Methods and devices for reducing vacular smooth muscle cell proliferation

A balloon catheter, polymer technology, applied in cardiovascular system diseases, catheters, pharmaceutical formulations, etc., can solve problems such as lack of drug-eluting balloons

Pending Publication Date: 2020-11-20
路易斯安那州立大学和农业机械学院监事会
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Despite advances in improved methods and devices for drug-eluting balloons, drug-eluting balloons that are not affected by side effects associated with paclitaxel and other antimitotic drugs are still lacking

Method used

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  • Methods and devices for reducing vacular smooth muscle cell proliferation
  • Methods and devices for reducing vacular smooth muscle cell proliferation
  • Methods and devices for reducing vacular smooth muscle cell proliferation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0203] Embodiment 1. nanoparticle synthesis method

[0204] In the examples described herein and other examples described herein below, certain materials were used in the studies and the following results were obtained: RG504H poly(lactic-co-glycolic acid) PLGA50:50, quercetin (QUER) and acetonitrile were obtained from Sigma Aldrich Corp. (St. Louis, MO); ethyl acetate, Tween 80, resveratrol (RESV) and Triacetyl resveratrol (TAR) was obtained from Thermo Fisher Scientific (Waltham, MA); Eudragit RL100 was obtained from Evonik Industries AG (Essen, Germany). Polymer nanoparticles were synthesized using single emulsion solvent evaporation technique (Astete C.E. and Sabliov C.M.J. Biomater Sci Polym Edi. 2006; 17(3):247-89).

[0205] Briefly, the organic phase was prepared by mixing Eudragit RL100 (60 mg) and PLGA (200 mg) in a mixed solution of ethyl acetate and acetone (8:2) (6 mL) and stirring gently at room temperature for 30 min. Next, quercetin and triacetyl resveratrol ...

Embodiment 2

[0206] Example 2. Drug loading and encapsulation efficiency assay method

[0207] The drug loading and encapsulation efficiency were determined using HPLC. A standard curve was first prepared in the extraction solvent dimethylformamide (DMF). Preliminary tests showed that quercetin needs to be added with ascorbic acid to reduce its degradation, and quercetin was analyzed in DMF without adding ascorbic acid. Drug loading was measured by suspending drug-loaded polymer nanoparticles in DMF at a concentration of 3.9 mg / mL. Collect 200 µL of samples and add 80 µL of ascorbic acid to each. Samples were clarified by centrifugation and analyzed by HPLC. The samples containing ascorbic acid were analyzed for quercetin, while the samples without ascorbic acid were analyzed for triacetyl resveratrol and resveratrol. Analysis was performed in triplicate. Calculate the theoretical loading based on the initial amounts of quercetin and tar added during the synthesis.

Embodiment 3

[0208] Example 3. Evaluation method of drug release curve.

[0209] Drug release profiles were used to measure the release of both drugs from pNPs over 10 days. Release studies were performed in a simulated blood solution at pH 7.4 to simulate physiological conditions. Nanoparticles were suspended at a concentration of 19.5 mg / L, and the suspension was transferred to a dialysis bag that was sealed and placed in a simulated blood solution. Place the whole system in a shaking incubator for 10 days. Samples were collected from the dialysis bag every day and analyzed by HPLC, which was similar to the method used to determine the drug loading.

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Abstract

In one aspect, the disclosure relates to compositions, methods, and devices pertaining to polymeric nanoparticle compositions (pNP), pNP compositions comprising a therapeutic agent, devices comprisinga drug-coated balloon comprising a disclosed pNP comprising a therapeutic agent, and methods for treating peripheral artery disease using the disclosed compositions and devices. In further aspects, the pNP comprises a poly(lactic-co-glycolic) acid possessing a positive charge for firm attachment to the balloon matrix, followed by adhesion to the negatively charged bilayer of the vascular wall. Instill further aspects, the therapeutic agent comprises a resveratrol or derivative thereof, a quercetin or derivative thereof, or combinations thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Description

[0001] cross reference [0002] This application claims priority to Provisional Application No. 62 / 625,026 filed with the USPTO on February 1, 2018, which is hereby incorporated by reference in its entirety. Background technique [0003] Cardiovascular disease (CVD), such as atherosclerosis, narrows arteries due to the formation of cholesterol-rich plaques in the blood vessel walls. These lesions eventually block blood flow to the tissues. One such type of CVD is peripheral arterial disease (PAD), which is characterized by narrowing of the arteries that supply blood to the extremities, especially the legs. Approximately 200 million people worldwide suffer from PAD (Fowkes, F.G. et al., The Lancet, 2013, 382(9901):1329-40). PAD is defined as occlusion of arteries in the extremities, resulting in pain, poor wound healing, and, in the absence of intervention, loss of a limb or even death. PAD is often associated with life-threatening situations and events. For example, a rece...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61F2/958A61L31/16C08F220/34
CPCA61F2/958C08F220/34A61K9/5153A61P9/00A61K9/5138C08F220/14C08L67/04C08L33/12A61L29/16A61L29/085A61L2300/416A61L2300/624A61L2300/608A61L29/06C08F220/1802C08L77/12A61K31/05A61K31/366A61L2300/216A61L2400/12A61M25/10A61M2025/105
Inventor 塔米·蕾妮·杜加斯克里斯蒂娜·萨布里奥夫卡洛斯·阿斯泰特
Owner 路易斯安那州立大学和农业机械学院监事会
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