Healthy energy strengthening and stasis removing formula for resisting non-small cell lung cancer and preparation method of healthy energy strengthening and stasis removing formula

Abstract

The invention relates to a body resistance strengthening and stagnation eliminating prescription for resisting non-small cell lung cancer and a preparation method thereof. The body resistance strengthening and stagnation eliminating prescription is prepared from the following raw material medicines in parts by weight: 2-50g / part of radix fici simplicissimae, 2-50g / part of radix pseudostellariae, 2-50g / part of poria cocos, 2-50g / part of rhizoma atractylodis macrocephalae, 2-50g / part of radix scutellariae, 2-50g / part of oldenlandia diffusa, 2-50g / part of radix ranunculi ternati, 2-50g / part of polygonum cuspidatum, 2-50g / part of curcuma zedoary, 2-50g / part of oyster, 2-50g / part of platycodon grandiflorum, 2-50g / part of edible tulip and 2-50g / part of sculellaria barbata. Cell tests and construction of an NSCLC osimertinib-resistant animal model prove that the body resistance strengthening and stagnation eliminating prescription can regulate a tumor microenvironment (TME) and inhibit growth of osimertinib-resistant non-small cell lung cancer cells. In addition, the formula for strengthening the body resistance and removing stasis can also inhibit growth of common non-small cell lung cancer cells. Meanwhile, clinical observation finds that the body resistance strengthening and stasis removing prescription can improve symptoms such as insomnia, rash and diarrhea of patients with lung accumulation (lung cancer and pulmonary nodule), and improve the life quality of the patients.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and in particular to a Fuzheng Sanjie prescription for treating non-small cell lung cancer and a preparation method thereof. Background Art

[0002] Lung cancer is the most common cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of patients. At present, the research status of non-small cell lung cancer shows a trend of diversification and rapid development. In recent years, the research on targeted drugs for multiple targets such as EGFR, ALK, ROS1, RET, HER-2, BRAF, MET, etc. has achieved remarkable results. These drugs can directly act on the lesions, especially for NSCLC patients with specific gene mutations, the therapeutic effect is particularly significant. Among them, more than 30% of NSCLC patients have epidermal growth factor receptor (EGFR) mutations, and tyrosine kinase inhibitors (TKI) have completely rewritten the diagnosis and treatment pattern of EGFR mutant NSCLC patients. The third-generation EGFR-TKI osimertinib is the first-line drug for patients with advanced EFGR mutations and the second-line drug for T790M mutations after resistance to the first and second generation EGFR-TKIs. It shows a high remission rate and durable disease control, but most patients will develop acquired resistance about one year after treatment. The resistance mechanism of osimertinib is relatively complex, and there is a lack of drugs that can be used to replace osimertinib. Actively exploring drugs that can delay osimertinib resistance is an important issue that needs to be solved in the current social development.

[0003] In terms of clinical treatment research, with the in-depth understanding of tumor biology, the treatment strategy of NSCLC has shifted from traditional chemotherapy to more precise targeted therapy and immunotherapy. At the same time, targeted drugs for specific gene mutations continue to emerge, allowing NSCLC patients with specific gene mutations to receive more precise treatment. In addition, researchers are constantly exploring new drug combinations and treatment strategies to improve patients' survival rate and quality of life. Traditional Chinese medicine plays a good role in enhancing efficacy and reducing toxicity in the treatment of non-small cell lung cancer (NSCLC). Studies have shown that (1) taking Chinese medicine during radiotherapy and chemotherapy can significantly reduce the toxicity of radiotherapy and chemotherapy, regulate immune function and increase blood cells. (2) After surgery and radiotherapy and chemotherapy, Chinese medicine can strengthen the body and eliminate evil, consolidate the therapeutic effect, and reduce the recurrence and metastasis of lung cancer; (3) Patients with advanced disease or lesions that are not suitable for surgery or radiotherapy and chemotherapy can take Chinese medicine to control tumor growth, alleviate symptoms, improve quality of life, and prolong survival. However, the current evidence summary is not sufficient, and further research and expansion of the effect of traditional Chinese medicine in the treatment of non-small cell lung cancer is needed in the future. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a Fuzheng Sanjie prescription for treating non-small cell lung cancer and a preparation method thereof in view of the above-mentioned defects of the prior art.

[0005] The technical solution adopted by the present invention to solve its technical problem is:

[0006] A Fuzheng Sanjie prescription for treating non-small cell lung cancer is constructed, wherein the prescription is made of the following raw materials in the following weight ratio:

[0007] Five-fingered peach 2g~50g / portion, Pseudostellaria pseudoginseng 2g~50g / portion, Poria 2g~50g / portion, Atractylodes macrocephala 2g~50g / portion, Scutellaria baicalensis 2g~50g / portion, Oldenlandia diffusa 2g~50g / portion, Cat's Claw 2g~50g / portion, Polygonum cuspidatum 2g~50g / portion, Curcuma 2g~50g / portion, Oyster 2g~50g / portion, Platycodon grandiflorum 2g~50g / portion, Trillium gracile 2g~50g / portion, Scutellaria barbata 2g~50g / portion.

[0008] The Fuzheng Sanjie prescription for treating non-small cell lung cancer of the present invention is prepared from the following raw materials in the following weight ratio:

[0009] Five-fingered peach 2g / portion, Pseudostellaria pseudoginseng 2g / portion, Poria 2g / portion, Atractylodes macrocephala 2g / portion, Scutellaria baicalensis 2g / portion, Oldenlandia diffusa 2g / portion, Cat's Claw 2g / portion, Polygonum cuspidatum 2g / portion, Curcuma 2g / portion, Oyster 2g / portion, Platycodon grandiflorum 2g / portion, Trillium gracile 2g / portion, Scutellaria barbata 2g / portion.

[0010] The Fuzheng Sanjie prescription for treating non-small cell lung cancer of the present invention is prepared from the following raw materials in the following weight ratio:

[0011] 50g / portion of Prunus mume, 50g / portion of Pseudostellaria chinensis, 50g / portion of Poria cocos, 50g / portion of Atractylodes macrocephala, 50g / portion of Scutellaria baicalensis, 50g / portion of Hedyotis diffusa, 50g / portion of Cat's Claw, 50g / portion of Polygonum cuspidatum, 50g / portion of Curcuma zedoaria, 50g / portion of Oyster, 50g / portion of Platycodon grandiflorum, 50g / portion of Trillium gracile, and 50g / portion of Scutellaria barbata.

[0012] The present invention also includes a method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, wherein the method comprises the following steps:

[0013] Step 11, take the raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellariae baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata;

[0014] Step 12, prepare water decoction: soak the medicine in water for 30 minutes, then boil it again. The amount of water for the first decoction is enough to cover the medicine by 5 cm. Boil it over high heat first and then simmer it over low heat for 20 minutes, and pour out the medicine liquid. For the second decoction, the amount of water is enough to cover the medicine by 2 cm. Boil it over high heat first and then simmer it over low heat for 15 minutes. Mix the two medicine liquids together, and then divide them into two equal parts.

[0015] The present invention also includes a method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, wherein the method comprises the following steps:

[0016] Step 21, take the raw materials according to the following weight ratio: 2g~50g / portion of fennel, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellaria baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata;

[0017] Step 22, preparing pills: the above-mentioned raw materials are made into drug powder or drug extract, and an appropriate amount of adhesive is added to make pills.

[0018] The preparation method of the Fuzheng Sanjie prescription for treating non-small cell lung cancer of the present invention, wherein the pills are honey pills, and the specific preparation method is: the medicine is beaten into fine powder, and then refined honey is used as a binder to make honey pills;

[0019] Alternatively, the pills are water pills, and the specific preparation method is: grind the medicine into fine powder, use water or vinegar, wine, or medicine juice as a binder, roll it into a ball shape, and make it into water pills;

[0020] Alternatively, the pills are paste pills, and the specific preparation method is: the drug is ground into fine powder, and rice paste, flour paste, koji paste and other materials are used as adhesives to make small pills;

[0021] Alternatively, the pills are concentrated pills, and the specific preparation method is: decoct part of the medicine in the medicine or prescription into juice, concentrate it into a paste, mix it with the remaining medicine fine powder, dry and crush it, and make it into pills with water, honey or medicine juice.

[0022] The present invention also includes a method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, wherein the method comprises the following steps:

[0023] Step 31, take the raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellariae baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata;

[0024] Step 32, prepare powder: wash and dry the above raw materials to remove impurities; mix different medicinal materials in proportion according to the requirements of the prescription; grind the dried Chinese herbal medicines into fine powder using traditional stone mortar grinding, mechanical grinding or ultrafine grinding methods, screen the ground medicinal materials through a sieve to remove large particles or impurities that have not been ground properly to ensure that the powder is uniform and fine; mix the screened medicinal material powders according to the formula ratio to ensure that the various medicinal materials are fully integrated so that the preparation has certain efficacy and stability.

[0025] The present invention also includes a method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, wherein the method comprises the following steps:

[0026] Step 41, taking the raw materials according to the following weight ratio: 2g~50g / portion of Prunus mume, 2g~50g / portion of Phellodendron chinense, 2g~50g / portion of Poria cocos, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellaria baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma zedoaria, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata;

[0027] Step 42, preparing an ointment: soak the above raw materials in 8 to 10 times the amount of water; decoct using a water decoction method to obtain a decoction; if required, a third decoction may be taken; combine the drug solutions for precipitation; after precipitation, sieve the solution to remove impurities; put the filtrate obtained into a copper pot or other large container and boil over high heat to concentrate; concentrate to a state close to the formation of an ointment, filter the drug solution again with gauze or a 100-mesh sieve to remove impurities, and use a low heat to collect the ointment. Stir continuously during the process of collecting the ointment, and boil for a period of time until the desired consistency is reached.

[0028] The beneficial effects of the present invention are as follows: the prescription for strengthening the body and dispersing the knots of the present invention comprises quinquefolius, pseudoginseng, tuckahoe, atractylodes, scutellaria, oldenlandia diffusa, cat's claw, knotweed, curcuma, oyster, platycodon, trillium, and scutellaria barbata; among them, quinquefolius is sweet in taste, neutral in nature, enters the spleen, lung, and liver meridians, has the effects of strengthening the spleen and tonifying the lungs, promoting qi and removing dampness, relaxing muscles and tendons, and can invigorate qi and tonify deficiency without causing warming and dryness; pseudoginseng is sweet, slightly bitter in taste, neutral in nature, enters the spleen and lung meridians, can invigorate qi and invigorate the spleen, promote fluid production and moisten the lungs, treat qi deficiency and invigorate spleen and earth, and is a product for clearing and tonifying the lungs and spleen. The two herbs have the effects of strengthening the body and tonifying deficiency, invigorating the lungs and invigorating the spleen, and are the main medicines together. Poria tastes sweet and mild, and is neutral in nature. It enters the heart, lung, spleen, and kidney meridians; Atractylodes tastes sweet and bitter, and is slightly warm in nature. It enters the spleen and stomach meridians. Both of them invigorate Qi and strengthen the spleen, promote diuresis and dry dampness, and together help Cistanche deserticola and Pseudostellaria pseudoginseng to nourish vital Qi, strengthen the spleen and replenish deficiency, and are both ministerial drugs. Scutellaria baicalensis is bitter and cold in nature. It enters the lung, gallbladder, spleen, large intestine and small intestine meridians, and can clear lung heat and eliminate evil toxins; Hedyotis diffusa tastes bitter and light and cold in nature. It enters the stomach, large intestine and small intestine meridians, and can clear away heat, detoxify and reduce swelling; Cat's Claw tastes sweet and pungent in nature and warm in nature. It enters the liver and lung meridians, and can resolve phlegm and relieve depression; Polygonum cuspidatum tastes bitter and slightly cold in nature. It enters the liver, gallbladder and lung meridians, and can resolve heat and toxins and eliminate blood stasis and swelling; Curcuma zedoaria tastes pungent and pungent in nature and warm in nature. It enters the liver and spleen meridians, and has the functions of breaking blood, promoting qi, dispersing blood stasis and eliminating accumulation; Radix Achyranthis Bidentatae tastes bitter and pungent in flavor and neutral in nature. It enters the heart and liver meridians, and can promote blood circulation, dispersing blood stasis, clearing away heat and detoxifying; Oyster tastes salty and slightly cold in nature. It enters the liver, gallbladder and kidney meridians, and can soften hard masses and eliminate symptoms. The seven medicines together have the effects of strengthening the body, replenishing deficiency, dispersing nodules and reducing swelling, and are collectively adjuvants. Platycodon grandiflorum is bitter and pungent, neutral in nature, and enters the lung meridian. It is the boat of all medicines, leading the medicinal power of each medicine upward and entering the lung meridian, and is the guiding medicine. All medicines are harmonious and compatible with each other, playing the effect of strengthening the body, replenishing the deficiency, reducing swelling and dispersing nodules, and treating lung accumulation of lung and spleen qi deficiency type.

[0029] In actual application, clinical observations have found that Fuzheng Sanjie Formula can improve symptoms such as insomnia, rash, diarrhea, etc. in patients with lung accumulation (lung cancer, lung nodules), and improve their quality of life. By constructing an animal model of NSCLC osimertinib resistance, and giving Fuzheng Sanjie Formula 1.5 mg / kg / d by gavage for 21 days, the tumor volume was measured every day and the tumor growth curve was drawn. The results showed that the rate of tumor growth curve decreased after treatment with Fuzheng Sanjie Formula. After 21 days, the tumor volume of the Fuzheng Sanjie Formula group was smaller than that of the model group, and the difference was statistically significant; by immunohistochemical staining of the tumor pathological sections of the two groups to mark the cell proliferation marker Ki67, the results showed that the Ki67 positive rate of the tumor sections of the Fuzheng Sanjie Formula group was lower than that of the model group, and the difference was statistically significant.

[0030] The serum containing Fuzheng Sanjie recipe was used to intervene in osimertinib-sensitive and -resistant cells (H1975N and H1975OR) with gradient concentrations for 48 to 96 hours, and the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results showed that the serum containing Fuzheng Sanjie recipe had no obvious direct killing effect on osimertinib-resistant cells, so Fuzheng Sanjie recipe may inhibit the growth of osimertinib-resistant cells by regulating TME. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the present invention will be further described below in conjunction with the accompanying drawings and embodiments. The accompanying drawings described below are only some implementation cases of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without creative work:

[0032] Figure 1 A reference diagram of drug-target prediction results of the Fuzheng Sanjie prescription network pharmacology according to a preferred embodiment of the present invention;

[0033] Figure 2 This is a graph showing the effect of Fuzheng Sanjie Recipe on the growth of osimertinib-resistant cells detected by in vitro and in vivo experiments in a preferred embodiment of the present invention;

[0034] in, Figure 2 A, Tumor growth curves of the in vivo experimental model group and the Fuzheng Sanjie prescription group; Figure 2 B. Statistical bar graph of Ki67 positive rate in tumor pathological sections of in vivo experimental model group and Fuzheng Sanjie prescription group (*P<0.05vs.Model); Figure 2 C, Representative images of Ki67 immunohistochemical staining of tumor pathological sections in the in vivo experimental model group and the Fuzheng Sanjie prescription group; Figure 2 DF and CCK8 were used to detect the effects of different concentrations of serum containing Fuzheng Sanjie prescription on the viability of H1975 N and H1975 OR cells.

[0035] Figure 3 This is the first test result of constructing an NSCLC osimertinib-resistant animal model according to a preferred embodiment of the present invention;

[0036] Figure 4 The second test result of constructing an NSCLC osimertinib-resistant animal model according to a preferred embodiment of the present invention;

[0037] Figure 5 This is a comparison of CT scans before and after the treatment of lung accumulation (lung cancer, lung nodules) by the Fuzheng Sanjie prescription in a preferred embodiment of the present invention;

[0038] Figure 6 The clinical statistics of the preferred embodiment of the present invention show the usage of the Fuzheng Sanjie Recipe, an in-hospital agreement prescription, in the past three years (clinical data statistical results);

[0039] Figure 7 The first result of the in vitro growth inhibition test of common types of non-small cell lung cancer cells by the Fuzheng Sanjie Formula (FZSJF) of the preferred embodiment of the present invention;

[0040] Figure 8The second result of the in vitro growth inhibition test of common types of non-small cell lung cancer cells by the Fuzheng Sanjie Formula (FZSJF) of the preferred embodiment of the present invention;

[0041] Fig. 9 The third result of the in vitro growth inhibition test on common types of non-small cell lung cancer cells by Fuzheng Sanjie Formula (FZSJF), a preferred embodiment of the present invention. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the following will be described clearly and completely in combination with the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are partial embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0043] A preferred embodiment of the present invention discloses a Fuzheng Sanjie prescription for treating non-small cell lung cancer, which is preferably prepared from the following raw materials in weight ratio: 2g-50g / portion of Wuzhiyi Cai, 2g-50g / portion of Pseudostellariae Radix, 2g-50g / portion of Poria, 2g-50g / portion of Atractylodes macrocephala, 2g-50g / portion of Scutellaria baicalensis, 2g-50g / portion of Hedyotis diffusa, 2g-50g / portion of Cat's Claw, 2g-50g / portion of Polygonum cuspidatum, 2g-50g / portion of Curcuma, 2g-50g / portion of Oyster, 2g-50g / portion of Platycodon grandiflorum, 2g-50g / portion of Trillium, and 2g-50g / portion of Scutellaria barbata.

[0044] In the Fuzheng Sanjie prescription of the present invention, the five-fingered ginseng is sweet and mild in nature, enters the spleen, lung and liver meridians, has the effects of strengthening the spleen and tonifying the lungs, promoting qi and removing dampness, relaxing muscles and activating collaterals, and can replenish qi and tonify deficiency without warming and drying; the Pseudostellariae Radix is ​​sweet and slightly bitter in nature and mild in nature, enters the spleen and lung meridians, can replenish qi and strengthen the spleen, promote fluid and moisten the lungs, treat qi deficiency and tonify spleen and earth, and is a product for clearing and tonifying the lungs and spleen, and the two play the effects of strengthening the body and tonifying deficiency, tonifying the lungs and strengthening the spleen, and are the main medicines. Poria cocos is sweet and mild in taste and mild in nature, enters the heart, lung, spleen and kidney meridians; Atractylodes macrocephala is sweet and bitter in taste and slightly warm in nature, enters the spleen and stomach meridians, and the two replenish qi and strengthen the spleen, promote diuresis and dry dampness, and help the five-fingered ginseng and Pseudostellariae Radix to cultivate and tonify the positive energy, strengthen the spleen and tonify deficiency, and are the minister medicines. Scutellaria baicalensis is bitter and cold in nature. It enters the lung, gallbladder, spleen, large intestine and small intestine meridians, and can clear lung heat and eliminate evil toxins; Hedyotis diffusa tastes bitter and light and cold in nature. It enters the stomach, large intestine and small intestine meridians, and can clear away heat, detoxify and reduce swelling; Cat's Claw tastes sweet and pungent in nature and warm in nature. It enters the liver and lung meridians, and can resolve phlegm and relieve depression; Polygonum cuspidatum tastes bitter and slightly cold in nature. It enters the liver, gallbladder and lung meridians, and can resolve heat and toxins and eliminate blood stasis and swelling; Curcuma zedoaria tastes pungent and pungent in nature and warm in nature. It enters the liver and spleen meridians, and has the functions of breaking blood, promoting qi, dispersing blood stasis and eliminating accumulation; Radix Achyranthis Bidentatae tastes bitter and pungent in flavor and neutral in nature. It enters the heart and liver meridians, and can promote blood circulation, dispersing blood stasis, clearing away heat and detoxifying; Oyster tastes salty and slightly cold in nature. It enters the liver, gallbladder and kidney meridians, and can soften hard masses and eliminate symptoms. The seven medicines together have the effects of strengthening the body, replenishing deficiency, dispersing nodules and reducing swelling, and are collectively adjuvants. Platycodon grandiflorum is bitter and pungent, neutral in nature, and enters the lung meridian. It is the boat of all medicines, leading the medicinal power of each medicine upward and entering the lung meridian, and is the guiding medicine. All medicines are harmonious and compatible with each other, playing the effect of strengthening the body, replenishing the deficiency, reducing swelling and dispersing nodules, and treating lung accumulation of lung and spleen qi deficiency type.

[0045] In actual application, clinical observations have found that Fuzheng Sanjie Formula can improve symptoms such as insomnia, rash, diarrhea, etc. in patients with lung accumulation (lung cancer, lung nodules), and improve their quality of life. By constructing an animal model of NSCLC osimertinib resistance, and giving Fuzheng Sanjie Formula 1.5 mg / kg / d by gavage for 21 days, the tumor volume was measured every day and the tumor growth curve was drawn. The results showed that the rate of tumor growth curve decreased after treatment with Fuzheng Sanjie Formula. After 21 days, the tumor volume of the Fuzheng Sanjie Formula group was smaller than that of the model group, and the difference was statistically significant; by immunohistochemical staining of the tumor pathological sections of the two groups to mark the cell proliferation marker Ki67, the results showed that the Ki67 positive rate of the tumor sections of the Fuzheng Sanjie Formula group was lower than that of the model group, and the difference was statistically significant.

[0046] The serum containing Fuzheng Sanjie recipe was used to intervene in osimertinib-sensitive and -resistant cells (H1975N and H1975OR) with gradient concentrations for 48 to 96 hours, and the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results showed that the serum containing Fuzheng Sanjie recipe had no obvious direct killing effect on osimertinib-resistant cells, so Fuzheng Sanjie recipe may inhibit the growth of osimertinib-resistant cells by regulating TME.

[0047] The following is a further detailed description of the present invention's Fuzheng Sanjie prescription and its preparation method through several specific implementation cases:

[0048] Example 1

[0049] The raw materials are taken according to the following weight ratio: 2g / portion of quinquefolius, 2g / portion of Pseudostellaria sutchuenensis, 2g / portion of Poria cocos, 2g / portion of Atractylodes macrocephala, 2g / portion of Scutellaria baicalensis, 2g / portion of Oldenlandia diffusa, 2g / portion of Cat's Claw, 2g / portion of Polygonum cuspidatum, 2g / portion of Curcuma zedoaria, 2g / portion of Oyster, 2g / portion of Platycodon grandiflorum, 2g / portion of Trillium gracile, and 2g / portion of Scutellaria barbata.

[0050] Preparation of pills: Grind the above-mentioned medicines into fine powder, and then use refined honey as a binder to make Fu Zheng San Jie Fang honey pills.

[0051] Example 2

[0052] The raw materials are taken according to the following weight ratio: 3g / portion of quinquefolius, 5g / portion of Pseudostellaria sutchuenensis, 6g / portion of Poria cocos, 3g / portion of Atractylodes macrocephala, 4g / portion of Scutellaria baicalensis, 2.5g / portion of Oldenlandia diffusa, 5g / portion of Cat's Claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma zedoaria, 8g / portion of Oyster, 11g / portion of Platycodon grandiflorum, 5g / portion of Trillium gracile, and 82g / portion of Scutellaria barbata.

[0053] Preparation of pills: Grind the above drugs into fine powder, add water or vinegar, wine, or medicinal juice as a binder, roll them into balls, and make them into Fu Zheng San Jie Fang water pills.

[0054] Example 3

[0055] The raw materials are taken according to the following weight ratio: 3g / portion of quinquefolius, 5g / portion of Pseudostellaria sutchuenensis, 6g / portion of Poria cocos, 3g / portion of Atractylodes macrocephala, 4g / portion of Scutellaria baicalensis, 2.5g / portion of Oldenlandia diffusa, 5g / portion of Cat's Claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma zedoaria, 8g / portion of Oyster, 11g / portion of Platycodon grandiflorum, 5g / portion of Trillium gracile, and 8g / portion of Scutellaria barbata.

[0056] Preparation of paste pills: Grind the medicine into fine powder, use rice paste, flour paste, koji paste and other materials as adhesives to make paste pills of Fu Zheng San Jie formula.

[0057] Example 4

[0058] The raw materials are taken according to the following weight ratio: 9g / portion of quinquefolius, 11g / portion of pseudoginseng, 6g / portion of Poria, 7g / portion of Atractylodes macrocephala, 5g / portion of Scutellaria baicalensis, 12g / portion of Oldenlandia diffusa, 5g / portion of Cat's Claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma, 8g / portion of Oyster, 9g / portion of Platycodon grandiflorum, 8g / portion of Trillium, and 8g / portion of Scutellaria barbata.

[0059] The concentrated pills are prepared by decocting the above-mentioned medicines or part of the medicines in the prescriptions, concentrating the decoction into a paste, mixing the decoction with the remaining medicine powder, drying and crushing the decoction, and making the Fuzheng Sanjie prescription concentrated pills with water, honey or the decoction.

[0060] Example 5

[0061] The raw materials are taken according to the following weight ratio: 50g / portion of quinquefolius, 50g / portion of Pseudostellaria chinensis, 50g / portion of Poria cocos, 50g / portion of Atractylodes macrocephala, 50g / portion of Scutellaria baicalensis, 50g / portion of Hedyotis diffusa, 50g / portion of Cat's Claw, 50g / portion of Polygonum cuspidatum, 50g / portion of Curcuma zedoaria, 50g / portion of Oyster, 50g / portion of Platycodon grandiflorum, 50g / portion of Trillium gracile, and 50g / portion of Scutellaria barbata.

[0062] Preparation of water decoction of Fuzheng Sanjie prescription: soak the above medicines in water for 30 minutes, then boil them. The amount of water for the first decoction should be enough to cover the medicines by 5 cm. Boil them over high heat first and then simmer for 20 minutes, then pour out the medicine liquid. For the second decoction, the amount of water should be enough to cover the medicines by 2 cm. Boil them over high heat first and then simmer for 15 minutes. Mix the two medicine liquids together (about 500 mL), then divide them into two portions, take one portion in the morning and evening (about 250 ml each), and take them warm.

[0063] Example 6

[0064] Take the raw materials according to the following weight ratio: 2g~50g / portion of Prunus mume, 2g~50g / portion of Pseudostellaria chinensis, 2g~50g / portion of Poria cocos, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellaria baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma zedoaria, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, 2g~50g / portion of Scutellaria barbata;

[0065] Preparation of Fuzheng Sanjie Formula Powder: Wash and dry the above raw materials to remove impurities; mix different medicinal materials in proportion according to the requirements of the prescription; grind the dried Chinese herbal medicines into fine powder using traditional stone mortar grinding, mechanical grinding or ultrafine grinding methods, screen the ground medicinal materials through a sieve to remove large particles or impurities that have not been ground properly to ensure that the powder is uniform and fine; mix the screened medicinal material powders according to the formula ratio to ensure that the various medicinal materials are fully integrated so that the preparation has certain efficacy and stability.

[0066] Example 7

[0067] Take the raw materials according to the following weight ratio: 45g / portion of Prunus mume, 42g / portion of Pseudostellaria chinensis, 38g / portion of Poria cocos, 35g / portion of Atractylodes macrocephala, 45g / portion of Scutellaria baicalensis, 23g / portion of Hedyotis diffusa, 42g / portion of Cat's Claw, 30g / portion of Polygonum cuspidatum, 23g / portion of Curcuma zedoaria, 25g / portion of Oyster, 40g / portion of Platycodon grandiflorum, 45g / portion of Tripterygium wilfordii, and 35g / portion of Scutellaria barbata;

[0068] Preparation of Fuzheng Sanjie prescription ointment: Soak the above raw materials in 8 to 10 times the amount of water; decoct using a water decoction method to obtain a decoction; a third decoction may be taken if required; combine the medicinal liquids for precipitation; sieve through a mesh to remove impurities after precipitation; put the filtrate obtained into a copper pot or other large container and boil over high heat to concentrate; concentrate to a state close to the formation of an ointment, filter the medicinal liquid again with gauze or a 100-mesh sieve to remove impurities, and use a low heat to collect the ointment, stirring constantly during the ointment collection process, and boil for a period of time until the desired consistency is reached.

[0069] The active ingredients, molecular targets and pathways of Fuzheng Sanjie prescription were predicted by network pharmacology drug-target, such as Figure 1 As shown: Network pharmacology drug-target prediction showed that the active ingredients of Fuzheng Sanjie prescription include resveratrol, acacetin, apigenin, etc., and its anti-NSCLC effect pathway suggests that it is related to EGER-TKI resistance.

[0070] like Figure 2 As shown in the results, an animal model of osimertinib-resistant NSCLC was constructed and given Fuzheng Sanjie Formula (FZSJF) 1.5 mg / kg / d by oral gavage for 21 days. The tumor volume was measured every 3 days and the tumor growth curve was drawn. The results showed that the tumor growth curve rate was reduced after treatment with FZSJF. After 21 days, the tumor volume in the FZSJF group was smaller than that in the model group, and the difference was statistically significant (see Figure 2 A); Immunohistochemical staining of the tumor sections of the two groups to mark the cell proliferation marker Ki67 showed that the Ki67 positive rate of the tumor sections of the Fuzheng Sanjie Fang group was lower than that of the model group (see Figure 2 C), the difference was statistically significant (see Figure 2 B).

[0071] The gradient concentration of serum containing Fuzheng Sanjie Formula (FZSJF) intervened in osimertinib-sensitive and -resistant cells (H1975N and H1975 OR) for 48-96 hours ( Figure 2 DF), the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results showed that the serum containing Fuzheng Sanjie Formula (FZSJF) had no obvious direct killing effect on osimertinib-resistant cells, so Fuzheng Sanjie Formula may inhibit the growth of osimertinib-resistant cells by regulating TME.

[0072] in: Figure 2 A, Tumor growth curves of the in vivo experimental model group and the Fuzheng Sanjie prescription group; Figure 2 B. Statistical bar graph of Ki67 positive rate in tumor pathological sections of in vivo experimental model group and Fuzheng Sanjie prescription group (*P<0.05vs.Model); Figure 2C, Representative images of Ki67 immunohistochemical staining of tumor pathological sections in the in vivo experimental model group and the Fuzheng Sanjie prescription group; Figure 2 DF and CCK8 were used to detect the effects of different concentrations of serum containing Fuzheng Sanjie prescription on the viability of H1975 N and H1975 OR cells; Figure 2 D. 48hr; Figure 2 E. 72hr; Figure 2 F. 96hr.

[0073] Clinical observations of a large number of actual cases have shown that the Fuzheng Sanjie prescriptions prepared in the embodiments of the present invention can improve symptoms such as insomnia, rash, diarrhea, etc. in patients with lung accumulation (lung cancer, lung nodules) and improve their quality of life.

[0074] Figure 3-4 In order to construct an animal model of osimertinib resistance in NSCLC, the model mice were randomly divided into 4 groups (NC group, FZSJF group, OSI group and combination group). The NC group (model group) was given 200 μL / d of normal saline by gavage for 11 days, the FZSJF group and the combination group were given Fuzheng Sanjie Formula (FZSJF) 3 mg / kg / d by gavage for 11 days, and the OSI group and the combination group were given osimertinib (OSI) 10 mg / kg / d by gavage for 11 days. The tumor volume was measured every 3 days and the tumor growth curve was drawn. The results showed that the tumor growth curve rate was reduced after treatment with Fuzheng Sanjie Formula or combined with osimertinib, as shown in Figure 2. Figure 3 The following is a general picture of the tumor volume in each group. After 11 days, the tumor volume in the Fuzheng Sanjie prescription group and the combined group was smaller than that in the model group, and the difference was statistically significant (see Figure 4 ).

[0075] Figure 5 Comparison of CT scans before and after treatment of lung accumulation (lung cancer, lung nodules) in our hospital with Fuzheng Sanjie prescription

[0076] Patients with solitary pulmonary nodules with ground-glass nodules who visited the respiratory outpatient clinic of our hospital between 2022 and 2023 were selected. Lung cancer was not excluded by pathology. They were clinically treated with Fuzheng Sanjie Fang for 6 months. The CT scans of the patients before and after treatment showed that the lesions in the lung imaging became smaller. The chest CT scan in the figure shows that the ground-glass nodules in the right upper lobe of the patient with "lung accumulation" were about 7*7mm in size before Fuzheng Sanjie Fang treatment, and the size of the nodules was about 7*3mm after treatment.

[0077] Figure 6 To clinically count the use of the Fuzheng Sanjie Recipe, an in-hospital prescription, in the past three years (clinical data statistics results)

[0078] Fuzheng Sanjie prescription has been used for several years to treat qi deficiency and blood stasis type lung accumulation, and has been used as an in-hospital agreement kitchen for a long time. The number of prescriptions prescribed each year is large, the patient compliance is high, and the dropout rate is low. Specifically, 270 doses were prescribed from June to August 2022, 672 doses were prescribed from September to November 2022, 612 doses were prescribed from December 2022 to February 2023, and 438 doses were prescribed from March to April 2023. Fuzheng Sanjie prescription has been used for several years to treat qi deficiency and blood stasis type lung accumulation, and has been used as an in-hospital preparation for a long time. The number of prescriptions prescribed each year is large and continues to increase, the patient compliance is high, and the dropout rate is low. In actual clinical application, clinical observations have found that Fuzheng Sanjie prescription can improve symptoms such as insomnia, rash, diarrhea, etc. in patients with lung accumulation (lung cancer, lung nodules), and improve their quality of life.

[0079] Case: Clinical trials of the Chinese medicine preparation described in the present invention were applied to patients with pulmonary nodules to improve their symptoms. Three cases:

[0080] 1. Deng Moumou, female, 57 years old, had a history of right lung nodule (carcinoma in situ) surgery, rheumatoid arthritis, and diabetes. After treatment, she had cough and white sputum, no chest tightness or pain, no hot flashes or night sweats, good appetite, constipation, and normal sleep.

[0081] 2. Dong, female, 40 years old, was diagnosed with lung nodules (CT showed: ground glass nodules in the apical segment of the right upper lobe were shallowly lobed, about 6*5mm in size) for 3 weeks. She had no cough or sputum, no hot flashes or night sweats, no chest tightness or pain, no shortness of breath, no nausea or vomiting, and usually stayed up late. She came to the clinic with good appetite, normal bowel movements, and poor sleep. After one month of treatment with Fuzheng Sanjie Decoction, the patient's insomnia symptoms improved.

[0082] 3. Huang, female, 52 years old, was found to have lung nodules during physical examination (CT showed: ground glass nodules in the left lower lobe of the lung, with a diameter of about 5mm.) for more than a month, and had no cough or sputum, no hot flashes or night sweats, no chest tightness or pain, no shortness of breath, no nausea or vomiting. She came to the clinic for a follow-up examination, and had a good appetite, regular bowel movements, and poor sleep. After one month of treatment with Fuzheng Sanjie Decoction, the patient's insomnia symptoms improved.

[0083] Figure 7-9 Three types of non-small cell lung cancer cells (H226, H1299, and A549) were intervened with Fu Zheng San Jie Fang (FZSJF) in vitro for 48 hours, and the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results showed that Fu Zheng San Jie Fang (FZSJF) had a certain inhibitory effect on the growth of non-small cell lung cancer cells in vitro.

[0084] Moreover, with the widespread application of traditional Chinese medicine in tumor prevention and treatment, a large amount of data suggests that traditional Chinese medicine combined with anti-tumor drugs has better clinical benefits for NSCLC patients. Traditional Chinese medicine combined with EGFR-TKIs can also play a synergistic role in enhancing efficacy and reducing toxicity, while delaying the occurrence of EGFR-TKIs resistance.

[0085] It should be understood that those skilled in the art can make improvements or changes based on the above description, and all these improvements and changes should fall within the scope of protection of the appended claims of the present invention.

Claims

1. A Fuzheng Sanjie prescription for treating non-small cell lung cancer, characterized in that: Made from the following raw materials in the following weight ratio: Five-fingered peach 2g~50g / portion, Pseudostellaria pseudoginseng 2g~50g / portion, Poria 2g~50g / portion, Atractylodes macrocephala 2g~50g / portion, Scutellaria baicalensis 2g~50g / portion, Oldenlandia diffusa 2g~50g / portion, Cat's Claw 2g~50g / portion, Polygonum cuspidatum 2g~50g / portion, Curcuma 2g~50g / portion, Oyster 2g~50g / portion, Platycodon grandiflorum 2g~50g / portion, Trillium gracile 2g~50g / portion, Scutellaria barbata 2g~50g / portion.

2. The Fuzheng Sanjie prescription for treating non-small cell lung cancer according to claim 1, characterized in that: Made from the following raw materials in the following weight ratio: Five-fingered peach 2g / portion, Pseudostellaria pseudoginseng 2g / portion, Poria 2g / portion, Atractylodes macrocephala 2g / portion, Scutellaria baicalensis 2g / portion, Oldenlandia diffusa 2g / portion, Cat's Claw 2g / portion, Polygonum cuspidatum 2g / portion, Curcuma 2g / portion, Oyster 2g / portion, Platycodon grandiflorum 2g / portion, Trillium gracile 2g / portion, Scutellaria barbata 2g / portion.

3. The Fuzheng Sanjie prescription for treating non-small cell lung cancer according to claim 1, characterized in that: Made from the following raw materials in the following weight ratio: 50g / portion of Prunus mume, 50g / portion of Pseudostellaria chinensis, 50g / portion of Poria cocos, 50g / portion of Atractylodes macrocephala, 50g / portion of Scutellaria baicalensis, 50g / portion of Hedyotis diffusa, 50g / portion of Cat's Claw, 50g / portion of Polygonum cuspidatum, 50g / portion of Curcuma zedoaria, 50g / portion of Oyster, 50g / portion of Platycodon grandiflorum, 50g / portion of Trillium gracile, and 50g / portion of Scutellaria barbata.

4. A method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 11, take the raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellariae baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata; Step 12, prepare water decoction: soak the medicine in water for 30 minutes, then boil it again. The amount of water for the first decoction is enough to cover the medicine by 5 cm. Boil it over high heat first and then simmer it over low heat for 20 minutes, and pour out the medicine liquid. For the second decoction, the amount of water is enough to cover the medicine by 2 cm. Boil it over high heat first and then simmer it over low heat for 15 minutes. Mix the two medicine liquids together, and then divide them into two equal parts.

5. A method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 21, take the raw materials according to the following weight ratio: 2g~50g / portion of fennel, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellaria baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata; Step 22, preparing pills: the above-mentioned raw materials are made into drug powder or drug extract, and an appropriate amount of adhesive is added to make pills.

6. The method for preparing the Fuzheng Sanjie prescription for treating non-small cell lung cancer according to claim 5, characterized in that: The pills are honey pills, and the specific preparation method is: the medicine is ground into fine powder, and then refined honey is used as a binder to make honey pills; Alternatively, the pills are water pills, and the specific preparation method is: grind the medicine into fine powder, use water or vinegar, wine, or medicine juice as a binder, roll it into a ball shape, and make it into water pills; Alternatively, the pills are paste pills, and the specific preparation method is: the drug is ground into fine powder, and rice paste, flour paste, koji paste and other materials are used as adhesives to make small pills; Alternatively, the pills are concentrated pills, and the specific preparation method is: decoct part of the medicine in the medicine or prescription into juice, concentrate it into a paste, mix it with the remaining medicine fine powder, dry and crush it, and make it into pills with water, honey or medicine juice.

7. A method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 31, take the raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of Pseudostellariae Radix, 2g~50g / portion of Poria, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellariae baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata; Step 32, prepare powder: wash and dry the above raw materials to remove impurities; mix different medicinal materials in proportion according to the requirements of the prescription; grind the dried Chinese herbal medicines into fine powder using traditional stone mortar grinding, mechanical grinding or ultrafine grinding methods, screen the ground medicinal materials through a sieve to remove large particles or impurities that have not been ground properly to ensure that the powder is uniform and fine; mix the screened medicinal material powders according to the formula ratio to ensure that the various medicinal materials are fully integrated so that the preparation has certain efficacy and stability.

8. A method for preparing a Fuzheng Sanjie prescription for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 41, taking the raw materials according to the following weight ratio: 2g~50g / portion of Prunus mume, 2g~50g / portion of Phellodendron chinense, 2g~50g / portion of Poria cocos, 2g~50g / portion of Atractylodes macrocephala, 2g~50g / portion of Scutellaria baicalensis, 2g~50g / portion of Hedyotis diffusa, 2g~50g / portion of Cat's Claw, 2g~50g / portion of Polygonum cuspidatum, 2g~50g / portion of Curcuma zedoaria, 2g~50g / portion of Oyster, 2g~50g / portion of Platycodon grandiflorum, 2g~50g / portion of Tripterygium wilfordii, and 2g~50g / portion of Scutellaria barbata; Step 42, preparing an ointment: soak the above raw materials in 8 to 10 times the amount of water; decoct using a water decoction method to obtain a decoction; if required, a third decoction may be taken; combine the drug solutions for precipitation; after precipitation, sieve the solution to remove impurities; put the filtrate obtained into a copper pot or other large container and boil over high heat to concentrate; concentrate to a state close to the formation of an ointment, filter the drug solution again with gauze or a 100-mesh sieve to remove impurities, and use a low heat to collect the ointment. Stir continuously during the process of collecting the ointment, and boil for a period of time until the desired consistency is reached.

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