阅读说明：本技术 Parp抑制剂联合vegfr抑制剂用于治疗卵巢癌或乳腺癌的用途 (Use of PARP inhibitors in combination with VEGFR inhibitors for the treatment of ovarian or breast cancer ) 是由 张连山 王泉人 李少荣 王昱婷 张蕾 于 2020-05-27 设计创作，主要内容包括：一种包含PARP抑制剂的药物组合物与VEGFR抑制剂联合在制备治疗卵巢癌、乳腺癌的药物中的用途。(Use of a pharmaceutical composition comprising a PARP inhibitor in combination with a VEGFR inhibitor for the manufacture of a medicament for the treatment of ovarian cancer, breast cancer.)

The application of the combination of a pharmaceutical composition containing a compound shown as a formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient and apatinib or a pharmaceutically acceptable salt thereof in preparing a medicament for treating ovarian cancer or breast cancer,

an application of a compound shown in a formula (I) or a pharmaceutically acceptable salt thereof and apatinib or a pharmaceutically acceptable salt thereof in preparing a medicament for reducing adverse reactions of the apatinib or the pharmaceutically acceptable salt thereof.

Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for reducing adverse effects of apatinib or a pharmaceutically acceptable salt thereof.

The use according to any one of claims 1 to 3, wherein the ovarian or breast cancer is chemotherapeutic drug-sensitive or chemotherapeutic drug-resistant ovarian or breast cancer.

The use according to claim 4, wherein the ovarian or breast cancer is a platinum-based compound-sensitive ovarian or breast cancer.

Use according to any one of claims 1 to 5, wherein the breast cancer is triple negative breast cancer, preferably recurrent metastatic triple negative breast cancer.

The use according to any one of claims 1 to 5, wherein the ovarian cancer is recurrent ovarian cancer.

The use according to any one of claims 1 to 7, wherein the ovarian or breast cancer is BRCA1/2 mutant ovarian or breast cancer or BRCA1/2 non-mutant ovarian or breast cancer.

Use according to any one of claims 1 to 8, wherein the pharmaceutically acceptable salt of apatinib is selected from the group consisting of hydrochloride, mesylate, maleate, malate or besylate salts and the like, preferably from the mesylate salt.

The use according to any one of claims 1 to 8, wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient in an amount of 0.1 to 1000 mg.

The use according to any one of claims 1 to 10, wherein the apatinib or the pharmaceutically acceptable salt thereof is administered in a dose of 100-500mg, preferably at least 375 mg.

The use according to any one of claims 1 to 11, wherein apatinib, or a pharmaceutically acceptable salt thereof, is administered once daily, once every two days, once every three days.

The use according to any one of claims 1 to 12, wherein the pharmaceutical composition comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient is administered once a day, twice a day, three times a day, once every two days, once every three days.

The use according to any one of claims 1 to 13, wherein the apatinib, or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of 250 mg/time or 375 mg/time or 500 mg/time; the administration frequency of the pharmaceutical composition containing the compound shown in the formula (I) or the pharmaceutically acceptable salt thereof and the pharmaceutically acceptable excipient is twice a day, and the administration dose is 100 mg/time, or 80 mg/time, or 60 mg/time, or 50 mg/time, or 40 mg/time.

The use according to any one of claims 1 to 14, wherein the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient and apatinib are both administered orally.

Use according to any one of claims 1-15, wherein the excipient is selected from the group consisting of fillers, binders, disintegrants, lubricants.

Use according to claims 1-16, wherein the pharmaceutically acceptable excipient comprises a lubricant in an amount of 0.01% to 25%, preferably 0.1% to 10%, relative to the total weight of the composition.

Use according to claims 1-17, wherein the pharmaceutically acceptable excipient comprises a disintegrant in an amount of 0.01% to 40%, preferably 1% to 20%, relative to the total weight of the composition.

Use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for reducing the AUC of apatinib or a pharmaceutically acceptable salt thereof in a patient.

The use according to claim 19, wherein the AUC of apatinib, or a pharmaceutically acceptable salt thereof, produced in the patient is reduced to no more than 90%, preferably reduced to 10% -90%, more preferably reduced to 10% -80%, compared to the AUC of apatinib, or a pharmaceutically acceptable salt thereof, administered alone at an equivalent dose.

The use according to claim 19, by administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which provides an AUC of 1200 + 6000ng h/mL in the patient, preferably wherein apatinib or a pharmaceutically acceptable salt thereof provides an AUC of 1700 + 5000ng h/mL in the patient, and an effective amount of apatinib or a pharmaceutically acceptable salt thereof, which provides an AUC of 2000 + 4500ng h/mL in the patient.