Preparation, Characterization, and <i>In Vitro</i> Release of Chitosan-Ecabet Electrolyte Complex for the Mucosal Delivery

Kim, Jae Yeol; Kim, Dae Hun; Min, Kyung Up; Maeng, Han‐Joo; Jang, Dong‐Jin; Cho, Kwan Hyung

doi:10.1166/jnn.2019.15961

Cited by 4 publications

(5 citation statements)

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“…1) similar structurally to the commercial drug Ecabet sodium (2, Fig. 1) [20,48]. To date, ecabet sodium is the only commercial drug based on abietane-type diterpenoids which it is clinically used in the treatment of gastritis and gastric ulcer in Japan, since possesses high affinity to gastric adherent mucosa, epithelial cells, albumin, and fibrinogen in the ulcer region [48].…”

Section: Discussionmentioning

confidence: 94%

“…1) [20,48]. To date, ecabet sodium is the only commercial drug based on abietane-type diterpenoids which it is clinically used in the treatment of gastritis and gastric ulcer in Japan, since possesses high affinity to gastric adherent mucosa, epithelial cells, albumin, and fibrinogen in the ulcer region [48]. Volunteers following a single oral administration of an ecabet disodium tablet (1 g) showed a plasma maximum concentration-time profile of 4926 ± 880 ng/mL at the first hour and a plasma elimination half-life of 6.63 ± 2.24 h [48,49].…”

Section: Discussionmentioning

confidence: 99%

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Synergistic in vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils and 18-(Phthalimid-2-yl)ferruginol Against Arboviruses and Herpesvirus

Betancur-Galvis,

Jimenez-Jarava,

Rivas

et al. 2023

Preprint

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Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction of antiviral effective concentration of drugs already approved by the FDA, such as ivermectin (IVM), ribavirin (RIBA) and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV) and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecule with broad-spectrum antiviral activity, the ferruginol analogue 18-(phthalimid-2-yl)ferruginol (phthFGL). In general, the combination of IVM, phthFGL and Oregano EO showed the greatest synergism potential against CHIKV, ZIKV and HHV-2, obtaining a reduction in the EC99 value of up to ~8, and ~27, and ~12-fold for CHIKV, in example, respectively. The ternary combination RIBA, phthFGL, Oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, Oregano EO which indicates that IVM could contribute more to the differentiations of cell targets (for example by inhibition of host heterodimeric importin IMP α/β1 complex) than ribavirin. PhthFGL showed a good pharmacokinetic profile.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Synergistic in vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils and 18-(Phthalimid-2-yl)ferruginol Against Arboviruses and Herpesvirus

Betancur-Galvis,

Jimenez-Jarava,

Rivas

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…PhthFGL (1a, Figure 1) is an abietane-derived analog of (+)-ferruginol (1, Figure 1), structurally similar to the commercial drug ecabet sodium (2, Figure 1) [20,48]. To date, ecabet sodium is the only commercial drug based on abietane-type diterpenoids which is clinically used in the treatment of gastritis and gastric ulcers in Japan since it possesses high affinity to gastric adherent mucosa, epithelial cells, albumin, and fibrinogen in the ulcer region [48]. Following a single oral administration of an ecabet disodium tablet (1 g) volunteers showed a plasma maximum concentration-time profile of 4926 ± 880 ng/mL at the first hour and a plasma elimination half-life of 6.63 ± 2.24 h [48,49].…”

Section: Discussionmentioning

confidence: 99%

“…To date, ecabet sodium is the only commercial drug based on abietane-type diterpenoids which is clinically used in the treatment of gastritis and gastric ulcers in Japan since it possesses high affinity to gastric adherent mucosa, epithelial cells, albumin, and fibrinogen in the ulcer region [48]. Following a single oral administration of an ecabet disodium tablet (1 g) volunteers showed a plasma maximum concentration-time profile of 4926 ± 880 ng/mL at the first hour and a plasma elimination half-life of 6.63 ± 2.24 h [48,49]. Meanwhile, for ferruginol (1, Figure 1), pharmacokinetic studies have been performed in rats obtaining a maximum concentration in plasma of 3140 ng/mL at 40 min after oral administration at a dose of 20 mg/kg (~1 g in adults), and a plasma elimination half-life of 41.73 min [50].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Synergistic In Vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils, and 18-(Phthalimid-2-yl)ferruginol against Arboviruses and Herpesvirus

Betancur-Galvis,

Jimenez-Jarava,

Rivas

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction in the antiviral effective concentration of drugs already approved by the FDA, such as ivermectin (IVM), ribavirin (RIBA), and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV), and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecules with broad-spectrum antiviral activity, the ferruginol analog 18-(phthalimid-2-yl)ferruginol (phthFGL), which presented an IC99 of 25.6 μM for the three types of virus. In general, the combination of IVM, phthFGL, and oregano EO showed the greatest synergism potential against CHIKV, ZIKV, and HHV-2. For instance, this combination achieved reductions in the IC99 value of each component up to ~8-, ~27-, and ~12-fold for CHIKV, respectively. The ternary combination of RIBA, phthFGL, and oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, and oregano EO, which indicates that IVM could contribute more to the differentiation of cell targets (for example via the inhibition of the host heterodimeric importin IMP α/β1 complex) than ribavirin. Statistical analysis showed significant differences among the combination groups tested, especially in the HHV-2 and CHIKV models, with p = 0.0098. Additionally, phthFGL showed a good pharmacokinetic profile that should encourage future optimization studies.

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Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery

et al. 2021

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Preparation, Characterization, and In Vitro Release of Chitosan-Ecabet Electrolyte Complex for the Mucosal Delivery

Cited by 4 publications

References 0 publications

Synergistic in vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils and 18-(Phthalimid-2-yl)ferruginol Against Arboviruses and Herpesvirus

Synergistic in vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils and 18-(Phthalimid-2-yl)ferruginol Against Arboviruses and Herpesvirus

Synergistic In Vitro Antiviral Effect of Combinations of Ivermectin, Essential Oils, and 18-(Phthalimid-2-yl)ferruginol against Arboviruses and Herpesvirus

Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery

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