Process for producing polymer-stabilized antioxidant crystals

Patent metadata

Field	Value
Publication number	US-2025195663-A1
Application number	US-202418980734-A
Country	US
Kind code	A1
Filing date	Dec 13, 2024
Priority date	Dec 15, 2023
Publication date	Jun 19, 2025
Grant date	—

Abstract

In one embodiment, the invention relates to a process for producing a crystalline antioxidant comprising: (1) providing an aqueous solution comprising a hydrophilic antioxidant; and a polymer selected from hyaluronate-dopamine, alginate-dopamine, chitosan-dopamine, poly(ethylene glycol) dopamine and their derivatives, or mixtures thereof; (2) forming a liquid droplet of the aqueous solution, the droplet having a diameter, wherein polymer-induced nucleation of the antioxidant occurs in the liquid droplets; (3) crystallizing the crystalline antioxidant by performing at least one of: (a) subjecting the liquid droplet to thermal cycling between a lower temperature and a higher temperature, wherein antioxidant crystal growth occurs at the lower temperature and crystal dissolution occurs at the upper temperature; and maintaining the thermal cycling until the droplet contains one or two antioxidant crystals, and (b) subjecting the liquid droplet to shear deformation using a shear-induced mixing-on-a-chip device, wherein a probability of nucleation and crystallization of each droplet is increased.

First claim

We claim:

1 . A process for producing a crystalline antioxidant comprising:
providing an aqueous solution comprising: a hydrophilic antioxidant; and a polymer selected from hyaluronate-dopamine, alginate-dopamine, chitosan-dopamine, poly(ethylene glycol) dopamine and their derivatives, or mixtures thereof; forming a liquid droplet of the aqueous solution, the droplet having a diameter, wherein polymer-induced nucleation of the antioxidant occurs in the liquid droplets; crystallizing the crystalline antioxidant by performing at least one of: (a) subjecting the liquid droplet to thermal cycling between a lower temperature and a higher temperature, wherein antioxidant crystal growth occurs at the lower temperature and crystal dissolution occurs at the upper temperature; and maintaining the thermal cycling until the droplet contains one or two antioxidant crystals, and (b) subjecting the liquid droplet to shear deformation using a shear-induced mixing-on-a-chip device, wherein a probability of nucleation and crystallization of each droplet is increased.

2 . The process of claim 1 wherein the droplet diameter is from 10 to 200 μm.

3 . The process of claim 2 wherein the droplet diameter is from 10 to 25 μm.

4 . The process of claim 1 wherein the hydrophilic antioxidant is selected from N-acetylcysteine, ascorbic acid, vitamin C, uric acid, and glutathione.

5 . The process of claim 4 wherein the hydrophilic antioxidant is selected from N-acetylcysteine and ascorbic acid.

6 . The process of claim 1 wherein the polymer is hyaluronate-dopamine.

7 . The process of claim 1 wherein the lower temperature is from 4° C. to 25° C.

8 . The process of claim 1 wherein the higher temperature is from 45° C. to 65° C.

9 . The process of claim 1 wherein a temperature difference between the lower temperature and the higher temperature is from 20° C. to 60° C.

10 . The process of claim 1 wherein the total number of cycles is 3 to 7.

11 . The process of claim 1 further comprising a hold time of the cycle at the low temperature and a hold time of the cycle at the high temperature.

12 . The process of claim 11 wherein the hold time of the cycle at the low temperature is from 20 to 60 min.

13 . The process of claim 11 wherein the hold time of the cycle at the high temperature is from 10 to 30 min.

14 . The process of claim 1 further comprising a total time for the temperature cycling.

15 . The process of claim 14 wherein the total time is from 12 to 24 hrs.

16 . The process of claim 1 wherein the concentration of the hydrophilic antioxidant in the aqueous solution is from 200 mg/mL to 800 mg/mL.

17 . The process of claim 16 wherein the concentration of the hydrophilic antioxidant in the aqueous solution is from 300 mg/mL to 400 mg/mL.

18 . The process of claim 1 wherein the concentration of the polymer in the aqueous solution is from 5 mg/mL to 80 mg/mL.

19 . The process of claim 18 wherein the concentration of the polymer in the aqueous solution is from 15 mg/mL to 20 mg/mL.

20 . The process of claim 1 wherein the thermal cycling is maintained until the droplet contains one crystal.

21 . The process of claim 1 further comprising a hold time following the low temperature of the last cycle.

22 . The process of claim 21 where the hold time is 10-14 hour.

Assignees

• Univ Illinois

Inventors

• Kong Hyunjoon
• Lee Jonghwi
• Kim Youngjun
• Han Hee Sun
• Miller Ryan Cree

Classifications

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/183 Primary

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title