Slow-releasing injection contg. platinum compounds and cytotoxin type anticarcinogen

Abstract

A slow-release anticancer injection contains the slow-release microspheres and solvent. Said slow-release microsphere contains the active anticancer component chosen from 6 Pt compounds including bicycloplatinum, etc and 3 cytotoxins including antimitotic medicine, anticancer antibiotic, or antimetabolic medicine, and the slow-release auxiliary.

Description

(1) Technical field

[0001] The invention relates to an anti-cancer slow-release injection simultaneously loaded with platinum compounds and cytotoxic drugs and a preparation method thereof, which belongs to the technical field of medicines. Specifically, the present invention provides a slow-release preparation of anticancer drugs containing platinum compounds and cytotoxic drugs, mainly slow-release injections and slow-release implants. (2) Background technology

[0002] As one of the conventional treatment methods for cancer, chemotherapy drugs have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its obvious systemic toxicity greatly limits the application of this drug.

[0003] Due to the excessive expansion and hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissues. Therefore, it is ...

Examples

Embodiment 1

[0115] Put 80mg of polyphenylpropane (p-CPP: 20:80 of sebacic acid (SA)) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg Hydroxycamptothecin and 10 mg succinoplatin were re-shaken and spray-dried to prepare microspheres for injection containing 10% hydroxycamptothecin and 10% succinoplatin. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection with a viscosity of 220cp-460cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 10-15 days, and the drug release time in mice subcutaneous is about 20-30 days.

Embodiment 2

[0117] The method step of processing into sustained-release injection is the same as that of Example 1, but the difference is that the contained anticancer active ingredients and their weight percentages are: 2-40% of sulfoplatin, dicycloplatin, eplatin, meciplatin, cyproplatin, etc. Alizarin or picoplatin with 2-40% hydroxycamptothecin, mitozolomide, 4-carboxytemozolomide, docetaxel, ifosfamide, lomustine, estramustine, formustine , samustine, etoposide, teniposide, vinblastine, anastrozole, tamoxifen, fluorouracil or mitomycin C; the sustained-release excipients used are racemic polylactic acid, Racemic Polylactic / Glycolic Acid Copolymer, Monomethylpolyethylene Glycol / Polylactic Acid, Monomethylpolyethylene Glycol / Polylactic Acid Copolymer, Polyethylene Glycol / Polylactic Acid, Polyethylene Glycol / Polylactic Acid Copolymer, carboxy-terminated polylactic acid or carboxyl-terminated polylactic acid / glycolic acid copolymer.

Embodiment 3

[0119] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 65,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of eplatin and 15 mg of lomustine, re-shake and dry in vacuum Remove organic solvents. The dried drug-containing solid composition was frozen and pulverized to make micropowder containing 15% eplatin and 15% lomustine, and then suspended in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding mixed Suspension-type sustained-release injection with a viscosity of 300cp-400cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 18-25 days, and the drug release time in mice subcutaneous is about 40-50 days.

(1) Technical field

[0001] The invention relates to an anti-cancer slow-release injection simultaneously loaded with platinum compounds and cytotoxic drugs and a preparation method thereof, which belongs to the technical field of medicines. Specifically, the present invention provides a slow-release preparation of anticancer drugs containing platinum compounds and cytotoxic drugs, mainly slow-release injections and slow-release implants. (2) Background technology

[0002] As one of the conventional treatment methods for cancer, chemotherapy drugs have been widely used in the treatment of various malignant tumors, and the effect is relatively obvious. However, its obvious systemic toxicity greatly limits the application of this drug.

[0003] Due to the excessive expansion and hyperplasia of solid tumors, the interstitial pressure, tissue elastic pressure, fluid pressure and interstitial viscosity are all higher than those of the surrounding normal tissues. Therefore, it is ...

Examples

Embodiment 1

[0115] Put 80mg of polyphenylpropane (p-CPP: 20:80 of sebacic acid (SA)) copolymer into a container, add 100ml of dichloromethane, dissolve and mix well, then add 10mg Hydroxycamptothecin and 10 mg succinoplatin were re-shaken and spray-dried to prepare microspheres for injection containing 10% hydroxycamptothecin and 10% succinoplatin. Then suspend the microspheres in physiological saline containing 15% mannitol to prepare the corresponding suspension-type sustained-release injection with a viscosity of 220cp-460cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 10-15 days, and the drug release time in mice subcutaneous is about 20-30 days.

Embodiment 2

[0117] The method step of processing into sustained-release injection is the same as that of Example 1, but the difference is that the contained anticancer active ingredients and their weight percentages are: 2-40% of sulfoplatin, dicycloplatin, eplatin, meciplatin, cyproplatin, etc. Alizarin or picoplatin with 2-40% hydroxycamptothecin, mitozolomide, 4-carboxytemozolomide, docetaxel, ifosfamide, lomustine, estramustine, formustine , samustine, etoposide, teniposide, vinblastine, anastrozole, tamoxifen, fluorouracil or mitomycin C; the sustained-release excipients used are racemic polylactic acid, Racemic Polylactic / Glycolic Acid Copolymer, Monomethylpolyethylene Glycol / Polylactic Acid, Monomethylpolyethylene Glycol / Polylactic Acid Copolymer, Polyethylene Glycol / Polylactic Acid, Polyethylene Glycol / Polylactic Acid Copolymer, carboxy-terminated polylactic acid or carboxyl-terminated polylactic acid / glycolic acid copolymer.

Embodiment 3

[0119] Put 70 mg of polylactic acid (PLGA, 75:25) with a peak molecular weight of 65,000 into a container, add 100 ml of dichloromethane, dissolve and mix well, add 15 mg of eplatin and 15 mg of lomustine, re-shake and dry in vacuum Remove organic solvents. The dried drug-containing solid composition was frozen and pulverized to make micropowder containing 15% eplatin and 15% lomustine, and then suspended in physiological saline containing 1.5% carboxymethylcellulose sodium to prepare the corresponding mixed Suspension-type sustained-release injection with a viscosity of 300cp-400cp (at 20°C-30°C). The drug release time of the slow-release injection in physiological saline in vitro is 18-25 days, and the drug release time in mice subcutaneous is about 40-50 days.