A fuzheng sanjie recipe for resisting non-small cell lung cancer and a preparation method thereof

Abstract

The present application relates to a kind of anti-non-small cell lung cancer for strengthening healthy qi and resolving stasis and preparation method thereof, strengthening healthy qi and resolving stasis is made from the following weight proportion of raw medicinal materials: Ficus pumila 2g~50g / portion, radix pseudostellariae 2g~50g / portion, poria cocos 2g~50g / portion, atractylodes 2g~50g / portion, radix scutellariae 2g~50g / portion, oldenlandia 2g~50g / portion, cat's paw grass 2g~50g / portion, giant knotweed 2g~50g / portion, curcuma zedoary 2g~50g / portion, oyster 2g~50g / portion, platycodon 2g~50g / portion, mountain bitterling 2g~50g / portion, half branch orchid 2g~50g / portion. By cell test and the construction NSCLC osimertin drug resistance animal model prove, strengthening healthy qi and resolving stasis of the present application can adjust tumor microenvironment (TME) and inhibit non-small cell lung cancer cell growth of osimertin drug resistance. Not only this, strengthening healthy qi and resolving stasis of the present application can also inhibit common non-small cell lung cancer cell growth. While clinical observation finds, strengthening healthy qi and resolving stasis of the present application can improve insomnia, skin rash, diarrhea and other symptoms of lung accumulation (lung cancer, lung nodule) patient, improve its quality of life.

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 approximately 85% of patients. Currently, NSCLC research is diverse and rapidly evolving. Recent research has yielded remarkable results targeting multiple targets, including EGFR, ALK, ROS1, RET, HER-2, BRAF, and MET. These drugs can act directly on lesions, demonstrating particularly significant therapeutic effects in NSCLC patients harboring specific genetic mutations. Over 30% of NSCLC patients harbor epidermal growth factor receptor (EGFR) mutations, and tyrosine kinase inhibitors (TKIs) have revolutionized the diagnosis and treatment of patients with EGFR-mutant NSCLC. The third-generation EGFR-TKI osimertinib is a first-line treatment for patients with advanced EGFR mutations and a second-line treatment for patients with the T790M mutation who develop resistance to first- and second-generation EGFR-TKIs. While it demonstrates high response rates and durable disease control, most patients develop acquired resistance approximately one year after treatment. Osimertinib resistance mechanisms are complex, and alternative drugs are relatively scarce. Actively exploring drugs that can delay osimertinib resistance is an important and pressing issue in 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 traditional 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, traditional 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 traditional 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 are 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 ratios:

[0007] Five-fingered ginseng 2g~50g / portion, Pseudostellaria 2g~50g / portion, Poria 2g~50g / portion, Atractylodes 2g~50g / portion, Scutellaria 2g~50g / portion, Hedyotis diffusa 2g~50g / portion, Cat's claw 2g~50g / portion, Polygonum cuspidatum 2g~50g / portion, Curcuma 2g~50g / portion, Oyster 2g~50g / portion, Platycodon 2g~50g / portion, Trillium 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 ratios:

[0009] Five-fingered ginseng 2g / portion, Pseudostellaria 2g / portion, Poria 2g / portion, Atractylodes macrocephala 2g / portion, Scutellaria baicalensis 2g / portion, Hedyotis diffusa 2g / portion, Cat's claw 2g / portion, Polygonum cuspidatum 2g / portion, Curcuma 2g / portion, Oyster 2g / portion, Platycodon grandiflorum 2g / portion, Tripterygium wilfordii 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 ratios:

[0011] 50g / portion of Prunus mume, 50g / portion of Pseudostellaria baicalensis, 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 pseudoginseng, 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 Psoralea corylifolia, 2g~50g / portion of Scutellaria barbata;

[0014] Step 12, prepare a decoction: soak the medicine in water for 30 minutes, then boil it again. The amount of water for the first decoction should be enough to cover the medicine by 5 cm. Boil it over high heat first and then simmer it over low heat for 20 minutes, then pour out the medicine liquid. For the second decoction, the amount of water should be enough to cover the medicine by 2 cm. Boil it over high heat first and then simmer it over low heat for 15 minutes. Combine the two medicine liquids, mix them evenly, 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 following raw materials according to the following weight ratio: five-fingered peach 2g ~ 50g / portion, Pseudostellaria 2g ~ 50g / portion, Poria 2g ~ 50g / portion, Atractylodes 2g ~ 50g / portion, Scutellaria 2g ~ 50g / portion, Hedyotis diffusa 2g ~ 50g / portion, Cat's Claw 2g ~ 50g / portion, Polygonum cuspidatum 2g ~ 50g / portion, Curcuma 2g ~ 50g / portion, Oyster 2g ~ 50g / portion, Platycodon 2g ~ 50g / portion, Psoralea corylifolia 2g ~ 50g / portion, Scutellaria barbata 2g ~ 50g / portion;

[0017] Step 22, preparing pills: the above-mentioned raw materials are made into drug powder or medicinal material extracts, and an appropriate amount of binder 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: grinding the medicine into fine powder, and then using refined honey 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 balls, and make water pills;

[0020] Alternatively, the pills are paste pills, which are specifically prepared by: grinding the medicine into fine powder, using rice paste, flour paste, koji paste or other materials as adhesives to form small pills;

[0021] Alternatively, the pills are concentrated pills, and the specific preparation method is: decocting part of the medicine or prescription into juice, concentrating it into a paste, then mixing it with the remaining medicine powder, drying, crushing, and making 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 following raw materials according to the following weight ratio: five-fingered peach 2g ~ 50g / portion, Pseudostellaria 2g ~ 50g / portion, Poria 2g ~ 50g / portion, Atractylodes 2g ~ 50g / portion, Scutellaria 2g ~ 50g / portion, Hedyotis diffusa 2g ~ 50g / portion, Cat's Claw 2g ~ 50g / portion, Polygonum cuspidatum 2g ~ 50g / portion, Curcuma 2g ~ 50g / portion, Oyster 2g ~ 50g / portion, Platycodon 2g ~ 50g / portion, Pseudobulbus Cervi Paniculata 2g ~ 50g / portion, Scutellaria barbata 2g ~ 50g / portion;

[0024] Step 32, preparing powder: washing and drying the above raw materials to remove impurities; mixing different medicinal materials in proportion according to the requirements of the prescription; grinding the dried Chinese herbal medicines into fine powder using traditional stone mortar grinding, mechanical grinding or ultrafine grinding methods, screening 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; mixing the screened medicinal material powder 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 following raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of pseudoginseng, 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 Psoralea corylifolia, 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; a third decoction may be performed if required; combine the medicinal liquids for precipitation; sieve the filtrate after precipitation to remove impurities; place the resulting filtrate in a copper pot or other large container and boil over high heat to concentrate; concentrate until close to the state of forming an ointment, filter the medicinal liquid again with gauze or a 100-mesh sieve to remove impurities, and use a low heat to reduce the ointment, stirring continuously during the ointment reduction process, and simmer 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 ginseng, pseudoginseng, poria, atractylodes, scutellaria, oldenlandia diffusa, cat's claw, polygonum cuspidatum, zedoaria, oyster, platycodon, trillium, and scutellaria barbata; among them, ginseng is sweet in taste and 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 tendons and activating collaterals, and can replenish qi and tonify deficiency without causing warming and dryness; pseudoginseng is sweet, slightly bitter in taste and neutral in nature, enters the spleen and lung meridians, can replenish qi and strengthen the spleen, promote fluid production and moisten the lungs, treat qi deficiency and replenish spleen and earth, and is a product for clearing and tonifying the lungs and spleen. The two herbs work together to strengthen the body and tonify deficiency, and replenish the lungs and strengthen the spleen, and are both monarch drugs. Poria tastes sweet and mild, is neutral in nature, and enters the heart, lung, spleen, and kidney meridians; Atractylodes macrocephala tastes sweet and bitter, is slightly warm in nature, and enters the spleen and stomach meridians. Both of them invigorate qi and strengthen the spleen, promote diuresis and dry dampness, and together help five-fingered ginseng and prince ginseng to nourish vital energy, strengthen the spleen and replenish deficiency, and are both ministerial medicines. Scutellaria baicalensis is bitter and cold in nature, entering the lung, gallbladder, spleen, large intestine, and small intestine meridians, clearing lung heat and dispelling pathogenic toxins; Hedyotis diffusa is bitter and cold in nature, entering the stomach, large intestine, and small intestine meridians, clearing heat, detoxifying, and reducing swelling; Cat's Claw is sweet and pungent in nature, warm in nature, entering the liver and lung meridians, resolving phlegm and stagnation; Polygonum cuspidatum is bitter and slightly cold in nature, entering the liver, gallbladder, and lung meridians, relieving heat and toxins and reducing blood stasis and swelling; Curcuma zedoaria is pungent and bitter in nature, warm in nature, entering the liver and spleen meridians, promoting blood circulation and qi circulation, dispersing blood stasis and eliminating accumulation; Oyster is salty and slightly cold in nature, entering the liver, gallbladder, and kidney meridians, softening and eliminating symptoms. Together, these seven herbs strengthen the body, replenish deficiency, and dissipate stagnation and swelling, serving as adjuvants. Platycodon grandiflorum is bitter and pungent in nature, neutral in nature, and entering the lung meridian, acting as a facilitator for all the other herbs, guiding their efficacy upward into the lung meridian. The seven properties of all the medicines are harmonious and compatible with each other to achieve the effect of strengthening the body, replenishing deficiency, reducing swelling and dispersing nodules, and treating lung accumulation caused by deficiency of lung and spleen qi.

[0029] In actual application, clinical observations have shown that Fuzheng Sanjie Formula can improve symptoms such as insomnia, rash, and diarrhea in patients with lung accumulation (lung cancer, lung nodules), thereby improving their quality of life. By establishing an animal model of NSCLC resistant to osimertinib and administering Fuzheng Sanjie Formula 1.5 mg / kg / day orally for 21 days, tumor volume was measured daily and a tumor growth curve was plotted. The results showed that the rate of tumor growth was reduced after treatment with Fuzheng Sanjie Formula. After 21 days, the tumor volume in the Fuzheng Sanjie Formula group was smaller than that in the model group, with a statistically significant difference. Immunohistochemical staining of tumor sections from both groups for the cell proliferation marker Ki67 revealed a statistically significant lower Ki67 positivity rate in the Fuzheng Sanjie Formula group compared to the model group.

[0030] Gradual concentrations of serum containing Fuzheng Sanjie recipe were used to intervene in osimertinib-sensitive and -resistant cells (H1975N and H1975OR) for 48 to 96 hours, and the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results suggested 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 with reference to the accompanying drawings and embodiments. The drawings described below are only some implementation cases of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive work:

[0032] Figure 1 A reference diagram of network pharmacology drug-target prediction results of the Fuzheng Sanjie prescription traditional Chinese medicine composition 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 tested in vitro and in vivo 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 histogram of Ki67 positive rates in tumor pathological sections of the in vivo experimental model group and the Fuzheng Sanjie prescription group (*P<0.05 vs. 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 experimental result of constructing an NSCLC osimertinib-resistant animal model according to a preferred embodiment of the present invention;

[0036] Figure 4 This is the second experimental 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 treatment of a patient with lung accumulation (lung cancer, lung nodules) with the Fuzheng Sanjie recipe according to 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 This is the first in vitro test result of the Fuzheng Sanjie Formula (FZSJF) of the preferred embodiment of the present invention on the growth inhibition of common types of non-small cell lung cancer cells;

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

[0041] Figure 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] To make the purpose, technical solutions, and advantages of the embodiments of the present invention more clear, the following will be a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are some 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 shall fall within the scope of protection of the present invention.

[0043] A preferred embodiment of the present invention discloses a reinforcing and dispersing prescription for treating non-small cell lung cancer, which is preferably prepared from the following raw materials in the following weight ratios: 2g-50g / portion of five-fingered ginseng, 2g-50g / portion of pseudoginseng, 2g-50g / portion of poria, 2g-50g / portion of atractylodes, 2g-50g / portion of scutellaria, 2g-50g / portion of oldenlandia diffusa, 2g-50g / portion of cat's claw, 2g-50g / portion of knotweed, 2g-50g / portion of zedoaria, 2g-50g / portion of oyster, 2g-50g / portion of platycodon, 2g-50g / portion of trifoliate mushroom, and 2g-50g / portion of bark lotus.

[0044] In the Fuzheng Sanjie prescription of the present invention, the five-fingered ginseng is sweet and neutral in nature, enters the spleen, lung, and liver meridians, and has the effects of strengthening the spleen and tonifying the lungs, promoting qi and removing dampness, relaxing tendons and activating collaterals, and can replenish qi and tonify deficiency without causing warming and drying; the pseudoginseng is sweet and slightly bitter in nature, enters the spleen and lung meridians, and can replenish qi and strengthen the spleen, promote fluid production and moisten the lungs, treat qi deficiency and tonify the spleen and earth, and is a product for clearing and tonifying the lungs and spleen. The two together play the effects of strengthening the body and tonifying deficiency, tonifying the lungs and strengthening the spleen, and are both monarch drugs. Poria has a sweet and light taste and neutral nature, enters the heart, lung, spleen, and kidney meridians; Atractylodes macrocephala has a sweet and bitter taste and slightly warm nature, enters the spleen and stomach meridians, and the two together replenish qi and strengthen the spleen, promote diuresis and remove dampness, and help the five-fingered ginseng and pseudoginseng to cultivate and tonify vital energy, strengthen the spleen and tonify deficiency, and are both minister drugs. Scutellaria baicalensis is bitter and cold in nature, entering the lung, gallbladder, spleen, large intestine, and small intestine meridians, clearing lung heat and dispelling pathogenic toxins; Hedyotis diffusa is bitter and cold in nature, entering the stomach, large intestine, and small intestine meridians, clearing heat, detoxifying, and reducing swelling; Cat's Claw is sweet and pungent in nature, warm in nature, entering the liver and lung meridians, resolving phlegm and stagnation; Polygonum cuspidatum is bitter and slightly cold in nature, entering the liver, gallbladder, and lung meridians, relieving heat and toxins and reducing blood stasis and swelling; Curcuma zedoaria is pungent and bitter in nature, warm in nature, entering the liver and spleen meridians, promoting blood circulation and qi circulation, dispersing blood stasis and eliminating accumulation; Oyster is salty and slightly cold in nature, entering the liver, gallbladder, and kidney meridians, softening and eliminating symptoms. Together, these seven herbs strengthen the body, replenish deficiency, and dissipate stagnation and swelling, serving as adjuvants. Platycodon grandiflorum is bitter and pungent in nature, neutral in nature, and entering the lung meridian, acting as a facilitator for all the other herbs, guiding their efficacy upward into the lung meridian. The seven properties of all the medicines are harmonious and compatible with each other to achieve the effect of strengthening the body, replenishing deficiency, reducing swelling and dispersing nodules, and treating lung accumulation caused by deficiency of lung and spleen qi.

[0045] In actual application, clinical observations have shown that Fuzheng Sanjie Formula can improve symptoms such as insomnia, rash, and diarrhea in patients with lung accumulation (lung cancer, lung nodules), thereby improving their quality of life. By establishing an animal model of NSCLC resistant to osimertinib and administering Fuzheng Sanjie Formula 1.5 mg / kg / day orally for 21 days, tumor volume was measured daily and a tumor growth curve was plotted. The results showed that the rate of tumor growth was reduced after treatment with Fuzheng Sanjie Formula. After 21 days, the tumor volume in the Fuzheng Sanjie Formula group was smaller than that in the model group, with a statistically significant difference. Immunohistochemical staining of tumor sections from both groups for the cell proliferation marker Ki67 revealed a statistically significant lower Ki67 positivity rate in the Fuzheng Sanjie Formula group compared to the model group.

[0046] Gradual concentrations of serum containing Fuzheng Sanjie recipe were used to intervene in osimertinib-sensitive and -resistant cells (H1975N and H1975OR) for 48 to 96 hours, and the cell proliferation activity of different treatment groups was detected by CCK8 cytotoxicity / proliferation assay. The results suggested 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 five-fingered peach, 2g / portion of pseudoginseng, 2g / portion of Poria, 2g / portion of Atractylodes, 2g / portion of Scutellaria, 2g / portion of Hedyotis diffusa, 2g / portion of cat's claw, 2g / portion of Polygonum cuspidatum, 2g / portion of Curcuma, 2g / portion of Oyster, 2g / portion of Platycodon, 2g / portion of Trillium, 2g / portion of Scutellaria barbata.

[0050] Preparation of pills: Grind the above 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 five-fingered peach, 5g / portion of prince ginseng, 6g / portion of Poria, 3g / portion of Atractylodes, 4g / portion of Scutellaria, 2.5g / portion of Hedyotis diffusa, 5g / portion of cat's claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma, 8g / portion of Oyster, 11g / portion of Platycodon grandiflorum, 5g / portion of Trillium, and 82g / portion of Scutellaria barbata.

[0053] Preparation of pills: Grind the above medicines into fine powder, use water or vinegar, wine, or medicinal juice as adhesive, roll them into balls, and make 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 five-fingered peach, 5g / portion of prince ginseng, 6g / portion of Poria, 3g / portion of Atractylodes, 4g / portion of Scutellaria, 2.5g / portion of Hedyotis diffusa, 5g / portion of cat's claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma, 8g / portion of Oyster, 11g / portion of Platycodon grandiflorum, 5g / portion of Trillium, 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 five-fingered peach, 11g / portion of prince ginseng, 6g / portion of Poria, 7g / portion of Atractylodes, 5g / portion of Scutellaria, 12g / portion of Hedyotis diffusa, 5g / portion of Cat's Claw, 4g / portion of Polygonum cuspidatum, 7g / portion of Curcuma, 8g / portion of Oyster, 9g / portion of Platycodon, 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 prescription, 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 five-fingered peach, 50g / portion of prince ginseng, 50g / portion of Poria, 50g / portion of Atractylodes, 50g / portion of Scutellaria, 50g / portion of Hedyotis diffusa, 50g / portion of cat's claw, 50g / portion of Polygonum cuspidatum, 50g / portion of Curcuma, 50g / portion of Oyster, 50g / portion of Platycodon, 50g / portion of Trillium, 50g / portion of Scutellaria barbata.

[0062] Preparation of the water decoction of Fuzheng Sanjie Recipe: Soak the above-mentioned drugs in water for 30 minutes, then boil them. The amount of water for the first decoction should be enough to cover the drugs by 5 cm. First, boil them over high heat, then simmer them over low heat for 20 minutes, and pour out the medicine liquid. For the second decoction, boil the water over high heat, then simmer them over low heat for 15 minutes, so that the water can cover the drugs by 2 cm. Combine the two medicine liquids and mix them evenly (about 500 mL), then divide them into two equal portions, take one portion in the morning and evening (about 250 ml each), and drink 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 Psoralea corylifolia, 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 powder according to the formula ratio to ensure that the various medicinal materials are fully integrated so that the preparation has certain medicinal efficacy and stability.

[0066] Example 7

[0067] Take the raw materials according to the following weight ratio: 45g / portion of five-fingered peach, 42g / portion of pseudoginseng, 38g / portion of Poria, 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 Psoralea corylifolia, 35g / portion of Scutellaria barbata;

[0068] Preparation of Fuzheng Sanjie prescription ointment: add 8 to 10 times the amount of water to the above raw materials and soak them; use the water decoction method to decoct to obtain a decoction; if special requirements are met, a third decoction can be taken; combine the medicinal liquids and precipitate; after precipitation, pass through a sieve to remove impurities; put the obtained filtrate 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, use a low heat to reduce the ointment, stir continuously during the ointment reduction process, and simmer for a period of time until the desired consistency is reached.

[0069] The effective ingredients, molecular targets and pathways of Fuzheng Sanjie prescription were predicted by network pharmacology drug-target method, such as Figure 1 As shown in the data, 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 2As 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 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 for the cell proliferation marker Ki67 revealed that the Ki67 positive rate in the tumor sections of the Fuzheng Sanjie prescription group was lower than that in the model group (see Figure 2 C), the difference was statistically significant (see Figure 2 B).

[0071] Fuzheng Sanjie Formula (FZSJF)-containing serum gradient concentrations intervened in osimertinib-sensitive and -resistant cells (H1975N, H1975 OR) for 48-96 hours ( Figure 2 DF), CCK8 cytotoxicity / proliferation assay was used to detect cell proliferation activity in different treatment groups. 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 histogram of Ki67 positive rates in tumor pathological sections of the in vivo experimental model group and the Fuzheng Sanjie prescription group (*P<0.05 vs. 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; 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 various 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 3-4To 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 3 mg / kg / d of Fuzheng Sanjie Formula (FZSJF) by gavage for 11 days, and the OSI group and the combination group were given 10 mg / kg / d of osimertinib 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 rate was reduced after treatment with Fuzheng Sanjie Formula or combined with osimertinib, as shown in Figure 3. Figure 3 The following is a general diagram 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 (GGOs) who presented to our respiratory outpatient clinic between 2022 and 2023 were treated with the Fuzheng Sanjie formula for six months without pathological exclusion of lung cancer. CT scans before and after treatment revealed a reduction in the size of the lung lesions. The chest CT scan in the figure shows a GGO nodule in the right upper lobe of a patient with "lung accumulation" (approximately 7 x 7 mm) before treatment with the Fuzheng Sanjie formula. After treatment, the nodule resized to approximately 7 x 3 mm.

[0077] Figure 6 To collect clinical statistics on the use of Fuzheng Sanjie Decoction, 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 pulmonary edema and has been used in the hospital's protocol kitchen for a long time. It is prescribed in large quantities annually, with high patient compliance and a low dropout rate. Specifically, 270 doses were prescribed from June to August 2022, 672 doses from September to November 2022, 612 doses from December 2022 to February 2023, and 438 doses from March to April 2023. Fuzheng Sanjie prescription has been used for several years to treat Qi deficiency and blood stasis-type pulmonary edema and has been used in the hospital for a long time. It is prescribed in large quantities annually and continues to increase, with high patient compliance and a low dropout rate. In actual clinical application, clinical observations have found that Fuzheng Sanjie prescription can improve symptoms such as insomnia, rash, and diarrhea in patients with pulmonary edema (lung cancer and pulmonary nodules), and improve their quality of life.

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

[0080] 1. Deng Moumou, female, 57 years old, had a history of postoperative right lung nodule (carcinoma in situ), 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, a 40-year-old female, presented with a pulmonary nodule (CT scan showed a shallowly lobed ground-glass opacity approximately 6 x 5 mm in the apical segment of the right upper lobe) for three weeks. She had no cough or sputum, hot flashes or night sweats, chest tightness or pain, shortness of breath, or nausea or vomiting. She frequently stayed up late. Upon presentation, she reported a normal appetite, regular bowel movements, and poor sleep. After one month of treatment with the Fuzheng Sanjie formula, her insomnia improved.

[0082] 3. Huang, female, 52 years old, presented with a pulmonary nodule (CT scan: ground-glass opacity in the left lower lobe, approximately 5 mm in diameter) after a physical examination. She had experienced no cough or sputum, hot flashes or night sweats, chest tightness or pain, shortness of breath, or nausea or vomiting for over a month. She requested a follow-up examination, reported good appetite, regular bowel movements, but poor sleep. After one month of treatment with the Fuzheng Sanjie formula, her insomnia improved.

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

[0084] Furthermore, with the widespread application of Traditional Chinese Medicine (TCM) in cancer prevention and treatment, a wealth of data suggests that combining TCM with anti-cancer drugs offers greater clinical benefits for NSCLC patients. Combining TCM with EGFR-TKIs can also synergistically enhance efficacy and reduce toxicity, while also delaying the development of EGFR-TKI resistance.

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

Claims

1. A Chinese medicine composition for treating non-small cell lung cancer, characterized in that: Made from the following raw materials in the following weight ratio: Five-fingered ginseng 2g~50g / portion, Pseudostellaria 2g~50g / portion, Poria 2g~50g / portion, Atractylodes 2g~50g / portion, Scutellaria 2g~50g / portion, Hedyotis diffusa 2g~50g / portion, Cat's claw 2g~50g / portion, Polygonum cuspidatum 2g~50g / portion, Curcuma 2g~50g / portion, Oyster 2g~50g / portion, Platycodon 2g~50g / portion, Trillium 2g~50g / portion, Scutellaria barbata 2g~50g / portion.

2. The Chinese medicine composition 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 ginseng 2g / portion, Pseudostellaria 2g / portion, Poria 2g / portion, Atractylodes macrocephala 2g / portion, Scutellaria baicalensis 2g / portion, Hedyotis diffusa 2g / portion, Cat's claw 2g / portion, Polygonum cuspidatum 2g / portion, Curcuma 2g / portion, Oyster 2g / portion, Platycodon grandiflorum 2g / portion, Tripterygium wilfordii 2g / portion, Scutellaria barbata 2g / portion.

3. The Chinese medicine composition 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 baicalensis, 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 traditional Chinese medicine composition 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 pseudoginseng, 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 Psoralea corylifolia, 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 should be enough to cover the medicine by 5 cm. Boil it with high heat first and then simmer it with low heat for 20 minutes, and pour out the medicine liquid. For the second decoction, boil it with high heat first and then simmer it with low heat for 15 minutes, so that the water can cover the medicine by 2 cm. Mix the two medicine liquids together, and then divide them into two equal parts.

5. A method for preparing a traditional Chinese medicine composition for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 21, take the following raw materials according to the following weight ratio: five-fingered peach 2g ~ 50g / portion, Pseudostellaria 2g ~ 50g / portion, Poria 2g ~ 50g / portion, Atractylodes 2g ~ 50g / portion, Scutellaria 2g ~ 50g / portion, Hedyotis diffusa 2g ~ 50g / portion, Cat's Claw 2g ~ 50g / portion, Polygonum cuspidatum 2g ~ 50g / portion, Curcuma 2g ~ 50g / portion, Oyster 2g ~ 50g / portion, Platycodon 2g ~ 50g / portion, Psoralea corylifolia 2g ~ 50g / portion, Scutellaria barbata 2g ~ 50g / portion; Step 22, preparing pills: the above raw materials are made into medicinal material powder or medicinal material extract, and an appropriate amount of binder is added to make pills.

6. The method for preparing the Chinese medicine composition for treating non-small cell lung cancer according to claim 5, wherein: 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 balls, and make water pills; Alternatively, the pills are paste pills, and the specific preparation method is: the medicine is ground into fine powder, and rice paste, flour paste, and koji paste are used as adhesives to make paste pills.

7. A method for preparing a traditional Chinese medicine composition for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 31, take the following raw materials according to the following weight ratio: five-fingered peach 2g ~ 50g / portion, Pseudostellaria 2g ~ 50g / portion, Poria 2g ~ 50g / portion, Atractylodes 2g ~ 50g / portion, Scutellaria 2g ~ 50g / portion, Hedyotis diffusa 2g ~ 50g / portion, Cat's Claw 2g ~ 50g / portion, Polygonum cuspidatum 2g ~ 50g / portion, Curcuma 2g ~ 50g / portion, Oyster 2g ~ 50g / portion, Platycodon 2g ~ 50g / portion, Pseudobulbus Cervi Paniculata 2g ~ 50g / portion, Scutellaria barbata 2g ~ 50g / portion; Step 32, preparing powder: washing and drying the above raw materials to remove impurities; mixing different medicinal materials in proportion according to the requirements of the prescription; grinding the dried Chinese herbal medicines into fine powder using traditional stone mortar grinding, mechanical grinding or ultrafine grinding methods, screening the ground medicinal materials through a sieve to remove large particles or impurities that have not been ground properly, and mixing the screened medicinal material powder according to the proportion of the raw materials to obtain.

8. A method for preparing a traditional Chinese medicine composition for treating non-small cell lung cancer, characterized in that: The method comprises the following steps: Step 41, taking the following raw materials according to the following weight ratio: 2g~50g / portion of five-fingered peach, 2g~50g / portion of pseudoginseng, 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 Psoralea corylifolia, 2g~50g / portion of Scutellaria barbata; Step 42, preparing the ointment: soaking the above raw materials in 8 to 10 times the amount of water; decocting using a water decoction method to obtain a decoction; and precipitating the decoction; After precipitation, sieve it to remove impurities; put the filtrate into a copper pot or other large container and boil it over high heat to concentrate; concentrate it until it is close to a paste, filter the liquid again with gauze or a 100-mesh sieve to remove impurities, use a low heat to make the paste, stir constantly during the process, and boil it until it becomes thick.

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