Compositions comprising blockers of L-DOPA renal cell transfer for treatment of Parkinson's disease

A technology for Parkinson's disease and a composition is applied in the field of L-DOPA renal cell extravasation blocker, which can solve problems such as impractical concentration

Inactive Publication Date: 2006-07-05
波特拉和康潘希亚股份有限公司
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  • Abstract
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AI Technical Summary

Problems solved by technology

Unfortunately, most of the P-glycoprotein inhibitors that could prove beneficial in increasing the bioavailability of L-DOPA in PD patients are well known cytotoxic agents or produce inhibitory effects on P-glycoprotein if not toxic The concentration required is not practical under in vivo conditions

Method used

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  • Compositions comprising blockers of L-DOPA renal cell transfer for treatment of Parkinson's disease
  • Compositions comprising blockers of L-DOPA renal cell transfer for treatment of Parkinson's disease
  • Compositions comprising blockers of L-DOPA renal cell transfer for treatment of Parkinson's disease

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Experimental program
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Embodiment Construction

[0071] Materials and methods

[0072] in vitro studies

[0073] Cell Culture LLC-PK 1 Cells were obtained from the American Type Culture Collection (Rockville, MD) and are a porcine-derived proximal tubular epithelial cell that retains several properties of proximal tubular epithelial cells in culture Tie. Will LLC-PK 1 (ATCCCRL 1392; passages 198-206) maintained at 37°C, 5% CO 2 -95% air humidified atmosphere supplemented with 100 U / mL penicillin G, 0.25 μg / mL amphotericin B, 100 μg / mL streptomycin (Sigma), 3% fetal bovine serum (Sigma) and 25 mM N-2- Hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES; Sigma) medium 199 (Sigma Chemical Company, St. Louis, Mo, USA) was grown. For subculture, cells were dissociated with 0.05% trypsin-EDTA, split 1:4 and grown in cells containing 75- or 162-cm 2 The growth zone was subcultured in Costar flasks (Costar, Badhoevedorp, The Netherlands). For uptake studies, cells were seeded at a density of 40,000 cells / well in collagen-t...

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Abstract

A pharmaceutical composition for the treatment of Parkinson's disease comprises L-DOPA and at least one compound capable of blocking the L-DOPA renal cell outward transfer pathway; said blocking compound being chose from (a) a flavonoid phenyl benzopyran derivative; (b) a trans-stilbene derivative; or (c) phloretin [3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)-1-propanone]. The composition may also comprise an inhibitor of the enzyme amino acid decarboxylase (AADC), such a carbidopa or benserazide, and / or an inhibitor of the enzyme catechol-O-methyl transferase (COMT), such as entacapone or tolcapone. The composition is preferably administered in soli form and the L-DOPA may be administered simultaneously or sequentially with the L-DOPA renal cell outward transfer blocking compound.

Description

field of invention [0001] The present invention relates to compositions useful in the treatment of Parkinson's disease. The invention relates in particular to the use of a blocker of renal cell efflux of L-DOPA as a component of said composition. technical background [0002] Parkinson's disease (PD) is a chronic neurodegenerative disorder of unknown etiology that largely affects brain dopaminergic neurons originating from the Substantia Nigra and projecting to the striatum. Clinically, patients with PD exhibit progressively progressive motor abnormalities, more commonly manifested as tremor, rigidity, and abnormal gait. Subjects with PD showed considerable motor improvement when given the brain neurotransmitter dopamine precursor L-DOPA plus carbidopa or benserazide at this time. The latter two compounds are potent inhibitors of peripheral aromatic L-amino acid decarboxylase (AADC) and their administration is intended to prevent the conversion of L-DOPA to dopamine in per...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/195A61P25/16A61K45/00A61K31/00A61K31/05A61K31/121A61K31/165A61K31/198A61K31/277A61K31/35A61K31/352A61P43/00
CPCA61K31/35A61K31/195A61P25/16A61P43/00A61K31/12A61K31/03A61K2300/00A61K31/352
Inventor 帕特里齐奥·索雷斯-达-西尔瓦
Owner 波特拉和康潘希亚股份有限公司
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