Solubilization and stabilization of lipoic acid trisulfide by creation of various β-cyclodextrin clathrates

  • Biosci Biotechnol Biochem. 2024 Apr 3:zbae042. doi: 10.1093/bbb/zbae042.
Shoichiro Tomonaga  1  2 ,  Hiroaki Ishimaru  1 ,  Takahiro Isobe  1 ,  Etsuo Ohshima  1  3 ,  Shinji Kitagaki  2
Affiliations
  • 1. Kyowa Pharma Chemical Co., Ltd., Chokeiji, Takaoka, Toyama 933-8511, Japan.
  • 2. Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
  • 3. Kyowa Hakko Bio Co., Ltd., Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
PMID: 38569654 DOI: 10.1093/bbb/zbae042
Abstract

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α-lipoic acid on a gram scale and obtained novel β-cyclodextrin clathrates (84-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in β-cyclodextrins. The resulting β-cyclodextrin clathrates exhibited significant improvements in water solubility and thermal stability. This pioneering study demonstrated a novel approach to the practical preparation of trisulfide and its β-cyclodextrin clathrates as active ingredients, paving the way for clinical development.

Keywords
β-cyclodextrin clathrates; Lipoic acid trisulfide; Sulfane sulfur-containing trisulfide.
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