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Preparation method of dabrafenib-loaded lipid nano-microbubble ultrasonic contrast agent

An ultrasound contrast agent, lipid nanotechnology, applied in echo/ultrasonic imaging agent, nanotechnology, nanotechnology and other directions, to achieve good stability, reliable connection, and overcome the effect of insufficient effect

Inactive Publication Date: 2020-09-04
SECOND AFFILIATED HOSPITAL OF COLLEGE OF MEDICINEOF XIAN JIAOTONG UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, there is still a lack of a kind of anchoring BRAF in the prior art V600E Ultrasound contrast agent carrying dabrafenib nano-microbubbles for ultrasound imaging and treatment of gene mutation tumors

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  • Preparation method of dabrafenib-loaded lipid nano-microbubble ultrasonic contrast agent
  • Preparation method of dabrafenib-loaded lipid nano-microbubble ultrasonic contrast agent
  • Preparation method of dabrafenib-loaded lipid nano-microbubble ultrasonic contrast agent

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Embodiment Construction

[0018] The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0019] The invention discloses a preparation method of an ultrasonic contrast agent carrying dabrafenib lipid nano-microbubbles, and the specific implementation steps are as follows:

[0020] Step 1: Establish a covalent link between Dabrafenib and DSPE-PEG2000-COOH (distearoylphosphatidylethanolamine-polyethylene glycol 2000-carboxyl cross-linked product) to synthesize DSPE-PEG2000-Dabrafenib. refer to figure 1 The molecular formula shown, Dabrafenib contains an amino group (-NH 2 ) functional group, therefore, introduce EDC and NHS, and establish the covalent combination of Dabrafenib and DSPE-PEG2000-COOH through amide reaction, thereby synthesizing DSPE-PEG2000-Dabrafenib, refer to figure 2 . The specific implementation process is as follows: First, add DSPE-PEG2000-COOH, EDC and NHS to medical grade DMSO, the molar ratio is 1:2:2, sh...

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Abstract

The invention discloses a preparation method of a dabrafenib-loaded lipid nano-microbubble ultrasonic contrast agent. The preparation method comprises the following steps, step 1, establishing covalent connection between dabrafenib and DSPE-PEG2000-COOH by EDC-NHS amide reaction method to synthesize DSPE-PEG2000-Dabrafenib; step 2, preparing a lipid suspension by membrane hydration method; and step 3, preparing the high-concentration lipid nano-microbubble ultrasonic contrast agent by mechanical oscillation method. Inert gas C3F8 constitutes a core, so that the nano-microbubble has good stability. The DSPE-PEG2000-Dabrafenib is used as a main component of a lipid nano-microbubble shell membrane to realize the effective and reliable connection between Dabrafenib and nano-microbubble. According to the present invention, one-stop contrast-enhanced ultrasonograhy and precise treatment on BRAFV600E gene mutant tumors is achieved.

Description

technical field [0001] The invention belongs to the technical field of ultrasonic molecular imaging, and relates to a nano-microbubble ultrasonic contrast agent, in particular to a method for treating BRAF V600E Preparation method of dabrafenib-carrying lipid nano-microbubble ultrasound contrast agent for gene mutation disease. Background technique [0002] BRAF V600E Gene mutations are closely related to clinical biological behaviors of malignant tumors such as thyroid cancer and melanoma, such as invasion and metastasis. The US Food and Drug Administration (FDA) has approved BRAF in May 2013 V600E Inhibitor Dabrafenib (Dabrafenib) entered clinical treatment. In 2018, Dabrafenib was approved for listing in my country. Although dabrafenib has a certain therapeutic effect, there are fundamental problems in the oral administration of dabrafenib during the treatment of patients, such as low target specificity and large side effects. Moreover, long-term and high-concentrati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/60A61K31/506A61K49/22A61P35/00B82Y5/00B82Y40/00
CPCA61K47/6925A61K47/60A61K31/506A61K49/223B82Y5/00B82Y40/00A61P35/00
Inventor 张浩刘娜樊帆张元榛
Owner SECOND AFFILIATED HOSPITAL OF COLLEGE OF MEDICINEOF XIAN JIAOTONG UNIV
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