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A low-molecular-weight heparin-modified bone-targeting liposome and its preparation method

A low-molecular-weight heparin and liposome technology, which is applied in the field of bone-targeted liposome and its preparation, can solve the problems of high bone hardness, difficulty reaching bone tumor sites, and poor permeability, so as to increase the possibility and reduce tumor Risk-shifting, drug-enhancing effects

Active Publication Date: 2021-07-20
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Moreover, due to the special physiological structure of the bone with high hardness and poor permeability, it is difficult to reach the bone tumor site by the general route of drug administration.

Method used

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  • A low-molecular-weight heparin-modified bone-targeting liposome and its preparation method
  • A low-molecular-weight heparin-modified bone-targeting liposome and its preparation method
  • A low-molecular-weight heparin-modified bone-targeting liposome and its preparation method

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Experimental program
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Effect test

Embodiment 1

[0031] 1. Synthesis of alendronate-low molecular weight heparin polymer (ALN-LMWH)

[0032] Add LWMH (1eq) into 10mL formamide, and heat to dissolve with magnetic stirring at 50°C. After complete dissolution, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) (10eq) and 1-hydroxybenzotriazole (HOBT) (10eq) were added, and stirred for 30 minutes to activate the carboxyl moiety. Then ALN ​​(1 eq and 10 eq) was added and stirred for 24 hours. After the reaction, dialyze with purified water for 24 hours in a 3500Da MWCO dialysis bag. The polymer in the remaining dialysis bag was freeze-dried to obtain the product. Control the feed molar ratio of ALN and LMWH to obtain product A respectively 1 -L and A 10 -L.

[0033] pass 1 H-NMR confirms the structure of ALN-LWMH, and the specific test results are as follows figure 2 shown. The formation of the amide bond between ALN ​​and LMWH can be judged by the shift at 8.00ppm in the hydrogen spectrum, and the ALN cha...

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Abstract

The invention discloses a bone targeting liposome modified by low molecular weight heparin and a preparation method thereof. The bone-targeted liposomes include cationic liposomes and alendronate-low molecular weight heparin polymers adsorbed on the surface of cationic liposomes; Sodium phosphonate and low molecular weight heparin are linked by an amide bond. The present invention introduces alendronate sodium with active targeting effect on low molecular weight heparin, and modifies it on the surface of cationic liposome by electrostatic adsorption for delivery of chemotherapeutic drugs, which not only improves the active targeting of the preparation It enhances the efficacy of the drug, reduces the potential risk of tumor metastasis, and further improves the possibility of clinical treatment.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to a low-molecular-weight heparin-based modified bone-targeting liposome and a preparation method thereof. Background technique [0002] Osteosarcoma (orthotopic osteosarcoma) is a common malignant tumor that mostly occurs in adolescents. The survival rate of patients is low and the treatment compliance is poor. The main reason for the poor clinical treatment effect is that its pathogenesis is often accompanied by tumor metastasis, and tumor metastasis has always been a major problem in clinical treatment, and is often the main reason for clinical treatment failure. At the same time, bone metastasis is also prone to occur in the course of other types of cancer. According to literature reports, more than 50% of patients with advanced breast cancer and prostate cancer will have bone metastasis. However, traditional radiotherapy and chemotherapy techniques lack certain t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/61A61K47/69A61K31/704A61P35/00A61P35/04A61P19/10
CPCA61K31/704A61K47/548A61K47/61A61K47/6911A61P19/10A61P35/00A61P35/04
Inventor 柯学吴豪罗媛慈天元
Owner CHINA PHARM UNIV
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