CN116603039B - Targeted medicine for treating lung cancer and preparation method thereof - Google Patents
Targeted medicine for treating lung cancer and preparation method thereof Download PDFInfo
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- CN116603039B CN116603039B CN202310632089.2A CN202310632089A CN116603039B CN 116603039 B CN116603039 B CN 116603039B CN 202310632089 A CN202310632089 A CN 202310632089A CN 116603039 B CN116603039 B CN 116603039B
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- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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Abstract
The invention relates to the technical field of lung cancer medicine preparation, in particular to a targeting medicine for treating lung cancer and a preparation method thereof. A targeted drug for lung cancer treatment, comprising wortmannin, CM-272 and traditional Chinese medicine extract; the traditional Chinese medicine extract is prepared from the following components in parts by weight: 18 to 22 parts of Cordyceps sinensis, 14 to 18 parts of selfheal, 11 to 15 parts of coix seed, 15 to 19 parts of coptis chinensis, 8 to 12 parts of snakegourd fruit, 8 to 12 parts of figwort root, 5 to 9 parts of cynanchum atratum and 4 to 8 parts of fritillaria cirrhosa. The pharmaceutical composition provided by the invention has a good inhibition effect on the proliferation of lung cancer cells, has definite action, has excellent anti-lung cancer activity, and has a treatment effect equivalent to that of the prior art.
Description
Technical Field
The invention relates to the technical field of lung cancer medicine preparation, in particular to a targeting medicine for treating lung cancer and a preparation method thereof.
Background
Lung cancer, which is a malignant tumor originating in the bronchus mucosa or glands of the lung, has increased incidence and mortality year by year, and is one of the most threatening malignant tumors today. In recent 50 years, many countries report that the incidence and death rate of lung cancer are obviously increased, the incidence and death rate of lung cancer in men are the first place of all malignant tumors, the incidence rate in women is the second place, and the death rate is the second place. The existing data show that a great deal of smoking for a long time has a very close relationship with the occurrence of lung cancer. Existing studies have demonstrated that: the probability of lung cancer of a large number of smokers in a long period is 10-20 times that of non-smokers, and the smaller the smoking starting age, the higher the probability of lung cancer.
In addition, smoking not only directly affects the physical health of the smoker, but also has adverse effects on the health of surrounding people, so that the lung cancer prevalence of the passive smoker is obviously increased. Urban resident lung cancer has a higher incidence than rural areas, which may be related to urban atmospheric pollution and the presence of carcinogens in smoke. Therefore, no smoking should be advocated and urban environmental sanitation work should be enhanced.
Lung cancer is classified into small cell lung cancer (SCLC, 20%) and non-small cell lung cancer (NSCLC, 80%), and its cause is complex. At present, the treatment of lung cancer at home and abroad is mainly performed by operation, radiotherapy and chemotherapy, but the methods are easy to cause larger side effects on normal organs of patients, and the prognosis and survival rate of the patients are poor.
The traditional Chinese medicine with the characteristics of eliminating pathogenic factors and strengthening body resistance plays a great role in treating lung cancer, has the advantages of consolidated curative effect, small toxic and side effects, no great damage to organisms and capability of achieving synergistic and toxicity-reducing effects when being used together with chemotherapy. Therefore, searching and developing high-efficiency low-toxicity anti-lung cancer drugs from traditional Chinese medicines and natural medicines is a hotspot and difficulty in oncology research.
The existing patents contain various traditional Chinese medicine compositions for treating cancers, such as a medicine and food dual-purpose composition suitable for cancer patients and a preparation method thereof (patent number: 200910266137.0) and a traditional Chinese medicine for treating cancers (patent number: 200710166579.9); "Chinese herbal medicine composition for treating liver, stomach, lung and blood cancer and its preparation method" (patent number: 201110125724.5); "Chinese medicinal composition for treating cancer and its preparation method" (patent number: 201110165923.9); the traditional Chinese medicine composition for treating malignant tumor and application thereof (patent number: 201110145442.1), the anti-cancer traditional Chinese medicine composition and application thereof (201110056786.5) and the like are provided, the medicine composition is more in medicine types, is mainly taken in decoction or is simpler in preparation process, the extract is directly prepared into an oral preparation after being extracted, the dosage of the preparation is larger, and the preparation has a certain clinical treatment effect, but the extraction rate of active ingredients is lower, the preparation method is complex, and the quality control of the preparation is not facilitated.
Patent 201010187617.0 discloses an anticancer pharmaceutical composition and a preparation method of a traditional Chinese medicine composition, and the invention focuses on the matching use of the traditional Chinese medicine composition (medicinal materials per se, decoction of medicinal materials, concentrated extract of decoction or concentrated dry powder of decoction) and polysaccharide components, but the medicinal materials contained in the pharmaceutical composition are more, and the polysaccharide components are not derived from medicinal materials in the composition, so that the components are complex and difficult to control quality. And all the medicines belong to traditional Chinese medicine medicines, have slow efficacy, and can not control the aggravation or spread of cancer in a short time.
Therefore, how to provide a medicine for treating lung cancer, so as to solve the technical problems of few medicine types, poor treatment effect and slow effect of the medicine for treating lung cancer in the prior art, and the medicine is a problem to be solved by the technicians in the field.
Disclosure of Invention
The invention aims to provide a targeted drug for lung cancer treatment and a preparation method thereof. The invention combines western medicine components with the traditional Chinese medicine prescription, not only solves the problem of slow drug effect of the traditional Chinese medicine, but also has better treatment effect compared with pure western medicine treatment.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a targeted drug for lung cancer treatment, which comprises wortmannin, CM-272 and a traditional Chinese medicine extract;
The traditional Chinese medicine extract is prepared from the following components in parts by weight: 18 to 22 parts of Cordyceps sinensis, 14 to 18 parts of selfheal, 11 to 15 parts of coix seed, 15 to 19 parts of coptis chinensis, 8 to 12 parts of snakegourd fruit, 8 to 12 parts of figwort root, 5 to 9 parts of cynanchum atratum and 4 to 8 parts of fritillaria cirrhosa.
Preferably, the mass ratio of wortmannin, CM-272 and traditional Chinese medicine extract is 5-9: 2 to 6: 12-18.
The invention also provides a preparation method of the targeted drug for treating lung cancer, which comprises the following steps:
(1) Mixing Cordyceps, prunellae Spica, coicis semen, coptidis rhizoma, fructus Trichosanthis, radix scrophulariae, rhizoma Cynanchi Stauntonii and Bulbus Fritillariae Cirrhosae to obtain material 1, mixing material 1 with water, leaching, and filtering to obtain leaching solution and residue 1;
(2) Mixing the filter residue 1 with water, decocting, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract, and drying to obtain Chinese medicinal extract;
(4) The wortmannin, CM-272 and the traditional Chinese medicine extract are mixed to obtain the targeted medicine for treating lung cancer.
Preferably, in the step (1), the mass ratio of the material 1 to water is 1:3 to 5.
Preferably, the leaching temperature in the step (1) is 50-60 ℃; the leaching time is 2-4 h.
Preferably, the time of the decoction in the step (2) is 3-5 hours.
Preferably, in the step (2), the mass ratio of the filter residue 1 to water is 1:2 to 4.
Preferably, the step (3) is concentrated under reduced pressure to an extract with a relative density of 1.15-1.25 at 55 ℃.
Preferably, the temperature of the drying in the step (3) is 50-60 ℃.
Preferably, the drying time in the step (3) is 2-4 hours.
Compared with the prior art, the invention has the following beneficial effects:
1. The CM-272 added by the invention is a novel histone methyltransferase (euchromatic histone-lysine N-METHYLTRANSFERASE 2, EHMT2) G9a reversible inhibitor, and researches show that the G9a inhibitor can promote cancer cell apoptosis by regulating PI3K-mTOR-Akt signaling pathway. Because wortmannin also has an effect on the PI3K-mTOR-Akt signaling pathway, the wortmannin and the mTOR-Akt signaling pathway have the possibility of being used for treating non-small cell lung cancer in a combined way, the wortmannin and the CM-272 are creatively used in a combined way, and the obtained pharmaceutical composition has an excellent effect of inhibiting the growth of lung cancer cells.
However, although the purple wortmannin and the CM-272 have a certain synergistic effect, the invention also has the problems of long treatment time and poor recovery of patients.
2. Among the added traditional Chinese medicine components, coptis chinensis and snakegourd fruit have cold and bitter taste and can clear away heat and toxic materials, resolve phlegm and dissipate stagnation, and resolve toxin caused by long-term phlegm and blood stasis; radix scrophulariae, and oyster have effects of clearing heat, nourishing yin, cooling blood, resolving hard mass, softening and resolving hard mass, and rhizoma Cynanchi Stauntonii (also can lower lung qi), and Prunellae Spica have effects of clearing liver-fire, clearing, resolving hard mass, and detumescence. The fritillary bulb has the effects of clearing heat and resolving phlegm, and the combination of the medicines can nourish yin and remove heat, resolve phlegm and dissipate nodulation. Cordyceps Gan Liang has effects of tonifying, not being drastic and not being dry, tonifying lung yin and kidney essence, and promoting the growth of golden water (lung and kidney). Can obviously improve the functional state of patients with deficiency of lung, spleen and kidney and improve the cellular immunity, and the coix seed enters spleen, stomach and lung channels. Has effects of promoting diuresis, removing dampness, invigorating spleen, relieving diarrhea, removing arthralgia, expelling pus, removing toxic substances, and resolving hard mass. Can be used for treating pulmonary abscess, appendicitis, wart, cancer, etc. The coix seed has anti-tumor pharmacological action and contains a plurality of anti-tumor active ingredients, mainly esters, fatty acid compounds and polysaccharide components. The traditional Chinese medicine components added in the invention are matched with each other, and are suitable for patients with deficiency of qi and yin and stagnation of water dampness in malignant tumors.
3. The pharmaceutical composition provided by the invention has excellent anti-lung cancer activity, definite action, good inhibition effect on the proliferation of lung cancer cells, and the treatment effect on lung cancer is equivalent to that of the prior art.
Detailed Description
The invention provides a targeted drug for lung cancer treatment, which comprises wortmannin, CM-272 and a traditional Chinese medicine extract;
the traditional Chinese medicine extract is prepared from the following components in parts by weight: 18 to 22 parts of Cordyceps sinensis, 14 to 18 parts of selfheal, 11 to 15 parts of coix seed, 15 to 19 parts of coptis chinensis, 8 to 12 parts of snakegourd fruit, 8 to 12 parts of figwort root, 5 to 9 parts of cynanchum atratum and 4 to 8 parts of fritillaria cirrhosa;
The preparation method is preferably prepared from the following components in parts by weight: 19-21 parts of cordyceps sinensis, 15-17 parts of selfheal, 12-14 parts of coix seed, 16-18 parts of coptis chinensis, 9-11 parts of snakegourd fruit, 9-11 parts of radix scrophulariae, 6-8 parts of rhizoma cynanchi bungei and 5-7 parts of fritillaria cirrhosa; the preparation method is further preferably prepared from the following components in parts by weight: 20 parts of cordyceps sinensis, 16 parts of selfheal, 13 parts of coix seed, 17 parts of coptis chinensis, 10 parts of snakegourd fruit, 9-11 parts of figwort root, 6-8 parts of cynanchum atratum and 5-7 parts of fritillaria cirrhosa;
More preferably, the composition is prepared from the following components in parts by weight: 20 parts of cordyceps sinensis, 16 parts of selfheal, 13 parts of coix seed, 17 parts of coptis chinensis, 10 parts of snakegourd fruit, 10 parts of figwort root, 7 parts of cynanchum atratum and 6 parts of fritillaria cirrhosa.
In the invention, the mass ratio of wortmannin, CM-272 and traditional Chinese medicine extract is 5-9: 2 to 6: 12-18; preferably, the mass ratio of wortmannin to CM-272 to the traditional Chinese medicine extract is 6-8: 3 to 5:13 to 17; further preferably, the mass ratio of wortmannin, CM-272 and the extract of chinese medicine is 7:4: 14-16; more preferably, the mass ratio of wortmannin, CM-272 and the chinese herbal extract is 7:4:15.
The invention also provides a preparation method of the targeted drug for treating lung cancer, which comprises the following steps:
(1) Mixing Cordyceps, prunellae Spica, coicis semen, coptidis rhizoma, fructus Trichosanthis, radix scrophulariae, rhizoma Cynanchi Stauntonii and Bulbus Fritillariae Cirrhosae to obtain material 1, mixing material 1 with water, leaching, and filtering to obtain leaching solution and residue 1;
(2) Mixing the filter residue 1 with water, decocting, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract, and drying to obtain Chinese medicinal extract;
(4) The wortmannin, CM-272 and the traditional Chinese medicine extract are mixed to obtain the targeted medicine for treating lung cancer.
In the invention, the mass ratio of the material 1 to water in the step (1) is 1:3 to 5; preferably 1:4.
In the invention, the leaching temperature in the step (1) is 50-60 ℃; preferably 52-58 ℃; further preferably 54 to 56 ℃; more preferably 55 ℃.
In the invention, the leaching time in the step (1) is 2-4 hours; preferably 3h.
In the invention, the time of the decoction in the step (2) is 3-5 hours; preferably 4h.
In the invention, the mass ratio of the filter residue 1 to the water in the step (2) is 1:2 to 4; preferably 1:3.
In the invention, the step (3) is decompressed and concentrated to an extract with the relative density of 1.15-1.25 at 55 ℃; preferably 1.17 to 1.23; further preferably 1.19 to 1.21; more preferably 1.20.
In the invention, the drying temperature in the step (3) is 50-60 ℃; preferably 52-58 ℃; further preferably 54 to 56 ℃; more preferably 55 ℃.
In the invention, the drying time in the step (3) is 2-4 hours; preferably 3h.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
A preparation method of a targeted drug for lung cancer treatment comprises the following steps:
(1) 18 parts of cordyceps sinensis, 14 parts of selfheal, 11 parts of coix seed, 15 parts of coptis chinensis, 8 parts of snakegourd fruit, 8 parts of figwort root, 5 parts of cynanchum glaucescens and 4 parts of fritillaria bulb are mixed to obtain a material 1, and the material 1 and water are mixed according to the mass ratio of 1:3 mixing and leaching for 2 hours at 50 ℃, and filtering to obtain leaching liquor and filter residue 1;
(2) Mixing filter residue 1 with water according to the mass ratio of 1:2, mixing and decocting for 3 hours, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract with relative density of 1.15 at 55deg.C, and drying the extract at 50deg.C for 2 hr to obtain Chinese medicinal extract;
(4) The wortmannin, the CM-272 and the traditional Chinese medicine extract are mixed according to the mass ratio of 5:2:12 to obtain the targeted drug for lung cancer treatment.
Example 2
A preparation method of a targeted drug for lung cancer treatment comprises the following steps:
(1) 22 parts of cordyceps sinensis, 18 parts of selfheal, 15 parts of coix seed, 19 parts of coptis chinensis, 12 parts of snakegourd fruit, 12 parts of figwort root, 9 parts of cynanchum atratum and 8 parts of fritillary bulb are mixed to obtain a material 1, and the material 1 and water are mixed according to the mass ratio of 1:5, mixing and leaching for 4 hours at 60 ℃, and filtering to obtain leaching liquor and filter residue 1;
(2) Mixing filter residue 1 with water according to the mass ratio of 1:4, mixing and decocting for 5 hours, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract with relative density of 1.25 at 55deg.C, and drying the extract at 60deg.C for 4 hr to obtain Chinese medicinal extract;
(4) The wortmannin, the CM-272 and the traditional Chinese medicine extract are mixed according to the mass ratio of 9:6:18 to obtain the target medicine for treating lung cancer.
Example 3
A preparation method of a targeted drug for lung cancer treatment comprises the following steps:
(1) Mixing 20 parts of cordyceps sinensis, 16 parts of selfheal, 13 parts of coix seed, 17 parts of coptis chinensis, 10 parts of snakegourd fruit, 10 parts of figwort root, 7 parts of cynanchum atratum and 6 parts of fritillaria bulb to obtain a material 1, wherein the mass ratio of the material 1 to water is 1:4, mixing and leaching for 3 hours at 55 ℃, and filtering to obtain leaching liquor and filter residue 1;
(2) Mixing filter residue 1 with water according to the mass ratio of 1:3, mixing and decocting for 4 hours, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract with relative density of 1.20 at 55deg.C, and drying the extract at 55deg.C for 3 hr to obtain Chinese medicinal extract;
(4) The wortmannin, the CM-272 and the traditional Chinese medicine extract are mixed according to the mass ratio of 7:4:15 are mixed to obtain the target medicine for treating lung cancer.
Example 4
A preparation method of a targeted drug for lung cancer treatment comprises the following steps:
(1) Mixing 19 parts of cordyceps sinensis, 17 parts of selfheal, 12 parts of coix seed, 16 parts of coptis chinensis, 9 parts of snakegourd fruit, 9 parts of figwort root, 9 parts of cynanchum atratum and 5 parts of fritillary bulb to obtain a material 1, and mixing the material 1 with water according to the mass ratio of 1:5, mixing and leaching for 3 hours at 58 ℃, and filtering to obtain leaching liquor and filter residue 1;
(2) Mixing filter residue 1 with water according to the mass ratio of 1:4, mixing and decocting for 4 hours, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract with relative density of 1.17 at 55deg.C, and drying the extract at 54 deg.C for 4 hr to obtain Chinese medicinal extract;
(4) The wortmannin, the CM-272 and the traditional Chinese medicine extract are mixed according to the mass ratio of 6:5:16 are mixed to obtain the targeted medicine for treating lung cancer.
Example 5
A preparation method of a targeted drug for lung cancer treatment comprises the following steps:
(1) 21 parts of cordyceps sinensis, 15 parts of selfheal, 15 parts of coix seed, 19 parts of coptis chinensis, 11 parts of snakegourd fruit, 10 parts of figwort root, 7 parts of cynanchum atratum and 7 parts of fritillary bulb are mixed to obtain a material 1, and the material 1 and water are mixed according to the mass ratio of 1:3 mixing and leaching for 3 hours at 52 ℃, and filtering to obtain leaching liquor and filter residue 1;
(2) Mixing filter residue 1 with water according to the mass ratio of 1:2, mixing and decocting for 5 hours, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract with relative density of 1.22 at 55deg.C, and drying the extract at 55deg.C for 4 hr to obtain Chinese medicinal extract;
(4) The wortmannin, the CM-272 and the traditional Chinese medicine extract are mixed according to the mass ratio of 6:4:17 to obtain the target medicine for treating lung cancer.
Experimental example 1
Comparison test: the effect of different drugs on proliferation of human non-small cell lung cancer cells A549 is explored.
The product obtained by the method of example 3 was used as an experimental group;
meanwhile, control groups 1-4 are arranged, and the influence of different components in the medicine on the medicine effect is explored.
Control group 1, other methods were the same as example 3, except that wortmannin was not added;
control group 2, other methods were the same as example 3, except that CM-272 was not added;
Control group 3, otherwise identical to example 3, except that wortmannin and CM-272 were not added;
control group 4, other methods were the same as in example 3, except that no herbal extract was added;
meanwhile, control groups 5 and 6 are provided, and the influence of different components in the traditional Chinese medicine components on the efficacy is explored.
Control group 5, other methods were the same as in example 3, except that no Cordyceps was added;
control 6, otherwise identical to example 3, except that radix scrophulariae and cynanchum glaucescens were not added;
Non-small cell lung cancer cells A549 were selected and cultured in vitro for 24 hours in DMEM medium containing 10% Fetal Bovine Serum (FBS), and then the products obtained from each test group were added to a final concentration of 0.8. Mu. Mol.L -1 (the optimal addition ratio obtained by pre-experiments was not described in the specification because of excessive experimental data), and the cells were allowed to act in vitro for 14 days, and the blank control group was added with the same amount of medium, photographed by crystal violet staining, and analyzed semi-quantitatively for proliferation of the cells using an enzyme marker. Two sets of replicates were set and the results averaged and the results are shown in table 1.
TABLE 1 questionnaire for cell proliferation status
| Relative clone numbers | |
| Experimental group | 0.39 |
| Control group 1 | 1.74 |
| Control group 2 | 1.25 |
| Control group 3 | 1.82 |
| Control group 4 | 1.78 |
| Control group 5 | 0.75 |
| Control group 6 | 0.87 |
| Blank control group | 2.45 |
The results show that compared with the control group, wortmannin, CM-272 and traditional Chinese medicine extracts all have inhibition effect on proliferation of non-small cell lung cancer cells, and the combined effect of the three is better than that of single use; and if part of the components are discarded, the therapeutic effect of the drug is significantly affected.
The data of the control groups 4-6 show that the optimal treatment effect can be achieved only by adopting the traditional Chinese medicine composition provided by the invention, and the drug effect can be obviously affected if part of components are discarded.
Example 2
Comparison test: exploring the influence of different drugs on the apoptosis of human non-small cell lung cancer cell A549
Experimental group and control group are the same as Experimental example 1
Selecting non-small cell lung cancer cells A549, culturing for 24 hours in an in vitro culture medium, respectively adding 3 mu mol/L -1 of products obtained by each test group, adding a blank control group into the culture medium, reacting with the cells in vitro for 24 hours, collecting the cells, adding Annexin V-FITC and PI for dyeing, and performing fluorescent shooting to analyze the apoptosis condition; cell proteins were extracted and analyzed for changes in apoptosis-related protein expression (Bax/Bcl-2) by Western Blot. Two parallel experiments were set up and the results averaged and the statistical results are shown in table 2.
Table 2 relative expression questionnaire
| Relative expression | |
| Experimental group | 3.46 |
| Control group 1 | 2.23 |
| Control group 2 | 2.10 |
| Control group 3 | 1.65 |
| Control group 4 | 2.87 |
| Control group 5 | 2.78 |
| Control group 6 | 2.84 |
| Blank control group | 1.15 |
The result shows that the product provided by the invention can promote apoptosis of non-small cell lung cancer cells, and the combined effect of the three components is better than that of single use; these results show that wortmannin and CM-272 can obviously inhibit proliferation and promote apoptosis of non-small cell lung cancer cell A549, and the effect is better after being used together with traditional Chinese medicine extraction, and the wortmannin and CM-272 are feasible as a medicine selection and treatment scheme selection for treating non-small cell lung cancer.
Experimental example 3
In vivo anti-tumor Activity assay
60T 739 mice (females, 18-20 g) were each given to the experimental group for in vivo efficacy testing of the mice LA795 lung adenocarcinoma metastasis model.
The LA795 lung adenocarcinoma metastasis model takes T739 tumor-bearing mice with good tumor growth on the 6 th to 8 th days after inoculating LA795 lung adenocarcinoma cells, the cervical vertebrae are broken to kill the mice, the tumors are stripped under the aseptic condition, fresh necrotic tumor tissues are selected, sheared and placed in a glass grinder, a proper amount of physiological saline is added for gentle grinding to prepare tumor cell suspension, the cell suspension is diluted and counted by the physiological saline after being filtered by a cell sieve, and the cell suspension with the cell concentration of 1X 10 7/mL is prepared and inoculated under the right forelimb armpit skin of a healthy mouse, and each 0.2mL of cell suspension is inoculated. LA795 lung adenocarcinoma metastasis model was administered starting on the day of inoculation, 1 time a day.
The model group is filled with physiological saline, and each model group is 0.3mL;
chemotherapy group: injecting cyclophosphamide into abdominal cavity according to 22 mg/kg;
The experimental group is the product obtained in example 3: diluting with water according to 300mg/kg, and then drenching;
Each test group is respectively used for treating 20 mice, the mice are killed by dislocation of the neck the next day after the administration is finished after two weeks, tumor tissues are dissected and weighed, and the tumor inhibition rate is calculated;
The liver, spleen, thymus, kidney, heart, brain, stomach, lung, ileum, colon of the mice were taken, and the liver, spleen were weighed separately to calculate spleen index and thymus index.
The removed tissue was preserved in 10% neutral formalin, sectioned in paraffin, stained using hematoxylin-eosin staining, wherein tumor tissue was stained for TUNEL, and apoptosis was observed. The data were averaged and the results are shown in tables 3 and 4.
Tumor inhibition rate (%) = (average tumor weight of 1-administration group/average tumor weight of physiological saline group) ×100%
Spleen index= (spleen weight/body weight) ×1000
Thymus index = (thymus weight/body weight) ×1000
TABLE 3 results of experimental results of tumor suppression rate in mice with lung adenocarcinoma metastasis of LA795
| Tumor inhibition rate% | |
| Experimental group | 39.57 |
| Chemotherapy group | 45.26 |
TABLE 4 comparison of the immune organ weight index of LA795 lung adenocarcinoma metastatic mice
| Spleen index mg/g | Thymus index mg/g | |
| Experimental group | 9.45 | 4.82 |
| Chemotherapy group | 9.18 | 4.70 |
| Model group | 9.14 | 4.67 |
As can be seen from the descriptions in tables 3 and 4, the drug provided by the present invention can significantly inhibit the growth of lung cancer cell lines such as LA 795; the experiment on the lung adenocarcinoma tumor-bearing mice model shows that the tumor inhibition rate of the experimental group is equivalent to that of the prior art medicines, the spleen index and thymus index of the mice are increased, the lung metastasis of subcutaneous transplanted tumors of the mice can be obviously inhibited, the apoptosis of tumor cells is caused, and no obvious toxic or side effect is caused.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (9)
1. A targeting drug for treating lung cancer, which is characterized by comprising wortmannin, CM-272 and traditional Chinese medicine extracts;
the traditional Chinese medicine extract is prepared from the following components in parts by weight: 18 to 22 parts of Cordyceps sinensis, 14 to 18 parts of selfheal, 11 to 15 parts of coix seed, 15 to 19 parts of coptis chinensis, 8 to 12 parts of snakegourd fruit, 8 to 12 parts of figwort root, 5 to 9 parts of cynanchum atratum and 4 to 8 parts of fritillaria cirrhosa;
The mass ratio of wortmannin to CM-272 to the traditional Chinese medicine extract is 5-9: 2 to 6: 12-18.
2. The method for preparing the targeted drug for treating lung cancer as claimed in claim 1, which is characterized by comprising the following steps:
(1) Mixing Cordyceps, prunellae Spica, coicis semen, coptidis rhizoma, fructus Trichosanthis, radix scrophulariae, rhizoma Cynanchi Stauntonii and Bulbus Fritillariae Cirrhosae to obtain material 1, mixing material 1 with water, leaching, and filtering to obtain leaching solution and residue 1;
(2) Mixing the filter residue 1 with water, decocting, and filtering to obtain filtrate;
(3) Mixing the leaching solution with the filtrate, concentrating under reduced pressure to obtain extract, and drying to obtain Chinese medicinal extract;
(4) The wortmannin, CM-272 and the traditional Chinese medicine extract are mixed to obtain the targeted medicine for treating lung cancer.
3. The method for preparing a targeted drug for lung cancer treatment according to claim 2, wherein the mass ratio of the material 1 to water in the step (1) is 1:3 to 5.
4. The method for preparing a targeted drug for lung cancer treatment according to claim 3, wherein the leaching temperature in the step (1) is 50-60 ℃; the leaching time is 2-4 h.
5. The method for preparing a targeted drug for lung cancer treatment according to claim 2, wherein the time of the decoction in the step (2) is 3-5 hours.
6. The method for preparing a targeted drug for lung cancer treatment according to claim 4, wherein the mass ratio of the filter residue 1 to water in the step (2) is 1:2 to 4.
7. The method for preparing a targeted drug for lung cancer treatment according to claim 2, wherein the step (3) is concentrated under reduced pressure to an extract with a relative density of 1.15-1.25 at 55 ℃.
8. The method for preparing a targeted drug for lung cancer treatment according to claim 2, wherein the drying temperature in the step (3) is 50-60 ℃.
9. The method for preparing a targeted drug for lung cancer treatment according to claim 2 or 8, wherein the drying time in step (3) is 2-4 hours.
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