CN103860561B - A kind of pharmaceutical composition and application thereof preventing and treating breast carcinoma - Google Patents

Abstract

The invention discloses a kind of pharmaceutical composition and the application thereof that prevent and treat breast carcinoma, the active component of this pharmaceutical composition comprises cetirizine hydrochloride and ftorafur, and in preferred active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 1-5.The pharmaceutical composition antitumor activity preventing and treating breast carcinoma provided by the invention is remarkable, and toxic and side effects is little.

Description

A kind of pharmaceutical composition for preventing and treating breast cancer and its application

technical field

The invention belongs to the technical field of medicine, and in particular relates to an anticancer drug, in particular to a pharmaceutical composition for preventing and treating breast cancer and its application.

Background technique

Breast cancer is one of the most common malignant tumors that seriously affects women's physical and mental health and even threatens their lives. It is the most common nauseating tumor in women worldwide. Its treatment is surgery combined with chemotherapy and radiotherapy. Chemotherapy is one of the non-surgical methods commonly used to treat breast cancer, but it has serious side effects. Therefore, improving the sensitivity and specificity of tumor cells to chemotherapeutic drugs has always been the focus of research.

Tegafur (Tegafur, FT, FT-207) is one of the pyrimidine anticancer drugs. It is the prodrug of 5-fluorouracil (5-FU), and has inhibitory effect on most solid tumors. In the body, it can interfere and block the biosynthesis of DNA, RHA and protein, thereby producing its anticancer effect. Basic medical research and clinical observation have proved that tegafur has less toxic and side effects, higher chemotherapy index, less impact on immunosuppression and related immune organs, and is a safe drug that can be used continuously in clinical practice. The drug is one of the few oral anticancer drugs. It is absorbed through the gastrointestinal tract after oral administration, and the blood concentration reaches the highest peak within 1-3 hours. The duration is longer than that of intravenous administration, so it can exert its better therapeutic effect. It is mainly used for gastric cancer, colon cancer, rectal cancer, and other gastrointestinal cancers, and can also be used for breast cancer, primary liver cancer, pancreatic cancer, and lung cancer. In addition, it has a certain effect on preventing recurrence and metastasis after surgery. The main adverse reactions of tegafur are gastrointestinal symptoms and bone marrow suppression, and gastrointestinal adverse reactions such as nausea, vomiting, and diarrhea can seriously affect the medication compliance of cancer patients.

Cetirizine (CetirizineHydrochloride) is a potent H1 receptor antagonist with strong drug activity, good anti-allergic and anti-inflammatory effects, and high bioavailability. Scope inhibits urticaria and skin redness, and at the same time inhibits the migration of inflammatory cells to the allergic reaction site, thereby inhibiting the later allergic reaction. It is a drug with dual anti-allergic effects. Oral preparations of cetirizine hydrochloride (tablets, capsules, etc.) are suitable for allergic diseases of the respiratory system, skin and eyes, including perennial allergic diseases, such as allergic skin diseases, hives, allergic rhinitis, and itchy eyes , conjunctivitis and asthma. Oral preparations of cetirizine hydrochloride are also used to treat various types of dermatological allergic diseases, such as chronic, artificial, cold, delayed pressure, solar urticaria and atopic dermatitis.

At present, there is no literature report that cetirizine hydrochloride can be used to fight breast cancer, and there is no literature report that cetirizine hydrochloride and tegafur are used in combination to treat breast cancer.

Contents of the invention

When the present inventor applied cetirizine hydrochloride clinically to treat allergic diseases of breast cancer patients, he unexpectedly found that cetirizine hydrochloride combined with tegafur had a more significant therapeutic effect on breast cancer patients. Subsequent in vitro and in vivo experiments confirmed that large doses of cetirizine hydrochloride did have a certain tumor-inhibiting activity, and it was also confirmed that cetirizine hydrochloride combined with tegafur had a more significant synergistic anti-breast cancer effect. Therefore, the object of the present invention is to provide a pharmaceutical composition for preventing and treating breast cancer and its pharmaceutical application.

The inventor finally obtained the following technical scheme through a large number of experimental studies:

A pharmaceutical composition for preventing and treating breast cancer, the active ingredients include cetirizine hydrochloride and tegafur.

Preferably, in the above-mentioned pharmaceutical composition for preventing and treating breast cancer, the weight ratio of cetirizine hydrochloride to tegafur in the active ingredient is 1:1-5.

Further preferably, in the above-mentioned pharmaceutical composition for preventing and treating breast cancer, the weight ratio of cetirizine hydrochloride to tegafur in the active ingredient is 1:2.5.

Still further preferably, the above-mentioned pharmaceutical composition for preventing and treating breast cancer can be made into oral preparations; the oral preparations are preferably tablets and capsules.

Still further preferably, the above-mentioned pharmaceutical composition for preventing and treating breast cancer, wherein each unit formulation in the tablet or capsule contains an effective amount of cetirizine hydrochloride of 50 mg, and an effective amount of tegafur of 100 mg- 250mg.

Experiments have confirmed that a large dose of cetirizine hydrochloride has certain anti-breast cancer activity, and can significantly inhibit the growth of human breast cancer MDA-MB-231 cell transplanted tumors in nude mice. Therefore, the second object of the present invention is to provide a pharmaceutical use of the compound, that is, the use of cetirizine hydrochloride in the preparation of anti-breast cancer drugs. In addition, the test also found that the high-dose tegafur + cetirizine hydrochloride group had a very significant tumor inhibitory effect, which was significantly different from the model control group and the single-drug group (P<0.01), which indicated that High doses of cetirizine hydrochloride can promote the anticancer activity of tegafur, and the combination of the two drugs shows a clear synergistic effect. Therefore, the third object of the present invention is to provide a pharmaceutical application of the composition, that is, the application of active ingredients including cetirizine hydrochloride and tegafur in the preparation of anti-breast cancer drugs.

Compared with the prior art, the pharmaceutical composition for preventing and treating breast cancer provided by the present invention has significant antitumor activity and less toxic and side effects, which enriches the prior art and adds a potential new anti-breast cancer drug to the clinic, which has very Significant social and economic significance.

Detailed ways

Now further describe the implementation process and effect test of the present invention by following examples, embodiment is only for the purpose of illustration, does not limit the scope of the present invention, while those of ordinary skill in the art make obvious changes and modifications according to the present invention It is also included in the scope of the present invention.

Embodiment 1: the preparation of tablet

Preparation Process:

Pass tegafur and cetirizine hydrochloride through a 120-mesh sieve, dissolve them in hot water at 60-80°C with β-cyclodextrin, keep for more than 60 minutes, cool, filter after the β-cyclodextrin precipitates, dry, and pass Sieve; mannitol, low-substituted hydroxypropyl cellulose, and aspartame are passed through a 100-mesh sieve, weighed according to the prescription amount, mixed evenly, add an appropriate amount of distilled water, granulate, dry, granulate, add the prescription amount of talcum powder, Mix well and press into tablets.

Embodiment 2: the preparation of tablet

Preparation Process:

Pass tegafur and cetirizine hydrochloride through a 120-mesh sieve, thoroughly grind and mix with β-cyclodextrin, pass through a 100-mesh sieve for lactose, sodium carboxymethyl starch, and lemon essence, weigh according to the prescription, and mix evenly. Add appropriate amount of distilled water, granulate, dry, granulate, add prescription amount of magnesium stearate, mix well, and tablet.

Embodiment 3: The combination of cetirizine hydrochloride and tegafur

40 SPF grade BALB/c-nu mice, 6 weeks old, weighing 18g-20g. In the logarithmic growth phase, the culture medium in the MDA-MB-231 breast cancer cell bottle with a confluence of 80% to 90% was aspirated and discarded, the cells were washed 2-3 times with phosphate buffer, digested with trypsin (0.25%), Cells were collected, washed again with phosphate buffered saline, mixed by pipetting, and counted; then the concentration was adjusted with serum-free RPMI-1640, and the number of cells inoculated subcutaneously on the back of each nude mouse was 1.0×10 ⁷ /0.2mL. Subcutaneously on the back of the mouse. From 7 days after the inoculation, small nodules were observed under the skin at the site of tumor cell inoculation, with a size of about 5mm×5mm; on the 10th day, the size of the tumor was about 7mm×7mm.

Thirty-five nude mice with tumors were taken and divided into 7 groups by random and balanced principles, with 5 mice in each group. Each group was intragastrically administered, and its test substance and dosage were: ① control group, pure water 0.6mL/; ② tegafur group (100mg/kg); ③ cetirizine hydrochloride low dose group (5mg/kg ); ④ cetirizine hydrochloride high dose group (20mg/kg); ⑤ tegafur (100mg/kg) + cetirizine hydrochloride low dose (5mg/kg) group; ⑥ tegafur (50mg/kg) +Cetirizine hydrochloride high dose (20mg/kg) group. Each group was given medicine for 2 weeks, once a day.

The nude mice were killed 48 hours after the last administration, and the transplanted tumor was taken to measure the tumor size. The method was as follows: respectively measure the Y-axis (L) and ×-axis (W) lengths of the bottom of the subcutaneous transplanted tumor with a vernier, according to the formula [V=0.52×L× W] Tumor volume was calculated. Tumor weight inhibition rate (%)=[1-(average tumor weight of experimental group/average tumor weight of control group)]×100%. The transplanted tumors were stripped, and each tumor tissue was excised for routine pathological sectioning and HE staining. Under the microscope, cancer tissue can be divided into cancer nests of different sizes by fibrous stroma, and glandular cavity and glandular tube-like structures can be seen; cancer cells are of different sizes, round or oval; large nuclei, obvious nucleoli, pathological Mitotic figures, slightly basophilic translucent cytoplasm. The growth of subcutaneous xenograft tumors in nude mice in each group is shown in Table 1.

Table 1 Comparison of inhibition rate of transplanted tumor weight in mice in each group

Compared with the control group, ^* P<0.05, ^** P<0.01;

Compared with Tegafur group, ^￥ P＜0.05, ^￥￥ P＜0.01;

Compared with the high dose of cetirizine hydrochloride, ^$ P<0.05, ^$$ P<0.01.

As can be seen from the test results in Table 1, except for the cetirizine hydrochloride low-dose group, the tumor volume and tumor weight of the other experimental groups were significantly lower than those of the control group (P<0.05 or P<0.01). The low-dose group did not show anti-tumor activity, but the high-dose cetirizine hydrochloride group showed a certain anti-tumor effect, especially the anti-tumor effect of the tegafur+cetirizine hydrochloride high-dose group was very significant. Compared with the control group and the single drug group, there is a very significant difference (P<0.01), which indicates that high doses of cetirizine hydrochloride can promote the anticancer activity of tegafur, and the combination of the two drugs shows an obvious synergistic effect .

In addition, during the experiment, it was observed that the mice in the high-dose tegafur group gradually showed signs of decreased activity, listlessness, diarrhea, decreased white blood cells and neutrophils, decreased food intake and body weight, etc., but no obvious adverse effects were seen in the nude mice in the other groups reaction. This shows that high doses of tegafur have obvious toxic effects on nude mice, and when the dose of tegafur is reduced, the toxic and side effects caused by chemotherapy have been effectively controlled.

Claims (2)

1. prevent and treat the pharmaceutical composition of breast carcinoma for one kind, be prepared from by active component and pharmaceutically acceptable auxiliaries, it is characterized in that: described active component is made up of cetirizine hydrochloride and ftorafur, described pharmaceutical composition is tablet, capsule, the effective dose that in described tablet or capsule, per unit preparation contains cetirizine hydrochloride is 50mg, and the effective dose containing ftorafur is 100mg-250mg.

2. the pharmaceutical composition preventing and treating breast carcinoma according to claim 1, is characterized in that: in described active component, the weight ratio of cetirizine hydrochloride and ftorafur is 1: 2.5.