CN110755438A

CN110755438A - Application of levofloxacin antibiotic in preparing anti-cancer drug sensitizing drug and anti-cancer drug thereof

Info

Publication number: CN110755438A
Application number: CN201911159715.0A
Authority: CN
Inventors: 贺小琼
Original assignee: Kunming Medical University
Current assignee: Kunming Medical University
Priority date: 2019-11-22
Filing date: 2019-11-22
Publication date: 2020-02-07

Abstract

The invention relates to application of levofloxacin antibiotic in preparing an anti-cancer drug sensitizing drug and an anti-cancer drug thereof, belonging to the technical field of drug research. The levofloxacin antibiotic has significant in-vitro and in-vivo anticancer effects on various human cancers; the anticancer effect has obvious dose-effect and time-effect relationship; when the levofloxacin antibiotic is combined with other anti-cancer drugs for use, the anti-cancer effect of the anti-cancer drugs on various cancers can be remarkably improved, and the levofloxacin antibiotic and the other anti-cancer drugs have synergistic or additive combined anti-cancer effect. At effective in vivo anti-cancer doses, levofloxacin does not significantly affect animal weight development. The results show that the levofloxacin antibiotics can be used as broad-spectrum anticancer drugs; in particular, the derivative can be used as a sensitizing medicament of other anticancer medicaments and can be combined with other anticancer medicaments for application or form a combined anticancer medicament composition with other anticancer medicaments; or used as health product for adjuvant treatment of cancer.

Description

Application of levofloxacin antibiotic in preparing anti-cancer drug sensitizing drug and anti-cancer drug thereof

Technical Field

The invention belongs to the technical field of medicine research, and particularly relates to application of levofloxacin antibiotic in preparing broad-spectrum anticancer drugs, application in preparing sensitizing drugs of other clinical anticancer drugs, application in preparing a combined anticancer drug composition, and an auxiliary anticancer health-care product.

Background

Malignant tumor is a serious disease seriously threatening human health and life safety, and is now the main cause of death of human beings and seriously threatening human health and life safety. Data published by Globocan of the international cancer institute of the world health organization show that 1266.1 ten thousand new cancer cases and 756.4 ten thousand deaths occur worldwide in 2008. In 2012, the number of newly added cancer cases is 1410 ten thousand, the death is 820 ten thousand, and 3260 thousands of people live with tumors. In 2015, 1750 ten thousand new cancer cases and 870 ten thousand deaths occur worldwide. The number of cancer cases and the number of deaths are increasing, and the number of new cancer cases is estimated to reach 1900 ten thousand in 2025 and 2400 ten thousand in 2035. The data show that the incidence of malignant tumors is rapidly increasing with the aging population, the aggravation of environmental pollution and the change of life patterns.

Cancer is still an incurable disease in the world at present. Chemotherapy for cancer plays an important role in cancer treatment as a systemic therapeutic measure, and is a promising approach to complete cancer treatment in the future. Most of the clinically used cancer chemotherapy drugs have the problems of great toxic and side effects, uncertain curative effect, poor selectivity, weak targeting property, cancer cell drug resistance and the like, so that the clinical application and effect of cancer chemotherapy drug treatment are greatly limited. Therefore, the development of new chemotherapeutic drugs with definite curative effect and sensitization drugs capable of improving the anticancer effect of clinical anticancer drugs has important value for the chemotherapy of cancer.

Disclosure of Invention

The invention aims to solve the defects of the prior art and provides the application of levofloxacin antibiotic in preparing broad-spectrum anticancer drugs, the application in preparing combined anticancer drug compositions, the application in serving as clinical anticancer drug sensitizing drugs, anticancer drugs thereof and auxiliary anticancer health care products.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

the levofloxacin antibiotic can be used in preparing broad-spectrum anticancer drugs, combined anticancer drug compositions, and anticancer drug sensitizing drugs or auxiliary anticancer health products.

Further, preferably, the broad spectrum anticancer drugs include drugs against gastric cancer, colon cancer, leukemia, lymphoma, glioma, nasopharyngeal carcinoma, esophageal cancer, cervical cancer, liver cancer, lung cancer, breast cancer, ovarian cancer, bile duct cancer, pancreatic cancer, bladder cancer, renal cancer, prostate cancer, osteosarcoma, and melanoma.

The levofloxacin antibiotic has significant anticancer effect on human gastric cancer, colon cancer, leukemia, lymphoma, glioma, nasopharyngeal carcinoma, esophageal cancer, cervical cancer, liver cancer, lung cancer, breast cancer, ovarian cancer, cholangiocarcinoma, pancreatic cancer, bladder cancer, renal cancer, prostate cancer, osteosarcoma, melanoma and the like. Levofloxacin antibiotics are broad-spectrum anticancer drugs, and have obvious dose-effect and time-effect relationships in anticancer effect.

A broad-spectrum anticancer medicine or the sensitizing medicine of anticancer medicine contains levofloxacin as active component. The levofloxacin antibiotic can significantly improve the anticancer drug effect of clinical anticancer drugs, and has synergistic or additive combined anticancer effect with the clinical anticancer drugs.

A combined anticancer medicinal composition contains levofloxacin antibiotic as active ingredient, and at least one of cisplatin, 5-fluorouracil and other clinical anticancer drugs.

Further, preferably, the medicament formulation is injection, powder injection, tablets, oral liquid, capsules, granules or electuary.

The active ingredients of the broad-spectrum anticancer drug and the anticancer drug sensitizing drug can be levofloxacin antibiotic only or a combined anticancer drug composition which comprises the levofloxacin antibiotic as one of the active ingredients. When the compound is a combined pharmaceutical composition, the compound has anticancer activity and also comprises at least one of other clinical anticancer drugs such as cisplatin, 5-fluorouracil and the like besides levofloxacin antibiotics. The levofloxacin antibiotic and other anticancer drugs in the combined anticancer drug composition have additive action or synergistic action in cancer treatment, and can improve clinical anticancer effect, reduce the dosage of the anticancer drugs and reduce toxic and side effects.

It will be appreciated by those skilled in the art that the anticancer drug, the anti-cancer drug sensitizing agent of the present invention may further comprise a pharmaceutically acceptable carrier in addition to the active ingredient.

The specific therapeutically effective amount of levofloxacin in the pharmaceutical composition may be determined by those skilled in the art based on the subject to be administered and the type of cancer. In some embodiments, an effective amount of levofloxacin may range from 1 to 99.99%, preferably from 10 to 99%, more preferably from 50 to 99% by weight of the composition.

An auxiliary anticancer health product contains levofloxacin antibiotic as active ingredient.

Further, the dosage form is preferably a tablet, an oral liquid, a capsule, a granule or a granule.

It will be appreciated by those skilled in the art that the levofloxacin antibiotics having anticancer activity of the present invention include various generations of quinolone antibiotics currently used in clinical practice, and are not limited to the ones indicated in the examples.

Compared with the prior art, the invention has the beneficial effects that:

the levofloxacin antibiotic of the invention is a clinical common antibacterial drug, can be purchased from the market, and can also be chemically synthesized. The levofloxacin antibiotic can be used as a chemotherapeutic drug for various cancers of human beings, or as a sensitizing drug for other clinical anticancer drugs, or as an anticancer drug composition of active ingredients of anticancer drugs, or as a component of a combined anticancer drug composition, and as an active ingredient of a health care product for assisting anticancer.

The levofloxacin antibiotic can remarkably kill and/or inhibit various human cancer cells in vitro, such as gastric cancer cells SGC-7901, colon cancer cells HCT-116, leukemia cells K-562, lymphomas L-428 and BJAB, glioma cells U-251, liver cancer cells HepG2 and QGY-7703, nasopharyngeal cancer cells CNE2, lung cancer cells A-549 and XWLC-05, esophageal cancer cells CaEs-17, cervical cancer cells Hela, ovarian cancer SKOV-3, bile duct cancer cells QBC-939, pancreatic cancer PANC-1, bladder cancer cells T-24, renal cancer cells ACHN, prostate cancer PC-3, osteosarcoma MNNG, breast cancer MCF-7 and MDA-MB-231, melanoma A-375 and the like.

The levofloxacin antibiotic has obvious growth inhibition effect on human cancers transplanted to balb/c nude mice in vivo. The levofloxacin antibiotic and clinically used anticancer chemotherapeutic drugs such as cisplatin, 5-fluorouracil and the like have significant synergistic or additive combined anticancer effects on various human cancers in vitro and/or in vivo, and can be combined and applied as an anticancer drug composition for cancer chemotherapy or as a sensitizing drug in cancer treatment.

Drawings

FIG. 1 shows the in vitro anticancer effect of levofloxacin hydrochloride on different cancer cell lines;

FIG. 2 shows the in vitro anticancer effect of levofloxacin lactate on different cancer cell lines;

FIG. 3 is a graph showing the relationship between dose-effect and time-effect of levofloxacin hydrochloride in vitro against nasopharyngeal carcinoma;

FIG. 4 shows the in vitro selective anticancer effect of levofloxacin hydrochloride;

FIG. 5 is a graph showing the in vivo anti-nasopharyngeal carcinoma effect (relative tumor volume, RTV) of levofloxacin hydrochloride;

FIG. 6 shows the in vivo anti-nasopharyngeal carcinoma effect (relative tumor proliferation rate, RPR,%) of levofloxacin hydrochloride;

FIG. 7 shows the in vivo anti-nasopharyngeal cancer effect (tumor weight, TW) of levofloxacin hydrochloride;

FIG. 8 shows the in vitro combined anticancer effects of levofloxacin hydrochloride and cisplatin;

FIG. 9 shows the in vitro combined anticancer effects of levofloxacin hydrochloride and 5-fluorouracil;

FIG. 10 shows the in vivo combined anti-nasopharyngeal effect (relative tumor volume) of levofloxacin hydrochloride and cisplatin;

FIG. 11 shows the combined anti-nasopharyngeal effect (relative tumor proliferation rate) of levofloxacin hydrochloride and cisplatin in vivo;

FIG. 12 shows the in vivo combined anti-nasopharyngeal effect (mean tumor weight) of levofloxacin hydrochloride and cisplatin;

FIG. 13 shows the cytotoxic effect of levofloxacin hydrochloride on normal cells;

FIG. 14 shows that levofloxacin hydrochloride affects the cytotoxic effects of cisplatin on normal cells (NO-free levofloxacin, LH-levofloxacin hydrochloride);

FIG. 15 is a graph of the effect of various doses of levofloxacin hydrochloride on tumor-bearing body weight in animals;

FIG. 16 shows the effect of levofloxacin hydrochloride in combination with cisplatin on tumor-bearing body weight in mice;

FIG. 17 is a graph comparing the in vitro anti-cancer effects of Levofloxacin Hydrochloride (LH) and Levofloxacin Lactate (LL);

note: the overlapping of characters and lines in the figure does not affect the expression meaning.

Detailed Description

The present invention will be described in further detail with reference to examples.

It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples do not specify particular techniques or conditions, and are performed according to the techniques or conditions described in the literature in the art or according to the product specifications. The materials or equipment used are not indicated by manufacturers, and all are conventional products available by purchase.

Definition of terms

Unless otherwise indicated, the terms used in the present invention have the following meanings:

the chemical name of the levofloxacin antibiotics is as follows: (S) - (-) -9-fluoro-2, 3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1, 2, 3-de ] - [1, 4] benzoxazine-6-carboxylic acid hemihydrate, belonging to quinolone antibiotics. Including all the various levofloxacin antibiotic preparations used clinically.

As used herein, "pharmaceutical composition" refers to a formulation of a levofloxacin antibiotic of the present application with a vehicle commonly accepted in the art for delivery of biologically active compounds to mammals, such as humans. Such media include all pharmaceutically acceptable carriers.

The combined anticancer medicine composition is the combined anticancer medicine comprising levofloxacin antibiotic and other clinical anticancer medicine.

The 'sensitization effect' in the application refers to that when the levofloxacin antibiotic is combined with other anticancer drugs, the drug effect of the other anticancer drugs can be obviously improved, and the anticancer effect of the combined application is stronger than that of a single anticancer drug.

As used herein, "pharmaceutically acceptable carrier" is intended to include, but is not limited to, any adjuvant, excipient, glidant, sweetener, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, disintegrating agent, solvent, or emulsifying agent that has been recognized by the united states Food and Drug Administration (FDA) as being useful in humans or animals in a variety of forms that have no adverse effects on the resulting pharmaceutical composition.

The term "treating" means administering the medicament of the present invention to prevent, ameliorate or eliminate a disease or one or more symptoms associated with the disease, and includes:

(i) preventing the occurrence of a disease or condition in a mammal, particularly when such mammal is susceptible to the disease condition, but has not yet been diagnosed as having the disease condition;

(ii) inhibiting the disease or disease state, i.e., arresting its development;

(iii) alleviating the disease or condition, i.e., causing regression of the disease or condition.

The auxiliary anticancer health product is used for auxiliary treatment of cancer patients in the treatment process of the cancer patients, and may have sensitization effect on the treatment of the cancer patients, but the health product is not used for treatment.

Example 1: the levofloxacin antibiotic has obvious in vitro anticancer effect.

In vitro anti-cancer test methods: the levofloxacin antibiotics are dissolved in sterile normal saline, and the final concentration of the levofloxacin antibiotics is 25, 50, 100, 200 and 400 mug/ml, so that an in-vitro anticancer test is carried out. Collecting human cancer cells in logarithmic growth phase, suspending by antibiotic-free DMEM/F12 complete culture solution added with 10% Fetal Bovine Serum (FBS) by volume, inoculating in 96-well plate, adding 100 μ l cell suspension per well (inoculating 1 × 10 cells per well except MCF-7)⁴Outside of each cell, the remaining cancer cell lines were inoculated 6X 10 cells per well³Individual cells). 37 ℃ and 5% CO₂After overnight culture in an incubator, the culture solution is sucked out, then 200 mul of culture solution containing levofloxacin antibiotics with corresponding concentrations is respectively added according to the design (the culture solution is antibiotic-free DMEM/F12 complete culture solution containing 10% fetal calf serum by volume), and a normal saline solvent control group and an anti-cancer drug positive control group are set at the same time. Adding the same volume of normal saline into the normal saline solvent control group; cisplatin solution is added into the anti-cancer drug positive control group, the concentration of the cisplatin in the culture solution is 2 mug/ml, and 8 holes are made in each group and each concentration in parallel. The cells were incubated at 37 ℃ with 5% CO₂And (3) continuously culturing in an incubator, measuring the OD value of each hole by adopting an MTT method 72 hours (24 hours, 48 hours and 72 hours in time-effect relation) after adding the medicine, drawing cell growth curves at different time and different doses, and observing the time-effect and dose-effect relation of the anti-cancer effect of the levofloxacin antibiotic body in vitro. The growth inhibition rate of cancer cells was calculated as follows:

inhibition (%) = (saline group corrected OD value-corrected OD value of drug treatment group)/saline group corrected OD value × 100

Corrected OD value = OD value actually measured-OD value of cell-free blank group

As a result: the levofloxacin antibiotic has very significant cytotoxic effect on various cancer cells, the growth inhibition rate on various cancer cells is increased along with the increase of the dose of the levofloxacin antibiotic, the levofloxacin antibiotic has significant in-vitro anticancer effect on various detected human cancer cells, and the in-vitro anticancer effect has significant concentration-effect relationship, and the results are shown in figure 1 (the in-vitro anticancer effect of levofloxacin hydrochloride) and figure 2 (the in-vitro anticancer effect of levofloxacin lactate). The anti-cancer effect of levofloxacin antibiotics has a dose-effect and time-effect relationship, and the anti-cancer effect is enhanced with the increase of concentration and/or the prolongation of drug treatment time, as shown in fig. 3 (HCT-116, the left graph in fig. 3 is the inhibition rate curve of each group at different time points, and the right graph is the optical density value of each group at different time points). In an in vitro anticancer activity screening test, after cancer cells are treated by levofloxacin antibiotic for 72 hours, under a microscope, the screening test has obvious in vitro growth inhibition or killing effects on various cancer cells of other human, such as cervical cancer cells Hela, liver cancer cells QGY-7703, lymphoma cells L-428, BJAB and WSU-FSCCL, esophageal cancer cells CaEs-17, breast cancer cells MDA-MB-231, bile duct cancer cells QBC-939, osteosarcoma MNNG, prostate cancer cells PC-3, bladder cancer cells T-24, renal cancer cells ACHN, ovarian cancer cells SKOV-3, pancreatic cancer PANC-1, melanoma cells A-375 and the like.

Example 2: the levofloxacin antibiotics have selective in vitro anticancer effect on partial human cancer cells

The experimental procedure was the same as in vitro anticancer experiment of example 1, and the selective cytotoxicity was compared with that of human normal vascular endothelial cell ECV-304. In vitro cell culture tests show that under the same dosage and test conditions, the cytotoxic effect of the levofloxacin antibiotics on human leukemia cells K-562, colon cancer cells HCT-116 and stomach cancer cells SGC-7901 is significantly greater than that of human normal vascular endothelial cell strain ECV-304, and the levofloxacin antibiotics have selective anticancer effect on partial human cancer cells. The results are shown in FIG. 4.

Example 3: the levofloxacin antibiotics have obvious in vivo anticancer effect

The test method for the anti-transplantation human nasopharyngeal carcinoma in the nude mouse comprises the following steps: preparing human nasopharyngeal carcinoma cell sample by cell culture, and adjusting cell concentration to 4 × 10 with sterile DMEM/F12 culture solution without FBS and antibiotics⁷And (4) obtaining cell suspension. Is suitable for menstruationBalb/c nude mice (body weight 19-21 g) were sexually fed for 3 days, and each was inoculated with 0.1ml of cell suspension by subcutaneous aseptic manipulation on the right back. Nude mice were housed in the SPF laboratory. The major diameter (a) and the transverse diameter (b) of each tumor-bearing mouse cancer were measured with automatically reading vernier calipers, using the formula: v = a × b²The cancer volume was calculated for each mouse. On day 8 after cell inoculation, most mice showed macroscopically visible tumors subcutaneously with an average tumor volume of 200-³On the left and right, dividing tumor-bearing mice into a normal saline solvent control group, an anticancer drug cisplatin (DDP, 2mg/kg, prepared by normal saline) positive control group and 3 levofloxacin hydrochloride antibiotic test groups with different doses after layering according to tumor volumes, wherein each group comprises 6 tumor-bearing mice. The solvent of the levofloxacin hydrochloride is normal saline, the administration dosage of the mice is respectively 25, 50 and 100mg/kg, and the normal saline with the same volume is administered to the control group of mice. Mice were administered by intraperitoneal injection starting on the day of the group 2 times a day (9: 00 am, 3:00 pm), and cisplatin once every other day. Tumor volume and body weight were measured 1 time every 4 days. After 12 days of administration, the mice were sacrificed by dislocation, the body weight and tumor volume of the mice were measured, the tumors were completely detached, and the tumor weight was measured with a precision electronic scale.

The relative tumor proliferation (%) at each time point was calculated according to the following formula:

relative increment rate (%) = T_RTV/C_RTV×100，T_RTVRelative tumor volume for the administered group, C_RTVRelative tumor volume for the solvent control group;

RTV=V_t/V_0，V₀is the tumor volume at the time of group administration, V_tTumor volume for each measurement.

Relative nasopharyngeal carcinoma tumor volume (RTV) for each group at different time points is shown in FIG. 5;

the Relative Proliferation Rate (RPR) of nasopharyngeal carcinoma tumors in each group at different time points is shown in FIG. 6;

mean Tumor Weight (TW) at the end of the experiment for each group of nasopharyngeal carcinomas is shown in FIG. 7;

wherein NS is a physiological saline solvent control group, DDP is an anticancer drug cis-platinum (2 mg/kg) positive control group, LH1 is a 25mg/kg levofloxacin hydrochloride antibiotic group, LH2 is a 50mg/kg levofloxacin hydrochloride antibiotic group, and LH3 is a 100mg/kg levofloxacin hydrochloride antibiotic group.

Example 4: combined anticancer effect of levofloxacin antibiotic and clinical anticancer drug

4.1 Combined anti-cancer Effect in vitro

The procedure was the same as in example 1 for in vitro anticancer experiments. The results of in vitro combined anticancer tests show that the levofloxacin hydrochloride antibiotic (200 mug/ml) has synergistic or additive anticancer effect on various human cancer cells when being combined with the clinical anticancer drugs cisplatin and 5-fluorouracil, and the levofloxacin antibiotic remarkably improves the anticancer efficacy of the clinical anticancer drugs, can be used as a sensitizing drug of clinical anticancer chemotherapeutic drugs, or forms an anticancer drug composition with the clinical anticancer drugs. The results are shown in FIG. 8 (combined effect with cisplatin), FIG. 9 (combined effect with 5-fluorouracil).

Wherein NO is the antibiotic contained in the culture solution, and LH is the levofloxacin hydrochloride antibiotic contained in the culture solution at the concentration of 200 mug/ml.

4.2 Combined anti-cancer Effect in vivo

The procedure was the same as in example 3 for in vivo anticancer experiments. When the levofloxacin hydrochloride antibiotic (

LH

2, 50 mg/kg) and the clinical anticancer drug cisplatin (2 mg/kg) are used in combination, the compound has significant in-vivo synergistic combined anticancer effect on animal transplantation nasopharyngeal carcinoma. At the end of the experiment (12 days of administration), the relative tumor volume, the relative tumor proliferation rate and the mean tumor weight of the saline control group (NS) were 12.11, 100% and 2.01g, respectively; the relative tumor volume, the relative tumor proliferation rate and the average tumor weight of the levofloxacin antibiotic group (LH 2) are respectively 8.57 percent, 70.75 percent and 1.84 g; the relative tumor volume, the tumor relative proliferation rate and the average tumor weight of the cisplatin drug group (DDP) were 6.83%, 54.70% and 1.25g, respectively; the relative tumor volume, the relative tumor proliferation rate and the average tumor weight of the combination of levofloxacin antibiotic and cisplatin (LH 2+ DDP) were 4.74, 39.16% and 0.86g, respectively. The relative tumor volume and tumor weight of the combined group are statistically significant different (p is less than 0.05) compared with the normal saline group, which indicates that the levofloxacin antibiotic can enhance the in vivo anticancer effect of the cancer chemotherapeutic drug. The results are shown in FIG. 10 (relative tumor volume, RTV), FIG. 11 (relative tumor proliferation rate, RPR), FIG. 12 (tumor weight, TW). In FIGS. 10, 11 and 12, NS is a normal saline control group, DDP is a cisplatin drug group, LH2 is a 50mg/kg levofloxacin hydrochloride antibiotic group, and LH2+ DDP is a combined administration group of levofloxacin hydrochloride antibiotic (50 mg/kg) and cisplatin (2 mg/kg).

Example 5: toxicity of levofloxacin antibiotics

The levofloxacin antibiotic is clinically applied to anti-infection treatment of patients, has a long application history in human, and has been extensively and deeply researched and reported for toxic effects at home and abroad. The research generally considers that the levofloxacin antibiotics are low-toxicity antibiotics, and have low toxic and side effects on human bodies under the recommended dosage. Our studies show that levofloxacin has significant cytotoxic effects on normal human cells in vitro, as shown in fig. 13; levofloxacin when used in combination with cisplatin increased cytotoxic effects on normal human cells, as shown in figure 14. In FIG. 14, NO is the cytotoxic effect of cisplatin on normal cells at different concentrations when levofloxacin antibiotic was not present in the cell culture broth; LH is the cytotoxic effect of cisplatin with different concentrations on normal cells when levofloxacin hydrochloride antibiotic (200 mug/ml) is contained in the cell culture solution. The research of the in vivo anticancer test shows that the in vivo use of the levofloxacin antibiotic does not significantly affect the weight development of animals, and the result is shown in figure 15; in FIG. 15, NS is a physiological saline solvent control group, DDP is an anticancer cisplatin positive control group (2 mg/kg), LH1 is a levofloxacin antibiotic group of 25mg/kg, LH2 is a levofloxacin antibiotic group of 50mg/kg, and LH3 is a levofloxacin antibiotic group of 100 mg/kg. The combined use of ofloxacin antibiotic and cisplatin did not significantly increase the effect of cisplatin on animal weight development, and the results are shown in fig. 16; in FIG. 16, NS is saline control, DDP is cisplatin drug (2 mg/kg), LH2 is levofloxacin antibiotic (50 mg/kg), LH2+ DDP is levofloxacin antibiotic (50 mg/kg) combined with cisplatin (2 mg/kg); the body weights of the DDP group and LH2+ DDP group were less significant than saline group (p < 0.05), but the body weights of the two groups at each time point were close and not statistically significant different (p > 0.05).

Example 6: influence of chemical structure modification on anti-cancer activity of levofloxacin

In-vitro anticancer tests are adopted to compare the in-vitro anticancer activity of levofloxacin hydrochloride and levofloxacin lactate, and the chemical structure modification group of levofloxacin is found to have certain influence on the anticancer activity. The in vitro anticancer effect of the levofloxacin hydrochloride on colon cancer HCT-116, gastric cancer SGC-7901 and liver cancer HepG2 is stronger than that of the levofloxacin lactate; the in vitro anticancer effect of levofloxacin lactate on nasopharyngeal carcinoma CNE2, non-small cell lung cancer A-549 and Xuanwei lung cancer XWLC-05 is stronger than that of levofloxacin hydrochloride. The results are shown in FIG. 17, wherein LH represents levofloxacin hydrochloride and LL represents levofloxacin lactate.

Example 7

The levofloxacin antibiotics can be used for the anticancer treatment and the anticancer sensitization treatment of cancers according to the using method in various dosage forms such as powder injection, tablets, powder, capsules, granules, medicinal granules and the like which are clinically used at present.

Example 8

The levofloxacin antibiotic can be prepared into oral liquid for use according to a conventional oral liquid preparation method.

Example 9

The levofloxacin antibiotic can be added with food or other carriers according to the required proportion of the product to prepare health products or other functional products for cancer patients.

Example 10

Levofloxacin antibiotics are mixed with other anti-cancer drugs according to different treatment needs and cancer types and prepared into various preparations to form a combined anti-cancer drug composition; or in the treatment of cancer, the composition can be combined with other clinical anticancer drugs to enhance the anticancer effect of the anticancer drugs. The anticancer drug composition can be combined with other anticancer drugs to improve the anticancer drug effect, reduce the dosage of the anticancer drugs and relieve the toxic and side effects in anticancer treatment.

The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims

1. The levofloxacin antibiotic is applied to the preparation of broad-spectrum anticancer drugs, anticancer drug sensitizing drugs, combined anticancer drug compositions or auxiliary anticancer health care products.

2. The use of levofloxacin antibiotics according to claim 1 in the preparation of broad-spectrum anticancer drugs, anticancer drug sensitizers, combined anticancer drug compositions or auxiliary anticancer health products, wherein the broad-spectrum anticancer drugs, anticancer drug sensitizers, combined anticancer drug compositions include drugs against gastric cancer, colon cancer, leukemia, lymphoma, glioma, nasopharyngeal carcinoma, esophageal cancer, cervical cancer, liver cancer, lung cancer, breast cancer, ovarian cancer, cholangiocarcinoma, pancreatic cancer, bladder cancer, renal cancer, prostate cancer, osteosarcoma, melanoma.

3. The use of levofloxacin antibiotic according to claim 1 in the preparation of a broad-spectrum anticancer drug, an anticancer drug sensitizing drug, a combined anticancer drug composition or an auxiliary anticancer health product, wherein the combined anticancer drug composition is a drug formed by combining levofloxacin antibiotic with other anticancer drugs.

4. The use of levofloxacin antibiotic according to claim 1 in the preparation of a broad-spectrum anticancer drug, an anticancer drug-sensitizing drug, a combination anticancer drug combination or an auxiliary anticancer health product, wherein the anticancer drug-sensitizing drug is a drug capable of enhancing the anticancer drug efficacy of various anticancer drugs clinically used for the treatment of cancer patients.

5. The broad-spectrum anticancer medicine is characterized in that the active component comprises levofloxacin antibiotic.

6. The anti-cancer drug sensitization drug is characterized in that the active component is levofloxacin antibiotic.

7. A combined anticancer medicine composition is characterized in that the active ingredients comprise at least one of other clinical anticancer drugs such as cisplatin, 5-fluorouracil and the like besides levofloxacin antibiotics.

8. The anticancer drug according to claim 5, the anticancer drug sensitizer according to claim 6, or the combined anticancer pharmaceutical composition according to claim 7, wherein the pharmaceutical dosage form is injection, powder injection, tablet, oral liquid, capsule, granule, or granule.

9. An auxiliary anticancer health product is characterized in that the active component comprises levofloxacin antibiotic.

10. The auxiliary anticancer health product of claim 9, wherein the dosage form is tablet, oral liquid, capsule, granule or granule.