Pro-drugs for the oral delivery of disodium cromoglycate.

Mori, Takeshi; Nishimura, Kenichi; Tamaki, Satoshi; Nakamura, Shohei; Tsuda, Hirokazu; Kakeya, Nobuharu

doi:10.1248/cpb.36.338

Cited by 19 publications

(11 citation statements)

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“…1 As a safe and effective drug for allergies, great effort has been put into developing an oral dosage form of cromolyn to improve patient compliance. 2,3 However, even today the pharmacology of cromolyn is not fully understood. Conformation and association properties of dilute aqueous cromolyn solutions have been examined using light-scattering and magnetic birefringence techniques.…”

Section: Introductionmentioning

confidence: 99%

Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy

Ding

Stringfellow

Robinson

2004

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy

Ding

Stringfellow

Robinson

2004

Journal of Pharmaceutical Sciences

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“…However, it is hardly absorbed from the digestive tract. Then, an orally deliverable prodrug, cromoglicate lisetil (CL), was designed (22). So we studied the effects of orally applied CL on arthritis in CII-immunized mice (23).…”

Section: Mast Cells As a Target Of Rheumatoid Arthritis Treatmentmentioning

confidence: 99%

Mast Cells as a Target of Rheumatoid Arthritis Treatment

Kobayashi

Okunishi

2002

Japanese Journal of Pharmacology

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ABSTRACT-Rheumatoid arthritis (RA) is a chronic inflammatory disease and its exact cause and pathophysiological process remain unclear. Fibroblast-like synoviocytes, macrophages and T lymphocytes are considered to be the major contributors in the pathophysiological process of RA; however, an increasing number of papers have drawn attention to the potential role of mast cells (MCs) in the process. In an animal model of RA, we reported an increase in MC numbers in the arthritic region, which agreed with the observation in human RA. In addition, a good correlation between the number of MCs and the development of disease was observed. However, there has been little experimental or clinical evidence of the beneficial effects of the modification of MC activity on the pathogenesis of RA and this is the weak point of the hypothesis. We therefore studied the effects of a MC-stabilizing compound, cromoglicate lisetil (CL), which is an orally deliverable prodrug of cromolyn sodium, on the RA disease model. The MC-stabilizer had efficacy in a mouse model. The beneficial effects of CL in this animal model further suggested the contribution of MCs in the pathophysiological process of RA. Concerning the contributive mechanism of MC on the pathogenesis of RA, our results using a disease model suggested that activation of MC chymase and matrix metalloproteinases might be involved. MC is now considered to be one of the targets of RA treatment.

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“…Cromolyn sodium is very hydrophilic, containing strong acidic twin carboxyl groups (pKa=2.0) and has tremendous H-bonding capability (2). These structural features contribute to its high hydrophilicity (n-octanol/ neutral aqueous buffer distribution coefficient less than 0.001) (3). Oral human bioavailability study of cromolyn sodium showed that it was poorly absorbed from the GI tract, less than 1% of the administered dose (500 mg) was absorbed in 12 volunteers (4).…”

Section: Introductionmentioning

confidence: 99%

“…Cromolyn sodium prodrugs have been synthesized to improve the oral absorption. These compounds shows higher oral absorption and thereby higher oral bioavailability in rat and rabbits, however the absorption mechanism is still unclear and the toxicity of these prodrugs has not yet been fully investigated (3,5).…”

Section: Introductionmentioning

confidence: 99%