Hydrogel composition for mucosal lifting procedures within lumenal anatomical structures

Abstract

An injectable medical composition includes an acrylate and a solvent. The composition has a first viscosity at temperatures below body temperature and a second viscosity at body temperature. The first viscosity is lower than the second viscosity.

1 . An injectable medical composition comprising:
 an acrylate and a solvent;   wherein the composition has a first viscosity at temperatures below body temperature and a second viscosity at body temperature, the first viscosity lower than the second viscosity.   
     
     
         2 . The injectable medical composition of  claim 1 , wherein the composition is configured to be in a Newtonian state at temperatures below body temperature and in a non-Newtonian state at body temperature. 
     
     
         3 . The injectable medical composition of  claim 1 , wherein the acrylate comprises a poly(acrylic acid) copolymer. 
     
     
         4 . The injectable medical composition of  claim 3 , wherein the poly(acrylic acid) copolymer comprises allyl sucrose or allyl pentaerythritol. 
     
     
         5 . The injectable medical composition of  claim 1 , wherein the composition further comprises poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide). 
     
     
         6 . The injectable medical composition of  claim 1 , wherein the acrylate in the composition is between 1.9% and 2.5% w/v. 
     
     
         7 . The injectable medical composition of  claim 1 , wherein body temperature is 35.5° C.-38.5° C. 
     
     
         8 . The injectable medical composition of  claim 1 , wherein the second viscosity is less than 4 Pa·s at shear rates of up to 10 s−1. 
     
     
         9 . The injectable medical composition of  claim 1 , wherein the second viscosity is greater than 0.2 Pa·s at shear rates of up to 10 s−1. 
     
     
         10 . The injectable medical composition of  claim 1 , the second viscosity at a shear rate of 10 s−1 is at least 30% less than the second viscosity at a shear rate of 1 s−1. 
     
     
         11 . The injectable medical composition of  claim 1 , wherein a shear stress of the composition at body temperature is less than 100 Pa at a rate of 0.1 s−1. 
     
     
         12 . The injectable medical composition of  claim 1 , wherein a hardness of the composition at body temperature is between 1N and 10N. 
     
     
         13 . The injectable medical composition of  claim 1 , wherein an adhesiveness of the composition at body temperature is less than 10N. 
     
     
         14 . The injectable medical composition of  claim 1 , wherein a compressibility of the composition at body temperature is less than 10N. 
     
     
         15 . The injectable medical composition of  claim 1 , wherein an elasticity of the composition at body temperature is less than 10N. 
     
     
         16 . The injectable medical composition of  claim 1 , wherein a maximum mucosal detachment force of the composition at body temperature is less than 5N. 
     
     
         17 . The injectable medical composition of  claim 1 , wherein a mucoadhesion force of the composition at body temperature is less than 5 mJ/cm2. 
     
     
         18 . The injectable medical composition of  claim 1 , wherein a work of adhesion of the composition at body temperature is less than 5N. 
     
     
         19 . The injectable medical composition of  claim 1 , wherein the composition is configured to generate a mucosal lift when injected submucosally, and wherein the mucosal lift retains over 60% of its original height for over 60 minutes. 
     
     
         20 . The injectable medical composition of  claim 1 , wherein the composition is configured such that a 5-10 cc syringe filled with the composition can be deposited within the submucosal space through an endoscopic needle injector using less than 20 Kg force in less than 90 seconds. 
     
     
         21 . The injectable medical composition of  claim 1 , wherein the viscosity of the composition is less than 800 mPa·s at 22° C. and greater than 2500 mPa·s at 37° C. 
     
     
         22 . The injectable medical composition of  claim 1 , wherein the composition, after injection submucosally, is configured to limit a transference of electrical energy to a deeper intestinal wall when electrosurgery is applied. 
     
     
         22 . The injectable medical composition of  claim 1 , wherein the viscosity of the composition reduces to less than 100 mPa·s within 90 minutes of injection submucosally. 
     
     
         24 . The injectable medical composition of  claim 1 , wherein the composition exhibits a G′ value of greater than 7000 Pa·s between 0.1-10.0 Hz at body temperature. 
     
     
         25 . The injectable medical composition of  claim 1 , wherein the composition exhibits a G″ value of greater than 1300 Pa·s. between 0.1-10.0 Hz at body temperature. 
     
     
         26 . The injectable medical composition of  claim 1 , wherein the composition is manufactured by mixing components thereof at a temperature less than 10° C. 
     
     
         27 . The injectable medical composition of  claim 1 , wherein the composition is manufactured by sequentially adding polymers to the solvent under magnetic stirring at less than 250 rpm. 
     
     
         28 . The injectable medical composition of  claim 1 , wherein the composition is manufactured by pre-mixing polymers at 100 rpm for 1 minute prior to addition to addition of the solvent to affect the final viscosity. 
     
     
         29 . The injectable medical composition of  claim 1 , further comprising polystyrene or other microspheres at a concentration of 4.2%, wherein the composition with the polystyrene or other microspheres has a viscosity that is 12% higher than a composition without the polystyrene or other microspheres. 
     
     
         30 . The injectable medical composition of  claim 1 , further comprising marking pigment, wherein the marking pigment allows for visible identification of the composition upon injection for up to 60 days. 
     
     
         31 . The injectable medical composition of  claim 1 , wherein the polymer does not include poly(propylene oxide). 
     
     
         32 . The injectable medical composition of  claim 1 , wherein the polymer does not include poly(ethylene oxide). 
     
     
         33 . The injectable medical composition of  claim 1 , wherein the composition does not include an oily component. 
     
     
         34 . The injectable composition of  claim 1 , wherein polymers comprise about 1% to about 10% of the composition by weight. 
     
     
         35 . The injectable medical composition of  claim 1 , wherein polymers comprise about 2% to about 4% of the composition by weight. 
     
     
         35 . The injectable medical composition of  claim 1 , wherein the solvent comprises distilled water. 
     
     
         36 . The injectable medical composition of  claim 35 , wherein the solvent comprises carbonic acid or sodium acetate. 
     
     
         37 . The injectable medical composition of  claim 1 , wherein a pH of the composition is approximately 5.1-7.4. 
     
     
         38 . The injectable medical composition of  claim 1 , further comprising a coloring agent. 
     
     
         39 . The injectable medical composition of  claim 38 , wherein the coloring agent is a dye. 
     
     
         40 . The injectable medical composition of  claim 39 , wherein the dye is methylene blue. 
     
     
         41 . A method of performing a surgical procedure at a surgical site in mucosal tissue, the method comprising:
 injecting an aliquot of a hydrogel composition to raise an outer mucosal layer of the mucosal tissue a distance away from a submucosal layer at the surgical site;   maintaining the outer mucosal tissue layer at least 60% of the distance away from the submucosal layer for at least one hour; and   performing the surgical procedure on the outer mucosal layer during the maintaining step.   
     
     
         42 . The method of  claim 41 , wherein the injecting step and performing step are performed endoscopically. 
     
     
         43 . The method of  claim 41 , wherein the hydrogel has lower viscosity at a first temperature and higher viscosity at a second temperature, the first temperature being lower than the second temperature. 
     
     
         44 . The method of  claim 41 , wherein the first temperature is room temperature having a temperature range of approximately 20 to 25 degrees Celsius and the second temperature is body temperature having a temperature range of approximately 35.5 to 38.5 degrees Celsius. 
     
     
         45 . The method of  claim 41 , further comprising maintaining the outer mucosal tissue layer at least 90% of the distance away from the submucosal layer for at least 90 minutes. 
     
     
         46 . The method of any of  claim 41 , wherein the aliquot has a volume of about 20 ml or less. 
     
     
         47 . A method of performing a surgical procedure at a surgical site in mucosal tissue, the method comprising:
 injecting an aliquot of an hydrogel composition to raise an outer mucosal layer of the mucosal tissue a distance away from a submucosal layer of the mucosal tissue at the surgical site, wherein the hydrogel composition has lower viscosity at a first temperature and higher viscosity at a second temperature, the first temperature being lower than the second temperature;   maintaining the distance for at least 90 min; and   performing the dissection on the outer mucosal layer.   
     
     
         48 . The method of  claim 47 , wherein the first temperature is room temperature having a temperature range of approximately 20 to 25 degrees Celsius and the second temperature is body temperature having a temperature range of approximately 35.5 to 38.5 degrees Celsius. 
     
     
         49 . A method of using a hydrogel composition as a marking agent in surgical procedure, the method comprising:
 injecting an aliquot of a hydrogel composition at a surgical site to visually distinguish the surgical site from surrounding tissue, wherein:
 the hydrogel composition has lower viscosity at a first temperature and higher viscosity at a second temperature, the first temperature being lower than the second temperature; 
 the hydrogel composition comprises a polymer composition and a coloring agent; and 
 the hydrogel composition provides visual delineation of the surgical site for at least 90 minutes; and 
   performing the procedure at the surgical site.   
     
     
         50 . The method of  claim 49 , wherein the first temperature is room temperature having a temperature range of approximately 20 to 25 degrees Celsius and the second temperature is body temperature.