CN116898942A

CN116898942A - Traditional Chinese medicine composition for treating qi deficiency and phlegm stasis syndrome of lung pure ground glass nodule and application thereof

Info

Publication number: CN116898942A
Application number: CN202311120615.3A
Authority: CN
Inventors: 张炜; 苏子舰; 张一乐; 史苗颜; 陈飞飞; 孙萌
Original assignee: Shuguang Hospital Affiliated to Shanghai University of TCM
Current assignee: Shuguang Hospital Affiliated to Shanghai University of TCM
Priority date: 2023-09-01
Filing date: 2023-09-01
Publication date: 2023-10-20

Abstract

The application relates to the technical field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for treating qi deficiency and phlegm stasis syndrome of a lung pure ground glass nodule and application thereof, wherein the traditional Chinese medicine composition is a formula for resolving masses and dredging collaterals, and is prepared from the following traditional Chinese medicines: 35-55 parts of safflower, 35-55 parts of mugwort leaf, 5-25 parts of asarum, 20-40 parts of cassia twig, 5-25 parts of evodia rutaecarpa, 20-40 parts of amur corktree bark, 35-55 parts of dandelion, 20-40 parts of kuh-seng and 35-55 parts of lycopodium clavatum. Clinically, the traditional Chinese medicine composition has definite curative effect on treating patients with the syndrome of qi deficiency and phlegm stasis of the pulmonary pure ground glass nodule, can reduce the maximum nodule long diameter, reduce the nodule malignant risk probability, improve the depressed emotion of the patients, has good safety, and is worthy of further researching the action mechanism and developing clinical application.

Description

Traditional Chinese medicine composition for treating qi deficiency and phlegm stasis syndrome of lung pure ground glass nodule and application thereof

Technical Field

The application relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating qi deficiency and phlegm stasis syndrome of a lung pure ground glass nodule and application thereof.

Background

A purely ground glass lung nodule (PureGroundGlassNoudle, PGGN) is a common pulmonary nodule, a property of which is observed by chest CT imaging. The change of the ground glass sample with uniform density in the lung appears as cloud. At chest CT, the morphology and trend of bronchi, blood vessels can be observed in the pure ground glass nodules. The presence of purely ground glass nodules in the lungs suggests that there may be infections of the lungs, sarcoidosis, tuberculosis, etc., although few patients may have malignant tumors in the lungs. In imaging examinations (such as CT or chest radiography), a lesion with a diameter of less than 3cm, which is approximately circular, is described as a node, and a lesion with a diameter of less than 1cm is described as a "small node".

In the traditional Chinese medicine, the traditional Chinese medicine has no expression of lung cancer or lung nodule, and more glass lung nodules are detected due to the popularization of low-dose thin-layer CT screening of lung cancer nowadays. The disease of the crowd is in early stage, so that the disease is hidden, and the clinical uncomfortable symptoms such as cough, wheezing, fatigue and the like are rarely generated. Traditional Chinese medicine can be classified into the category of "lung accumulation" according to its main clinical symptoms and signs and combining the pathological features that the disease location is in the lung, the physical excess evil accumulated in the lung and the pathology is more malignant. "Jingyue full book. Congress" records: patients with spleen and kidney deficiency and weakness and disorder have accumulated diseases. The longer volume multiplication time of the ground glass lung nodule, limitation to the focus of the lung and 'peace and no pain' and the characteristics of triggering when in "in the moral grass", as far as the phlegm of the bag is concerned, such as the cave of the bee is in the room, such as the lotus seed is embedded in the bag, the growth is easy, and the peeling is difficult, so the study indicates the disease of the lung nodule 'phlegm fatigue bag'. In addition, lung nodules are also found to be marked by deficiency of both qi and yin and internal fatigue. In general, the glass-grinding nodule in the lung has the characteristics of difficult transformation of deficiency phlegm and fatigue, and the qi deficiency of the lung, dysfunction of viscera, disorder of triple energizer and qi transformation, and inseparable disease, and long-term persistent tumor.

The syndrome is a summary of a certain period characteristic and a corresponding rule in the progress of the disease, and is a true reflection of the current disease condition. The disease refers to a series of complex and dynamic changes with regularity caused by unbalance of yin and yang viscera under the action of pathological factors, and is a precondition of dialectical treatment. The modern Chinese medicine diagnosis and treatment of diseases mainly has seven modes, wherein the traditional Chinese medicine differentiation, the diagnosis and treatment of the traditional Chinese medicine differentiation and the special prescription special medicine belongs to the diagnosis and treatment of the traditional Chinese medicine differentiation, the first-stage phenotype of the disease and the modern medicine differentiation are products which are developed in compliance with the age, the diagnosis and treatment of the disease belongs to the change of the diagnosis and treatment of the disease differentiation, and the other diagnosis and treatment is another characteristic of traditional medicine used from ancient times of traditional Chinese medicine.

The possibility of traditional Chinese medicine in early lung cancer prevention and treatment characterized by GGN is explored in literature (Xiaoyu. Pulmonary glass nodule patient physique feature and traditional Chinese medicine intervention influence [ D ]. Shanghai university of traditional Chinese medicine, 2019.DOI: 10.27320/d.cnki.gszyu.2019.000215.) and the treatment scheme adopts a disease combination method to carry out individuation treatment, and different symptoms correspond to different treatment rules and prescriptions. The traditional Chinese medicine composition for treating the qi deficiency and phlegm stasis of the pulmonary pure ground glass nodule and the application thereof are not reported at present.

Disclosure of Invention

The first object of the present application is to provide a Chinese medicinal composition for overcoming the defects in the prior art.

A second object of the present application is to provide a use of a medicament.

In order to achieve the first object, the application adopts the following technical scheme:

a traditional Chinese medicine composition for treating qi deficiency and phlegm stasis syndrome of lung pure ground glass nodule is prepared from the following raw materials in parts by weight: 5-13 parts of radix astragali preparata, 11-19 parts of adenophora stricta, 1-5 parts of tangerine pith, 2-10 parts of loofah sponge, 2-10 parts of pummelo peel, 5-13 parts of moutan bark, 5-13 parts of red sage root, 5-13 parts of rhizoma curcumae, 11-19 parts of herba selaginellae, 11-19 parts of herba lycopodii, 11-19 parts of barbed skullcap herb, 11-19 parts of oldenlandia diffusa, 5-13 parts of buttercup root, 6-14 parts of coix seed, 5-13 parts of radix curcumae, 11-19 parts of ganoderma lucidum and 2-10 parts of platycodon grandiflorum.

As a preferred example, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 7-11 parts of radix astragali preparata, 13-17 parts of adenophora stricta, 2-4 parts of tangerine pith, 4-8 parts of loofah sponge, 4-8 parts of pummelo peel, 7-11 parts of moutan bark, 7-11 parts of red sage root, 7-11 parts of rhizoma curcumae, 13-17 parts of herba selaginellae, 13-17 parts of herba lycopodii, 13-17 parts of barbed skullcap herb, 13-17 parts of oldenlandia diffusa, 7-11 parts of buttercup root, 8-12 parts of coix seed, 7-11 parts of radix curcumae, 13-17 parts of lucid ganoderma and 4-8 parts of platycodon grandiflorum.

More preferably, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9 parts of roasted astragalus root, 15 parts of radix adenophorae, 3 parts of tangerine pith, 6 parts of loofah sponge, 6 parts of pummelo peel, 9 parts of moutan bark, 9 parts of red sage root, 9 parts of zedoary, 15 parts of selaginella, 15 parts of herba lycopodii, 15 parts of barbed skullcap herb, 15 parts of oldenlandia diffusa, 9 parts of catclaw, 10 parts of coix seed, 9 parts of radix curcumae, 15 parts of lucid ganoderma and 6 parts of platycodon grandiflorum.

More preferably, the dosage form of the traditional Chinese medicine composition is an oral dosage form.

More preferably, the oral dosage form is a granule.

In order to achieve the second purpose, the application adopts the following technical scheme:

the application of the traditional Chinese medicine composition in preparing the medicine for treating the qi deficiency and phlegm stasis syndrome of the lung pure ground glass nodule.

As a preferred example, the medicament can reduce the maximum nodule length and diameter, reduce the risk of malignancy of the nodule and improve the depressed mood of the patient.

The application has the advantages that:

the recipe of resolving hard mass and dredging collaterals is a proved recipe of clinical summary of pneumology department in an dao hospital, aims at the key links of the pathogenesis of the disease, namely lung qi collateral damage, the "collaterals are used as the principal points", "great collaterals are deficient", and the "most suitable for dredging and tonifying" are the principal points for treating the collateral disease, so the recipe takes astragalus and radix adenophorae as the principal points, the astragalus has the effects of tonifying qi and promoting blood circulation, the radix astragali has the effect of dredging collaterals when qi is exuberant, the radix adenophorae enters upper jiao to nourish lung yin, moisten lung dryness, and has the effect of resolving phlegm, and is also used as a principal drug for dredging and tonifying. The lung nodule is the initial stage of lung malignant tumor, emphasizes on the treatment of clearing heat and detoxicating and cutting off disease, improves pathological links, and attaches importance to 'phlegm toxin' and 'stasis toxin' pathogeny, promotes toxin resolution and 'phlegm stasis and resolving', and is derived from the pathogenic factors of lung collaterals, and the lung collaterals are unobstructed, so the orange collaterals, pummelo peel and luffa collaterals are used as ministers in the prescription for regulating qi, reducing phlegm and dredging collaterals; herba Selaginellae Doederleinii, herba Salviae chinensis, herba Scutellariae Barbatae, herba Hedyotidis Diffusae, and radix Ranunculi Ternati with effects of clearing heat and detoxicating; the red sage root, the tree peony bark and the aizoon stonecrop herb have the effects of promoting blood circulation and removing obstruction in channels; with the assistance of radix curcumae for promoting qi circulation and resolving depression, coix seeds for strengthening spleen and excreting dampness, lucid ganoderma for tonifying deficiency and strengthening body resistance, and platycodon grandiflorum for leading medicine into lung, the whole formula plays a role in strengthening body resistance and dredging collaterals, and attack and tonification.

The particle for resolving hard mass and dredging collaterals has definite curative effect on treating patients with the symptoms of qi deficiency and phlegm stasis of the pulmonary pure ground glass small nodules, can reduce the maximum nodule long diameter, reduce the risk probability of malignancy of the nodules, improve the depressed emotion of the patients, and has good safety.

Detailed Description

The application is further described below in conjunction with the detailed description. It is to be understood that these examples are illustrative of the present application and are not intended to limit the scope of the present application. Further, it is understood that various changes and modifications of the present application may be made by those skilled in the art after reading the description of the present application, and such equivalents are intended to fall within the scope of the application as defined in the appended claims.

Example 1 the application is a prescription for resolving hard mass and dredging collaterals

9 parts of roasted astragalus root, 15 parts of radix adenophorae, 3 parts of tangerine pith, 6 parts of loofah sponge, 6 parts of pummelo peel, 9 parts of moutan bark, 9 parts of red sage root, 9 parts of zedoary, 15 parts of selaginella, 15 parts of herba lycopodii, 15 parts of barbed skullcap herb, 15 parts of oldenlandia diffusa, 9 parts of catclaw, 10 parts of coix seed, 9 parts of radix curcumae, 15 parts of lucid ganoderma and 6 parts of platycodon grandiflorum.

Example 2 the application is a prescription for resolving hard mass and dredging collaterals (II)

9 parts of roasted astragalus membranaceus, 13 parts of radix adenophorae, 4 parts of tangerine pith, 2 parts of loofah sponge, 10 parts of pummelo peel, 9 parts of tree peony bark, 7 parts of red sage root, 11 parts of curcuma zedoary, 11 parts of selaginella, 19 parts of herba lycopodii, 15 parts of barbed skullcap herb, 13 parts of oldenlandia diffusa, 11 parts of catclaw, 6 parts of coix seed, 13 parts of radix curcumae, 15 parts of ganoderma lucidum and 4 parts of platycodon grandiflorum.

Example 3 the application is a prescription (III)

7 parts of roasted astragalus membranaceus, 17 parts of adenophora tetraphylla, 1 part of tangerine pith, 10 parts of loofah sponge, 6 parts of pummelo peel, 7 parts of tree peony bark, 11 parts of red-rooted salvia root, 5 parts of curcuma zedoary, 19 parts of selaginella chinensis, 15 parts of herba lycopodii, 13 parts of barbed skullcap herb, 17 parts of oldenlandia diffusa, 5 parts of catclaw, 14 parts of coix seed, 9 parts of radix curcumae, 13 parts of lucid ganoderma and 8 parts of platycodon grandiflorum.

Example 4 the application is a formula (IV) for resolving hard mass and dredging collaterals

11 parts of roasted astragalus root, 11 parts of radix adenophorae, 5 parts of tangerine pith, 6 parts of loofah sponge, 4 parts of pummelo peel, 11 parts of moutan bark, 5 parts of red sage root, 13 parts of curcuma zedoary, 15 parts of selaginella, 13 parts of herba lycopodii, 17 parts of barbed skullcap herb, 11 parts of oldenlandia diffusa, 13 parts of catclaw, 10 parts of coix seed, 7 parts of radix curcumae, 17 parts of lucid ganoderma and 2 parts of platycodon grandiflorum.

Example 5 the application is a formula for resolving hard mass and dredging collaterals

5 parts of roasted astragalus root, 19 parts of adenophora root, 3 parts of tangerine pith, 4 parts of loofah sponge, 8 parts of pummelo peel, 5 parts of moutan bark, 13 parts of red sage root, 9 parts of zedoary, 13 parts of selaginella, 17 parts of herba lycopodii, 11 parts of barbed skullcap herb, 19 parts of oldenlandia diffusa, 9 parts of catclaw, 8 parts of coix seed, 11 parts of radix curcumae, 11 parts of lucid ganoderma and 10 parts of platycodon grandiflorum.

Example 6 the present application is a formula (six)

13 parts of roasted astragalus membranaceus, 15 parts of radix adenophorae, 2 parts of tangerine pith, 8 parts of loofah sponge, 2 parts of pummelo peel, 13 parts of moutan bark, 9 parts of red sage root, 7 parts of curcuma zedoary, 17 parts of selaginella, 11 parts of lithospermum, 19 parts of barbed skullcap herb, 15 parts of oldenlandia diffusa, 7 parts of catclaw, 12 parts of coix seed, 5 parts of radix curcumae, 19 parts of ganoderma lucidum and 6 parts of platycodon grandiflorum.

Example 7 the application is a formula for resolving hard mass and dredging collaterals (seven)

9 parts of roasted astragalus membranaceus, 17 parts of adenophora tetraphylla, 1 part of tangerine pith, 10 parts of loofah sponge, 6 parts of pummelo peel, 7 parts of tree peony bark, 11 parts of red-rooted salvia root, 5 parts of curcuma zedoary, 19 parts of selaginella chinensis, 15 parts of herba lycopodii, 13 parts of barbed skullcap herb, 17 parts of oldenlandia diffusa, 5 parts of catclaw, 14 parts of coix seed, 9 parts of radix curcumae, 13 parts of lucid ganoderma and 8 parts of platycodon grandiflorum.

Example 8 the application is a formula (eight)

7 parts of roasted astragalus membranaceus, 11 parts of adenophora tetraphylla, 5 parts of tangerine pith, 6 parts of loofah sponge, 4 parts of pummelo peel, 11 parts of moutan bark, 5 parts of red-rooted salvia root, 13 parts of curcuma zedoary, 15 parts of selaginella, 13 parts of herba lycopodii, 17 parts of barbed skullcap herb, 11 parts of oldenlandia diffusa, 13 parts of catclaw, 10 parts of coix seed, 7 parts of radix curcumae, 17 parts of lucid ganoderma and 2 parts of platycodon grandiflorum.

Example 9 the application resolving hard mass and dredging collaterals prescription (nine)

11 parts of roasted astragalus root, 19 parts of adenophora root, 3 parts of tangerine pith, 4 parts of loofah sponge, 8 parts of pummelo peel, 5 parts of moutan bark, 13 parts of red sage root, 9 parts of zedoary, 13 parts of selaginella, 17 parts of herba lycopodii, 11 parts of barbed skullcap herb, 19 parts of oldenlandia diffusa, 9 parts of catclaw, 8 parts of coix seed, 11 parts of radix curcumae, 11 parts of lucid ganoderma and 10 parts of platycodon grandiflorum.

Example 10 the application is a prescription (ten)

5 parts of roasted astragalus membranaceus, 15 parts of adenophora tetraphylla, 2 parts of tangerine pith, 8 parts of loofah sponge, 2 parts of pummelo peel, 13 parts of moutan bark, 9 parts of red-rooted salvia root, 7 parts of curcuma zedoary, 17 parts of selaginella tamariscina, 11 parts of lithospermum, 19 parts of barbed skullcap herb, 15 parts of oldenlandia diffusa, 7 parts of catclaw, 12 parts of coix seed, 5 parts of radix curcumae, 19 parts of ganoderma lucidum and 6 parts of platycodon grandiflorum.

Example 11 the application is a prescription for resolving hard mass and dredging collaterals (eleven)

13 parts of roasted astragalus membranaceus, 13 parts of radix adenophorae, 4 parts of tangerine pith, 2 parts of loofah sponge, 10 parts of pummelo peel, 9 parts of tree peony bark, 7 parts of red sage root, 11 parts of curcuma zedoary, 11 parts of selaginella, 19 parts of herba lycopodii, 15 parts of barbed skullcap herb, 13 parts of oldenlandia diffusa, 11 parts of catclaw, 6 parts of coix seed, 13 parts of radix curcumae, 15 parts of lucid ganoderma and 4 parts of platycodon grandiflorum.

Example 12 clinical efficacy experiment

1 clinical data

1.1 general data

86 patients were enrolled in the study from 5 months 2021 to 10 months 2021 at the clinic of the pulmonary department of the university of Shanghai traditional Chinese medicine affiliated with dawn hospital.

1.2 diagnostic criteria

Western diagnosis standard refers to 2018 lung nodule diagnosis and treatment Chinese expert consensus standard ^[1] . The diagnosis standard of traditional Chinese medicine refers to the guidelines (trial) of clinical research on new drugs of traditional Chinese medicine ^[2] (diagnostic science of traditional Chinese medicine) ^[3] The definition of qi deficiency and phlegm stasis in the middle energizer, and the characteristic of pulmonary nodule diseases are combined to formulate dialectical standards of qi deficiency and phlegm stasis in pulmonary nodule: main symptoms are as follows: short breath, debilitation, cough,expectoration and chest distress. Secondary symptoms: listlessness and lazy speaking, shortness of breath after activity, numbness of hands and feet, sweating after movement, discomfort of the pharynx, and pricking pain in the chest and hypochondrium. Tongue diagnosis: pale tongue, purple and dark tongue or ecchymosis under tongue; a white and greasy tongue coating. Pulse diagnosis: the pulse conditions can be the deficient pulse, wiry pulse, and astringent pulse. Dialectical description: for those without obvious clinical symptoms, the differentiation of symptoms is mainly based on tongue pulse diagnosis; in symptomatic patients, the number of the main symptoms is 2, and the number of the secondary symptoms is more than or equal to 1; or more than or equal to 1 main symptoms and more than or equal to 2 secondary symptoms, and can be distinguished as qi deficiency and phlegm stasis by combining tongue pulse.

1.3 inclusion criteria

(1) Meets the diagnosis of pure ground glass nodes (pGGN) of the lung, and the length and the diameter of the maximum ground glass node are less than or equal to 5mm and less than 10mm. If the lung nodule is a multiple nodule, the lung nodule with the longest length is evaluated (the obtained imaging image after CT examination is completed is analyzed by two radiologists with abundant clinical experience at the same time, each imaging feature is analyzed and described, and a person with a bifurcation is identified after the discussion conclusion of the two parties is consistent);

(2) age 18-75 years old, unlimited in sex;

(3) meets the diagnosis standard of qi deficiency and phlegm stasis syndrome in traditional Chinese medicine;

(4) the disease course is within 3 months of the diagnosis pGGN;

(5) no traditional Chinese medicine treatment has been applied.

1.4 exclusion criteria

(1) The largest lung nodule is an impure ground glass nodule;

(2) first chest CT suggests pGGN with clear respiratory tract infection;

(3) pregnant women or other primary diseases accompanied by severe cardiovascular and cerebrovascular diseases, liver diseases, kidney diseases and the like;

(4) has a clear history of autoimmune disease;

(5) have participated in other clinical studies;

(6) the first diagnosis is to determine the period selection operation;

(7) is combined with chronic respiratory diseases such as chronic obstructive pulmonary disease, pulmonary interstitial fibrosis and asthma.

2 study method

Sample size calculation: the book is provided withResearch uses the maximum pGGN long-diameter reduction curative effect of the particle for resolving hard mass and dredging collaterals as a main curative effect index to calculate the sample size, and searches according to literature ^[4] And the result of the earlier stage study, the total effective rate treatment group takes 40%, the control group takes 10%, consider this study to be the best performance test, so choose the unilateral to examine, the error (a) of one kind is set as 0.025, the error (β) of the second kind is set as 0.1, two groups study sample size is equal, calculate the sample size with PASS15 software, consider the factor such as patient withdraw, terminate or clinical data are incomplete in the test process, increase the sample size of 10%, confirm the sample number 86 cases finally, treat the group, control group 43 cases each.

Referring to the standardized operation steps of double-blind clinical test, SPSS26.0 software is used for manufacturing a random distribution table according to the proportion of 1:1, random distribution cards are manufactured through the random distribution table and are filled into sealed envelopes, envelopes with the same number are opened according to the sequence of patient group entering, grouping is carried out according to the number specified by the cards in the envelopes, and the grouping result is a first-level blind bottom (A group or B group). The second blind bottom is two groups of corresponding treatments (treatment group and control group), and after the researchers screen qualified subjects, the test administration manager sends medicines according to the sequence of subjects entering the group and the sequence of medicine numbers from small to large. Each coded medicine is provided with a corresponding emergency letter for emergency blind breaking, the blind bottoms are uniformly retracted after the test is finished, the blind bottoms are stored by the personnel participating in the test, and both doctors and patients keep the blind state for the medicine. Blind uncovering after the test was ended, and group A was shown as treatment group and group B as control group.

The two groups are subjected to pulmonary nodule related science popularization education once a month, and smoking cessation ventilating and teaching and emotion coaching are performed on patients. The treatment group is prepared from the particles for resolving hard mass and dredging collaterals, the control group is prepared from the particles for resolving hard mass and dredging collaterals, which simulate placebo (the particles for resolving hard mass and dredging collaterals with the concentration of 5 percent are formed, and auxiliary materials and flavoring agents are added to realize the same appearance and taste with the particles for resolving hard mass and dredging collaterals), and the administration method is 2 bags each time, half an hour after breakfast and supper, and warm water is used for taking. Both the particle for resolving hard mass and the simulator are produced by Jiang Yintian river pharmaceutical industry Co., ltd, and the treatment course is 24 weeks.

In the clinical observation process, 2 patients in the treatment group fall off due to refusal to continue the treatment of the particles for resolving masses and dredging collaterals, and 3 patients in the control group lose the fall off after follow-up, and the fall off rate is 5.81%. The final inclusion was 81, 41 of the treatment groups and 40 of the control groups.

3 clinical observations index

3.1 major efficacy index

The study uses the maximum pGGN long diameter as a main curative effect index, and the measurement is referred to the lung nodule measurement suggestion guide of the Fleischner association in 2017. The measuring method comprises the following steps: CT imaging images are analyzed by two radiologists with abundant clinical experience, pure ground glass nodules are marked on lung window images (window width 1400HU, window level-700 HU), the maximum diameter of cross section CT images on the maximum layer of the lung nodules is measured, and the average value is obtained for 3 times, and the average value is taken as an integer and is measured as a unit of mm.

3.2 secondary efficacy index

(1) Total integral of clinical symptoms of Chinese medicine

Referring to the definition of qi deficiency and phlegm stasis syndrome in the "clinical study guidelines of new traditional Chinese medicine" (trial run) and "diagnosis of traditional Chinese medicine", and combining with the clinical experience of the pneumology department of the dawn hospital, the integral observation table of the traditional Chinese medicine symptoms of the lung pure ground glass nodule (qi deficiency and phlegm stasis syndrome) is developed. The primary and secondary symptoms are according to the diagnosis standard of traditional Chinese medicine. The symptoms were classified into none, mild, moderate and severe, the main symptoms were respectively marked as 0, 2, 4 and 6, the secondary symptoms were respectively marked as 0, 1, 2 and 3, and the total score was recorded.

(2) Density of maximum pGGN

The maximum pure ground glass nodule is marked on a CT lung window image (window width 1400HU, window level-700 HU), distinguishable blood vessels, bronchi and pleura tissues are avoided during marking, two radiologists with abundant experience mark the maximum window surface, 60% -80% of the area in the maximum ground glass nodule surface is selected to measure density for 3 times, and an average CT value is obtained.

(3) Brock model malignant risk probability

Reference Brock model ^[5] And (5) calculating a prediction formula and calculating the malignant risk probability of the lung nodule. Multiple nodules were calculated as the most dangerous nodules. Lung nodule malignancy probability = ex/(1+ex), where e is the natural logarithm, x= -6.6144+ (0.646X sex) +(-5.5537X diameter) + (0.9309X burr) + (0.6009X upper leaf). Sex parameters female=1, male=0; representing knots for knot diameterMaximum diameter number of the section, unit is millimeter; the burr record is 1, otherwise 0; the nodule location is recorded as 1 on the upper lobe and 0 on the opposite.

(4) SDS depression self-scoring scale

The answer that most corresponds to the situation is selected based on the actual experience of the patient within the last week. The forward score questions were recorded as 1, 2, 3, and 4 points, respectively, and the reverse score questions were recorded as 4, 3, 2, and 1 point. The total score of the scale is multiplied by 1.25, the whole number is taken, and the specific severity judgment standard is as follows: < 50, normal; more than or equal to 50 and less than 60, and slight depression;

more than or equal to 60 and less than 70, and moderately depressed; not less than 70% and high depression.

The above indexes are recorded before and after treatment.

3.3 safety index

Electrocardiogram, blood routine, liver function and kidney function are detected 1 time before and after treatment, and adverse reaction condition is observed.

3.4 disease efficacy assessment criteria

The maximum pGGN diameter reduction rate was calculated, maximum diameter reduction rate= (maximum diameter of pre-treatment pulmonary nodule-maximum diameter of post-treatment pulmonary nodule)/maximum diameter of pre-treatment pulmonary nodule x 100%. The treatment effect is classified as follows: clinical cure: the nodule disappears; the effect is shown: the nodule is reduced, and the maximum diameter reduction rate is more than or equal to 50%; the method is effective: the nodule is reduced, and the reduction rate of the maximum diameter is more than 50 percent and is more than or equal to 25 percent; invalidation: the nodule is reduced, and the maximum diameter reduction rate is less than 25%. Total effective rate= (cure rate + significant efficiency + effective rate) x 100%.

4 statistical method

And (5) carrying out data entry by using the EpiData, and establishing a database. The study used SPSS26.0 and GraphPadprism9 statistical analysis software to statistically analyze the data. In general, the statistical test is performed on both sides, and P <0.05 is considered to be statistically significant. If the measurement data accords with the normalization and has uniform variance, the comparison between groups adopts two independent sample t-tests, the comparison in the group adopts paired sample t-tests, and the statistics are expressed by mean value +/-standard deviation (+/-s); if the normal distribution and variance alignment are not met, non-parametric inspection is used. The statistics adopt a median (M) and an upper and a lower quartile [ M ](P ₂₅ ，P ₇₅ )]Description. The count data is expressed using frequency and composition ratio (%), using chi-square test and nonparametric test.

5 experimental results

5.1 maximum pGGN diameter comparison

Comparison of maximum pGGN diameters before and after treatment of the two groups, the difference in maximum pGGN diameters between the two groups of patients before treatment was not statistically significant (P > 0.05). Compared with the treatment before the treatment of the group, the maximum pGGN diameter after the treatment of the treatment group is obviously reduced (P is less than 0.01), and the difference before and after the treatment of the maximum pGGN diameter of the control group has no statistical significance (P is more than 0.05). The maximum pGGN diameter of the treated group after treatment was smaller than that of the control group (P < 0.01) compared between groups. After treatment, the maximum pGGN diameter reduction value of the treatment group is 1.67+/-1.40 mm, which is obviously larger than that of the control group by 0.15+/-0.98 mm (P < 0.05), and the maximum pGGN diameter reduction rate of the treatment group is obviously larger than that of the control group (P < 0.01), as shown in tables 1 and 2.

Table 1 comparison of maximum pGGN diameters (mm) before and after treatment for both groups

Note that: a is compared with the group before treatment, and P is less than 0.01; b is compared with the control group in the same period, and P is less than 0.01; c, P is less than 0.05 compared with the difference before and after the treatment of the control group.

TABLE 2 comparison of maximum pGGN diameter reduction rates before and after treatment [ M (P25, P75) ]

Note that: a is compared with the control group, P is less than 0.001

5.2 comparison of clinical efficacy

The total effective rate of the treatment effect of the maximum ground glass nodule diameter reduction after treatment of the two groups of clinical treatment effect comparison treatment groups is 48.78%, which is obviously higher than that of the control group by 10.00%, and the difference has statistical significance (P is less than 0.01), as shown in Table 3.

Table 3 comparison of clinical efficacy before and after treatment of the two groups [ n (%) ]

Note that: a is compared with the control group, P is less than 0.01

5.3 integral comparison of clinical symptoms of traditional Chinese medicine

The difference between the total integral comparison of the clinical symptoms of the two groups of traditional Chinese medicine before treatment has no statistical significance (P is more than 0.05). In-group comparison, the total integral of the clinical symptoms of the traditional Chinese medicine after treatment of the treatment group is obviously reduced (P is less than 0.01) compared with that before treatment, and the comparison difference of the integral of the clinical symptoms of the traditional Chinese medicine before and after treatment of the control group has no statistical significance (P is more than 0.05). Comparing between groups, total integral of clinical symptoms of traditional Chinese medicine after treatment of the treatment group is lower than that of the control group (P < 0.01), and see table 4.

Table 4 Total integral comparison of two groups of clinical symptoms [ (+ -s) ]

Note that: a is compared with the group before treatment, and P is less than 0.01; after treatment b, the treatment group was compared with the control group, and P < 0.01

5.4 maximum pGGN Density comparison

In this study, one patient had no nodules after treatment, so 1 patient was excluded from the density observations. The comparative differences in the densities of the two groups of patients before treatment were not statistically significant (P > 0.05). There was no statistical difference (P > 0.05) between the maximum pGGN densities before and after treatment in both groups compared, treatment and control, as shown in Table 5.

TABLE 5 comparison of the maximum lung ground glass nodule density of the two groups before and after treatment [ (+ -s), HU ]

Note that: * One patient in the treatment group had no nodules and the actual patients involved in densitometry had 40

5.5 Brock model malignancy risk probability comparison

The probability of malignancy in the two groups of patients before treatment is relatively unchanged. The probability of malignancy of Brock model is significantly reduced (P < 0.01) after treatment of treatment group; the difference of the malignant risk probability of the Brock model after the control group treatment has no statistical significance (P is more than 0.05). The two groups are compared, the statistical difference (P < 0.01) exists after treatment, and the probability of malignancy risk of a Brock model in the treated group is reduced by 4.41+/-4.47% after treatment, which is obviously higher than-0.26+/-2.64% (P < 0.05) of the control group. See table 6.

Table 6 comparison of Brock model malignancy risk probabilities for two groups of patients before and after treatment [ (+ -s),% ]

Note that: a is compared with the group before treatment, and P is less than 0.01; b is compared with the control group in the same period, and P is less than 0.01; c is compared with the difference before and after the treatment of the control group, and P is less than 0.01

5.7 self-scoring score comparison for SDS depression

The difference in SDS depression score was judged statistically significant from the scores of the two pre-treatment groups of patients (P > 0.05). In-group comparison, the SDS scale score judgment difference before and after treatment of the treatment group has obvious statistical significance (P < 0.01); the SDS-scale score before and after treatment of the control group determined that the difference was not statistically significant (P > 0.05). The comparison between the two groups shows that there was a statistical difference (P < 0.05) after treatment, see Table 7.

Table 7 two groups of patients were SDS depression self-assessed and scored for comparative assessment [ n (%) ]

Note that: a is compared with the group before treatment, and P is less than 0.01; b is compared with the control group in the same period, and P is less than 0.05

5.8 patient safety outcome

The 41 patients taking the particles for resolving hard mass and dredging collaterals for treating pulmonary nodules have the occurrence rate of gastrectasia after taking the particles for treating pulmonary nodules of 1 patient, the occurrence rate of adverse events is 2.44%, the patients can tolerate and then release the particles by themselves, the patients are judged to be mild adverse events, adverse reactions such as nausea and vomiting after taking the particles do not occur in other patients, and adverse events are not found in the control group. The liver function (ALT, AST), kidney function (Cr, BUN) and electrocardiogram of the patient are respectively checked before being put into the group, and no obvious biochemical index and no abnormality of the electrocardiogram exist.

The results show that the powder of the application has definite curative effect on treating patients with the syndrome of qi deficiency and phlegm stasis of the pulmonary pure ground glass nodule, can reduce the maximum nodule long diameter, reduce the risk probability of malignancy of the nodule, improve the depressed emotion of the patients, and has good safety.

Example 13 animal experiments

1. Experimental materials

1.1 animals

Common class C57BL/6 mice were purchased from Shanghai Sipuler-BiKai laboratory animal Co., ltd in 100 animals, weight (18-20) g, male and female halves.

1.2 drugs and Agents

Medicament:

the preparation of the medicine of the treatment group I: weighing the raw materials according to the weight parts described in the embodiment 1, and preparing into granules;

the preparation of the treatment group II medicine comprises the following steps: weighing the raw materials according to the weight parts described in the example 2, and preparing into granules;

preparation of control group drug: 9 parts of roasted astragalus membranaceus, 15 parts of radix adenophorae, 3 parts of black-bone vegetable, 6 parts of loofah sponge, 6 parts of pummelo peel, 9 parts of red paeony root, 9 parts of root of red-rooted salvia, 9 parts of rhizoma curcumae, 15 parts of herba selaginellae chinensis, 15 parts of herba lycopodii, 15 parts of solidago, 15 parts of oldenlandia diffusa, 9 parts of radix ranunculi ternati, 10 parts of coix seed, 9 parts of storax, 15 parts of lucid ganoderma and 6 parts of platycodon grandiflorum, and weighing the raw materials to prepare granules;

reagent:

lewis lung cancer cells are purchased from Shanghai Biochemical and cell biology institute of China academy of sciences, and other reagents are commercially available.

2 method

2.1 animal Molding

All mice were fed adaptively for 1 week, during which time normal feed was given. 10 mice were randomly selected as blank group 1 week later and continued to be fed with normal feedFeeding to end, remaining 90 mouse references ^[6] And (3) preparing a disease combination model of a virtual blood stasis model and Lewis lung cancer cell inoculation. And after 3 weeks of molding, judging whether molding is successful or not according to the appearance characteristics and the changes of various indexes, wherein the occurrence of listlessness, weight reduction, diet reduction, dark tongue and the like, and the significant increase of the viscosity of whole blood and the viscosity of blood plasma can be regarded as the successful molding, and the final molding is 72. The number of mice which are successfully molded is randomly selected to be divided into 6 groups of the first group (10) of the application, the second group (10) of the application, the first control group (10), the second control group (10), the model group (10) and the western medicine group (10).

2.2 Experimental protocol

Placing the mice in groups at room temperature of 20-25 ℃, and in an environment with good indoor dryness, lighting and ventilation, freely feeding water and administering for 3 weeks in the following manner:

the first group of the application: the granules prepared according to the above-described group I of the present application were administered 60 g/(kg.d) by intragastric administration.

The application is two: the granules prepared according to the above-described group II of the application were administered 60 g/(kg.d) by intragastric administration.

Control group: 60 g/(kg.d) of the pellets prepared in the control group were administered by gavage.

Blank and model groups: the distilled water is filled into the stomach, and the dosage is 5 ml/kg.d.

The body weight of the mice was weighed and recorded before and after the administration, the mice were sacrificed after the end of the administration, tumor tissues were peeled off, and the tumor mass and tumor suppression rate of each group of mice were calculated.

3 statistical method

Data were statistically processed using SPSS25.0 software. The metering data is expressed by (x+/-s), the t test is adopted by the normal distributor, and the non-parametric rank sum test is adopted by the non-normal distributor; the counting data is represented by examples or percentages, the non-grade data is checked by chi-square, and the grade data is checked by rank sum. The difference of P <0.05 is statistically significant.

Results 4 results

The body mass of each group of mice before and after administration is shown in Table 1, and the body mass of the group of the application, the control group and the model group is reduced (P < 0.05) compared with that of the blank group before administration, which shows that the modeling can affect the body weight of the mice, and the body weight of the group of the application is increased (P < 0.05) compared with that of the control group after administration.

TABLE 1 weight variation of mice of each group [ (]g)

Note that: comparison with blank group ¹⁾ P is less than 0.05; comparison with model group ²⁾ P＜0.05

The comparison of tumor mass of mice in each group is shown in Table 2, wherein compared with a model group, the tumor mass of the mice in the group and the control group is obviously lower than that in the model group (P is less than 0.05), compared with the control group, the tumor mass of the mice in the group I and the group II is lower (P is less than 0.05), and the result shows that the traditional Chinese medicine composition has a certain inhibition effect on lung cancer tissues of the mice.

Table 2 comparison of tumor mass in mice of each group

Note that: comparison with model group ¹⁾ P <0.05, compared with the control group ²⁾ P＜0.05

Reference to the literature

[1] Zhang Xiaoju A.E. Bright, gold shines, et al, pulmonary nodule diagnosis and treatment Chinese expert consensus (2018 edition) [ J ]. Chinese tuberculosis and respiratory journal, 2018,41 (10): 763-771.

[2] Zhengyu the guidelines for clinical study of new Chinese medicinal materials [ J ]. Chinese medical science and technology Press, 2002.

[3] Li Candong and Wu Chengyu the diagnosis of Chinese medicine [ M ] Beijing, chinese traditional medicine Press 2012.

[4] Hou Qiuyue clinical research on treating pulmonary nodules by regulating qi, resolving stagnation, resolving phlegm and resolving masses [ D ] university of Nanjing traditional Chinese medicine, 2019.

[5]Mcwilliams A,Tammemagi M C,Mayo J R,et al.Probability of cancer in pulmonary nodules detec ted on first screening CT[J].N Engl J Med,2013,369(10):910-9.

[6] Li Li the factors of deficiency and stasis affect the establishment and study of a mouse lung cancer model [ D ]. University of Shanxi, 2020.DOI:10.27820/d.cnki.gszxy.2020.000235.

The foregoing is merely a preferred embodiment of the present application, and it should be noted that modifications and additions may be made to those skilled in the art without departing from the method of the present application, which modifications and additions are also to be considered as within the scope of the present application.

Claims

1. The traditional Chinese medicine composition for treating the syndrome of qi deficiency and phlegm stasis of the lung pure ground glass nodule is characterized by being prepared from the following raw materials in parts by weight: 5-13 parts of radix astragali preparata, 11-19 parts of adenophora stricta, 1-5 parts of tangerine pith, 2-10 parts of loofah sponge, 2-10 parts of pummelo peel, 5-13 parts of moutan bark, 5-13 parts of red sage root, 5-13 parts of rhizoma curcumae, 11-19 parts of herba selaginellae, 11-19 parts of herba lycopodii, 11-19 parts of barbed skullcap herb, 11-19 parts of oldenlandia diffusa, 5-13 parts of buttercup root, 6-14 parts of coix seed, 5-13 parts of radix curcumae, 11-19 parts of ganoderma lucidum and 2-10 parts of platycodon grandiflorum.

2. The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 7-11 parts of radix astragali preparata, 13-17 parts of adenophora stricta, 2-4 parts of tangerine pith, 4-8 parts of loofah sponge, 4-8 parts of pummelo peel, 7-11 parts of moutan bark, 7-11 parts of red sage root, 7-11 parts of rhizoma curcumae, 13-17 parts of herba selaginellae, 13-17 parts of herba lycopodii, 13-17 parts of barbed skullcap herb, 13-17 parts of oldenlandia diffusa, 7-11 parts of buttercup root, 8-12 parts of coix seed, 7-11 parts of radix curcumae, 13-17 parts of lucid ganoderma and 4-8 parts of platycodon grandiflorum.

3. The traditional Chinese medicine composition according to claim 2, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9 parts of roasted astragalus root, 15 parts of radix adenophorae, 3 parts of tangerine pith, 6 parts of loofah sponge, 6 parts of pummelo peel, 9 parts of moutan bark, 9 parts of red sage root, 9 parts of zedoary, 15 parts of selaginella, 15 parts of herba lycopodii, 15 parts of barbed skullcap herb, 15 parts of oldenlandia diffusa, 9 parts of catclaw, 10 parts of coix seed, 9 parts of radix curcumae, 15 parts of lucid ganoderma and 6 parts of platycodon grandiflorum.

4. The traditional Chinese medicine composition according to claims 1-3, wherein the dosage form of the traditional Chinese medicine composition is an oral dosage form.

5. The traditional Chinese medicine composition according to claim 4, wherein the oral administration dosage form is a granule.

6. The use of the Chinese medicinal composition according to any one of claims 1-5 in the preparation of a medicament for treating qi deficiency and phlegm stasis syndrome of pure ground glass nodules in the lung.

7. The use of claim 6, wherein the medicament reduces the maximum nodule length, reduces the risk of malignancy of the nodule and improves the depressed mood of the patient.