Process for synthesizing oil and surfactant-free hyaluronic acid nanoparticles and microparticles
AssigneeUniversity of North Texas
InventorsZhibing Hu, Xiaohu Xia, Liping Tang
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Abstract
A method for synthesizing uniformly sized hyaluronic acid (“HA”) particles that are substantially free from oil and surfactant contaminants. The method comprises crosslinking HA chains with 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide hydrochloride (“EDAC”) and adipic acid dihydrazide in a water/acetone mixture.
Claims33
1) A method for synthesizing hyaluronic acid (“HA”) particles comprising:
- crosslinking HA chains with 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide hydrochloride (“EDAC”) and adipic acid dihydrazide in a water/acetone mixture.
14) A method of synthesizing uniformly sized hyaluronic acid (“HA”) particles substantially free from oil and surfactant contaminants, comprising:
- combining about 8 grams of an HA aqueous solution, about 80 grams of distilled water and about 108 grams of acetone into a covered container to give a mixture;
- mixing the mixture of the covered container for a first period of time forming a HA/acetone mixture;
- adding about 2 ml of an 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide hydrochloride (“EDAC”) and adipic acid dihydrazide solution to the HA/acetone mixture forming an EDAC/adipic acid/HA/acetone mixture;
- mixing the EDAC/adipic/HA/acetone mixture at a controlled temperature for a second period of time;
- adding about 104 grams of acetone to the EDAC/adipic/HA/acetone mixture at a controlled temperature for a third period of time forming the uniformed sized HA particles;
- and
- isolating the uniformly sized HA particles.
22) A uniformed sized hyaluronic acid (“HA”) particle substantially free from oil and surfactant contaminants made by a method comprising:
- crosslinking HA chains with 1-ethyl-3-(3-dimethlyaminopropyl) carbodiimide hydrochloride (“EDAC”) and adipic acid dihydrazide in a water/acetone mixture.
23) The composition of claim 24, the method further comprises:
- isolating the synthesized HA particles from the water/acetone mixture.
24) The composition of claim 25, wherein isolating comprises:
- (a) dialyzing the synthesized HA particles against de-ionized water for about 3 weeks;
- and
- (b) changing the deionized water about every 10 hours;
- wherein dialyzing in a dialysis membrane allows free diffusion of molecules having a size less than 13,000 Dalton.
27) The composition of claim 28, wherein the HA chains have a concentration of about 0.1% wt/volume in the water/acetone mixture.
33) The composition of claim 34, wherein the synthesized HA particles comprise a uniform size of about 200 nanometers in the time range of about 44 hours of crosslinking.
Dependencies are inferred from the claim text.