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Preparation method and application of capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent

A technology of magnetic resonance contrast agent and angiogenesis, applied in preparations for in vivo experiments, pharmaceutical formulations, etc., can solve problems such as instability of nano-iron oxide particles, achieve good application prospects and potential application value, uniform particle distribution, Highly stable effect

Inactive Publication Date: 2020-01-17
刘城
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the nano-iron oxide particles without surface treatment are extremely unstable, and their surface needs to be prepared to increase their stability.

Method used

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  • Preparation method and application of capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent
  • Preparation method and application of capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent
  • Preparation method and application of capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent

Examples

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Embodiment 1

[0032] Example 1 Microvascular Reconstruction (Therapeutic Angiogenesis) Targeted Magnetic Resonance Contrast Agent Preparation Method

[0033] Provides a magnetic resonance contrast agent targeting microvascular reconstruction (therapeutic angiogenesis) (ultrasmall superparamagnetic iron oxide-polylactic acid-polyethylene glycol-maleimide-cRGDfC nanoparticles / cRGDfC-Maleimide- PEG-PLA-USPIO) preparation method, its reaction principle is as follows:

[0034] (I)D,1-Lactic+PEG-Maleimide→PLA-PEG-Maleimide

[0035] (II)2Fe 3+ +Fe 2+ +8OH - +PLA-PEG-Maleimide→ Maleimide-PEG-PLA-Fe 3 o 4 (USPIO)+4H 2 o

[0036] (III)cRGDfC+Maleimide-PEG-PLA-USPIO→ cRGDfC-Maleimide-PEG-PLA-USPIO

[0037] Step 1, the synthesis of PLA-PEG-Maleimide: according to equation (I), adopt ring-opening polymerization (Lee, Li et al.2006, Yu, Lu et al.2010): PEG2000-Maleimide, PEG3400-Maleimide, PEG5000 -Maleimide was reacted with D,l-lactide (D,l-Lactic) to synthesize PLA-PEG2000-Maleimide, PLA-PEG34...

Embodiment 2

[0047] Example 2 Application of MRI Contrast Agent Targeted to Microvascular Reconstruction (Therapeutic Angiogenesis) Step 1: Construction of Diabetic Rabbit Chronic Hind Limb Ischemia Model

[0048] First, referring to the method of Wang et al. (Breen, Mc Redmond et al.2008, Jablecka, Czaplicka et al.2009, Wang, Wan et al.2010), a small dose (50mg / kg ) alloxan (ALX) injection to induce diabetes. The results showed that compared with the blank group, the rabbits in the diabetic group had symptoms such as three more and one less, hair loss, and decreased activity after injection of ALX; 1 rabbit died of hypoglycemia 12 hours after ALX injection, and 1 rabbit died before the end of the experiment in infection. In some animals, the blood sugar gradually decreased after 1 month of injection of ALX, which may be related to the repair of islet cells. Free drinking of 5-10% glucose water (concentration depends on individual blood sugar) throughout the whole process is beneficial t...

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Abstract

The invention discloses a preparation method and application of a capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent, and belongs to the crisscross fields of nanometer material science and biomedical engineering. The capillary reconstruction (therapeutic angiogenesis) targeted magnetic resonance contrast agent is supermini super paramagnetism ferric oxide-polylactic acid-polyethylene glycol-maleimide-RGD cyclic pentapeptide (cRGDfC) nanoparticles, wherein the expression is cRGDfC-Maleimide-PEG-PLA-USPIO. The synthetical magnetic resonance contrast agent is a T2 weighting contrast medium, and the particle-size distribution is uniform. The contrast medium is high in targeting properties (specificity), high in stability, favorable in relaxation properties, and small in side effects in accordance with new vessels, and has favorable application prospects and potential using value for assessment of capillary stable reconstruction (therapeutic angiogenesis) of microvascular dysfunction related diseases.

Description

[0001] field of invention [0002] The invention belongs to the cross field of nanomaterial science and biomedical engineering, relates to a magnetic resonance contrast agent, in particular to a preparation method and application of a magnetic resonance contrast agent for targeted evaluation of microvascular reconstruction (therapeutic angiogenesis). Background technique [0003] Microvascular dysfunction related disease (MRD), such as: ischemic heart disease (IHD), cardiomyopathy, atrial fibrillation, heart failure, ischemic cerebrovascular disease and peripheral vascular disease, etc. It has become a major disease threatening human health. Although many treatment options for MRD (such as: conventional drug therapy, revascularization, etc.) The morbidity rate, disability rate and fatality rate remain at a high level. With the deepening of the research on the pathogenesis of MRD, MRD is a multi-factor syndrome, which is the result of the participation of multiple vascular an...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/14
CPCA61K49/126A61K49/14
Inventor 刘城
Owner 刘城
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