Anti-lung cancer traditional Chinese medicine composition and preparation method thereof
By combining extracts from the roots of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia lily and Rhizoma Atractylodis Macrocephalae, the problems of unclear activity and lack of synergistic mechanism of existing anti-lung cancer Chinese medicine preparations were solved, achieving highly effective tumor inhibition and anti-metastasis effects while avoiding toxic side effects.
Patent Information
- Application Number
- CN202510730378.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-03
- Publication Date
- 2025-09-26
AI Technical Summary
Existing Chinese medicine preparations for lung cancer have problems such as unclear active ingredients, lack of synergistic mechanism, and limited tumor inhibition and anti-metastasis effects. In addition, traditional processes result in low dissolution rate of active ingredients and large interference from impurities.
The extracts of Rhizoma Cibotii, Herba Pulmonariae, Herba Manglietiae and Herba Atractylodis Macrocephalae are combined in a specific ratio and extracted by different methods such as reflux, decoction, ultrasound, Soxhlet extraction and chromatographic separation to prepare an anti-lung cancer Chinese medicine composition.
It significantly improved the tumor inhibition rate, enhanced the inhibitory effect on lung cancer, inhibited lung metastasis and caused tumor cell apoptosis without obvious toxic side effects.
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Figure BDA0005431768060000041
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of pharmaceuticals, and particularly relates to an anti-lung cancer Chinese medicine composition and a preparation method thereof. Background Art
[0002] Lung cancer is one of the malignant tumors with the highest morbidity and mortality rates worldwide. Current clinical treatments rely primarily on surgical resection, radiotherapy, and chemotherapy. However, traditional chemotherapy drugs (such as platinum and paclitaxel) suffer from poor selectivity, significant toxic side effects, and the development of drug resistance, severely impacting patients' quality of life. In recent years, traditional Chinese medicine (TCM) compound formulations, owing to their multi-component and multi-target properties, have demonstrated unique advantages in the anti-tumor field. However, existing TCM preparations for lung cancer, which mostly utilize single herbal extracts (such as astragalus polysaccharides and Ganoderma lucidum triterpenes) or traditional heat-clearing and detoxifying formulas (such as the Hedyotis diffusa-Scutellaria barbata combination), still face three major limitations: First, the active ingredients are unknown; most compound formulations rely on a decoction process, resulting in low dissolution rates of the active ingredients and significant impurity interference; second, synergistic mechanisms are lacking; existing formulations are often based on empirical combinations and lack systematic validation of the synergistic effects between herbs; and third, metastasis inhibition is insufficient; while traditional formulations can inhibit primary lesion growth, they have limited efficacy in blocking lung metastasis. Therefore, there is an urgent need to develop a Chinese medicine composition that has clear active ingredients, synergistic compatibility, dual functions of tumor inhibition and anti-metastasis, and controllable process to break through the existing technical bottleneck. Summary of the Invention
[0003] To address the deficiencies of the prior art, the present invention aims to provide a traditional Chinese medicine composition for lung cancer and a preparation method thereof, which can significantly improve the tumor inhibition rate, inhibit lung metastasis of tumors and induce apoptosis of tumor cells without obvious toxic side effects.
[0004] In order to achieve the above objectives, the present invention adopts the following technical solutions:
[0005] A traditional Chinese medicine composition for preventing lung cancer is prepared from the following raw materials in parts by weight: 10-20 parts of a rhizome of hyssop root extract, 15-25 parts of a lungwort extract, 8-15 parts of a magnolia officinalis extract and 10-18 parts of a smilax china extract.
[0006] The preparation method of the anti-lung cancer Chinese medicine composition comprises the following steps:
[0007] S1. Raw material pretreatment: Wash the roots of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia officinalis, and Rhizoma Aesculapii separately and grind them into coarse powder;
[0008] S2. performing distribution extraction on the crude powder of each raw material to obtain the extract of Rhizoma Cibotii, the extract of Pulmonaria officinalis, the extract of Manglietia paniculata, and the extract of Rhizoma Aesculapiatae;
[0009] S3. Evenly mix the raw material extracts according to the ratio to obtain an anti-lung cancer Chinese medicine composition.
[0010] Preferably, in the aforementioned step S1, each raw material is washed and then dried in the shade to a moisture content of ≤12%, and then pulverized into a coarse powder of 40-60 mesh.
[0011] Preferably, in the aforementioned step S2, the specific method for extracting the root of Rhizoma Cibotii is: mixing the crude powder of the root of Rhizoma Cibotii with 70% ethanol solution, refluxing the solution, concentrating the extract under reduced pressure until there is no alcohol taste, eluting, collecting the eluate for later use, and obtaining the root of Rhizoma Cibotii extract.
[0012] Preferably, the mass ratio of the aforementioned coarse powder of the rhizome of Caryophyllus serrata to the 70% ethanol solution is 2-3:16-20, and the reflux temperature is 50-70°C.
[0013] Preferably, in the aforementioned step S2, the specific method for extracting Pulmonaria officinalis is: mixing Pulmonaria officinalis coarse powder with pure water, decocting at high temperature, centrifuging the decoction, filtering and drying to obtain the Pulmonaria officinalis extract.
[0014] Preferably, the mass ratio of the aforementioned pulmonaria coarse powder to pure water is 1-3:9-12, the decoction temperature is 80-90°C, the centrifugal speed is 2500-3500rpm, the centrifugation time is 12-15min, and the drying temperature is 150-180°C.
[0015] Preferably, in the aforementioned step S2, the specific method of extracting Manglietia odorata is: mixing Manglietia odorata crude powder with pure water, performing ultrasound-assisted extraction, concentrating the extract under reduced pressure, precipitating with ethanol, collecting the precipitate by centrifugation, and freeze-drying to obtain the Manglietia odorata extract.
[0016] Preferably, the mass ratio of the aforementioned Manglietia coarse powder to pure water is 1:12-15, the ultrasonic extraction temperature is 80-100°C, the time is 30-45 minutes, the alcohol precipitation is 12-24 hours, the centrifugal speed is 3500-4000rpm, and the centrifugal time is 15-20 minutes.
[0017] Preferably, in the aforementioned step S2, the specific method for extracting the A. sibiricum is as follows: mixing the A. sibiricum crude powder with 95% ethanol, extracting in a Soxhlet extractor, extracting the extract with an organic solvent, combining the organic phases, separating by chromatography, collecting the target fractions, and rotary evaporating to dryness to obtain the A. sibiricum extract.
[0018] Preferably, the mass ratio of the aforementioned August twig coarse powder and 95% ethanol is 1-2:6-10, the organic solvent is ethyl acetate, and the eluent for chromatography is petroleum ether-ethyl acetate = 4-5:1.
[0019] Application of the above-mentioned traditional Chinese medicine composition in the preparation of anti-lung cancer drugs.
[0020] The benefits of the present invention are that the Chinese medicine composition of the present invention can significantly improve the tumor inhibition rate, and the various components have a synergistic effect. Compared with the same dose of each effective component used alone, the anti-lung cancer effect is significantly improved, and the spleen index and liver index are increased. It can inhibit the lung metastasis of the tumor and cause the apoptosis of tumor cells without obvious toxic side effects. DETAILED DESCRIPTION
[0021] The present invention is described in detail below with reference to specific embodiments.
[0022] Example 1: A method for preparing an anti-lung cancer Chinese medicine composition, comprising the following steps:
[0023] S1. Raw material pretreatment: Wash the roots of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia officinalis, and Rhizoma Aesculapii, dry them in the shade until the moisture content is ≤12%, and grind them into 40-60 mesh coarse powder;
[0024] S2. Distribute and extract the raw material coarse powder:
[0025] (1) Extraction of the root of Myrica oleracea: Mix the crude powder of the root of Myrica oleracea with 70% ethanol solution, extract under reflux at 60°C twice, each time for 1.5 hours, concentrate the extract under reduced pressure until there is no alcohol smell, and pass it through an AB-8 macroporous resin column (column volume: medicinal material amount = 1:5). First, elute the impurities with 3 times the column volume of pure water, then elute the target component with 50% ethanol, collect the eluate for later use, and obtain the extract of the root of Myrica oleracea;
[0026] (2) Extraction of Pulmonaria officinalis: Pulmonaria officinalis coarse powder was decocted with 10 times the amount of pure water at 80°C for 3 times, each time for 1 hour. The decoction was soaked for 30 minutes before the first decoction. The decoction was centrifuged (3000 rpm, 15 minutes), and the supernatant was filtered through a 0.22 μm microfiltration membrane to remove suspended particles. The supernatant was spray-dried (inlet air temperature 160°C, outlet air temperature 80°C) to obtain the Pulmonaria officinalis extract.
[0027] (3) Manglietia Extraction: Manglietia crude powder was mixed with 12 times the amount of pure water and subjected to ultrasonic-assisted extraction (power 300 W) at 90°C for 2 times, 40 minutes each time. The extract was concentrated to 1 / 3 of the original volume under reduced pressure, and 3 times the volume of 95% ethanol was added for precipitation for 24 hours. The precipitate was collected by centrifugation (4000 rpm, 20 minutes) and freeze-dried to obtain the Manglietia extract.
[0028] (4) Extraction of Psoralea corylifolia: Extract the crude powder of Psoralea corylifolia with 6 times the amount of 95% ethanol in a Soxhlet extractor for 6 hours, and recover the ethanol until the alcohol taste is gone; the residue is extracted with ethyl acetate three times, and the organic phases are combined and separated by silica gel column chromatography (eluent: petroleum ether-ethyl acetate = 5:1). The target fractions are collected and rotary evaporated to dryness to obtain the Psoralea corylifolia extract;
[0029] S3. Weigh 10 parts of Rhizoma Cibotii root extract, 18 parts of Pulmonaria officinalis extract, 10 parts of Magnolia officinalis extract and 10 parts of Atractylodes macrocephala extract respectively by weight, mix them evenly, and obtain an anti-lung cancer Chinese medicine composition.
[0030] Example 2
[0031] The preparation method of this embodiment is the same as that of Example 1, with the specific difference being the different amounts of raw materials: 15 parts of Rhizoma Cibotii root extract, 15 parts of Pulmonaria officinalis extract, 10 parts of Magnolia officinalis extract, and 12 parts of Atractylodes macrocephala extract.
[0032] Example 3
[0033] The preparation method of this embodiment is the same as that of Example 1, with the specific difference being the different amounts of raw materials: 20 parts of Rhizoma Cibotii root extract, 25 parts of Pulmonaria officinalis extract, 8 parts of Magnolia officinalis extract, and 10 parts of Atractylodes macrocephala extract.
[0034] Example 4
[0035] The preparation method of this embodiment is the same as that of Example 1, with the specific difference being the different amounts of raw materials: 20 parts of Rhizoma Cibotii root extract, 20 parts of Pulmonaria officinalis extract, 15 parts of Magnolia officinalis extract, and 18 parts of Atractylodes macrocephala extract.
[0036] Comparative Example 1
[0037] The specific difference between this comparative example and Example 1 is that the Chinese medicinal component is only the extract of the root of Rhizoma Cibotii.
[0038] Comparative Example 2
[0039] The specific difference between this comparative example and Example 1 is that the Chinese medicinal component is only the extract of Pulmonaria officinalis.
[0040] Comparative Example 3
[0041] The specific difference between this comparative example and Example 1 is that the Chinese medicinal component is only the Manglietia extract.
[0042] Comparative Example 4
[0043] The specific difference between this comparative example and Example 1 is that the Chinese medicinal component is only the extract of Atractylodes macrocephala.
[0044] The efficacy test of the Chinese medicine composition of the present invention is as follows:
[0045] 1. In vitro anti-lung cancer activity test
[0046] Mouse lung adenocarcinoma LA795 cells and human lung adenocarcinoma A549 cells were selected as research subjects and cultured in RPMI-1640 or DMEM medium containing 10% inactivated fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin. The cells were subcultured every 4-5 days in an incubator at 35°C and 5% CO2 under saturated humidity. The anti-tumor activity of the drugs was determined using the MTT assay. The specific method was as follows: the cells in the logarithmic growth phase were trypsinized and then prepared into 3×10 4 / mL suspension, inoculated in a 96-well plate, 200μL per well, and replaced with serum-free culture medium to synchronize cells after 24h. On the 4th day, the anti-lung cancer Chinese medicine composition prepared by Examples 1-4 of the present invention and the aqueous solution of the deletion group of Comparative Example 1-4 were added respectively, and a 0.1% DMSO control group was set at the same time, 200μL per well. The drug concentration gradient was 0.01, 0.1, 1, 10, 100, 1000μg / mL, and 8 replicates were set for each concentration. After continuing to culture at 35°C for 24h, 100μL 0.5mg / mL MTT was added to each well, and 100μLDMSO was added to dissolve MTT formazan crystals after continuing to culture for 5h. After oscillation and mixing, the OD value was measured on a microplate reader, and the experiment was repeated three times to take the average value. The calculation formula is: Cell growth inhibition rate = (control group OD value-experimental group OD value) / control group OD value × 100%, with drug concentration as the horizontal axis and OD value as the vertical axis, to draw the growth curve and calculate IC 50 At the same time, the activity differences between the examples and the comparative examples were compared to verify the synergistic anti-lung cancer effect of the combination of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia officinalis and Rhizoma Atractylodis Macrocephalae in the composition. The specific results are shown in Table 1.
[0047] Table 1 In vitro anti-lung cancer activity test results
[0048]
[0049] As can be seen from Table 1, the in vitro MTT test proves that the traditional Chinese medicine composition prepared in Examples 1-4 can significantly inhibit the growth of mouse lung adenocarcinoma LA795 cell line and human lung adenocarcinoma A549 cell line, and there is a synergistic effect between the components, and the anti-lung cancer effect is significantly improved compared with the same dose of each active component used alone.
[0050] 2. In vivo anti-lung cancer activity test
[0051] Healthy female T739 mice (18-22 g) were used to establish the LA795 lung adenocarcinoma metastasis model. Mice in good growth condition were killed by cervical dislocation 8-10 days after inoculation with LA795 lung adenocarcinoma cells. Fresh tumor tissue was removed under sterile conditions, suspended in saline, filtered, and diluted with saline to adjust the cell concentration to 1×10 7 / mL, to obtain a tumor cell suspension, and each healthy mouse was subcutaneously inoculated with 0.2mL of tumor cell suspension in the right forelimb axilla. The day after tumor inoculation, 100 mice were randomly divided into 10 groups (10 mice in each group), namely, a model control group (normal saline gavage, 0.2mL each), a cyclophosphamide positive group (25mg / kg intraperitoneal injection), Example 1-2 group (at 2g (raw drug amount) / kg·bw, gavage), Example 1-2 group (at 1g (raw drug amount) / kg·bw, gavage), Comparative Example 1-2 group (at 2g (raw drug amount) / kg·bw, gavage), and Comparative Example 1-2 group (at 1g (raw drug amount) / kg·bw, gavage). After 14 consecutive days of administration, the mice were killed by cervical dislocation 24 hours after the last administration, the tumor tissue was completely removed and weighed, and the liver and spleen were removed and weighed. The tumor inhibition rate was calculated using the formula: (1 - average tumor weight of the treatment group / average tumor weight of the model control group) × 100%. Organ indices were also calculated: liver index = (liver weight / body weight) × 1000, spleen index = (spleen weight / body weight) × 1000. Comparison of the tumor inhibition rates between the compositions of each example and the comparative example group confirmed the synergistic effect of the combination of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia lily, and Rhizoma Aesculapii. Drug safety was also assessed using organ indices. Specific results are shown in Tables 2 and 3.
[0052] Table 2 Experimental results of the Chinese medicine composition on the inhibition rate of LA795 lung adenocarcinoma cell metastasis
[0053] Group Dosage Tumor inhibition rate / % Cyclophosphamide positive group 25 mg / kg 56.92 Example 1 2g / kg 62.13 Example 2 2g / kg 60.58 Example 1 1g / kg 58.42 Example 2 1g / kg 57.17 Comparative Example 1 2g / kg 26.89 Comparative Example 2 2g / kg 23.54 Comparative Example 1 1g / kg 18.26 Comparative Example 2 1g / kg 16.48
[0054] Table 3 Comparison of immune organ weight index in mice with T739 lung cancer metastasis
[0055] Group Dosage Liver index (mg / g) Spleen index (mg / g) Model control group - 9.24±0.65 6.49±0.63 Cyclophosphamide positive group 25 mg / kg 8.25±0.27* 5.18±0.46** Example 1 2g / kg 10.83±0.35* 7.95±0.39** Example 2 2g / kg 10.21±0.78* 7.32±0.34** Example 1 1g / kg 10.33±0.75* 7.18±0.42** Example 2 1g / kg 9.91±0.13* 7.02±0.56** Comparative Example 1 2g / kg 8.42±0.14 5.61±0.35 Comparative Example 2 2g / kg 8.66±0.58 5.34±0.47 Comparative Example 1 1g / kg 8.06±0.84 5.23±0.59 Comparative Example 2 1g / kg 8.35±0.38 5.37±0.78
[0056] Note: Compared with the model control group, *P<0.05, **P<0.01.
[0057] As can be seen from Tables 2 and 3, compared with Comparative Examples 1-2, the Chinese medicine compositions in Examples 1-4 significantly improved the tumor inhibition rate, indicating that the combination of the four drugs can enhance the anti-tumor effect, and the spleen index and liver index of mice increased, and can significantly inhibit the lung metastasis of subcutaneously transplanted tumors in mice and cause tumor cell apoptosis without obvious toxic side effects.
[0058] Throughout this specification, reference to terms such as "one embodiment," "some embodiments," "examples," "specific examples," or "some examples" means that a specific feature, structure, material, or characteristic described in conjunction with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
[0059] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the above embodiments do not limit the present invention in any form, and any technical solutions obtained by equivalent replacement or equivalent transformation fall within the scope of protection of the present invention.
Claims
1. A traditional Chinese medicine composition for treating lung cancer, characterized in that: The drug is prepared from the following raw materials in parts by weight: 10-20 parts of rhizome of hyssop root extract, 15-25 parts of pulmonary artemisia extract, 8-15 parts of magnolia officinalis extract and 10-18 parts of scutellaria baicalensis extract.
2. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 1, characterized in that: The following steps are involved: S1. Raw material pretreatment: Wash the roots of Rhizoma Cibotii, Pulmonaria officinalis, Magnolia officinalis, and Rhizoma Aesculapii separately and grind them into coarse powder; S2. performing distribution extraction on the crude powder of each raw material to obtain the extract of Rhizoma Cibotii, the extract of Pulmonaria officinalis, the extract of Manglietia paniculata, and the extract of Rhizoma Aesculapiatae; S3. Evenly mix the raw material extracts according to the ratio to obtain an anti-lung cancer Chinese medicine composition.
3. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 2, wherein: In the step S1, each raw material is washed and then dried in the shade to a moisture content of ≤12%, and then pulverized into a coarse powder of 40-60 mesh.
4. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 2, wherein: In the step S2, the specific method for extracting the root of Rhizoma Cibotii is as follows: mixing the crude powder of the root of Rhizoma Cibotii with 70% ethanol solution, performing reflux extraction, concentrating the extract under reduced pressure until there is no alcohol taste, eluting, collecting the eluate for standby use, and obtaining the root of Rhizoma Cibotii extract.
5. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 2, wherein: In step S2, the specific method for extracting the lungwort is: mixing the lungwort coarse powder with pure water, decocting at high temperature, centrifuging the decoction, filtering and drying to obtain the lungwort extract.
6. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 2, characterized in that: In the step S2, the specific method of extracting Manglietia odorata is as follows: mixing Manglietia odorata crude powder with pure water, performing ultrasound-assisted extraction, concentrating the extract under reduced pressure, precipitating with ethanol, collecting the precipitate by centrifugation, and freeze-drying to obtain the Manglietia odorata extract.
7. The method for preparing the anti-lung cancer Chinese medicine composition according to claim 2, wherein: In step S2, the specific method of extracting the August 24th jasmine is as follows: mixing the August 24th jasmine crude powder with 95% ethanol, extracting it in a Soxhlet extractor, extracting the extract with an organic solvent, combining the organic phases, separating them by chromatography, collecting the target fractions, and rotary evaporating them to dryness to obtain the August 24th jasmine extract.
8. Use of the traditional Chinese medicine composition according to claim 1 in the preparation of anti-lung cancer drugs.