Preferential plugging of vascular sytems of mammals using microstructure particles comprising hydrolytically degradable crosslinked gels

Inventors

Schwarz, Alexander • Zhang, Hongmin

Assignees

Biosphere Medical Inc

Abstract

One aspect of the present invention relates to a method of temporarily embolizing a blood vessel using a hydrolytically degradable crosslinked hydrogel as an embolus. In certain embodiments, the hydrolytically degradable crosslinked hydrogel substantially hydrolyzes only at about physiological pH. In certain embodiments of the method, the hydrolytically degradable crosslinked hydrogel is stable at low pH. In certain embodiments of the method, the hydrolytically degradable crosslinked hydrogel comprises a marker molecule, such as a dye, radiopaque, or an MRI-visible compound. It is to be understood that both the foregoing general description and the following detailed description are exemplary, and are intended to provide further explanation of the invention as claimed.

Core Innovation

The invention provides a method of embolizing a vascular site in a mammal by introducing into the vasculature microparticles comprising a hydrolytically degradable crosslinked hydrogel. The hydrogel is crosslinked with a crosslink derived from a compound selected from a compound of formula 1 or a compound of formula 2, and the microparticle thereby embolizes a vascular site of the mammal.

The hydrolytically degradable crosslinked hydrogel hydrolyzes substantially only at physiological pH, while being stable at low pH. In selected embodiments, the hydrogel includes imaging marker molecules, such as dyes and radiopaque or MRI-visible compounds, including contrast-enhancing agents. The microparticles are described as flexible, catheter-deliverable beads having hydrolytically degradable crosslinked hydrogel.

The disclosure further defines the hydrogel crosslink compounds by structural variables in formula 1 and formula 2, including X representing O or S, L or M representing -NH-O-Q or -O-NH-Q linkages, Q representing acrylamide/acrylate-type groups, R representing H or alkyl, Z representing substituted (CR2)n or related moieties, and Ar representing aryl or heteroaryl. It further specifies that J represents O, S, NR, cycloalkyl, heterocyclyl, or (CH2CH2O)n or (CH2CH2N(R))n, and that n and m are integers within stated ranges; for formula 2 an additional G variable is defined, with t being 3 or 4.

A documented example context indicates temporary embolization using the degradable hydrogel microparticles, including observation of temporary occlusion followed by recanalization over weeks in a canine renal artery study. Histopathology in the described example includes particle degradation and phagocytosis, together with reduced infarction compared with permanent embolic microspheres. The described imaging context includes angiograms to support evaluation of embolization and recanalization behavior.

Claims Coverage

The partial content includes one independent claim. Across the dependent set indicated, the claim set narrows the hydrogel crosslink composition and variables from formula 1/formula 2 and adds limitations directed to degradation behavior at pH, embolization duration, and optional functional components such as imaging contrast-enhancing agents and particle dimensional or shape constraints.

The claim coverage centers on a method that embolizes a vascular site in a mammal using catheter-deliverable microparticles formed from a hydrolytically degradable crosslinked hydrogel whose crosslink is derived from compounds defined by formula 1 or formula 2. The dependent claims indicated in the partial content further narrow hydrogel behavior by pH constraints, impose embolization duration limits, and optionally add imaging functionality and particle shape or diameter constraints.

Stated Advantages

Documented Applications