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Marimastat sustained-release implant for treating solid tumor

A marimastat and slow-release implant technology, applied in the field of medicine, can solve the problems of failure to prolong the survival period of patients, decline in quality of life, systemic toxicity and side effects that limit clinical application, etc.

Inactive Publication Date: 2008-05-28
SHANDONG LANJIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the results of the trial for the treatment of colorectal cancer liver metastases showed that the median survival time of the Marimastat group (n=57) was 410 days, with no statistical difference; the results of the randomized double-blind trial for the treatment of gastric cancer (n=369) showed that, Compared with the placebo group, there was no significant difference in the survival of the two groups at the completion of the study; the results of a multicenter study (n=532) of Marimastat in the treatment of small cell lung cancer after chemotherapy showed that Marimastat failed to prolong the survival of patients. Survival, but the quality of life is reduced due to musculoskeletal adverse reactions; the study of Marimastat in the treatment of pancreatic cancer showed that compared with Gemze combined with placebo, Gemze combined with Marimastat had a better median survival time, 1-year survival rate, and objective effective rate. no significant difference
[0004] Although the combination with other anticancer drugs may have a certain effect on some tumors, the systemic side effects caused by conventional administration limit its clinical application
The key problem is that the current application situation can not give full play to its clinical effect

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Put the weighed (95 mg) sustained-release excipient (polylactic acid (PLA) with a molecular weight of 15000-25000) into a container, add a certain amount of organic solvent to dissolve and mix (subject to full dissolution), then add 5 mg of horse Immediately shake the mixture and dry it in vacuum to remove the organic solvent. The dried solid composition is shaped immediately, subpackaged and sterilized by radiation to obtain a slow-release implant containing 5% marimastat. The release time of the slow-release implant in physiological saline in vitro is 25-36 days, and the release time in mouse subcutaneous is 26-35 days.

Embodiment 2

[0077] Sustained-release implants were made according to the method described in Example 1, but the anti-cancer active ingredients contained were one of the following:

[0078] (A) 1% marimastat and 99% polylactic acid;

[0079] (B) 5% marimastat and 95% polylactic acid;

[0080] (C) 10% marimastat and 90% polylactic acid;

[0081] (D) 15% marimastat and 85% polylactic acid;

[0082] (E) 20% marimastat and 80% polylactic acid.

Embodiment 3

[0084] Put the weighed (97mg) sustained-release excipient (PLGA with a molecular weight of 15000-25000, 50:50) into the container, add a certain amount of organic solvent to dissolve and mix well (subject to complete dissolution), then add 3mg of Malima Sestat, re-shake, and then vacuum-dry to remove the organic solvent. The dried solid composition is shaped immediately, subpackaged and sterilized by radiation to obtain a sustained-release implant containing 3% marimastat. The release time of the sustained-release implant in physiological saline in vitro is 20-28 days, and the release time in mice subcutaneous is 24-28 days.

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PUM

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Abstract

A marimastat sustained release implant for treating solid tumors is characterized in that the sustained release implant includes effective dose of anticancer marimastat, sustained release excipients and a certain quantity of sustained release moderator. Solid tumors include pancreatic cancer, lung cancer, liver cancer, breast cancer, cerebroma, ovarian cancer, prostatic carcinoma, esophageal carcinoma, lymphadenoma, osteosarcoma and colorectal cancer. Sustained release excipients are mainly copolymer of glycolic acid and hydroxyacetic acid and one or combination of the multipolymer of glycollic acid and hydroxyacetic acid, polifeprosan, poly(L-lactide-co-ethyl phosphate), poly (L-lactide-co- phosphoric acid propyl); in the process of decompression, marimastat can be slowly released to local tumor, thus maintaining effective drug concentration in the local tumor as well as significantly reducing overall toxic reaction. Being placed in local tumor, the sustained release implant not only reduces overall toxic reaction of marimastat, but also selectively improves drug concentration in local tumor, enhancing the therapeutic effects of non-operative therapy such as chemotherapy drugs and radiotherapy.

Description

(1) Technical field [0001] The invention relates to a marimastat sustained-release implant for treating solid tumors, belonging to the technical field of medicines. (2) Background technology [0002] Although the research on cancer has made great progress, its mortality rate is still in the forefront of various common causes of death. The latest data show that in 2006, 3 million people died of cancer in my country. The incidence of cancer is increasing year by year and tends to be younger. Statistics show that in less than 20 years, the incidence of cancer in my country has increased by 69%, and the mortality rate has increased by 29.4%. According to the latest statistics from the World Health Organization, the global cancer incidence rate will increase by 50% by 2020, and the number of patients will increase to 15 million. It is estimated that 4 million people will die of cancer every year in my country in 2020. Therefore, exploring an effective method or drug for treatin...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K31/16A61K47/34A61P35/00
Inventor 孔庆忠朱本兰
Owner SHANDONG LANJIN PHARMA
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