CN112569215A - Application of domiphen bromide in preparation of medicine for preventing and treating colorectal cancer - Google Patents
Application of domiphen bromide in preparation of medicine for preventing and treating colorectal cancer Download PDFInfo
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- CN112569215A CN112569215A CN202011618783.1A CN202011618783A CN112569215A CN 112569215 A CN112569215 A CN 112569215A CN 202011618783 A CN202011618783 A CN 202011618783A CN 112569215 A CN112569215 A CN 112569215A
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- colorectal cancer
- domiphen bromide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention belongs to the technical field of medicines, and particularly relates to application of domiphen bromide in preparation of a medicine for preventing and treating colorectal cancer; the research of the invention shows that domiphen bromide can effectively inhibit the activity of colorectal cancer cells from different sources, can also inhibit the proliferation of the colorectal cancer cells, induces the apoptosis of the colorectal cancer cells, shows obvious curative effect on the colorectal cancer, and can be applied to the development of medicaments for efficiently preventing and treating the colorectal cancer. The invention not only provides a new application of domiphen bromide, but also provides a new therapeutic drug and therapeutic approach for the treatment of colorectal cancer.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of domiphen bromide in preparation of a medicine for preventing and treating colorectal cancer.
Background
Colorectal cancer is one of the most common and high-mortality malignant tumors, and the incidence rate is higher at the 4 th position and the mortality rate is higher at the 5 th position worldwide. According to the data of the annual report of Chinese tumor registration in 2019, the incidence rate of colorectal cancer in China is 3 rd. At present, the combination therapy of surgery and radiotherapy and chemotherapy is still the main treatment means for colorectal cancer. As for chemotherapy, with the continuous development of modern medical research, chemotherapy drugs for treating colorectal cancer are continuously developed, and the chemotherapy drugs for clinically treating colorectal cancer comprise 5-fluorouracil, irinotecan, oxaliplatin, capecitabine and the like; in addition, chemotherapeutic regimens have been continually improved, for example, the FOLFOX regimen of oxaliplatin in combination with 5-fluorouracil and calcium folinate is widely used clinically for the treatment of stage ii/iii colorectal cancer. The application of chemotherapy drugs enables the survival rate of colorectal cancer patients to be remarkably improved, for example, compared with simple operation, the death risk of colorectal cancer patients in stage III can be reduced by about 15% through the adjuvant therapy of 5-fluorouracil, and the death risk can be further reduced by about 5% through combined therapy with oxaliplatin. However, the treatment effect of the chemotherapeutic drugs is still unsatisfactory due to the limitations of problems such as chemotherapy non-response, chemotherapy tolerance and toxic and side effects, and the median survival time of patients with unresectable metastatic colorectal cancer is only 5-6 months under the condition of receiving chemotherapy only. Therefore, the development of new drugs for treating colorectal cancer is very slow.
Domiphen bromide, belonging to quaternary ammonium salt compound with molecular formula C22H40The bactericidal composition has the advantages of low dosage, good effect, low toxic and side effects and the like. Currently, domiphen bromide is widely used in hospitals for disinfection of skin mucosa, and is also applied to sterilization and disease prevention in agriculture and animal husbandry. However, there is no report on domiphen bromide anti-tumor activity.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention mainly aims to provide the application of domiphen bromide in preparing the medicine for preventing and treating colorectal cancer.
The second purpose of the invention is to provide a medicine for preventing and treating colorectal cancer.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides application of domiphen bromide in preparing a medicine for preventing and treating colorectal cancer.
According to research, the domiphen bromide can obviously inhibit the activity of colorectal cancer cells (human colorectal cancer cells HCT116, SW480, RKO and HCT-15) of different sources; further research shows that the domiphen bromide can also inhibit the proliferation of colorectal cancer cells and induce the apoptosis of the colorectal cancer cells; the domiphen bromide has good anti-colorectal cancer effect, and is expected to be developed into a novel medicament for efficiently treating colorectal cancer.
Preferably, the colorectal cancer includes, but is not limited to, human colorectal cancer cells HCT116, SW480, RKO, HCT-15.
Preferably, the drug is a drug that inhibits colorectal cancer cell viability. Research shows that domiphen bromide can effectively inhibit the activity of HCT116, SW480, RKO and HCT-15 cell strains, and the fact that domiphen bromide can inhibit the activity of colorectal cancer cells is demonstrated.
Preferably, the drug is a drug that inhibits proliferation of colorectal cancer cells. Studies show that both domiphen bromide can inhibit the proliferation of HCT116 cells, which indicates that domiphen bromide can inhibit the proliferation of colorectal cancer cells.
Preferably, the drug is a drug that induces apoptosis in colorectal cancer cells. Research shows that domiphen bromide has an induction effect on apoptosis of the colorectal cancer cell HCT116, and the fact that domiphen bromide can induce apoptosis of the colorectal cancer cell is proved.
The invention also provides a medicine for preventing and treating colorectal cancer, which comprises domiphen bromide as a main active ingredient.
Preferably, the medicament further comprises a pharmaceutically acceptable carrier and/or excipient. Namely, the medicine can be mixed with a pharmaceutically acceptable carrier or excipient to prepare a composition.
The excipient refers to diluents, binders, lubricants, disintegrants, cosolvents, stabilizers and the like which can be used in the pharmaceutical field, and some medicinal matrixes. The carrier is functional pharmaceutical adjuvant available in the pharmaceutical field, and comprises surfactant, suspending agent, emulsifier and some novel medicinal polymer materials, such as cyclodextrin, chitosan, polylactic acid (PLA), polyglycolic acid polylactic acid copolymer (PLGA), hyaluronic acid, etc.
Preferably, the medicament can be prepared into clinically acceptable dosage forms, wherein the dosage forms include but are not limited to tablets, capsules, granules, dripping pills, infusion solutions and injections.
The preparation is a clinically common preparation. Pharmaceutical formulations may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) and, if certain drugs are unstable under gastric conditions, may be formulated as enteric coated tablets.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a new application of domiphen bromide, namely, application of domiphen bromide in preventing and treating colorectal cancer; the research of the invention shows that domiphen bromide can effectively inhibit the activity of colorectal cancer cells from different sources, can also inhibit the proliferation of the colorectal cancer cells, induces the apoptosis of the colorectal cancer cells, shows obvious curative effect on the colorectal cancer, and can be applied to the development of medicaments for efficiently preventing and treating the colorectal cancer. The invention not only provides a new application of domiphen bromide, but also provides a new therapeutic drug and therapeutic approach for the treatment of colorectal cancer.
Drawings
FIG. 1 is a graph of the inhibitory effect of domiphen bromide on the viability of different colorectal cancer cells;
FIG. 2 is a graph of the inhibitory effect of domiphen bromide on the proliferative capacity of colorectal cancer cells;
FIG. 3 is a graph of the induction of apoptosis in colorectal cancer cells by domiphen bromide.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
Experimental example 1 inhibitory Effect of domiphen bromide on cell viability of colorectal cancer
Colorectal cancer cells in logarithmic growth phase (human colorectal cancer cells HCT116, SW480, RKO, HCT-15) were plated in 96-well plates at 5000 cells per well in 200. mu.LRPMI-1640 medium. Drug treatment, control and blank groups were set separately. The drug treatment groups were groups containing different domiphen concentrations (0. mu.M, 1. mu.M, 10. mu.M, 50. mu.M, 100. mu.M), the control group contained cells alone without drug, and the blank group contained no cells and medium alone. 4h before the treatment, 20 μ of LCCK8 solution was added to each well and incubation was continued for 4 h. And reading the absorbance value at the wavelength of 450nm by using a full-wavelength multifunctional microplate reader, and calculating the cell activity according to the absorbance value.
Cell viability ═ 100% (drug treatment OD-blank OD)/(control OD-blank OD). Cell viability halfInhibition of solubility (IC)50) Calculated using Graphpad software.
The results are shown in FIG. 1, and 10 μ M to 100 μ M domiphen bromide can effectively inhibit the activity of HCT116, SW480, RKO and HCT-15 cell strains, which shows that domiphen bromide can inhibit the activity of colorectal cancer cells.
Experimental example 2 inhibitory Effect of domiphen bromide on the proliferative Capacity of colorectal cancer cells
Colorectal cancer cells (HCT116) in log phase were plated in six-well plates at 500 cells per well in 200. mu.L RPMI-1640 medium, and a control group (cells alone without drug) was set. After the cells were fully adherent, the cells were treated with different concentrations of domiphen bromide (0.625. mu.M, 1.25. mu.M, 2.5. mu.M) for 9 days. The medium was changed every 3 days. After the treatment, the cells were discarded from the medium, washed with PBS 2 times, fixed with ice bath methanol for 5min, and finally stained with crystal violet.
As shown in FIG. 2, domiphen bromide at concentrations of 0.625. mu.M, 1.25. mu.M, and 2.5. mu.M all inhibited HCT116 cell proliferation, with the best inhibitory effect of domiphen bromide at 2.5. mu.M indicating that domiphen bromide inhibited colorectal cancer cell proliferation.
Experimental example 3 Induction of apoptosis in colorectal cancer cells by domiphen bromide
Colorectal cancer cells (HCT116) in log phase were plated in six-well plates at 500 cells per well in 200. mu.L RPMI-1640 medium, and a control group (cells alone without drug) was set. After the cells were fully attached, the cells were treated with 10 μ M domiphen bromide for 48h, then digested with EDTA-free trypsin, centrifuged at 2000rpm for 5min, and washed 2 times with PBS. Then, the working solution (500. mu. Lbinding buffer, 5. mu. Lannexin V-FITC dye and 5. mu. LPI dye) was added to the cells, and after scattering and mixing, the cells were left to react in the dark for 15 min. The apoptosis rate was measured using a BD FACSCAnto II flow cytometer. Cells that were Annexin V-FITC single positive and Annexin V-FITC/PI double positive were counted as apoptotic cells.
The results are shown in fig. 3, and the domiphen bromide has an induction effect on the apoptosis of the colorectal cancer cell HCT116, which indicates that the domiphen bromide can induce the apoptosis of the colorectal cancer cell.
From the comprehensive examples 1-3, the domiphen bromide can obviously inhibit the activity of colorectal cancer cells of different sources; meanwhile, the proliferation of the colorectal cancer cells can be inhibited, and the apoptosis of the colorectal cancer cells can be induced; proved that the domiphen bromide has good anti-colorectal cancer effect, and is expected to be developed into a novel medicament for efficiently treating colorectal cancer.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (8)
1. Application of domiphen bromide in preparing medicine for preventing and treating colorectal cancer.
2. Use according to claim 1, wherein the colorectal cancer includes but is not limited to human colorectal cancer cells HCT116, SW480, RKO, HCT-15.
3. The use of claim 1, wherein the medicament is a medicament for inhibiting the viability of colorectal cancer cells.
4. The use of claim 1, wherein the medicament is a medicament for inhibiting proliferation of colorectal cancer cells.
5. The use of claim 1, wherein the medicament is a medicament for inducing apoptosis in colorectal cancer cells.
6. A medicament for preventing and treating colorectal cancer, which is characterized by comprising domiphen bromide.
7. The drug for preventing and treating colorectal cancer according to claim 6, further comprising a pharmaceutically acceptable carrier and/or excipient.
8. The drug for preventing and treating colorectal cancer according to claim 6, wherein the dosage form of the drug comprises but is not limited to tablets, capsules, granules, dripping pills, infusion solutions and injections.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170304387A1 (en) * | 2014-10-24 | 2017-10-26 | Launx Biomedical Co., Ltd. | New indication of antibiotic drugs for preparation of cancer inhibition pharmaceutical composition |
WO2019241636A1 (en) * | 2018-06-14 | 2019-12-19 | The Uab Research Foundation | Identifying compounds for treating cancer and use thereof |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170304387A1 (en) * | 2014-10-24 | 2017-10-26 | Launx Biomedical Co., Ltd. | New indication of antibiotic drugs for preparation of cancer inhibition pharmaceutical composition |
WO2019241636A1 (en) * | 2018-06-14 | 2019-12-19 | The Uab Research Foundation | Identifying compounds for treating cancer and use thereof |
Non-Patent Citations (2)
Title |
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覃源才: "50%硫酸镁溶液用度米芬做防腐剂的试验", 《广西医学院学报》 * |
邵芳: "度米芬联合麝香草酚治疗化疗后口腔溃疡", 《中国社区医师(医学专业)》 * |
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