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Cis-platinum lung cancer-resistant active targeting stealth liposomes and preparation method thereof

An active targeting, anti-lung cancer technology, applied in the direction of liposome delivery, anti-tumor drugs, heavy metal active ingredients, etc., can solve the problems of low activity, unstable nature, and easy to produce drug resistance

Active Publication Date: 2011-04-13
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, gastrointestinal toxicity, ototoxicity, and neurotoxicity cannot be ignored; (2) have low activity against certain cancer cells, such as breast cancer, colon cancer, etc.; (3) are prone to drug resistance; (4) only Slightly soluble in water, unstable in nature, decomposed when exposed to light, its aqueous solution will undergo hydrolysis and become invalid after being placed at room temperature, and will be transformed into transplatinum, which is toxic but has no tumor inhibitory effect

Method used

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  • Cis-platinum lung cancer-resistant active targeting stealth liposomes and preparation method thereof
  • Cis-platinum lung cancer-resistant active targeting stealth liposomes and preparation method thereof
  • Cis-platinum lung cancer-resistant active targeting stealth liposomes and preparation method thereof

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preparation example Construction

[0025] The preparation process of the present invention not only can contain polymer-antibody F(ab') 2 The buffer solution of the fragment conjugate solution is mixed with the organic phase containing the prescription amount of cisplatin and the fat-soluble membrane material, and the stealth lipoid body with the anti-lung cancer monoclonal antibody fragment connected on the surface is prepared through the self-assembly process, which can also be obtained by prescription Adjustment, the same preparation process was used to prepare cisplatin-like liposomes with different charges on the surface, cisplatin-stealth liposomes with different proteins on the surface, and cisplatin-like liposomes and cisplatin-stealth liposomes .

[0026] Under the premise that the main prescription ingredients and dosage are basically unchanged, the individual prescription ingredients and ratios are adjusted to obtain ordinary liposomes with no charge on the surface, positively charged liposomes, and ...

Embodiment

[0032] 1 polymer-anti-cancer cell monoclonal antibody F(ab') 2 Preparation of Fragment Modifier (A):

[0033] Preparation, separation, purification and identification methods of the anti-lung cancer monoclonal antibody and its Fab fragment: according to conventional methods. Human lung squamous cell carcinoma (Yunnan silicon lung cancer, YTMLC-90) cell line was prepared and purified according to conventional monoclonal antibody, followed by enzyme digestion. The test group (YTMLC-90), small cell lung cancer (NCL-H446), lung adenocarcinoma (A 2 ) and the control group (human bronchial epithelial cells HBE), were confirmed by immunohistochemistry and Western-blot tests, and have lung cancer targeting. In order to avoid modifying the surface of liposomes, the monoclonal antibody as a heterologous protein has an Fc fragment, which is discovered by specific proteins in the plasma and cleared by the endothelial reticulum system, and also avoids secondary activation of the bo...

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Abstract

The invention relates to a cis-platinum active lung targeting stealth liposome drug delivery system. Injection or a lyophilized product prepared from cis-platinum, a self-prepared polymer-monoclonal antibody F(ab') 2 fragment modifier, a self-prepared cholesterol-polymer conjugate, cholesterol and the like in a self-assembly mode is applied to treating solid tumors of human lung squamous carcinoma. The drug delivery system has the encapsulation rate of 71.25+ / -1.14 percent, and the loading rate of 8.81+ / -0.23 percent; and results of cell experiments and animal experiments show that the drug delivery system has obvious medical sustained-release effect, can avoid removal of a reticuloendothelial system (RES) in blood, has the inhibition rate for growth of carcinoma blocks of a corresponding lung cancer-loaded nude mouse improved by 80.34 percent compared with that of cis-platinum solution, has obvious effect of treating corresponding lung cancer in a targeting way, does not have obvious toxin and also can reduce the local irritation of a technical material.

Description

[0001] The biological materials involved in the present invention have been biologically deposited. technical field [0002] The present invention relates to cisplatin-anti-lung cancer actively targeting stealth lipoid and its preparation, and as injection or freeze-dried product for injection, through intravenous injection, cisplatin-stealth lipoid is synthesized by human anti-lung cancer monoclonal antibody fragment The in vivo drug delivery system is specifically directed to lung cancer cells to play a role in the treatment of corresponding lung cancer. Background technique [0003] Targeted drug delivery system refers to a drug delivery system prepared by using new technology and new technology, which can concentrate the drug at the site of action. It can maximize the delivery of drugs to target organs or target cells, thereby reducing the impact on non-target organs and non-target cells, achieving the purpose of reducing systemic side effects and improving curative effe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K33/24A61K47/42A61P35/00
Inventor 杨红武晶晶刘慧敏周映聪黄娟彭丽琳
Owner SUZHOU UNIV
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