CN116492423A - Traditional Chinese medicine composition for preventing and treating lung cancer - Google Patents
Traditional Chinese medicine composition for preventing and treating lung cancer Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicine composition for preventing and treating lung cancer, which is prepared from traditional Chinese medicines of rhizoma polygonati, astragalus, scutellaria baicalensis, peach kernel, rhizoma atractylodis and liquorice. The traditional Chinese medicine composition is applied to strengthen body resistance and support the traditional Chinese medicine as an immunomodulator, plays the role advantages of multiple ways, multiple targets and multiple links of the traditional Chinese medicine, can be used as a medicine for treating lung tumors, can improve the anti-tumor immunity of lung cancer patients, inhibit the formation, proliferation, invasion and metastasis of tumors, has very good lung cancer inhibition effect on the basis of lung in-situ cancer models, subcutaneous tumors and in-vitro cytology experiments, and can obviously improve tumor immunity microenvironment.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine therapeutic drug which is prepared by taking Chinese herbal medicines as raw material medicines and is used for preventing lung cancer progression and treating lung cancer.
Background
Lung cancer is the most common cause of cancer-related death worldwide, with 180 ten thousand people diagnosed with lung cancer each year, 160 ten thousand of which die from the disease. In the 11 th year from 2000 to 2011, chinese male lung cancer incidence and mortality were the first of all cancers. Lung cancer patients have poor prognosis, with survival rates of only 18% 5 years.
The main reason for the high mortality of lung cancer is that most patients are already late at diagnosis and are accompanied by metastasis. Standard treatments for lung cancer are mainly surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc., and have achieved remarkable clinical effects. But also causes various adverse reactions, such as bone marrow depression, digestive tract reaction and organ function injury, and symptoms such as nausea, emesis, listlessness, etc., which affect the normal chemotherapy cycle. The targeted therapy and the immunotherapy are the manifestations of accurate treatment of lung cancer, but the toxic and side effects are quite common, such as rash, diarrhea, hypodynamia, hemorrhage and other symptoms, not only affect the life quality of patients, but also need to be forced to stop the medicine.
The current clinical practice lacks effective prevention and treatment means for precancerous lesions and early tumors, and almost all of the effective prevention and treatment means are in the stage of observation follow-up or repeated excision of new lesions. Therefore, a non-invasive lung tumor prevention and treatment scheme without obvious toxic and side effects is needed to appear.
The traditional Chinese medicine is taken as cultural treasure of China, has unique theoretical basis and abundant clinical practice experience, emphasizes the concept of 'people-oriented and tumor-bearing survival', and plays an indispensable role in a comprehensive prevention and treatment system of tumors by improving the constitution of the easily-developed tumor of human body and maximally inhibiting the regrowth of the tumor.
Recurrent metastasis of lung cancer is the leading cause of death. Clinical practice proves that the early intervention of the postoperative traditional Chinese medicine of the tumor patient is beneficial to restoring body vital energy, promoting the recovery of the body after the wound, improving the immune function, relieving postoperative complications, effectively preventing postoperative recurrence and metastasis and prolonging the survival time.
After many clinical patients are treated by operations, radiotherapy, chemotherapy and other rounds of treatment, no medicine is available due to the generation of medicine resistance; or some patients with advanced tumors do not have the indication of radiotherapy and chemotherapy due to the conditions of advanced ages, poor physical conditions and the like. At this time, according to the specific conditions of the patients with the exuberance of pathogenic factors and the healthy energy, a corresponding therapeutic method is formulated, and the purposes of stabilizing focus, preventing recurrence and metastasis, improving life quality and achieving tumor survival can be achieved by adopting the traditional Chinese medicine alone.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine composition for preventing and treating lung cancer, which uses a strengthening body resistance and banking up root traditional Chinese medicine as an immunomodulator, plays the role advantages of multiple ways, multiple targets and multiple links of the traditional Chinese medicine, and improves the anti-tumor immunity of a lung cancer patient and inhibits the formation, proliferation, invasion and metastasis of tumors.
The traditional Chinese medicine composition for preventing and treating lung cancer is prepared from traditional Chinese medicines of rhizoma polygonati, astragalus, scutellaria baicalensis, peach kernels, rhizoma atractylodis and liquorice.
Further, in the traditional Chinese medicine composition for preventing and treating lung cancer, the weight parts of the raw materials are as follows: 50-200 parts of rhizoma polygonati, 20-80 parts of astragalus, 10-50 parts of radix scutellariae, 10-50 parts of peach kernel, 15-60 parts of rhizoma atractylodis and 5-20 parts of liquorice.
Further, the weight portions of the raw materials are as follows: 50-100 parts of rhizoma polygonati, 30-50 parts of astragalus, 15-30 parts of radix scutellariae, 15-30 parts of peach kernel, 20-40 parts of rhizoma atractylodis and 5-10 parts of liquorice.
More specifically, the weight portions of the raw material medicines are as follows: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of radix scutellariae, 20 parts of peach kernel, 30 parts of rhizoma atractylodis and 10 parts of liquorice.
The specific preparation method of the traditional Chinese medicine composition comprises the steps of mixing the traditional Chinese medicine raw materials according to the parts by weight, adding water for decoction, filtering to obtain an extracting solution, concentrating and drying to obtain the medicinal active component.
Preferably, the traditional Chinese medicine composition is any oral preparation prepared by adding pharmaceutically acceptable auxiliary materials or carriers into the active pharmaceutical components. The oral dosage form can be any one of tablets, capsules, pills, syrups, granules, powder, ointment, dripping pills, suspension or emulsion.
Furthermore, the traditional Chinese medicine composition can be prepared into a slow release preparation or a controlled release preparation.
Furthermore, the invention also provides application of the traditional Chinese medicine composition for preventing and treating lung cancer in preparing medicines for treating lung tumor.
The method of strengthening body resistance and banking up root is the essence of traditional Chinese medicine and is the main characteristic of traditional Chinese medicine for preventing and treating tumors. The body resistance strengthening, namely strengthening the body resistance, the body resistance strengthening, namely cultivating the primordial qi, has the overall regulation effect of multiple links and multiple targets on tumors, and is the most important rule in the treatment of traditional Chinese medicine tumors.
Clinical practice shows that early lung cancer is closely related to viscera dysfunction such as deficiency of vital qi, imbalance of qi and blood, lung, spleen and kidney, and the basic pathogenesis takes the deficiency of vital qi as the principal and the excess of pathogenic factors as the principal, so the treatment should be compatible with strengthening vital qi and eliminating pathogenic factors.
The traditional Chinese medicine composition is based on the therapeutic principle of strengthening body resistance and banking up root, takes rhizoma polygonati, astragalus and baikal skullcap root as monarch drugs, wherein the rhizoma polygonati nourishes liver and kidney, nourishes yin and nourishes blood, and researches prove that the traditional Chinese medicine composition can play an anti-tumor role by inhibiting cell cycle and inducing apoptosis; the astragalus root has the effects of strengthening spleen and tonifying middle-jiao, invigorating yang and strengthening superficies, and has the main anti-tumor action mechanisms of inhibiting proliferation and metastasis of tumor cells, promoting apoptosis of the tumor cells, retarding tumor cell cycle, regulating autophagy of the tumor cells, targeting tumor microenvironment, resisting tumor angiogenesis and enhancing the immune function of an organism; the baikal skullcap root has the functions of clearing heat, detoxicating and purging fire, can effectively remove pathological products damaging mitochondria, improve the internal environment of the mitochondria, promote the repair of the mitochondria, provide sufficient energy for organisms and prevent the transformation of inflammatory cancers. The above three drugs are used together, and have the effects of tonifying lung, tonifying qi, removing toxin, resolving masses, strengthening body resistance, eliminating pathogenic factors and keeping the same.
Peach kernel is used as ministerial drug to break blood circulation and remove stasis, moisten dryness and smooth intestine, remove stasis and promote tissue regeneration, and is compatible with monarch drug to inhibit cyclin B1, so that tumor cell division is stopped in G2 phase, thereby inhibiting tumor cell proliferation, and simultaneously inhibiting expression of mitochondria related genes to interfere with tumor cell power station to play a role in inhibiting tumor; the rhizoma atractylodis active ingredient has an inhibition effect on the growth of various tumor cells including lung cancer, cervical cancer and melanoma, and the rhizoma atractylodis active ingredient is taken as an adjuvant, so that the inhibition effect on the proliferation of tumor cells of the monarch drug can be obviously improved; the licorice has the effects of anti-inflammatory, antiallergic, analgesic and anti-tumor, especially in the aspect of anti-tumor, the licorice has the effects of protecting normal cells and regulating organism immunity, and is used as a medicament for compatibility, so that the licorice is used for preventing and treating tumors, can jointly improve the immunocyte energy of sub-healthy people, inhibit oxidative stress and chronic inflammatory reaction, inhibit the growth of tumor cells, and possibly break through the prevention and treatment of tumors.
The traditional Chinese medicine composition for preventing and treating lung cancer provided by the invention aims at the common hypoimmunity of the organism of a patient with tumor, uses traditional Chinese medicines mainly used for strengthening body resistance and banking up root as immunomodulators, and plays the role advantages of multiple ways, multiple targets and multiple links of the traditional Chinese medicine compound, thereby improving the anti-tumor immunity of the patient with lung cancer and inhibiting the formation, proliferation, invasion and metastasis of tumor.
The damp evil, especially damp heat evil, is an inflammatory reaction generated by pathogenic infection of the organism or autoimmune disease of the organism, the inflammatory reaction damages an electron transfer chain on an inner membrane of mitochondria, ATP synthesis is damaged, and oxidative stress and energy metabolism function are regulated to be weakened. The traditional Chinese medicine composition can achieve the clinical effects of replenishing essence and increasing energy, activating spleen and resolving dampness, detoxifying and activating blood, strengthening vital qi and eliminating evil, repairing and resolving hard mass, fundamentally and effectively repairing damaged mitochondria of organisms, improving ATP, effectively eliminating tumors, regulating organism immunity, inhibiting the development of residual nodules into a second primary cancer focus and achieving balance in internal environment.
The traditional Chinese medicine composition provided by the invention has a very good lung cancer inhibiting effect on the basis of lung in-situ cancer models, subcutaneous tumors and in-vitro cytology experiments, can obviously improve tumor immunity microenvironment, can be used for preventing lung cancer, and can also be used for early stage lung nodule, postoperative chemoradiotherapy and later stage conditioning of immune targeting treatment of lung cancer, so that the effect of improving prognosis is achieved.
Drawings
Fig. 1 shows the results of pharmacodynamic experiments of in-situ cancer in animals of different traditional Chinese medicine compositions.
FIG. 2 shows the immunohistochemical quantification results of CK19 by different Chinese medicinal compositions.
Fig. 3 shows the effect of different Chinese medicinal compositions in inhibiting proliferation of subcutaneous tumor.
FIG. 4 is the effect of different Chinese medicinal compositions on tumor-associated macrophages and T cells.
Fig. 5 is the effect of different traditional Chinese medicine compositions on the mitochondrial ATP-producing capacity of tumor-associated macrophages and T cells.
FIG. 6 shows the inhibition of various lung cancer tumor cells by the Chinese medicinal composition of the present invention.
Description of the embodiments
The following describes in further detail the embodiments of the present invention with reference to the drawings and examples. The following examples are presented only to more clearly illustrate the technical aspects of the present invention so that those skilled in the art can better understand and utilize the present invention without limiting the scope of the present invention.
The production process, experimental method or detection method according to the embodiments of the present invention and comparative examples are all conventional methods in the prior art unless otherwise specified, and the names and/or abbreviations thereof are all conventional names in the art, which are clearly understood in the relevant fields of use, and those skilled in the art can understand the conventional process steps according to the names and apply the corresponding equipment, and perform according to the conventional conditions or the conditions suggested by the manufacturer.
The various instruments, equipment, materials or reagents used in the examples of the present invention are not particularly limited in source, and may be conventional products commercially available through regular commercial routes or may be prepared according to conventional methods well known to those skilled in the art.
Examples
Example 1
The raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of radix scutellariae, 20 parts of peach kernel, 30 parts of rhizoma atractylodis and 10 parts of liquorice.
Placing the above materials into an extraction tank, adding 12 times of water, decocting for 2 hr, filtering out decoction, adding 10 times of water, decocting for 1.5 hr, and filtering out decoction. Mixing the decoctions, filtering, concentrating into fluid extract with relative density of 1.20-1.24, drying, pulverizing into 80 mesh fine powder, adding appropriate amount of adjuvant, and making into capsule.
Example 2
The raw materials are prepared according to the following formula proportion: 80 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of radix scutellariae, 30 parts of peach kernel, 40 parts of rhizoma atractylodis and 10 parts of liquorice.
The preparation method is the same as in example 1.
Example 3
The raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 30 parts of astragalus, 30 parts of scutellaria baicalensis, 30 parts of peach kernel, 20 parts of rhizoma atractylodis and 10 parts of liquorice.
The preparation method is the same as in example 1.
Comparative example 1
On the basis of the embodiment 1, no ministerial peach seed is added, and the raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of scutellaria baicalensis, 30 parts of rhizoma atractylodis and 10 parts of liquorice, and the preparation method is the same as that of example 1.
Comparative example 2
On the basis of the embodiment 1, no ministerial drug peach kernel and the conductant drug liquorice are added, and the raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of scutellaria baicalensis, 30 parts of rhizoma atractylodis and the preparation method is the same as that of example 1.
Comparative example 3
Other raw materials are the same, only ministerial drug peach kernels are replaced by bighead atractylodes rhizome with the same dosage, and the raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of scutellaria baicalensis, 20 parts of bighead atractylodes rhizome, 30 parts of rhizoma atractylodis and 10 parts of liquorice, and the preparation method is the same as that of example 1.
Comparative example 4
On the basis of comparative example 3, one of the monarch drugs of astragalus membranaceus is removed, and raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 20 parts of radix scutellariae, 20 parts of rhizoma atractylodis, 30 parts of rhizoma atractylodis and 10 parts of liquorice, and the preparation method is the same as that of example 1.
Comparative example 5
On the basis of comparative example 3, the adjuvant drug rhizoma atractylodis is removed, and the raw materials are prepared according to the following formulation proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of scutellaria baicalensis, 20 parts of bighead atractylodes rhizome and 10 parts of liquorice, and the preparation method is the same as that of example 1.
Comparative example 6
On the basis of comparative example 3, the radix glycyrrhizae is removed, and the raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of scutellaria baicalensis, 20 parts of bighead atractylodes rhizome and 30 parts of rhizoma atractylodis, and the preparation method is the same as that of example 1.
Comparative example 7
On the basis of comparative example 3, two principal drugs of astragalus and baikal skullcap root are removed, and then the adjuvant drug of rhizoma atractylodis is removed, and the raw materials are prepared according to the following formula proportion: 100 parts of rhizoma polygonati, 20 parts of bighead atractylodes rhizome and 10 parts of liquorice, and the preparation method is the same as that of example 1.
Application example 1: pharmacodynamic experiments of in-situ cancer in animals with different traditional Chinese medicine compositions
This application example uses 6 week old male SPF grade C57 model mice (C57 BL/6 LSL-KrasG12D/p53 flox/flox) given by southern model animal company as test animals.
Model mice were randomly divided into 9 groups of a blank group, a group administered with example 1, and a group administered with comparative examples 1 to 7, 6 animals each, and a group administered with comparative examples 1 to 7 was used as a control group.
After the mice of each test group were given deep sleep by ether inhalation, cre virus was inhaled at 0.5X10 7 pfu, simultaneously initiating Kras mutation and p53 cancer suppressor knockout, initiates lung in situ cancer modeling. The blank group was not dosed, and each dosing group was given the drug-containing feed while the modeling was started.
The lung tissue was fixed with 4% paraformaldehyde and paraffin-embedded 8 weeks after administration, immunohistochemical staining was performed on the cancerous index CK-19, and the pathological morphological changes of the lung tissue of each experimental group were observed, and the results are shown in FIG. 1. The stained CK-19 (brown area) was scan quantified with Image J software and the results are shown in Table 1 and FIG. 2.
The results show that compared with the blank, the drug of example 1 has statistically significant inhibition on lung carcinoma in situ tumors, while the drugs of comparative examples 1-7 have no obvious inhibition.
Application example 2: pharmacodynamic experiments of inhibiting animal subcutaneous tumor proliferation by different traditional Chinese medicine compositions
Four groups of 4 week old C57L mice were divided into blank, example 1, comparative example 1 and comparative example 3 groups, 4 each, and inoculated subcutaneously with 2X 10 6 LLC (mouse lung cancer cell) cells were subjected to mouse subcutaneous tumor modelling.
The mice weight and rumen size were recorded every two days on the day of each of the other groups except the blank group, the experiment was ended after 14 days of administration, the mice were euthanized, the tumor tissues were completely stripped, and the tumor volumes were recorded, and the results are shown in fig. 3, which show that the drug of example 1 had a significant inhibitory effect on subcutaneous tumors compared to the blank group, while the two comparative examples had no significant inhibitory effect on subcutaneous tumors of mice.
Application example 3: effect of different Chinese medicinal compositions on tumor-associated macrophages and cytotoxic T cells of subcutaneous tumors
Typically, there are two types of macrophages in the tumor microenvironment. Wherein, M1 macrophage has antigen presenting function, can promote CD8 cytotoxicity T cell (CD 8T) function, CD8T can further kill tumor cells, and M2 macrophage has function of promoting proliferation of tumor cells. If M2 macrophages are increased, CD8T is decreased and the tumor is enlarged and invasive. Thus, the immunotherapeutic strategy for tumors is to increase CD8T while inhibiting the proportion of M2 macrophages.
Single cell suspensions were prepared from subcutaneous tumor tissue of each test group in application example 2, and the ratio of immune cells M2 (CD 45, CD11B, F4/80, CD86+, CD206+) to CD8T (CD 45, CD3+, CD8+) and the ability of mitochondria to produce ATP were examined using flow cytometry and sorted, and the results are shown in FIGS. 4 and 5.
In fig. 4, the drug of example 1 can decrease the proportion of M2 macrophages in the tumor microenvironment of subcutaneous tumor, and can decrease M2 macrophages by one time compared with the blank group, and correspondingly, the drug of example 1 has a remarkable lifting effect on cytotoxic T cells, and the drug of example 1 increases TC cells in tumor cells by 3 times compared with the blank group.
However, the comparative drug did not have a lifting effect on CD8T nor an inhibitory effect on M2.
Further, mitochondrial function assays were performed on the above-described flow-sorted CD8T and macrophage M2 (fig. 5), example 1 increased the ability of CD8T to produce ATP by mitochondria, decreased the ability of M2 to produce ATP, and the comparative group had no effect on ATP productivity of immune cells.
Application example 4: inhibition of lung cancer cell lines by different Chinese medicinal compositions
In order to prove the effect of the traditional Chinese medicine composition on treating lung cancer, the CCK8 experiment is carried out after treating lung cancer cell lines A549, H1299 and PC9 tumor cells for 48 hours in vitro by adopting the medicine of the example 1, and the result is shown in figure 6.
As can be seen from FIG. 6, the Chinese medicinal composition of the present invention inhibits proliferation of tumor cells in a concentration-dependent manner, and A549, H1299 and PC9 intervene in IC for 48H 50 The concentrations were 4.7mg/mL, 4.8mg/mL and 2.8mg/mL, respectively.
The invention is explored by a series of formulas, and on the basis that three monarch drugs of rhizoma polygonati, radix scutellariae and radix astragali have anti-tumor and immunity-regulating functions, peach kernels are added as ministerial drugs, rhizoma atractylodis is taken as adjuvant drugs, and traditional liquorice is taken as conductant drugs, so that the traditional Chinese medicine composition with remarkable effects for preventing and treating lung cancer is obtained.
However, the formula of comparative example 3, in which only the ministerial drug peach kernel is replaced by the bighead atractylodes rhizome, has no effect of inhibiting lung carcinoma in situ in mice. Also, neither comparative example 1 and comparative example 2, in which any drugs were deleted on the basis of the Chinese medicinal composition of the present invention nor comparative examples 4, 5, 6 and 7, in which any drugs were deleted on the basis of comparative example 3, had a remarkable effect of inhibiting lung carcinoma in situ in mice. Compared with the comparative examples, the traditional Chinese medicine composition has obvious lung carcinoma in situ resistance, is particularly expressed on the expression of the immunohistochemical analysis tumor marker CK19, and has obvious statistical difference compared with the comparative examplesP＞0.05）。
Similarly, the mouse subcutaneous tumor and in-vitro cytology experiments also prove that the traditional Chinese medicine composition has obvious effect of inhibiting the subcutaneous tumor compared with other comparative example compositions. Further immune cell analysis proves that the cell can inhibit M2 cells, promote immune killer T cells and play a role in improving tumor immunity.
The above embodiments of the invention are not intended to be exhaustive or to limit the invention to the precise forms disclosed. Various changes, modifications, substitutions and alterations may be made by those skilled in the art without departing from the principles and spirit of the invention, and it is intended that the invention encompass all such changes, modifications and alterations as fall within the scope of the invention.
Claims (8)
1. A traditional Chinese medicine composition for preventing and treating lung cancer is prepared from traditional Chinese medicines of rhizoma polygonati, astragalus, radix scutellariae, peach kernel, rhizoma atractylodis and liquorice.
2. The traditional Chinese medicine composition according to claim 1, wherein the weight parts of the raw materials are as follows: 50-200 parts of rhizoma polygonati, 20-80 parts of astragalus, 10-50 parts of radix scutellariae, 10-50 parts of peach kernel, 15-60 parts of rhizoma atractylodis and 5-20 parts of liquorice.
3. The traditional Chinese medicine composition according to claim 1, wherein the weight parts of the raw materials are as follows: 50-100 parts of rhizoma polygonati, 30-50 parts of astragalus, 15-30 parts of radix scutellariae, 15-30 parts of peach kernel, 20-40 parts of rhizoma atractylodis and 5-10 parts of liquorice.
4. The traditional Chinese medicine composition according to claim 1, wherein the weight parts of the raw materials are as follows: 100 parts of rhizoma polygonati, 40 parts of astragalus, 20 parts of radix scutellariae, 20 parts of peach kernel, 30 parts of rhizoma atractylodis and 10 parts of liquorice.
5. The use of a Chinese medicinal composition according to any one of claims 1 to 4 in the manufacture of a medicament for the treatment of lung tumours.
6. The preparation method of the traditional Chinese medicine composition of claim 1, wherein the traditional Chinese medicine raw materials are mixed according to the parts by weight, then water is added for decoction, an extracting solution is obtained by filtration, and a medicine active component is obtained by concentration and drying.
7. The method for preparing a Chinese medicinal composition according to claim 6, wherein the pharmaceutically acceptable auxiliary materials or carriers are added into the active pharmaceutical ingredients to prepare any oral preparation.
8. The method for preparing a pharmaceutical composition according to claim 7, wherein the oral preparation is a tablet, capsule, pill, syrup, granule, powder, paste, drop pill, suspension or emulsion.
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