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Systems and methods for gel-based neuromodulation

A kind of nerve and gel technology, applied in subacute and chronic pain, relieve the acute field of patients, and can solve the problems of excitotoxicity and pain of cells

Pending Publication Date: 2020-12-22
TULAVI THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional neurolytic agents cause significant pain after injection because they are excitotoxic to cells

Method used

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  • Systems and methods for gel-based neuromodulation
  • Systems and methods for gel-based neuromodulation
  • Systems and methods for gel-based neuromodulation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0221] Example 1. Adhesion was assessed on 4-arm PEG-SC hydrogels crosslinked with trilysine amine. The force is between 90 and 200kPa.

[0222] other hydrogels. In situ formed polyanhydrides are also beneficial for the development of neural-targeted applications. In one embodiment, the polyanhydride polymers can be acrylated such that they can be formed in situ by free radical polymerization. Alternatively, they can be formed by photocrosslinking. At lower concentrations, the polymer is water soluble, eg 10%. Part of what prevents nerve regeneration is its hydrophobicity. The entire contents of US20180177913A1 and US201562181270 are incorporated herein by reference.

[0223] In some embodiments, it may be desirable to combine non-growth-permissive hydrogels (e.g., cross-linked PEG hydrogels, alginate, methacryloyl-substituted tropoelastin MeTro hydrogels) with growth-permissive hydrogels. (eg gelatin-methacryloyl GelM, GelM / PEG or GelMA / MeTro complexes) PMID: 29580168 ...

Embodiment 2

[0229] In another example, 8-arm 15K PEG-SC is cross-linked with trilysine. PEG-SC was suspended in buffered trilysine solution and then mixed with accelerator buffer by static mixer. The formulation gels within 2 seconds, and the compressive strength of the gel is as high as 200 kPa.

Embodiment 3

[0231] In another embodiment, 8-arm 20K PEG-thioisocyanate is cross-linked with trilysine in a 1:1 ratio. The formulation gelled within 3 seconds, had a compressive strength of 120 kPa, and a swelling rate of 5%.

[0232] In vivo degradation, swelling, compressive and tensile strength, and gel time of hydrogels all play a crucial role in determining a suitable hydrogel for delivery to the nerve.

[0233] Equilibrium swelling. For applications where hydrogels are delivered to nerves to prevent nerve regeneration, maintaining a tight bond and fit between the nerve and the conformable hydrogel is ideal. Therefore, it is desirable to minimize equilibrium swelling after hydrogel delivery. Equilibrium swelling occurs within minutes to days when the hydrogel is equilibrated with a fluid in an in situ environment. It is preferred to keep the equilibrium swelling less than 30%, more preferably less than 20%, even more preferably less than 10%. Furthermore, in some embodiments it is...

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Abstract

Methods, devices and systems are described for gel-based modulation of neural tissue, including prevention of nerve regeneration and neuroma formation. The gel can be delivered to selected target locations within or proximate nerves, including interfascicularly and intrafascicularly. Gel delivery associated with an operative procedure for the treatment of pain and other indications is also disclosed.

Description

[0001] Incorporation by reference of any priority application [0002] Pursuant to 35 U.S.C. §119(e), this application claims the benefit of the non-provisional application of U.S. Provisional Application No. 62 / 643,174, filed March 15, 2018, the entire contents of which are incorporated herein by reference. In addition, any and all applications for which foreign or domestic priority claims are identified on the Application Data Sheet filed with this application are hereby incorporated by reference pursuant to 37 CFR 1.57. technical field [0003] The present invention relates in some aspects to systems and methods utilizing hydrogels for neuromodulation, including sympathetic, parasympathetic, central nervous system, and peripheral systemic neuromodulation, including sensory and motor neuromodulation. In particular, the development of in situ formation of injectable neural barriers composed of synthetic polymers is disclosed. Many neurally mediated diseases can be treated us...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/34A61K45/00A61K31/5415A61K31/445A61P23/02A61P25/02A61L27/18A61L27/52A61L27/54A61L31/06A61L31/14A61L31/16
CPCA61L27/52A61N7/02A61L27/18A61L27/54A61N2007/0021A61N2007/003A61L2430/32A61L27/56A61M2025/0073A61M25/007A61B18/1477A61B2018/0293A61B2090/378A61B18/1492A61B2018/0212C08L75/08C08L71/02C08L2203/02
Inventor 科琳·布赖特
Owner TULAVI THERAPEUTICS INC
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