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Modified hyaluronic acid polymer compositions and related methods

A technology of hyaluronic acid and composition, applied in the field of hyaluronic acid, can solve problems such as inability to convert into beneficial performance

Inactive Publication Date: 2014-10-29
CARBYLAN THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While polymer gels or gel precursors may exhibit favorable properties for reaction chemistry and conditions, gelation properties, and / or therapeutic effect in more than one in vitro model, in some cases this effect cannot be replicated in translates into beneficial properties in vivo or in the clinical setting

Method used

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  • Modified hyaluronic acid polymer compositions and related methods
  • Modified hyaluronic acid polymer compositions and related methods
  • Modified hyaluronic acid polymer compositions and related methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0171] Synthesis of vinyl sulfone derivatized hyaluronic acid (HA-VS)-low degree of modification

[0172]

[0173] Weigh 5g hyaluronic acid (HA) (9.4×10 4 cps (3% in water)] was added to a 1L round bottom flask. Add 500 mL of sterile filtered water to the HA. Place the flask on a rotary evaporator that has been set to rotate between 20-100 rpm. The solution is rotated until all HA is dissolved (about 16-18 hours). The HA solution (10 mg / mL) was then transferred to a 1L glass beaker. The stirring paddle connected to the overhead stirrer is inserted into the solution and set to a stirring speed that ensures effective stirring of the solution. Add 333 mL of 0.25 N NaOH solution (83.2 mL of 1 N NaOH was added to 249.8 mL of deionized water) to the stirring HA solution. After about 1 minute, 150 mL of divinyl sulfone solution (18 mL of divinyl sulfone dissolved in 132 mL of deionized water) was quickly added to the stirring solution. After 15 seconds (calculated from the end of t...

Embodiment 2

[0180] Synthesis of gel prepared from vinyl sulfone modified hyaluronic acid (HA-VS) and PEG3400-dithiol

[0181] The HA-VS solution prepared according to the method described in Example 1 was diluted with deionized water to a concentration of 14 mg / mL. Add 11 mL of HA-VS solution to a 20 mL sterile syringe. The HA-VS solution was filtered through a 0.2 μm sterile syringe filter into a sterile 50 mL centrifuge tube. PEG-(SH) 2 [Laysan Bio Inc, ltem# SH-PEG-SH-3400-1g] 50 mg / mL solution is obtained by adding 40.1 mg PEG-(SH) 2 Prepared by dissolving in 0.802 mL of deionized water. PEG-(SH) 2 The solution was transferred to a 1 mL sterile syringe and filtered through a 0.2 μm sterile syringe filter. Transfer 10 mL of sterile filtered HA-VS to a sterile 50 mL centrifuge tube. 250 μL of 0.5 M sodium phosphate solution (filtered through a 0.2 μm sterile syringe filter) was added to the HA-VS solution. The resulting solution was mixed thoroughly. 380μL [19 mg PEG-(SH) 2 ] Of ster...

Embodiment 3

[0183] HA-VS / PEG-(SH) 2 Preparation of gel slurry-single extrusion

[0184] Use a glass rod to combine HA-VS / PEG-(SH) from Example 2 2 The gel is physically broken into pieces. The gel is transferred to a sterile 60 mL syringe and then sealed with the syringe cap. Add 40 mL of 0.9% sterile NaCl to the gel. Insert the plunger into the syringe barrel and turn the syringe upside down. The syringe cap is opened to relieve any pressure and then closed. The syringe was inverted several times to ensure good mixing of the saline and gel fragments. Allow the gel to swell overnight (at least 16 hours).

[0185] Die-cutting polyester mesh (McMaster Carr, Cat# 9218T13, mesh size: 20.3×20.3, square / rectangular size: 0.0331", micron rating: 840 microns, open area percentage: 46, by using a 23mm leather punch Wire diameter: 0.0157”) 23mm diameter disc. Insert the disc into a 25 mm syringe filter holder (Cole Palmer, Cat# EW-29550-42), and close the filter holder. The filter holder contai...

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Abstract

The present application provides compositions comprising hyaluronic acid having low levels of functional group modification, mixtures formed by controlled reaction of such lightly modified hyaluronic acid with suitable difunctional or multi-functional crosslinkers, and hydrogel precursor compositions and the resulting hydrogels. The compositions are lightly cross-linked and possess low pro-inflammatory properties when injected in vivo, and can be used as, for example, medical devices, biomedical adhesives and sealants, and for localized delivery of bioactive agents, among other uses.

Description

[0001] Cross reference for related applications [0002] The application request for this application requirement on July 30, 2009 The U.S. temporary application No.61 / 230,074 and the US temporary application NO.61 / 311,953 applied on March 09, 2010, their respective contents are incorporated into this article by introducing them. Technical field [0003] The present invention is generally involved in hyaluronic acid with low levels of functional group modification. Through the mixture formed by the control response of the mild modifiers and the appropriate two -official or multi -official reactor, and related water, related water, and related waterGel and hydrogel foretophyde composition.The composition described here is mild cross -linking and has low inflammatory characteristics when injection in the living body, and can be used as a medical equipment, biomedical adhesives and sealing agents, and local transmission for biological active agentswait. Background technique [0004] ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/20C08B37/00A61L27/52C08J3/075
CPCA61L27/52A61L2430/24C08J3/075C08B37/0072A61L27/26A61K31/58A61K9/14A61K31/573A61K45/06A61K47/36A61P19/02A61P19/04A61P19/08A61P25/00A61P29/00A61P9/00C08L5/08C08L71/02A61L27/20C08B37/00A61L2400/06A61K9/0019A61K9/06A61K9/10A61K35/00A61K47/02A61K47/10C08J2305/08
Inventor 何平人D.M.格拉韦特G.Y.丹尼洛夫
Owner CARBYLAN THERAPEUTICS