阅读说明：本技术 富马酸比索洛尔联合多西他赛在制备抗肿瘤药物中的应用 (Application of bisoprolol fumarate and docetaxel in preparation of antitumor drugs ) 是由 郝延璋 王平 杨静 王峰 兰卫光 马隆波 于 2020-07-03 设计创作，主要内容包括：本发明涉及富马酸比索洛尔联合多西他赛在制备抗肿瘤药物中的应用,富马酸比索洛尔与化疗药物多西他赛联用有显著的协同作用,而且可以增加肿瘤对化疗药物的敏感性,在患有心绞痛、心律不齐和高血压合并癌症的患者中联用富马酸比索洛尔与化疗药物多西他赛将同时起到“一举两得”的作用。(The invention relates to application of bisoprolol fumarate and docetaxel in preparation of antitumor drugs, wherein the combination of bisoprolol fumarate and docetaxel serving as chemotherapeutic drugs has an obvious synergistic effect, can increase the sensitivity of tumors to the chemotherapeutic drugs, and can play a role of 'killing two birds with one stone' simultaneously in patients with angina, arrhythmia and hypertension combined cancers.)

1. A pharmaceutical composition is characterized by comprising bisoprolol fumarate and docetaxel in a mass ratio of 1: 1-10.

2. The pharmaceutical composition according to claim 1, wherein in the pharmaceutical composition, bisoprolol fumarate and docetaxel are separately packaged.

3. The pharmaceutical composition according to claim 1, wherein in the pharmaceutical composition, the bisoprolol fumarate and docetaxel are packaged together.

4. The pharmaceutical composition of any one of claims 1-3, wherein the pharmaceutical composition is a single administration formulation, wherein the pharmaceutical composition comprises 1-5mg bisoprolol fumarate and 5-10mg docetaxel.

5. The pharmaceutical composition of any one of claims 1-4, wherein the pharmaceutical composition is in the form of an injection or a lyophilized powder.

6. Use of a pharmaceutical composition according to any one of claims 1 to 5 for the manufacture of a medicament for combating malignant tumours.

7. The use of claim 6, wherein the malignant tumor is selected from liver cancer, non-small cell lung cancer, head and neck tumor, gastric cancer, pancreatic cancer, melanoma, breast cancer or ovarian cancer.

8. The use of claim 7, wherein the malignant tumor is liver cancer.

9. The bisoprolol fumarate is applied to the preparation of a chemotherapeutic drug sensitization drug, wherein the chemotherapeutic drug is docetaxel.

10. The use according to claim 9, wherein the mass ratio of bisoprolol fumarate to docetaxel is 1:1 to 10.

Technical Field

The invention relates to the technical field of antitumor drugs, and particularly discloses application of bisoprolol fumarate and docetaxel in preparation of an antitumor drug.

Background

Malignant tumors (also called cancers) are mainly caused by diseases caused by uncontrolled cell growth and proliferation mechanism, and further local invasion of normal tissues, even metastasis to other parts through lymphatic system and internal circulation system. Liver cancer is one of common tumors, the liver cancer proportion of Chinese accounts for half of the world, and liver cancer is a serious disease which jeopardizes the life of Chinese. The tumor therapy applied in clinic is mainly through surgery, physical therapy, chemotherapy and biological therapy. Chemotherapy is one of the main means for treating liver cancer, and especially plays a major role in the systemic treatment of late-stage liver cancer. The chemotherapy drug resistance phenomenon is an important reason for the failure of late-stage liver cancer treatment, so that the discovery of a new drug treatment method, the improvement of the sensitivity of chemotherapy drugs and the reversal or reduction of the occurrence of chemotherapy drug resistance are of great significance for the treatment of liver cancer. The search for safe, low-toxicity and small-side-effect drugs and chemotherapy sensitization are important means for treating tumors and solving chemotherapy drug resistance.

Bisoprolol Fumarate (Bisoprolol Fumarate), chemical name: (±)1- [4- [ [2- (1-methylethoxy) ethoxy ] methyl ] -phenoxy ] -3[ (1-methylethyl) amino ] -2-propanol fumarate of the formula:

bisoprolol fumarate is a long-acting beta 1 receptor blocker with high cardiac selectivity. Is clinically used for treating angina, arrhythmia and hypertension. It has high affinity to the beta 1 receptor of bronchial and vascular smooth muscle, resulting in blood vessel dilation and blood pressure reduction. The oral liquid blocks a neuroendocrine system, more importantly, the oral liquid aims at a myocardial remodeling mechanism, prevents and delays the development of myocardial remodeling, improves myocardial compliance and obviously improves left ventricular diastolic function, so that an enlarged left ventricular cavity is gradually recovered to be normal, the bisoprolol fumarate is used for treating hypertension for a long time, the systolic and diastolic functions can be improved while the blood pressure is reduced, ventricular remodeling is reversed, and the oral liquid has the effects of oxidation resistance and apoptosis resistance, so that the cardiac function is comprehensively protected. Clinical research shows that the medicine has high oral absorption rate, the half-life period of 10-12 h and the duration of the medicine effect. On the basis of a large number of experimental researches, the inventor finds that bisoprolol fumarate has a certain sensitization effect on chemotherapeutic drug docetaxel, and is expected to develop a pharmaceutical composition for treating tumors.

Disclosure of Invention

The invention aims to solve the technical problem of drug resistance of antitumor drugs in the prior art, and provides application of bisoprolol fumarate and chemotherapeutic drugs in preparation of antitumor drugs.

The technical scheme of the invention can be realized by the following technical measures:

the invention provides application of a composition containing bisoprolol fumarate and docetaxel in preparing a medicament for resisting tumors.

The invention also provides application of bisoprolol fumarate in preparation of a chemotherapeutic drug sensitization drug, and preferably, the chemotherapeutic drug is docetaxel.

When the bisoprolol fumarate is used for any one of the applications, the using dosage range is 1-200 mg/day according to the body weight of a medicine receiving object, and the preferable dosage range is 5-150 mg/day.

In any of the above uses of the invention, the mass ratio of bisoprolol fumarate to docetaxel is 1:1-10, preferably 1:1, 1:5 or 1: 10.

In some embodiments, in the pharmaceutical composition, the bisoprolol fumarate and docetaxel are separately packaged. In some embodiments, in the pharmaceutical composition, the bisoprolol fumarate and docetaxel are packaged together. In some embodiments, the pharmaceutical composition is a single administration formulation, wherein the pharmaceutical composition comprises 1-5mg bisoprolol fumarate and 5-10mg docetaxel.

The invention also provides a pharmaceutical composition for treating tumors, which comprises a chemotherapeutic drug docetaxel and bisoprolol fumarate for combined use with the chemotherapeutic drug.

The bisoprolol fumarate is a liquid preparation, a granule, a tablet, a medicinal granule, a capsule, a sustained-release agent, a dropping pill, an orally disintegrating preparation or an injection, and is prepared from the bisoprolol fumarate and a pharmaceutically acceptable carrier. The chemotherapeutic drug docetaxel can be in the dosage forms of liquid preparation, injection, freeze-dried powder and the like. The chemotherapy drug docetaxel can be injected into abdominal cavity or intravenous injection. Bisoprolol fumarate and the chemotherapeutic drug can be administered simultaneously, separately or sequentially, and the combination of the two drugs has obvious synergistic effect on tumors.

In some embodiments, the pharmaceutical composition of the present invention may be in the form of injection or lyophilized powder (which may be reconstituted prior to use to meet injection requirements).

In some embodiments, the pharmaceutical composition of the present invention further comprises a pharmaceutically acceptable pharmaceutical excipient. Such pharmaceutically acceptable pharmaceutical excipients include, but are not limited to, solvents, solubilizers, solubilizing agents, emulsifiers, colorants, stabilizers, glidants, suspending agents, antioxidants, pH adjusters, diluents, and the like. For pharmaceutically acceptable pharmaceutical excipients, see, for example, handbook of pharmaceutical excipients (4 th edition), monograph of r.c. ro, zheng folk translation, 2005, chemical industry press.

Tumors in which bisoprolol fumarate in combination with docetaxel may act include: liver cancer, non-small cell lung cancer, head and neck tumor, gastric cancer, pancreatic cancer, melanoma, breast cancer, and ovarian cancer.

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

(1) the bisoprolol fumarate and the chemotherapy medicament docetaxel have obvious synergistic effect in combination, and can increase the sensitivity of tumors to the chemotherapy medicaments.

(2) The antitumor effect obtained by the combined use of the bisoprolol fumarate and the chemotherapy medicament docetaxel is obviously superior to that of single bisoprolol fumarate or docetaxel, the obvious synergistic effect is achieved, the basis is provided for clinical combined application of the bisoprolol fumarate and the docetaxel for resisting tumors, and the bisoprolol fumarate and docetaxel are potential high-efficiency low-toxicity tumor medicaments.

(3) The bisoprolol fumarate and the chemotherapy drug docetaxel are combined to greatly reduce the dosage of each drug, reduce the toxic and side effects, obviously enhance the drug effect and overcome the single drug resistance of tumor cells.

(4) In the prior art, docetaxel and other anticancer drugs are usually not taken simultaneously in the form of pharmaceutical compositions, and are mostly taken sequentially in sequence, but the pharmaceutical composition of docetaxel and bisoprolol fumarate can be simultaneously prepared into an injection, and the administration is simultaneously carried out to treat liver cancer, so that the use of patients is greatly facilitated, and the compliance of cancer treatment is improved.

(5) Bisoprolol fumarate is a common drug for clinically treating angina, arrhythmia and hypertension, and the bisoprolol fumarate and a chemotherapeutic drug docetaxel can play a role of killing two birds with one stone simultaneously in patients with the diseases and cancers.

Detailed Description