Traditional Chinese medicine composition for treating pulmonary nodule as well as preparation method and application thereof and traditional Chinese medicine granules

Abstract

The invention relates to a traditional Chinese medicine composition for treating pulmonary nodules, a preparation method and application thereof and traditional Chinese medicine granules, and relates to the technical field of traditional Chinese medicine, the preparation method comprises the following steps: mixing and crushing ephedra, mangnolia officinalis, platycodon grandiflorum, scalded semen armeniacae amarae, fructus aurantii, wine-processed ligusticum wallichii, curcuma zedoary, fried mustard seeds and bryozoatum to obtain a first mixture; performing corona discharge treatment on the first mixture to obtain a second mixture; and adding the second mixture into water, carrying out reduced pressure reflux extraction, and concentrating and drying the obtained water extract to obtain the traditional Chinese medicine composition for treating pulmonary nodules. The traditional Chinese medicine composition for treating pulmonary nodules is prepared by selecting proper types of traditional Chinese medicines as raw materials and combining a corona discharge process and a reduced pressure reflux extraction process. Animal experiment results show that the traditional Chinese medicine composition has a remarkable inhibition effect on pulmonary nodule swelling of modeling rats, a new means is provided for treatment of pulmonary nodule patients, and the traditional Chinese medicine composition has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of thermal insulation materials, and in particular to a traditional Chinese medicine composition for treating pulmonary nodules, a preparation method and application thereof, and traditional Chinese medicine granules. Background Art

[0002] Pulmonary nodules, as a type of small nodular lesion that appears in the lungs, have always attracted much attention in the medical community for their clinical diagnosis and treatment. The causes of pulmonary nodules are diverse and may be related to inflammation, infection, tumors (including benign and malignant tumors), and other factors. This lesion may not only affect the patient's respiratory function, but may also have a serious impact on the patient's mental health and quality of life. In some cases, pulmonary nodules may even be an early manifestation of lung cancer, posing a serious threat to the patient's life safety.

[0003] At present, Western medicine mainly uses surgery, radiotherapy, chemotherapy and other methods to treat lung nodules. Although surgery can directly remove nodules, it is more difficult to perform for some nodules that are deeper or more numerous, and may cause greater trauma to the patient. Radiotherapy and chemotherapy may be accompanied by greater side effects, such as nausea, vomiting, and hair loss. For some types of lung nodules, the treatment effect is not ideal and may even lead to worsening of the condition.

[0004] As a treasure of traditional Chinese medicine, Chinese medicine has a long history and rich clinical experience. In the treatment of pulmonary nodules, Chinese medicine has attracted widespread attention for its unique efficacy and less side effects. Chinese medicine has potential value in the treatment of pulmonary nodules by adjusting the balance of yin and yang in the human body, improving the circulation of qi and blood, and enhancing the body's immunity. However, the preparation methods of traditional Chinese medicine often have problems such as low extraction efficiency, large loss of effective ingredients, and poor therapeutic effect, which affect the efficacy and stability of Chinese medicine and limit its application in the treatment of pulmonary nodules. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a traditional Chinese medicine composition for treating pulmonary nodules, a preparation method and application thereof, and traditional Chinese medicine granules.

[0006] In a first aspect, the present invention provides a method for preparing a Chinese medicine composition for treating pulmonary nodules, the preparation method comprising the following steps:

[0007] Mix and grind ephedra, Magnolia officinalis, Platycodon grandiflorum, stewed bitter almond, Fructus Aurantii Immaturus, Rhizoma Chuanxiong, Curcuma zedoariae, stir-fried mustard seeds and pumice to obtain a first mixed material;

[0008] subjecting the first mixed material to a corona discharge treatment to obtain a second mixed material;

[0009] The second mixed material is added into water for decompression reflux extraction, and then the obtained water extract is concentrated and dried to obtain the traditional Chinese medicine composition for treating pulmonary nodules;

[0010] The working condition parameters of the reduced pressure reflux extraction include: pressure of 20 kPa to 35 kPa and temperature of 65° C. to 75° C.

[0011] Furthermore, the Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0012] 8-12 parts of ephedra, 10-20 parts of magnolia bark, 10-20 parts of platycodon, 10-20 parts of stewed bitter almonds, 8-12 parts of bitter orange peel, 18-24 parts of wine-cooked chuanxiong, 18-24 parts of zedoaria, 18-24 parts of stir-fried mustard seeds and 25-35 parts of pumice.

[0013] Furthermore, the Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0014] 10 parts of Ephedra, 15 parts of Magnolia officinalis, 15 parts of Platycodon grandiflorum, 15 parts of stewed bitter almonds, 10 parts of Fructus Aurantii Immaturus, 20 parts of wine-cooked Rhizoma Chuanxiong, 20 parts of Curcuma, 20 parts of stir-fried mustard seeds and 30 parts of pumice.

[0015] Furthermore, the working condition parameters of the reduced pressure reflux extraction include: pressure of 28 kPa, temperature of 70° C., time of 1 to 2 hours, number of times of 1 to 3 times, and the added weight of water is 5 to 10 times of the second mixture.

[0016] Furthermore, the step of subjecting the first mixed material to corona discharge treatment to obtain the second mixed material comprises the following process:

[0017] 3~8kV / m 2 The first mixture is subjected to corona discharge treatment for 20 to 40 seconds under the following conditions to obtain the second mixture.

[0018] In a second aspect, the present invention provides a traditional Chinese medicine composition for treating pulmonary nodules, wherein the traditional Chinese medicine composition for treating pulmonary nodules is prepared by the preparation method of the traditional Chinese medicine composition for treating pulmonary nodules described in any one of the first aspects.

[0019] In a third aspect, the present invention provides a use of a traditional Chinese medicine composition for treating pulmonary nodules as described in any one of the second aspects in the preparation of a medicine for treating pulmonary nodules.

[0020] Furthermore, the dosage form of the drug includes tablets, capsules, decoctions or granules.

[0021] In a fourth aspect, the present invention provides a Chinese medicine granule, which comprises the following raw materials in parts by weight:

[0022] 40-50 parts of the Chinese medicine composition for treating pulmonary nodules according to any one of the second aspects and 110-125 parts of pharmaceutical excipients;

[0023] The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of (6-9):(2-5):(0.8-1.3).

[0024] Furthermore, the filler includes at least one of lactose, mannitol and β-cyclodextrin; the disintegrant includes at least one of sodium carboxymethyl starch and microcrystalline cellulose; and the wetting agent includes ethanol with a volume fraction of 80 to 90%.

[0025] The above technical solution provided by the embodiment of the present invention has at least the following advantages compared with the prior art:

[0026] The embodiment of the present invention provides a Chinese medicine composition for treating lung nodules, a preparation method and application thereof, and Chinese medicine granules. The present invention selects appropriate types of Chinese medicine as raw materials, and uses them in combination through a corona discharge process and a decompression reflux extraction process to prepare a Chinese medicine composition for treating lung nodules. The results of animal experiments show that the Chinese medicine composition has a significant inhibitory effect on the swelling of lung nodules in model rats, providing a new means for the treatment of patients with lung nodules, and has broad application prospects and important clinical significance. Specifically:

[0027] 1. Improve extraction efficiency: Corona discharge treatment can destroy the cell walls of Chinese medicinal materials and improve their surface dissolution behavior, making the effective ingredients of Chinese medicine easier to dissolve and extract; while the reduced pressure reflux extraction process can achieve efficient extraction at a lower and more suitable temperature. The combination of the two can greatly improve the extraction efficiency of Chinese medicine ingredients.

[0028] 2. Improve the efficacy of drugs: Corona discharge treatment can reduce the loss of components caused by cell wall obstruction. At the same time, the decompression reflux extraction process under appropriate parameters can not only reduce the degradation of heat-sensitive components at a lower temperature, but also extract the target active ingredients more specifically. The combination of the two can retain the active ingredients of traditional Chinese medicine to the greatest extent, thereby improving the efficacy of drugs and quality stability.

[0029] In summary, the present invention selects ephedra, magnolia bark, platycodon, stewed bitter almond, bitter orange peel, wine chuanxiong, zedoaria, stir-fried mustard seeds and pumice as raw materials, and uses a corona discharge process and a reduced pressure reflux extraction process under specific parameters in combination, thereby effectively overcoming the problems of low efficiency, large loss of effective ingredients and poor therapeutic effect existing in the extraction process of traditional Chinese medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0032] Figure 1 A schematic flow chart of a method for preparing a traditional Chinese medicine composition for treating pulmonary nodules provided in an embodiment of the present invention. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0035] In a first aspect, the present invention provides a method for preparing a Chinese medicine composition for treating pulmonary nodules, such as Figure 1 As shown, the preparation method comprises the following steps:

[0036] Mix and grind ephedra, Magnolia officinalis, Platycodon grandiflorum, stewed bitter almond, Fructus Aurantii Immaturus, Rhizoma Chuanxiong, Curcuma zedoariae, stir-fried mustard seeds and pumice to obtain a first mixed material;

[0037] subjecting the first mixed material to a corona discharge treatment to obtain a second mixed material;

[0038] The second mixed material is added into water for decompression reflux extraction, and then the obtained water extract is concentrated and dried to obtain the traditional Chinese medicine composition for treating pulmonary nodules;

[0039] The working condition parameters of the reduced pressure reflux extraction include: pressure of 20 kPa to 35 kPa and temperature of 65° C. to 75° C.

[0040] The embodiment of the present invention provides a method for preparing a Chinese medicine composition for treating pulmonary nodules. The present invention selects appropriate types of Chinese medicine as raw materials, and uses them in combination with a corona discharge process and a decompression reflux extraction process to prepare a Chinese medicine composition for treating pulmonary nodules. The results of animal experiments show that the Chinese medicine composition has a significant inhibitory effect on the swelling of pulmonary nodules in model rats, providing a new means for the treatment of patients with pulmonary nodules, and has broad application prospects and important clinical significance.

[0041] The ephedra in the present invention is the dried herbaceous stem of Ephedra sinica Stapf, Ephedra intermedia Schrenket C.A. Mey. or Ephedra equisetina Bge. of the Ephedraceae family. Nature and flavor and meridians: pungent, slightly bitter, warm. It enters the lung and bladder meridians; functions and indications: sweating and dispelling cold, promoting lung function and relieving asthma, promoting diuresis and reducing swelling. It is used for colds caused by wind and cold, chest tightness, cough and wheezing, edema caused by wind and water, and honey ephedra moistens the lungs and relieves cough. It is mostly used for the symptoms of the exterior syndrome being resolved, asthma and cough.

[0042] The Magnolia officinalis in the present invention is the dried bark, root bark and branch bark of Magnolia officinalis Rehd. et Wils. or Magnolia officinalis Rehd. et Wils. var. biloba Rehd. et Wils. of the Magnoliaceae family. Nature and flavor and meridians: bitter, pungent, warm. It enters the spleen, stomach, lung and large intestine meridians. Functions and indications: drying dampness and eliminating phlegm, lowering qi and eliminating fullness. It is used for dampness stagnation, abdominal distension, vomiting and diarrhea, food stagnation and qi stagnation, abdominal distension and constipation, phlegm and cough.

[0043] The Platycodon grandiflorum in the present invention is the dried root of Platycodongrandiflorum (Jacq.) A.DC. of the Campanulaceae family. It is excavated in spring and autumn, washed, the fibrous roots are removed, the outer skin is peeled off while fresh or not, and dried. Nature and flavor and meridians: bitter, pungent, flat. It enters the lung meridian. Functions and indications: clearing the lungs, relieving sore throat, removing phlegm, and draining pus. It is used for cough with a lot of phlegm, chest tightness, sore throat, hoarseness, and vomiting pus due to lung abscess.

[0044] The stewed bitter almonds in the present invention are obtained by processing bitter almonds as raw materials, and can be directly prepared by using commercial products or according to existing processing methods. Specifically, the processing method of stewed bitter almonds generally includes the following steps:

[0045] Raw material selection: Choose ripe, plump, insect-free and mildew-free bitter almonds as raw materials.

[0046] Cleaning: Wash the bitter almonds with clean water to remove dust and impurities on the surface.

[0047] Stewing: Put the washed bitter almonds into boiling water and cook for 60 minutes, then take them out and let them cool. The purpose of stewing is to remove some of the bitter and toxic components in the bitter almonds, and at the same time make them easier to decoct and take.

[0048] Drying: Dry or bake the steamed bitter almonds for easy storage and use.

[0049] The Citrus aurantium in the present invention is the dried immature fruit of Citrus aurantium L. and its cultivars of the Rutaceae family. Nature and flavor and meridians: bitter, pungent, sour, slightly cold. It enters the spleen and stomach meridians. Functions and indications: regulating qi and relieving fullness, relieving stagnation and relieving swelling. It is used for qi stagnation in the chest and flanks, fullness and pain, indigestion, phlegm and fluid retention, and sagging of internal organs.

[0050] The wine-processed Chuanxiong in the present invention is obtained by processing Chuanxiong with wine, and can be directly prepared by using commercial products or according to existing processing methods. Specifically, the processing method of wine-processed Chuanxiong generally includes the following steps: after washing and slicing Chuanxiong, soaking in yellow wine for 2 days, and finally drying to obtain wine-processed Chuanxiong.

[0051] The zedoaria in the present invention is the dried rhizome of the zingiberaceae plant Curcumaphaeocaulis Val., Curcuma wangsiensis S.G.Leeet C.F.Liang or Curcuma wenyujin YH Chenet C.Ling. Nature and flavor and meridians: pungent, bitter, warm. It enters the liver and spleen meridians. Functions and indications: promoting qi and removing blood, eliminating accumulation and relieving pain. It is used for lumps and masses, blood stasis and amenorrhea, chest pain and heartache, and food accumulation and distension and pain.

[0052] The stir-fried mustard in the present invention is prepared by stir-frying mustard (dried mature seeds of white mustard or mustard of the cruciferous plant) as a raw material, and can be directly prepared by using a commercial product or according to an existing processing method. Specifically, the processing method of stir-fried mustard generally comprises the following steps: placing clean mustard in a stir-frying container, heating with a slow fire, and taking out when stir-frying to a dark yellow color with a spicy smell, and then crushing it after cooling for use.

[0053] The pumice stone in the present invention is the skeleton of the cysticercus lizard, the tumor lizard and the like of the Porifera family, and has the functions of clearing lung fire, resolving old phlegm, softening hard masses, and relieving stranguria. It can treat phlegm-heat cough, old phlegm accumulation, gonorrhea, hernia, sores, eye opacity, etc., and commercial products can be directly used.

[0054] In some specific embodiments, the Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0055] 8-12 parts of ephedra, 10-20 parts of magnolia bark, 10-20 parts of platycodon, 10-20 parts of stewed bitter almonds, 8-12 parts of bitter orange peel, 18-24 parts of wine-cooked chuanxiong, 18-24 parts of zedoaria, 18-24 parts of stir-fried mustard seeds and 25-35 parts of pumice.

[0056] In some specific embodiments, the Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0057] 10 parts of Ephedra, 15 parts of Magnolia officinalis, 15 parts of Platycodon grandiflorum, 15 parts of stewed bitter almonds, 10 parts of Fructus Aurantii Immaturus, 20 parts of wine-cooked Rhizoma Chuanxiong, 20 parts of Curcuma zedoariae, 20 parts of stir-fried mustard seeds and 30 parts of pumice.

[0058] In some specific embodiments, the working condition parameters of the reduced pressure reflux extraction include: pressure of 28 kPa, temperature of 70°C, time of 1 to 2 hours, number of times of 1 to 3 times, and the added weight of water is 5 to 10 times of the second mixture.

[0059] In some specific embodiments, the step of subjecting the first mixed material to corona discharge treatment to obtain the second mixed material comprises the following process:

[0060] 3~8kV / m 2 The first mixture is subjected to corona discharge treatment for 20 to 40 seconds under the following conditions to obtain the second mixture.

[0061] In a second aspect, based on the same inventive concept, the present invention provides a traditional Chinese medicine composition for treating lung nodules, wherein the traditional Chinese medicine composition for treating lung nodules is prepared by the preparation method of the traditional Chinese medicine composition for treating lung nodules described in any one of the first aspects.

[0062] In a third aspect, based on the same inventive concept, the present invention provides a use of a traditional Chinese medicine composition for treating pulmonary nodules as described in any one of the second aspects in the preparation of a medicine for treating pulmonary nodules.

[0063] In some specific embodiments, the dosage form of the drug includes tablets, capsules, decoctions or granules.

[0064] In a fourth aspect, based on the same inventive concept, the present invention provides a Chinese medicine granule, which comprises the following raw materials in parts by weight:

[0065] 40-50 parts of the Chinese medicine composition for treating pulmonary nodules according to any one of the second aspects and 110-125 parts of pharmaceutical excipients;

[0066] The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of (6-9):(2-5):(0.8-1.3).

[0067] In some specific embodiments, the filler includes at least one of lactose, mannitol and β-cyclodextrin, preferably β-cyclodextrin; the disintegrant includes at least one of sodium carboxymethyl starch and microcrystalline cellulose, preferably sodium carboxymethyl starch; the wetting agent includes ethanol with a volume fraction of 80 to 90%, preferably ethanol with a volume fraction of 85%.

[0068] In some specific embodiments, the method for preparing Chinese medicine granules comprises the following steps:

[0069] The Chinese medicine composition, filler and disintegrant are crushed separately, passed through a 100-mesh sieve, and set aside;

[0070] The crushed and sieved Chinese medicine composition, filler and disintegrant are placed in a high-speed mixing granulator for mixing and stirring, and a wetting agent is added for mixing and stirring for 10 minutes. After mixing evenly, granulation is performed through a 14-mesh sieve to obtain wet granules;

[0071] The wet granules were transferred into a horizontal fluidized bed dryer, the inlet air temperature was set to 115°C, the outlet air temperature was set to 85°C, the material temperature was 60°C and dried for 30 minutes, the material was discharged to obtain dry granules, and the dry granules were sieved through a 12-40 mesh sieve to obtain the traditional Chinese medicine granules.

[0072] It should be noted that the Chinese medicine composition for treating pulmonary nodules provided in the embodiments of the present invention, its preparation method and application, and the components and raw materials involved in the Chinese medicine granules, unless otherwise specified or specified, can directly use commercially available products or use existing public preparation methods to make them themselves; at the same time, the steps and parameters involved, unless otherwise specified or specified, can be carried out according to the processing technology of existing Chinese medicine compositions or directly using existing equipment, and the present invention document will not describe them one by one.

[0073] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples that do not specify specific conditions are usually measured according to national standards. If there is no corresponding national standard, then the conditions recommended by the manufacturer are followed.

[0074] Example 1

[0075] This example provides a Chinese medicine composition for treating pulmonary nodules. The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0076] 10 parts of Ephedra, 15 parts of Magnolia officinalis, 15 parts of Platycodon grandiflorum, 15 parts of stewed bitter almonds, 10 parts of Fructus Aurantii Immaturus, 20 parts of wine-cooked Rhizoma Chuanxiong, 20 parts of Curcuma, 20 parts of stir-fried mustard seeds and 30 parts of pumice.

[0077] The preparation method of the above-mentioned Chinese medicine composition for treating pulmonary nodules comprises the following steps:

[0078] Step (1): mixing and grinding ephedra, Magnolia officinalis, Platycodon grandiflorum, stewed bitter almond, Citrus aurantium, wine-cooked Chuanxiong, Curcuma zedoaria, stir-fried mustard seeds and pumice to obtain a first mixed material;

[0079] Step (2): At 6 kV / m 2 The first mixed material obtained in step (1) is subjected to corona discharge treatment for 30 seconds under the following conditions to obtain the second mixed material;

[0080] Step (3): adding the second mixed material obtained in step (2) into water for vacuum reflux extraction, wherein the weight of the water added is 8 times that of the second mixed material, the pressure of the vacuum reflux extraction is 28 kPa, the temperature of the vacuum reflux extraction is 70°C, the time of the vacuum reflux extraction is 1.5 h, and the number of vacuum reflux extractions is 2 times; then concentrating the obtained water extract to a clear paste with a relative density of 1.25 (80°C), and drying to obtain the Chinese medicine composition for treating lung nodules.

[0081] Example 2

[0082] This example provides a Chinese medicine composition for treating pulmonary nodules. The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0083] 8 parts of Ephedra, 10 parts of Magnolia officinalis, 10 parts of Platycodon grandiflorum, 10 parts of stewed bitter almonds, 8 parts of Fructus Aurantii Immaturus, 18 parts of wine-cooked Rhizoma Chuanxiong, 18 parts of Curcuma, 18 parts of stir-fried mustard seeds and 25 parts of pumice.

[0084] The preparation method of the above-mentioned Chinese medicine composition for treating pulmonary nodules comprises the following steps:

[0085] Step (1): mixing and grinding ephedra, magnolia bark, platycodon grandiflorum, stewed bitter almond, fructus aurantii, wine-cooked chuanxiong, zedoaria, fried mustard seeds and pumice to obtain a first mixed material;

[0086] Step (2): At 3kV / m 2 The first mixed material obtained in step (1) is subjected to corona discharge treatment for 40 seconds under the following conditions to obtain the second mixed material;

[0087] Step (3): adding the second mixed material obtained in step (2) into water for vacuum reflux extraction, wherein the weight of the water added is 5 times that of the second mixed material, the pressure of the vacuum reflux extraction is 20 kPa, the temperature of the vacuum reflux extraction is 65°C, the time of the vacuum reflux extraction is 1.5 h, and the number of vacuum reflux extractions is 2 times; then concentrating the obtained water extract to a clear paste with a relative density of 1.25 (80°C), drying, and obtaining the Chinese medicine composition for treating lung nodules.

[0088] Example 3

[0089] This example provides a Chinese medicine composition for treating pulmonary nodules. The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0090] 12 parts of Ephedra, 20 parts of Magnolia officinalis, 20 parts of Platycodon grandiflorum, 20 parts of stewed bitter almonds, 12 parts of Fructus Aurantii Immaturus, 24 parts of wine-cooked Rhizoma Chuanxiong, 24 parts of Curcuma zedoariae, 24 parts of stir-fried mustard seeds and 35 parts of pumice.

[0091] The preparation method of the above-mentioned Chinese medicine composition for treating pulmonary nodules comprises the following steps:

[0092] Step (1): mixing and grinding ephedra, magnolia bark, platycodon grandiflorum, stewed bitter almond, fructus aurantii, wine-cooked chuanxiong, zedoaria, fried mustard seeds and pumice to obtain a first mixed material;

[0093] Step (2): At 8kV / m 2 The first mixed material obtained in step (1) is subjected to corona discharge treatment for 20 seconds under the following conditions to obtain the second mixed material;

[0094] Step (3): adding the second mixed material obtained in step (2) into water for vacuum reflux extraction, wherein the weight of the water added is 5 times that of the second mixed material, the pressure of the vacuum reflux extraction is 35 kPa, the temperature of the vacuum reflux extraction is 75°C, the time of the vacuum reflux extraction is 1.5 h, and the number of vacuum reflux extractions is 2 times. The obtained water extract is then concentrated to a clear paste with a relative density of 1.25 (80°C), and dried to obtain the Chinese medicine composition for treating lung nodules.

[0095] Example 4

[0096] This example provides a Chinese medicine granule, which includes the following raw materials in parts by weight:

[0097] 45 parts of the Chinese medicine composition for treating pulmonary nodules obtained in Example 1 and 120 parts of pharmaceutical excipients;

[0098] The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of 8:3:1, the filler is beta-cyclodextrin, the disintegrant is sodium carboxymethyl starch, and the wetting agent is ethanol with a volume fraction of 85%.

[0099] The preparation method of the above-mentioned Chinese medicine granules comprises the following steps:

[0100] The Chinese medicine composition, filler and disintegrant are crushed separately, passed through a 100-mesh sieve, and set aside;

[0101] The crushed and sieved Chinese medicine composition, filler and disintegrant are placed in a high-speed mixing granulator for mixing and stirring, and a wetting agent is added for mixing and stirring for 10 minutes. After mixing evenly, granulation is performed through a 14-mesh sieve to obtain wet granules;

[0102] The wet granules were transferred into a horizontal fluidized bed dryer, the inlet air temperature was set to 115°C, the outlet air temperature was set to 85°C, the material temperature was 60°C and dried for 30 minutes, the material was discharged to obtain dry granules, and the dry granules were sieved through a 12-40 mesh sieve to obtain the traditional Chinese medicine granules.

[0103] Example 5

[0104] This example provides a Chinese medicine granule, which includes the following raw materials in parts by weight:

[0105] 40 parts of the Chinese medicine composition for treating pulmonary nodules obtained in Example 2 and 110 parts of pharmaceutical excipients;

[0106] The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of 6:2:0.8, the filler is beta-cyclodextrin, the disintegrant is sodium carboxymethyl starch, and the wetting agent is ethanol with a volume fraction of 80%.

[0107] The preparation method of the above-mentioned Chinese medicine granules is the same as that of Example 4.

[0108] Example 6

[0109] This example provides a Chinese medicine granule, which includes the following raw materials in parts by weight:

[0110] 50 parts of the Chinese medicine composition for treating pulmonary nodules obtained in Example 3 and 125 parts of pharmaceutical excipients;

[0111] The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of 9:5:1.3, the filler is beta-cyclodextrin, the disintegrant is sodium carboxymethyl starch, and the wetting agent is ethanol with a volume fraction of 90%.

[0112] The preparation method of the above-mentioned Chinese medicine granules is the same as that of Example 4.

[0113] Comparative Example 1

[0114] This example provides a Chinese medicine composition for treating pulmonary nodules and a preparation method thereof, which is different from Example 1 only in that no corona discharge treatment is performed in the preparation method; the remaining steps and parameters are the same.

[0115] This example provides a Chinese medicine composition for treating pulmonary nodules. The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight:

[0116] 10 parts of Ephedra, 15 parts of Magnolia officinalis, 15 parts of Platycodon grandiflorum, 15 parts of stewed bitter almonds, 10 parts of Fructus Aurantii Immaturus, 20 parts of wine-cooked Rhizoma Chuanxiong, 20 parts of Curcuma zedoariae, 20 parts of stir-fried mustard seeds and 30 parts of pumice.

[0117] The preparation method of the above-mentioned Chinese medicine composition for treating pulmonary nodules comprises the following steps:

[0118] Step (1): mixing and grinding ephedra, magnolia bark, platycodon grandiflorum, stewed bitter almond, fructus aurantii, wine-cooked chuanxiong, zedoaria, fried mustard seeds and pumice to obtain a first mixed material;

[0119] Step (2): adding the first mixture obtained in step (1) into water for vacuum reflux extraction, wherein the weight of the water added is 8 times that of the first mixture, the pressure of the vacuum reflux extraction is 28 kPa, the temperature of the vacuum reflux extraction is 70°C, the time of the vacuum reflux extraction is 1.5 h, and the number of vacuum reflux extractions is 2 times; then concentrating the obtained water extract to a clear paste with a relative density of 1.25 (80°C), and drying to obtain the Chinese medicine composition for treating lung nodules.

[0120] Comparative Example 2

[0121] This example provides a Chinese medicine composition for treating pulmonary nodules and a preparation method thereof, which is different from Example 1 only in that the pressure of the reduced pressure reflux extraction in the preparation method is 5 kPa, and the temperature of the reduced pressure reflux extraction is 38°C; the remaining steps and parameters are the same.

[0122] Test Example 1

[0123] In this example, the efficacy of the Chinese medicine composition for treating pulmonary nodules obtained in the above Examples 1 to 3 and Comparative Examples 1 to 2 was tested.

[0124] The test method is as follows:

[0125] 1. Experimental animals and groups:

[0126] A total of 70 healthy SD male rats were selected and randomly divided into 7 groups, with 10 rats in each group.

[0127] Group 1 was set as the normal control group, which was not subjected to modeling treatment, was fed normally, and was given an equal amount of normal saline as a placebo daily.

[0128] Five groups were set as the drug-dosing groups, and modeling was performed. The mice were given the aqueous solution (with a concentration of 1 g / ml) prepared from the Chinese medicine composition for treating pulmonary nodules provided in the examples and comparative examples, respectively, by gavage, 2 ml each time, once a day.

[0129] Group 1 was set as the model control group, which was treated with modeling and given an equal amount of normal saline every day.

[0130] 2. Modeling method:

[0131] Rats in each group were anesthetized by intraperitoneal injection of 3.0% sodium pentobarbital solution (dose: 45 mg / kg body weight).

[0132] After anesthesia, the rat was fixed, and the neck skin of the rat was disinfected with 75.0% ethanol.

[0133] The skin was incised along the midline of the neck, and the muscles were bluntly separated to expose the trachea.

[0134] Using non-exposed endotracheal intubation, 200 μL of silica suspension with a mass concentration of 250 g / L was injected into the trachea at one time to induce a pulmonary nodule model.

[0135] 3. Medication and observation:

[0136] The medication group was administered with an aqueous solution of the traditional Chinese medicine composition according to the set dosage and frequency.

[0137] The normal control group and the model control group were given an equal amount of normal saline.

[0138] The dosing cycle lasts for 60 days.

[0139] 4. Index detection and calculation:

[0140] After the administration, the rats in each group were anesthetized and killed, and the wet weight of the lung tissues of the rats was weighed.

[0141] The lung swelling coefficient was calculated according to Formula 1: Lung swelling coefficient = lung wet weight (g) / body weight (g) × 100%.

[0142] The lung nodule swelling inhibition rate was calculated according to Formula 2, which is: Lung nodule swelling inhibition rate (%) = (lung swelling coefficient of the drug group - lung swelling coefficient of the normal control group) / (lung swelling coefficient of the model control group - lung swelling coefficient of the normal control group) × 100%.

[0143] 5. Result recording and analysis:

[0144] The test results were statistically analyzed to compare the differences among the groups and evaluate the therapeutic effect of the Chinese medicine composition, as shown in Table 1.

[0145] Table 1

[0146] Test samples Pulmonary nodule swelling inhibition rate (%) Example 1 96.8 Example 2 85.1 Example 3 92.5 Comparative Example 1 68.3 Comparative Example 2 59.6

[0147] As can be seen from Table 1, compared with Comparative Examples 1 to 2, the Chinese medicine composition for treating pulmonary nodules provided by the embodiment of the present invention has a more significant inhibitory effect on the swelling of pulmonary nodules in model rats, and the pulmonary nodule swelling inhibition rate can reach up to 96.8%.

[0148] Test Example 2

[0149] In this example, the Chinese medicine granules obtained in Example 4 are applied to the treatment of patients with pulmonary nodules, specifically including the following process:

[0150] 1. Source of cases

[0151] The subjects included in this study were patients with lung nodules who visited the lung nodule specialty clinic of our hospital from April to December 2022.

[0152] 2. Diagnostic criteria

[0153] 2.1 Western medicine diagnostic criteria

[0154] The 2018 Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules defines pulmonary nodules as: imaging manifestations of focal, round, increased density, solid or subsolid lung shadows with a diameter of ≤3 cm, which may be solitary or multiple, and are not accompanied by atelectasis, hilar lymphadenopathy, and pleural effusion.

[0155] 2.2 TCM diagnostic criteria

[0156] There is currently no standard for disease differentiation and syndrome differentiation in traditional Chinese medicine for lung nodules. Patients may have no obvious symptoms or signs and no syndrome to differentiate. In this study, all patients with lung nodules seen on lung imaging, excluding patients with tuberculosis and wind-heat lung heat disease, can be included in the category of "lung nodules" in traditional Chinese medicine.

[0157] 3. Case screening criteria

[0158] 3.1 Inclusion criteria

[0159] ① Patients diagnosed with pulmonary nodules according to the "Chinese Expert Consensus on Diagnosis and Treatment of Pulmonary Nodules (2018 Edition)";

[0160] ② Patients who only need CT follow-up according to the Chinese guidelines and expert consensus, or patients who need surgery but refuse or are unable to undergo surgery, and patients who relapse after surgery;

[0161] ③Age ≥ 18 years old;

[0162] ④ Voluntarily accept TCM intervention and follow the research protocol to participate in the entire research process;

[0163] ⑤Voluntarily participate in this project and sign the informed consent form.

[0164] 3.2 Exclusion criteria

[0165] ① Patients whose imaging and / or laboratory and / or puncture biopsy examinations indicate high-risk pulmonary nodules and who are recommended or request pulmonary nodule resection on their own;

[0166] ② Patients with malignant tumors;

[0167] ③ Active infection that is not clinically controlled, such as acute pneumonia, tuberculosis, etc.;

[0168] ④ Patients who cannot take American cockroach (powder) due to intestinal obstruction or other reasons, or who have difficulty swallowing, vomiting, drug allergy and malabsorption;

[0169] ⑤ Patients with serious primary diseases of cardiovascular, cerebrovascular, liver, kidney, blood system, etc.;

[0170] ⑥ Patients who have recently taken psychiatric drugs or received psychological treatment;

[0171] ⑦ Those suffering from difficult-to-control mental illness, communication or behavioral disorders;

[0172] ⑧ Patients who have received any pulmonary nodule-related treatments such as antibiotics and hormones in the past 4 weeks or are participating in other clinical trials;

[0173] ⑨Pregnant or lactating patients.

[0174] 3.3 Elimination criteria

[0175] ①Those who were included without meeting the inclusion criteria;

[0176] ②Those who meet the inclusion criteria but fail to implement the trial plan after inclusion;

[0177] ③ Cases where the observation data are seriously incomplete, affecting the evaluation of efficacy.

[0178] 3.4 Shedding Standard

[0179] ① Those who voluntarily withdrew from the study or were lost to follow-up;

[0180] ② Those who have serious adverse events, complications and special physiological changes and are not suitable to continue the trial;

[0181] ③ Patients whose medical imaging examinations indicate disease progression and who are deemed unsuitable to continue the trial by the doctor.

[0182] 3.5 Study termination criteria

[0183] ① During the study period, the nodule progressively enlarged to more than 3 cm;

[0184] ②Received pulmonary nodule resection during the course of treatment;

[0185] ③ Poor compliance and unable to continue to cooperate in completing clinical research / information collection;

[0186] ④ If serious adverse reactions occur, the trial should not be continued;

[0187] ⑤ Actively withdraw from the experiment.

[0188] 4. Intervention therapy

[0189] Experimental group: on the basis of conventional care, the Chinese medicine granules obtained in Example 4 were used. Dosage: three times a day, before meals (dissolved in 100 ml of hot water, dissolved, stirred, covered and sealed, orally taken at 30-37°C). The treatment time is 12 weeks.

[0190] 5. Main efficacy indicators: Measure the maximum diameter of the cross-sectional CT image on the largest level of the lung nodule and calculate the maximum diameter reduction rate of the lung nodule. Maximum diameter reduction rate (%) = (maximum diameter of the lung nodule before treatment - maximum diameter of the lung nodule after treatment) / maximum diameter of the lung nodule before treatment × 100%.

[0191] The efficacy levels are as follows:

[0192] Clinical cure: nodules disappear;

[0193] Significantly effective: nodules are reduced in size, with the maximum diameter reduction rate ≥ 50%;

[0194] Effective: nodule shrinkage, 25%≤maximum diameter reduction rate<50%;

[0195] Ineffective: The nodule shrinks, and the maximum diameter reduction rate is <25%.

[0196] Total effective rate (%) = (cure rate + marked effective rate + effective rate).

[0197] The test results are shown in Table 2.

[0198] Table 2

[0199] Total number of cases Number of recovered people Number of people with significant effect Effective number of people Invalid number of people Total Effectiveness 22 8 5 8 1 95.5％

[0200] Typical Case 1

[0201] Qiao Moumou, male, 46 years old, had a pure ground glass nodule of about 4mm×3mm in size at the posterior segment of the left upper lobe apex before treatment. After treatment, the lung CT imaging diagnosis results showed that the nodule disappeared and no obvious abnormalities were found.

[0202] Typical Case 2

[0203] Zhang Moumou, female, 49 years old, before treatment, the lung CT imaging diagnosis results showed that there were multiple nodules in both lungs, some of which were solid nodules and some were ground glass nodules, with an average diameter of 8.8mm; after treatment, the lung CT imaging diagnosis results showed that the patient had scattered solid and ground glass nodules in both lungs, the largest of which was about 5mm in long diameter, and the size of the nodules was significantly reduced.

[0204] In summary, the embodiment of the present invention provides a Chinese medicine composition for treating pulmonary nodules, a preparation method and application thereof, and Chinese medicine granules. The present invention selects appropriate types of Chinese medicine as raw materials, and uses them in combination with a corona discharge process and a decompression reflux extraction process to prepare a Chinese medicine composition for treating pulmonary nodules. The results of animal experiments show that the Chinese medicine composition has a significant inhibitory effect on the swelling of pulmonary nodules in model rats, providing a new means for the treatment of patients with pulmonary nodules, and has broad application prospects and important clinical significance.

[0205] Various embodiments of the present invention may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be understood as a rigid limitation on the scope of the present invention; therefore, the range description should be considered to have specifically disclosed all possible sub-ranges and single numerical values ​​within the range. For example, the range description from 1 to 6 should be considered to have specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which apply regardless of the range. In addition, whenever a numerical range is indicated herein, it is meant to include any cited number (fractional or integer) within the indicated range.

[0206] The foregoing is merely a specific embodiment of the present invention, which enables those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A method for preparing a Chinese medicine composition for treating pulmonary nodules, characterized in that: The preparation method comprises the following steps: Mix and grind ephedra, Magnolia officinalis, Platycodon grandiflorum, stewed bitter almond, Citrus aurantium, wine-cooked Chuanxiong, Curcuma zedoaria, stir-fried mustard seeds and pumice to obtain a first mixed material; subjecting the first mixed material to a corona discharge treatment to obtain a second mixed material; The second mixed material is added into water for decompression reflux extraction, and then the obtained water extract is concentrated and dried to obtain the traditional Chinese medicine composition for treating pulmonary nodules; The working condition parameters of the reduced pressure reflux extraction include: pressure of 20 kPa to 35 kPa and temperature of 65° C. to 75° C.

2. The method for preparing the Chinese medicine composition for treating pulmonary nodules according to claim 1, characterized in that: The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight: 8-12 parts of ephedra, 10-20 parts of magnolia bark, 10-20 parts of platycodon, 10-20 parts of stewed bitter almonds, 8-12 parts of bitter orange peel, 18-24 parts of wine-cooked chuanxiong, 18-24 parts of zedoaria, 18-24 parts of stir-fried mustard seeds and 25-35 parts of pumice.

3. The method for preparing the Chinese medicine composition for treating pulmonary nodules according to claim 1, characterized in that: The Chinese medicine composition for treating pulmonary nodules comprises the following raw materials in parts by weight: 10 parts of Ephedra, 15 parts of Magnolia officinalis, 15 parts of Platycodon grandiflorum, 15 parts of stewed bitter almonds, 10 parts of Fructus Aurantii Immaturus, 20 parts of wine-cooked Rhizoma Chuanxiong, 20 parts of Curcuma zedoariae, 20 parts of stir-fried mustard seeds and 30 parts of pumice.

4. The method for preparing the Chinese medicine composition for treating pulmonary nodules according to claim 1, characterized in that: The working condition parameters of the reduced pressure reflux extraction include: pressure of 28 kPa, temperature of 70° C., time of 1 to 2 hours, number of times of 1 to 3 times, and the added weight of water is 5 to 10 times of the second mixed material.

5. The method for preparing the Chinese medicine composition for treating pulmonary nodules according to claim 1, characterized in that: The step of subjecting the first mixed material to corona discharge treatment to obtain the second mixed material comprises the following process: 3~8kV / m 2 The first mixture is subjected to corona discharge treatment for 20 to 40 seconds under the following conditions to obtain the second mixture.

6. A Chinese medicine composition for treating pulmonary nodules, characterized in that: The Chinese medicine composition for treating pulmonary nodules is prepared by the preparation method of the Chinese medicine composition for treating pulmonary nodules according to any one of claims 1 to 5.

7. Use of the Chinese medicine composition for treating pulmonary nodules according to claim 6 in preparing a medicine for treating pulmonary nodules.

8. The use according to claim 7, characterized in that: The dosage form of the drug includes tablets, capsules, decoctions or granules.

9. A Chinese medicine granule, characterized in that: In parts by weight, the Chinese medicine granules Including the following ingredients: 40-50 parts of the Chinese medicine composition for treating pulmonary nodules according to claim 6 and 110-125 parts of pharmaceutical excipients; The pharmaceutical excipients include a filler, a disintegrant and a wetting agent in a weight ratio of (6-9):(2-5):(0.8-1.3).

10. The Chinese medicine granules according to claim 9, characterized in that: The filler comprises at least one of lactose, mannitol and beta-cyclodextrin; the disintegrant comprises at least one of sodium carboxymethyl starch and microcrystalline cellulose; and the wetting agent comprises ethanol with a volume fraction of 80-90%.

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