening the spleen, eliminating stagnation, clearing heat and detoxifying, moistening the lungs and relieving cough, reducing swelling, and replenishing deficiency. It can prevent the entire formula from being too warm and dry, thus protecting yin, and it can also strengthen the spleen. A healthy spleen ensures the source of qi and blood production and normal circulation. The combined use of these herbs treats both the root cause and the symptoms, achieving the combined effects of replenishing qi, promoting blood circulation, removing blood stasis, and dispersing nodules, and is used to disperse pulmonary nodules in patients with qi deficiency and blood stasis.

[0011] Pharmacological analysis:

[0012] Codonopsis pilosula (also known as wild ginseng) is the dried root of *Campanumoea javanica* BL. subsp. japonica (Makino) Hong, a perennial herb commonly found in roadside grasses and shrublands below 2400m altitude. It is sweet and neutral in nature, and enters the spleen and lung meridians. It has the effects of tonifying the middle energizer and replenishing qi, moistening the lungs and promoting fluid production, stopping bleeding, and promoting lactation. It is mainly used to treat post-illness weakness, lung deficiency cough, excessive sweating, neurasthenia, infantile malnutrition, loss of appetite, chronic diarrhea, and postpartum lactation insufficiency. Modern research shows that Codonopsis pilosula contains various components such as polysaccharides, alkynyl glycosides, saponins, and flavonoids, with alkynyl glycosides and total polysaccharides being the main components. Alynyl glycosides have anti-tumor, anti-ulcer, anti-inflammatory, and anti-pathogenic microbial effects, while total polysaccharides have anti-fatigue, immune-enhancing, anti-hypoxia, and anti-cerebral ischemia effects.

[0013] *Tetrastigma trifoliata*, also known as three-leaf vine, is the fresh or dried tuberous root of a perennial herbaceous climbing vine belonging to the genus *Tetrastigma* in the family Vitaceae. It has a bitter and pungent taste, is neutral in nature, and possesses properties such as clearing heat and detoxifying, dispelling wind and resolving phlegm, and dispersing nodules and reducing swelling. Modern research indicates that it contains various compounds including flavonoids, phenolic acids, polysaccharides, volatile oils, and fatty acids. Flavonoids and polysaccharides are the main bioactive components of *Tetrastigma trifoliata*, exhibiting anti-tumor, anti-inflammatory, antibacterial, antiviral, and immunomodulatory effects.

[0014] Small Red Ginseng: The dried root of *Rubia yunnanensis* (Fr.) Diels., a plant belonging to the Rubiaceae family; it mainly grows in sparse forests on sunny mountain slopes, among weeds or by roadsides; distributed in central, northwestern, and northeastern Yunnan. It has a sweet and neutral taste and functions to soften hardened masses, nourish blood, promote blood circulation, remove blood stasis, and calm the mind. To date, more than 30 chemical components have been reported extracted and isolated from small red ginseng, with anthraquinones and their glycosides, and triterpenoids being the most prevalent. In addition, cyclohexyl peptides and naphthoquinones have also been isolated. Modern pharmacological experiments have demonstrated that extracts of small red ginseng possess anti-tumor, anti-myocardial ischemia, T-lymphocyte regulation, and expectorant effects.

[0015] Black-hearted ginger: The dried rhizome of *Curcuma phaeocaulis* VaL, *Curcuma wangsiensis* SGLee et CFLiang, or *Curcuma wenyujin* YHChen et C.Ling (all belonging to the ginger family). It has a pungent and bitter taste, is warm in nature, and enters the liver and spleen meridians. It possesses the effects of relieving pain and promoting blood circulation, and is considered a "key medicine for breaking up blood stasis." Modern research shows that black-hearted ginger contains volatile oils and curcumin-like active chemical components, both of which have anti-tumor, anticoagulant, and antiplatelet aggregation effects.

[0016] *Codonopsis pilosula*, a perennial herb belonging to the genus *Codonopsis* in the family Asteraceae, is used medicinally for its roots. It possesses properties that nourish the lungs, clear heat and detoxify, aid digestion, regulate qi, and promote lactation. It is used to treat weakness and dizziness, limb weakness, pneumonia, bronchitis, infantile malnutrition, insufficient lactation in women, muscle and bone pain, traumatic injuries, and boils and carbuncles. Modern pharmacological research indicates that it contains tannins, polysaccharides, sugars, glycosides, volatile oils, and reducing compounds, exhibiting anti-cancer, anti-inflammatory, anti-thrombotic, liver-protective, and lipid-lowering effects.

[0017] Another aspect of the present invention provides a pharmaceutical composition formulation for invigorating qi, promoting blood circulation, and resolving stagnation, comprising an alcohol extract and a water extract of the pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation as described above, and pharmaceutically acceptable excipients required for the formulation.

[0018] According to a preferred embodiment, the formulation is a capsule or a pill.

[0019] According to a preferred embodiment, the capsules are prepared using the following method:

[0020] Step (1): An alcohol extract of a drug composition for invigorating qi, promoting blood circulation and resolving stagnation was obtained by ethanol extraction, and an aqueous extract was obtained by adding water to the residue after alcohol extraction.

[0021] Step (2): The alcohol extract and water extract are concentrated separately and then mixed, dried and pulverized to obtain a dry extract powder;

[0022] Step (3): Add excipients to the dry powder prepared in step (2) and mix well to obtain a mixture;

[0023] Step (4): Add 60%-80% ethanol to the mixture to obtain wet granules, dry them at 55-75℃ to obtain dry granules, add lubricant, mix thoroughly, and fill into empty capsule shells to obtain the capsule of the Qi-invigorating, blood-activating and nodule-dispersing drug composition.

[0024] Preferably, step (1) specifically includes the following sub-steps:

[0025] Step (1.1): Weigh each herb according to the formula, dry and pulverize them separately, and then mix them evenly to obtain a mixture.

[0026] Step (1.2): Add 65%-75% ethanol by volume to the mixture and reflux for extraction. The amount of ethanol added is 6-8 times the mass of the mixture. The extraction time is 1-2 hours. Repeat the extraction 1-2 times, using the same amount of ethanol each time. Filter to obtain filtrate and residue.

[0027] Step (1.3): The filtrate is subjected to reduced pressure to recover ethanol, resulting in an alcohol extract; water is then added to the residue for extraction once, with a mass ratio of residue to water of 1:7-10 and an extraction time of 1-2 hours, to obtain an aqueous extract.

[0028] Preferably, step (2) specifically involves: concentrating the alcohol extract and the water extract at 60-80°C to obtain an extract with a relative density of 1.20-1.35; mixing the extract; and then drying and pulverizing the extract to obtain a dry extract powder with a water content of 6%-8%.

[0029] Preferably, the excipients in step (3) include starch, lactose and microcrystalline cellulose, and the mass ratio of dry powder, starch, lactose and microcrystalline cellulose is 1:0.1-0.2:0.1-0.2:0.1-0.2.

[0030] Preferably, the lubricant used in step (4) is selected from at least one of silica and magnesium stearate, and the total amount used is 0.6%-1% of the dry particles.

[0031] Preferably, in step (4), each capsule contains 0.6 grams.

[0032] According to a preferred embodiment, the pills are prepared using the following method:

[0033] Step (1): An alcohol extract of a drug composition for invigorating qi, promoting blood circulation and resolving stagnation was obtained by ethanol extraction, and an aqueous extract was obtained by adding water to the residue after alcohol extraction.

[0034] Step (2): The alcohol extract and water extract are concentrated separately and then mixed, dried and pulverized to obtain a dry extract powder;

[0035] Step (3): Add a disintegrant to the dry powder prepared in step (2) and mix well to obtain a mixture;

[0036] Step (4): Add 60%-80% ethanol to the mixture prepared in step (3) to make micro-pills, and dry to obtain the pills of the Qi-invigorating, blood-activating and nodule-dispersing drug composition.

[0037] Preferably, step (1) specifically includes the following sub-steps:

[0038] Step (1.1): Weigh each herb according to the formula, dry and pulverize them separately, and then mix them evenly to obtain a mixture.

[0039] Step (1.2): Add 65%-75% ethanol by volume to the mixture and reflux for extraction. The amount of ethanol added is 6-8 times the mass of the mixture. The extraction time is 1-2 hours. Repeat the extraction 1-2 times, using the same amount of ethanol each time. Filter to obtain filtrate and residue.

[0040] Step (1.3): The filtrate is subjected to reduced pressure to recover ethanol, resulting in an alcohol extract; water is then added to the residue for extraction once, with a mass ratio of residue to water of 1:7-10 and an extraction time of 1-2 hours, to obtain an aqueous extract.

[0041] Preferably, step (2) specifically involves: concentrating the alcohol extract and the water extract at 60-80°C to obtain an extract with a relative density of 1.20-1.35; mixing the extract; and then drying and pulverizing the extract to obtain a dry extract powder with a water content of 6%-8%.

[0042] Preferably, the disintegrant in step (3) is selected from at least one of sodium carboxymethyl starch (CMS-Na), croscarmellose sodium (CC-Na), croscarmellose PVPP, low-substituted hydroxypropyl cellulose (L-HPC), and microcrystalline cellulose (MCC), and the total amount of the disintegrant is 0.6%-1% of the mass of the dry powder prepared in step (2).

[0043] Preferably, the pills of the Qi-invigorating, blood-activating, and nodule-dispersing drug composition after drying in step (4) are selected.

[0044] In another aspect, the present invention provides the application of a qi-invigorating, blood-activating, and nodule-dispersing pharmaceutical composition as described above in the preparation of a medicament for treating pulmonary nodules of qi deficiency and blood stasis type.

[0045] In another aspect, the present invention provides the application of a pharmaceutical composition preparation as described above, which invigorates qi, promotes blood circulation, and disperses nodules, in the preparation of a drug for treating pulmonary nodules of the qi deficiency and blood stasis type.

[0046] Compared with existing technologies, the advantages of this invention are:

[0047] 1. A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing nodules is provided, with Codonopsis pilosula and Clematis armandii as the principal herbs to tonify the middle energizer, invigorate qi, disperse nodules, and reduce swelling; Panax ginseng as the assistant herb and Zingiber officinale as the adjuvant herb, which, together with the principal and assistant herbs, break up blood stasis, promote qi circulation, and assist in dispersing nodules; and the combination of the adjuvant herbs further enhances the effect. The combined effects of these herbs focus on tonifying the middle energizer, invigorating qi, promoting blood circulation, removing blood stasis, dispersing nodules, and reducing swelling, addressing both the root cause and the symptoms. This combination achieves the effects of invigorating qi, promoting blood circulation, removing blood stasis, and dispersing nodules. It has been used to disperse pulmonary nodules in patients with qi deficiency and blood stasis, achieving significant therapeutic effects, with no toxic side effects and is safe and reliable.

[0048] 2. It also provides a pharmaceutical composition preparation that invigorates qi, promotes blood circulation, and dissipates nodules. The traditional Chinese medicine composition is prepared into capsules or pills for use, which has the advantages of being convenient to use, easy to store and take; it can achieve long-term sustained release of drugs, which is beneficial to the application of traditional Chinese medicine resources.

[0049] 3. A pharmaceutical composition preparation for invigorating qi, promoting blood circulation, and dispersing nodules, which uses a combination of alcohol extraction and water extraction to extract and collect the effective components in the composition, and then mixes the effective components to prepare the pharmaceutical preparation; it can fully extract the effective components in the pharmaceutical composition; it can be applied to the treatment of pulmonary nodules of qi deficiency and blood stasis type, forming a unique preparation of Yunnan ethnic medicine resources, with scientific prescription and reasonable material use, significant curative effect, and safety without side effects. Detailed Implementation

[0050] The specific embodiments listed in this invention are merely examples, and the invention is not limited to the specific embodiments described below. For those skilled in the art, any equivalent modifications and substitutions to the embodiments described below are also within the scope of this invention. Therefore, all equivalent transformations and modifications made without departing from the spirit and scope of this invention should be covered within its scope. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are commercially available conventional products. To better illustrate this invention, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that this invention can be practiced even without certain specific details. In other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main points of this invention.

[0051] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Unless otherwise specified, all units used in this specification are International Standard Units (SI), and all numerical values ​​and ranges appearing in this invention should be understood to include systematic errors unavoidable in industrial production.

[0052] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0053] Example 1: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0054] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 30 parts of Codonopsis pilosula, 20 parts of Clematis armandii, 20 parts of Panax quinquefolius, 15 parts of Zingiber officinale, and 15 parts of Panax quinquefolius.

[0055] Example 2: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0056] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 10 parts of Codonopsis pilosula, 5 parts of Clematis armandii, 10 parts of Panax quinquefolius, 5 parts of Zingiber officinale, and 5 parts of Panax quinquefolius.

[0057] Example 3: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0058] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 12 parts of Codonopsis pilosula, 7 parts of Clematis armandii, 12 parts of Panax quinquefolius, 7 parts of Zingiber officinale, and 7 parts of Panax quinquefolius.

[0059] Example 4: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0060] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 28 parts of Codonopsis pilosula, 18 parts of Clematis armandii, 18 parts of Panax quinquefolius, 18 parts of Zingiber officinale, and 18 parts of Panax quinquefolius.

[0061] Example 5: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0062] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 15 parts of Codonopsis pilosula, 8 parts of Clematis armandii, 13 parts of Panax quinquefolius, 10 parts of Zingiber officinale, and 10 parts of Panax quinquefolius.

[0063] Example 6: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0064] A pharmaceutical composition for invigorating qi, promoting blood circulation, and dispersing stagnation, comprising the following components by weight: 25 parts of Codonopsis pilosula, 16 parts of Clematis armandii, 18 parts of Panax quinquefolius, 15 parts of Zingiber officinale, and 15 parts of Panax quinquefolius.

[0065] Example 7: A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation

[0066] A pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation, comprising the following components by weight: 20 parts of Codonopsis pilosula, 12 parts of Clematis armandii, 15 parts of Panax quinquefolius, 12 parts of Zingiber officinale, and 12 parts of Panax quinquefolius.

[0067] Example 8: A pill-shaped pharmaceutical composition for invigorating qi, promoting blood circulation, and resolving stagnation.

[0068] According to the composition formulation of Example 7, the pills were prepared according to the following steps:

[0069] Step (1):

[0070] Step (1.1): Weigh each herb according to the formula described above, dry and pulverize them separately, and then mix them evenly to obtain a mixture.

[0071] Step (1.2): Add 65% ethanol (volume concentration) to the mixture and reflux for extraction. The amount of ethanol added is 8 times the mass of the mixture. The extraction time is 1 hour. Repeat the extraction twice, using the same amount of ethanol each time. Filter to obtain filtrate and residue.

[0072] Step (1.3): The filtrate is subjected to reduced pressure to recover ethanol, resulting in an alcohol extract; water is then added to the residue for extraction once, with a mass ratio of residue to water of 1:10 and an extraction time of 1 hour, to obtain an aqueous extract.

[0073] Step (2) The alcohol extract and the water extract are concentrated separately to obtain an extract with a relative density of 1.30 (60°C). The extracts are mixed, dried and pulverized to obtain a dry extract powder (with a water content of 6%).

[0074] Step (3): Add disintegrant sodium carboxymethyl starch (CMS-Na) to the dry powder, the total amount of which is 1% of the mass of the dry powder prepared in step (2), mix well, and obtain a mixture.

[0075] Step (4): Add 70% ethanol to the mixture obtained in step (3) to make micro-pills, with the amount of ethanol being 0.2 times that of the mixture. Dry the micro-pills at 65°C to obtain the pills of the Qi-invigorating, blood-activating, and nodule-dispersing drug composition.

[0076] Example 9

[0077] According to the traditional Chinese medicine composition formula of Example 1, capsules were prepared according to the following steps:

[0078] Step (1):

[0079] Step (1.1): Weigh each herb according to the formula described above, dry and pulverize them separately, and then mix them evenly to obtain a mixture.

[0080] Step (1.2): Add 65% ethanol (volume concentration) to the mixture and reflux for extraction. The amount of ethanol added is 8 times the mass of the mixture. The extraction time is 1 hour. Repeat the extraction twice, using the same amount of ethanol each time. Filter to obtain filtrate and residue.

[0081] Step (1.3): The filtrate is subjected to reduced pressure to recover ethanol, resulting in an alcohol extract; water is then added to the residue for extraction once, with a mass ratio of residue to water of 1:10 and an extraction time of 1 hour, to obtain an aqueous extract.

[0082] Step (2) The alcohol extract and the water extract are concentrated separately to obtain an extract with a relative density of 1.30 (60°C). The extracts are mixed, dried and pulverized to obtain a dry extract powder (with a water content of 6%).

[0083] Step (3): Add excipients to the dry powder, including starch, lactose and microcrystalline cellulose; the mass ratio of dry powder, starch, lactose and microcrystalline cellulose is 1:0.2:0.2:0.2, mix well to obtain a mixture.

[0084] Step (4): Add 70% ethanol to the mixture to obtain wet granules, dry (at 65°C) to obtain dry granules, add lubricant silica, the total amount of which is 1% of the dry granules, mix thoroughly, fill into empty capsule shells, each capsule containing 0.6g, polish, package, and obtain the capsule of the Qi-invigorating, blood-activating and stasis-dispersing drug composition.

[0085] Application Example 1: Clinical observation of the pharmaceutical composition of the present invention in patients with pulmonary nodules of the Qi deficiency and blood stasis type.

[0086] 1. Materials and Methods

[0087] 1.1 Clinical Data

[0088] This study included 200 patients with benign pulmonary nodules of the Qi deficiency and blood stasis type detected at the Dongchuan District Traditional Chinese Medicine Hospital in Kunming City from September 2020 to June 2023. A double-blind design was adopted, and the patients were randomly divided into two groups of 100 each using a random number table.

[0089] A total of 184 valid cases were collected. Among the general information of the collected valid cases, the control group consisted of 86 patients, including 28 males and 58 females, aged 38-66 years (mean 53.06 ± 6.83 years); their body mass index (BMI) ranged from 18.68 to 24.85 kg / m². 2 The average weight was (22.18 ± 1.38) kg / m³. 2 The average diameter of the lung nodules (mm) was 6.56±0.42. Among the types of lung nodules detected, there were 92 solid nodules and 105 ground-glass nodules.

[0090] The treatment group consisted of 98 patients, including 31 males and 67 females, aged 33-69 years, with a mean age of 51.68 ± 7.54 years; their body mass index (BMI) ranged from 19.16 to 25.29 kg / m². 2 The average weight was (22.36±1.27) kg / m³. 2 The average diameter of the lung nodules (mm) was 6.49 ± 0.38. Among the detected lung nodule types, 106 were solid nodules and 104 were ground-glass nodules. There were no statistically significant differences in general characteristics between the two groups (P > 0.05), as detailed in Table 1.

[0091] Table 1 Comparison of baseline data between the two groups of patients

[0092]

[0093] 1.2 Diagnostic criteria

[0094] (1) The pulmonary nodules meet the relevant diagnostic criteria in the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)" and are clearly diagnosed by physical examination and chest CT scan;

[0095] (2) Traditional Chinese Medicine (TCM) Differentiation: Referring to the "Guiding Principles for Clinical Research of New Chinese Medicine Drugs," the "Standards for Diagnosis and Efficacy of TCM Diseases," and TCM diagnostics, the TCM syndrome differentiation is classified as Qi Deficiency and Blood Stasis. Primary symptoms: cough, expectoration, stabbing pain in the chest and hypochondrium; Secondary symptoms: fatigue, spontaneous sweating, poor appetite, hemoptysis or blood-tinged sputum; Tongue and pulse: dark purple tongue or with ecchymosis, thickened sublingual veins, thin white or greasy white tongue coating, teeth marks, thready or choppy pulse. If two or more primary symptoms and one or more secondary symptoms are met, or if one or more primary symptoms and two or more secondary symptoms are met, combined with tongue and pulse findings, a diagnosis of Qi Deficiency and Blood Stasis can be made.

[0096] 1.3 Inclusion Criteria

[0097] (1) Meets the diagnostic criteria;

[0098] (2) The first disease, CT examination showed that the pulmonary nodule was a benign nodule with solid or ground-glass opacity in the lung, with a diameter of 0.5cm≤1.0cm;

[0099] (3) 18 years old ≤ age ≤ 85 years old;

[0100] (4) The patient is conscious, has good compliance, and can cooperate with this trial.

[0101] 1.4 Exclusion Criteria

[0102] (1) Alcoholics and / or substance / drug abusers and addicts;

[0103] (2) Patients with serious primary diseases;

[0104] (3) Comorbid malignant tumors or systemic infectious diseases;

[0105] (4) Intolerance or allergy to the drug being studied in this trial;

[0106] (5) The pulmonary nodules are diffuse in the lungs (more than 10 pulmonary nodules).

[0107] 1.5 Rejection Criteria

[0108] (1) Those who have poor compliance during the trial, fail to take medication as prescribed, or violate the trial protocol, thereby affecting the judgment of drug efficacy;

[0109] (2) Unwilling to continue clinical trials or voluntarily withdrawing from clinical trials.

[0110] 1.6 Grouping and Treatment Methods

[0111] Control group: No Chinese medicine or Western medicine treatment was given. The patients were admitted to the hospital for follow-up examinations at 3 months and 6 months. The focus was on observing the patients' clinical symptoms and detecting changes in the size of the lung nodules.

[0112] Treatment group: The nodule-dispersing drug combination capsules prepared in Example 9 of this invention are taken orally, 5 capsules each time, three times a day, half an hour after meals.

[0113] 1.7 Treatment duration and follow-up period

[0114] Treatment was continued for 6 months. Patients in both groups were followed up at the time of initial consultation, at 3 months of treatment, and at 6 months of treatment to assess changes in TCM syndrome scores, lung nodule size, and tumor marker levels before and after medication.

[0115] 1.8 Evaluation Indicators

[0116] 1.8.1 Traditional Chinese Medicine Syndrome Scoring

[0117] The TCM syndrome evaluation, based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," is determined by the patient's primary and secondary symptoms, as well as tongue and pulse diagnosis. The primary and secondary symptoms are scored as follows: 6, 4, 2, 0 points for severe symptoms, 3, 2, 1, 0 points for moderate symptoms, and 1 point for abnormal symptoms, depending on the severity of the patient's clinical symptoms (severe, moderate, mild, absent). The total TCM syndrome score ranges from 0 to 37 points, with higher scores indicating more severe clinical symptoms.

[0118] Traditional Chinese Medicine Syndrome Scoring: Quantifying and scoring symptoms.

[0119] Main symptoms:

[0120] ① Cough: No symptoms (0 points); intermittent cough during the day, which does not affect daily life or work (mild: 2 points); cough during the day or occasional cough at night, but still able to go to work (moderate: 4 points); frequent cough or paroxysmal cough during the day and night, affecting work and rest (severe: 6 points).

[0121] ② Sputum expectoration: No symptoms (0 points); 10-50ml of sputum expectoration per day and night (mild: 2 points); 50-100ml of sputum expectoration per day and night (moderate: 4 points); more than 100ml of sputum expectoration per day and night (severe: 6 points).

[0122] ③ Chest and rib pain: No symptoms (0 points); mild pain that does not affect daily life and can be relieved on its own (mild: 2 points); mild pain that lasts for a long time and requires painkillers (moderate: 4 points); frequent pain attacks that last for a long time and require painkillers (severe: 6 points).

[0123] Secondary symptoms:

[0124] ① Fatigue and weakness: No symptoms (0 points); obvious fatigue and lethargy after activity (mild: 1 point); feeling weak and tired after activity (moderate: 2 points); feeling obvious fatigue and lethargy even at rest (severe: 3 points).

[0125] ② Spontaneous sweating: No symptoms (none: 0 points); excessive sweating after strenuous activity (mild: 1 point); sweating with slight activity (moderate: 2 points); excessive sweating, sweating even when still (severe: 3 points).

[0126] ③ Poor appetite: No symptoms (0 points); Bland taste in food every day, food intake remains unchanged (mild: 1 point); Poor appetite, food intake reduced by about 1 / 3 (moderate: 2 points); Dislike of food, food intake reduced by 1 / 2 (severe: 3 points).

[0127] ④ Coughing up blood or blood in sputum: No symptoms (0 points); blood streaks in sputum (mild: 1 point); blood in sputum (moderate: 2 points); frequent hemoptysis (severe: 3 points).

[0128] 1.8.2 Changes in pulmonary nodule size: ① Complete disappearance: The target lesion disappears and remains so for at least 4 weeks; ② Partial shrinkage: The maximum diameter of the baseline lesion decreases by at least 30% and remains so for at least 4 weeks; ③ Disease progression: The maximum diameter of the baseline lesion increases by at least 20%; ④ Disease stability: The change in the maximum diameter of the baseline lesion falls between partial shrinkage and disease progression. Pulmonary nodule reduction rate = (Number of completely disappeared + Number of partially shrunken nodules) / Total number of pulmonary nodules × 100%.

[0129] 1.8.3 Tumor markers: Fasting peripheral antecubital venous blood (3 ml) was collected from patients at the time of admission, 3 months and 6 months of follow-up. The blood was centrifuged (3500 r / min, centrifugation radius 10 cm, centrifugation for 15 min) to obtain serum. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) were measured using a fully automated biochemical analyzer. The specific operation followed the equipment instruction manual and standard operating procedure.

[0130] 1.8.4 Drug safety: All patients in the treatment group underwent routine blood and urine tests and liver and kidney function tests at the time of consultation and at the end of the study. If any serious adverse reactions occurred during the treatment, they were dealt with promptly.

[0131] 1.9 Statistical Methods

[0132] SPSS 25.0 statistical software was used to analyze the research data. Quantitative data conforming to a normal distribution were analyzed using... Expressed using t-tests, count data are expressed as [n(%)], and dichotomous data or sample composition ratio data are expressed using χ². 2 For ordinal data, the rank-sum test was used, and p < 0.05 was considered statistically significant.

[0133] 2. Results

[0134] 2.1 Comparison of TCM syndrome scores between the two groups of patients

[0135] At 3 and 6 months of follow-up, the TCM syndrome scores of both groups were lower than at the time of consultation, and the treatment group was lower than the control group (P<0.05); at 6 months of follow-up, the TCM syndrome scores of both groups were lower than at 3 months, and the treatment group was lower than the control group (P<0.05), as shown in Table 2.

[0136] Table 2 Comparison of TCM syndrome scores between the two groups [ point]

[0137]

[0138] Note: Compared with the same group of patients at the time of visit. ◇ P<0.05; compared with the same group at 3 months follow-up, ● P<0.05.

[0139] 2.2 Comparison of changes in lung nodule size between the two groups of patients

[0140] At 3 and 6 months of follow-up, the reduction rate of pulmonary nodules in the treatment group was higher than that in the control group, and the overall percentage of pulmonary nodules that disappeared or shrank was higher in the treatment group than in the control group (P<0.05), as shown in Tables 3 and 4.

[0141] Table 3. Comparison of changes in the size and number of pulmonary nodules between the two groups during the 3-month follow-up period [n(%)]

[0142]

[0143]

[0144] Table 4. Comparison of changes in lung nodule size between the two groups at 6 months of follow-up [n(%)]

[0145]

[0146] 2.3 Comparison of tumor marker levels between the two groups of patients

[0147] At 3 and 6 months of follow-up, serum CEA and CYFRA21-1 levels in the treatment group were lower than at the time of admission, and the treatment group was lower than the control group (P<0.05). At 6 months of follow-up, serum CEA levels in both groups were lower than at 3 months, and the treatment group was lower than the control group (P<0.05); while there was no significant difference in serum CYFRA21-1 levels in the control group compared to 3 months (P>0.05), but the treatment group showed a statistically significant decrease compared to 3 months (P<0.05), and the treatment group was lower than the control group (P<0.05). See Tables 5 and 6.

[0148] Table 5 Comparison of serum CEA levels between the two groups [ ng / ml]

[0149]

[0150] Note: Compared with the same group of patients at the time of visit. ◇ P<0.05; compared with the same group at 3 months follow-up, ● P<0.05.

[0151] Table 6 Comparison of serum CYFRA21-1 levels between the two groups [ ng / ml]

[0152]

[0153] Note: Compared with the same group of patients at the time of visit. ◇ P<0.05; compared with the same group at 3 months follow-up, ● P<0.05.

[0154] 2.4 Medication Safety

[0155] During the treatment period, the blood and urine routine tests and liver and kidney function indicators of the patients in the treatment group were all within the normal range, and no adverse reactions were observed during the treatment.

[0156] 3. Conclusion

[0157] The pharmaceutical composition of this invention has good clinical efficacy in treating patients with pulmonary nodules of the Qi deficiency and blood stasis type. It can effectively reduce the patient's TCM syndrome score, increase the pulmonary nodule reduction rate, and reduce tumor marker levels. It also has high safety for clinical use.

[0158] Application Example 2: Clinical observation of the pharmaceutical composition of the present invention in patients with sub-centimeter pulmonary nodules of the Qi deficiency and blood stasis type.

[0159] 1. Materials and Methods

[0160] 1.1 Clinical Data

[0161] This study included 72 patients with sub-centimeter pulmonary nodules of Qi deficiency and blood stasis type admitted to the Dongchuan District Traditional Chinese Medicine Hospital of Kunming City from June 2022 to June 2023. Patients were divided into a treatment group and a control group, with 36 patients in each group. All patients in both groups signed informed consent forms and voluntarily participated in the study. The study protocol was approved by the hospital's medical ethics committee. A single-blind method was used to group the patients. At the end of the study, 2 patients in the control group voluntarily withdrew from the study, and 2 patients were lost to follow-up. The final effective cases were 36 in the treatment group and 32 in the control group. There were no statistically significant differences in baseline characteristics between the two groups (P>0.05). See Table 6 for details.

[0162] Table 6 Comparison of baseline data between the two groups of patients

[0163]

[0164] 1.2 Case Selection Criteria

[0165] 1.2.1 Diagnostic criteria

[0166] (1) Western medicine diagnostic criteria: Referring to the diagnostic criteria for pulmonary nodules in the Fleischner Society and the "Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)": Focal lesions in the lungs, with imaging manifestations of single or multiple nearly round, high-density shadows with a diameter ≤3cm. Based on different densities, they are divided into solid and subsolid nodules. Subsolid nodules include ground-glass nodules and mixed nodules. Among them, subcentimeter pulmonary nodules refer to pulmonary nodules with a diameter ≤1cm.

[0167] (2) Traditional Chinese Medicine Diagnostic Criteria: Referring to the relevant content of the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases" and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," and combined with the patient's clinical symptoms, the following TCM diagnostic criteria for patients with pulmonary nodules of Qi deficiency and blood stasis type were formulated: ① Patients with pulmonary nodules may have symptoms such as cough, sputum production, chest tightness, chest pain, and shortness of breath, but may also have no clinical manifestations. ② Manifestations of Qi deficiency and blood stasis syndrome: fatigue, spontaneous sweating, poor appetite, hemoptysis, or blood in sputum. If imaging supports the diagnosis of pulmonary nodules and meets the above symptoms of Qi deficiency and blood stasis syndrome ≥3, with or without the manifestation of ①, a diagnosis can be made by combining the tongue and pulse. Tongue and pulse appearance: dark tongue, or with ecchymosis, thickened sublingual veins, thin white or white and greasy tongue coating, teeth marks, and thin or hesitant pulse.

[0168] 1.2.2 Inclusion criteria:

[0169] (1) Those who meet the above-mentioned diagnostic criteria of traditional Chinese medicine and Western medicine.

[0170] (2) A single lung nodule with a diameter ≤1cm; or multiple lung nodules, the largest of which has a diameter ≤1cm and the number of lung nodules ≤5.

[0171] (3) Patients who have no indication for surgery and are advised to have regular follow-up after comprehensive assessment; or patients who have indications for surgery but refuse surgery and are required to have regular follow-up.

[0172] (4) Age 30-70 years old; gender not limited, patients or their families must give informed consent to participate in the clinical trial.

[0173] 1.2.3 Exclusion Criteria

[0174] (1) Those who do not meet the diagnostic criteria and / or inclusion criteria of Western medicine and traditional Chinese medicine.

[0175] (2) The nodule is highly likely to be malignant based on comprehensive assessment, and the clinical recommendation is to undergo surgical treatment and / or related follow-up treatment in the near future.

[0176] (3) Patients with serious chronic respiratory diseases (such as chronic obstructive pulmonary disease, bronchopulmonary tumors, bronchial asthma, silicosis, idiopathic pulmonary fibrosis, etc.).

[0177] (4) Patients with serious diseases of the cardiovascular, cerebrovascular, liver, kidney and blood systems, as well as mental illness.

[0178] (5) Individuals who have used inhaled, oral, or intravenous medications containing glucocorticoids within 6 months prior to enrollment.

[0179] (6) Women who are pregnant or breastfeeding, those with allergies, and those allergic to related drugs.

[0180] 1.2.4 Exit Criteria

[0181] Cases in which drug treatment is suspended or terminated during the study, or cases lost to follow-up during the study period, are considered as withdrawn cases.

[0182] 1.3 Treatment Methods

[0183] Treatment group: The pills prepared according to the method described in Example 8 were administered orally half an hour after meals, twice a day, one packet each time, each packet containing 8g.

[0184] Control group: those who refused medication but were willing to undergo follow-up.

[0185] Both groups of patients were followed up at enrollment and 3 months after enrollment.

[0186] 1.4 Observation Indicators

[0187] 1.4.1 Diameter of a single pulmonary nodule or the largest of multiple pulmonary nodules: The diameter of pulmonary nodules in lung CT scans before treatment and at the end of 3 months after treatment were compared between the two groups of patients.

[0188] 1.4.2 Lung function indicators: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV1 / FVC%) were measured and compared between the two groups of patients before treatment and at the end of 3 months of treatment.

[0189] 1.4.3 Immune and Inflammatory Markers: Fasting peripheral venous blood samples were collected from both groups of patients before treatment and at the end of 3 months of treatment. Serum levels of tumor necrosis factor-α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 were detected using enzyme-linked immunosorbent assay (ELISA). Serum levels of immunoglobulin G (IgG), IgA, and IgM were detected using immunoturbidimetry. Peripheral blood CD4 levels were detected using flow cytometry. + T lymphocyte percentage, CD8+ T lymphocyte percentage, CD4 + / CD8 + The T lymphocyte ratio was measured.

[0190] 1.4.4 Medication safety: All patients in the treatment group underwent routine blood and urine tests and liver and kidney function tests at the time of consultation and at the end of the study. If any serious adverse reactions occurred during the treatment, they were dealt with promptly.

[0191] 1.5 Statistical Methods

[0192] Data were analyzed using SPSS 22.0. Normally distributed data are expressed as (x±s), and non-normally distributed data are expressed as Median (P25, P75). For continuous data, the Kolmogorov-Smirnov method was used to test whether the variables followed a normal distribution; paired-samples t-tests were used for within-group comparisons, and independent-samples t-tests were used for between-group comparisons. For non-normally distributed data, the Wilcoxon test was used for within-group comparisons, and the Mann-Whitney U test was used for between-group comparisons. Count data are expressed as n (%) and expressed as χ². 2 Test. P < 0.05 is considered statistically significant.

[0193] 2. Results

[0194] 2.1 Comparison of pulmonary nodule diameter before and after treatment in the two groups of patients

[0195] Before treatment, there was no significant difference in the diameter of pulmonary nodules between the two groups (P>0.05). After 3 months of treatment, the diameter of pulmonary nodules in the treatment group decreased significantly compared with that before treatment (P<0.05); while there was no significant difference in the diameter of pulmonary nodules in the control group compared with that before treatment (P>0.05); and the diameter of pulmonary nodules in the treatment group was significantly smaller than that in the control group (P<0.05). See Table 7 for details.

[0196] Table 7 Comparison of lung nodule diameters before and after treatment in the two groups of patients ( mm)

[0197]

[0198] 2.2 Comparison of pulmonary function indicators before and after treatment in the two groups of patients

[0199] Before treatment, there were no significant differences in pulmonary function indicators between the treatment group and the control group (P>0.05). After 3 months of treatment, there were no significant differences in pulmonary function indicators between the control group and before treatment (P>0.05); however, the pulmonary function indicators of the treatment group were significantly higher after treatment than before treatment (P<0.05), and the treatment group's indicators were significantly higher than those of the control group (P<0.05). See Table 8 for details.

[0200] Table 8 Comparison of pulmonary function before and after treatment in the two groups of patients

[0201]

[0202] 2.3 Comparison of immune inflammatory markers before and after treatment in the two groups of patients

[0203] Before treatment, there were no significant differences in immune inflammatory markers between the treatment group and the control group (P>0.05). Three months after treatment, there were no significant differences in immune inflammatory markers between the control group and before treatment (P>0.05). In the treatment group, serum IL-10, IgG, IgA, IgM levels, peripheral blood CD4+ T lymphocyte ratio, and CD4+ / CD8+ T lymphocyte ratio were all higher than before treatment, while serum TNF-α, IL-1β, IL-6 levels, and peripheral blood CD8+ T lymphocyte ratio were all lower than before treatment, with significant differences (P<0.05). Furthermore, the treatment group had significantly higher serum IL-10, IgG, IgA, IgM levels, peripheral blood CD4+ T lymphocyte ratio, and CD4+ / CD8+ T lymphocyte ratio than the control group, while serum TNF-α, IL-1β, IL-6 levels, and peripheral blood CD8+ T lymphocyte ratio were significantly lower than the control group, with all differences being statistically significant (P<0.05). See Table 9 for details.

[0204] Table 9 Comparison of immune inflammatory markers between the two groups of patients before and after treatment

[0205]

[0206] 2.4 Medication Safety

[0207] During the treatment period, the blood and urine routine tests and liver and kidney function indicators of the patients in the treatment group were all within the normal range, and no adverse reactions were observed during the treatment.

[0208] 3. Conclusion: Applying the pharmaceutical composition described in Example 1 to the treatment of patients with sub-centimeter pulmonary nodules of the Qi deficiency and blood stasis type can shrink pulmonary nodules, reduce inflammatory response, improve immune imbalance and enhance lung function.

[0209] The specific embodiments described in this application are illustrated and are quite detailed, but they should not be construed as...

[0210] This should be understood as a limitation on the scope of protection of this application. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the technical solution of this application, and these all fall within the scope of protection of this application.

Claims

1. A pharmaceutical composition for treating sub-centimeter pulmonary nodules of the qi deficiency and blood stasis type, characterized in that, By weight, it consists of the following components: 10-30 parts of Codonopsis pilosula, 5-20 parts of Clematis armandii, 10-20 parts of Panax quinquefolius, 5-15 parts of Zingiber officinale, and 5-15 parts of Panax quinquefolius.

2. A pharmaceutical composition for treating sub-centimeter pulmonary nodules of the qi deficiency and blood stasis type, characterized in that, By weight, it consists of the following components: 12-28 parts of Codonopsis pilosula, 7-18 parts of Clematis armandii, 12-18 parts of Panax quinquefolius, 7-18 parts of Zingiber officinale, and 7-18 parts of Panax quinquefolius.

3. The pharmaceutical composition according to claim 2, which invigorates qi, promotes blood circulation, and dissipates nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, is characterized in that... By weight, it consists of the following components: 15-25 parts of Codonopsis pilosula, 8-16 parts of Clematis armandii, 13-18 parts of Panax quinquefolius, 10-15 parts of Zingiber officinale, and 10-15 parts of Panax quinquefolius.

4. A pharmaceutical composition preparation for treating sub-centimeter pulmonary nodules of the qi deficiency and blood stasis type, characterized in that, The pharmaceutically acceptable excipients required for the preparation of an alcoholic extract and a aqueous extract of a pharmaceutical composition for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type as described in any one of claims 1-3.

5. The pharmaceutical composition preparation according to claim 4, which invigorates qi, promotes blood circulation, and dissipates nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, is characterized in that... The preparation is a capsule or a pill.

6. The pharmaceutical composition preparation according to claim 5, which invigorates qi, promotes blood circulation, and dissipates nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, is characterized in that... The capsules are prepared using the following method: Step (1): An alcohol extract of a drug composition for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type was obtained by ethanol extraction. Water was added to the residue after alcohol extraction to obtain an aqueous extract. Step (2): The alcohol extract and water extract are concentrated separately and then mixed, dried and pulverized to obtain a dry extract powder; Step (3): Add excipients to the dry powder prepared in step (2) and mix well to obtain a mixture; Step (4): Add 60%-80% ethanol to the mixture to obtain wet granules, dry them at 55-75℃ to obtain dry granules, add lubricant, mix thoroughly, and fill into empty capsule shells to obtain a drug composition capsule for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type.

7. The pharmaceutical composition preparation according to claim 6, which invigorates qi, promotes blood circulation, and dissipates nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, is characterized in that... The excipients mentioned in step (3) include starch, lactose and microcrystalline cellulose. The mass ratio of dry powder, starch, lactose and microcrystalline cellulose is 1:0.1-0.2:0.1-0.2:0.1-0.

2. The lubricant mentioned in step (4) is selected from at least one of silicon dioxide and magnesium stearate, and the total amount used is 0.6%-1% of the dry particles.

8. A pharmaceutical composition preparation according to claim 5, which invigorates qi, promotes blood circulation, and dissipates nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, characterized in that, The pills are prepared using the following method: Step (1): An alcohol extract of a drug composition for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type was obtained by ethanol extraction. Water was added to the residue after alcohol extraction to obtain an aqueous extract. Step (2): The alcohol extract and water extract are concentrated separately and then mixed, dried and pulverized to obtain a dry extract powder; Step (3): Add disintegrant to the dry powder prepared in step (2) and mix well to obtain a mixture; Step (4): Add 60%-80% ethanol to the mixture prepared in step (3) to make micro-pills, and dry them to obtain a pharmaceutical composition pill for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type.

9. The use of the pharmaceutical composition for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type as described in any one of claims 1-3 in the preparation of a medicament for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type.

10. The use of the pharmaceutical composition formulation according to any one of claims 5-8, which invigorates qi, promotes blood circulation, and disperses nodules for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type, in the preparation of a medicament for treating sub-centimeter pulmonary nodules of qi deficiency and blood stasis type.

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