Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-11-14
2003-02-11
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S023000, C514S027000, C514S032000, C514S053000, C514S054000, C514S824000, C514S878000, C514S925000, C514S926000
Reexamination Certificate
active
06518250
ABSTRACT:
TECHNICAL FIELD
This invention relates to a novel agent for preventing and curing the hindrance of ischemic reperfusion. More particularly, the invention relates to an agent having a water-soluble chromanol glycoside as an active component and used for preventing and curing the hindrance of ischemic reperfusion.
BACKGROUND ART
If the human cells and tissues are exposed to ischemic condition for long time, they suffer serious damage and eventually result in cell death. On the other hand, when a sudden oxygen load is exerted thereon by an ischemic reperfusion for a certain duration, they sustain further serious hindrance. Clinically, these hindrance of the ischemic reperfusion have been heretofore recognized as diseases to be observed during the transplantation of an internal organ or the reconstruction of the coronary blood flow for a myocardial infarct. In recent years, since the involvement of a free radical reaction in the histological hindrance due to the ischemic reperfusion in a feline intestine was pointed out (Granger, D. N. et al.: Superoxide radicals in feline intestinal ischemia. Gastroenterol. 22-29, 1981), the studies in this field have been widely disseminated and the involvement of active oxygen free radical in the hindrance of ischemic reperfusion in not only the small intestine but also the brain, heart, stomach, liver, kidney, and so on has been appearing in reports. Therefore, numerous studies have been being promoted with a view to seeking out ways of alleviating the relevant diseases by the administration of an exogenous radical eliminating agent. However, owing to various problems concerning the in vivo action and the field of reaction, however, all the radical eliminating agents are not capable of effectively restraining the histological hindrance due to the ischemic reperfusion (Hirofumi Kazumori et al.: Proposal of problems concerning the hindrance of reperfusion and free radicals, J. Act. Oxyg. FreeRad.: 757-766, 1991). This fact is self-evident from a present state that virtually no radical eliminating agent has been authorized as a drug.
The chromanol glycoside to be used in this invention is a known compound (the official gazette of JP-A-07-118,287). The chromanol glycoside is obtained by substituting an alcohol for the phytyl group at the 2 position of a chroman ring of &agr;-tocopherol, which is a typical vitamin E and further binding a sugar thereto. It possesses high water solubility and excellent resistance to oxidation. The utilization of the chromanol glycoside for the prevention and the cure of the hindrance of the ischemic reperfusion, however, has not been known.
This invention has been initiated with a view to solving the problems entailed by the prior art mentioned above. An object of this invention is to provide a novel agent for preventing and curing hindrance of ischemic reperfusion, which agent effectively acts at a small dosage without entailing any side reaction and prevents various hindrance induced by the ischemic reperfusion or permits the condition of disease to be alleviated or eliminated.
Another object of this invention is to provide a novel agent for preventing and curing hindrance of ischemic reperfusion, which agent is capable of offering commendable resistance to oxidation and bringing effective repression and control of free radical reactions in the parts of various internal organs affected by the hindrance of ischemic reperfusion.
Still another object of this invention is to provide a novel agent for preventing and curing hindrance of ischemic reperfusion, which agent can be formulated as an aqueous pharmaceutical agent containing an active component at high concentration.
DISCLOSURE OF THE INVENTION
The present inventors have performed diligent studies one after another in search of an agent for preventing and curing hindrance of the ischemic reperfusion and, consequently, have discovered that the chromanol glycoside mentioned above is capable of dramatically preventing and curing morbid alterations of the hindrance of the ischemic reperfusion.
Specifically, this invention concerns an agent for preventing and curing the hindrance of the ischemic reperfusion, which agent has as an active component thereof a chromanol glycoside represented by the following general formula:
[wherein R
1
, R
2
, R
3
, and R
4
independently denote a hydrogen atom or a lower alkyl group, R
5
denotes a hydrogen atom, a lower alkyl group, or a lower acyl group, X denotes a monosaccharide residue or an oligosaccharide residue which may have a lower alkyl group or a lower acyl group substituted for the hydrogen atom of the hydroxyl group of the saccharide residue, n denotes an integer of 0-6, and m denotes an integer of 1-6].
This invention also concerns the agent mentioned above, wherein said chromanol glycoside mentioned above is 2-(&agr;-D-glucopyranosyl) methyl -2,5,7,8-tetramethylchroman-6-ol.
This invention further concerns the agent mentioned above, wherein said hindrance of ischemic reperfusion is a hindrance of small intestinal mucous membrane or a hindrance of cerebral ischemic reperfusion.
This invention also concerns an agent for preventing and curing the hindrance of ischemic reperfusion which is an aqueous pharmaceutical agent.
BEST MODE OF EMBODYING THE INVENTION
The agent of this invention for preventing and curing the hindrance of ischemic reperfusion is characterized by having a chromanol glycoside represented by the general formula (1) mentioned above as an active component.
In the general formula (1) mentioned above, the lower alkyl groups of R
1
, R
2
, R
3
, R
4
and R
5
are favorably to be lower alkyl groups of carbon atoms 1-8, preferably 1-6. As concrete examples of the lower alkyl groups, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group, hexyl group, hyptyl group, and octyl group may be cited. Among other lower alkyl groups mentioned above, methyl group or ethyl group proves particularly advantageous. The lower acyl groups of R
5
are favorably to be lower acyl groups of 1-8, preferably 1-6, carbon atoms. As concrete examples of the lower acyl groups, formyl group, acetyl group, propionyl group, butylyl group, isobutylyl group, valeryl group, isovaleryl group, pivaloyl group, hexanoyl group, heptanoyl group, and octanoyl group may be cited. Among other lower acyl groups mentioned above, acetyl group, propionyl group, or butylyl group proves particularly advantageous. As concrete examples of the monosaccharide residues of X, sugar residues such as glycose, qalactose, fucose, xylose, mannose, rhamnose, fructose, arabinose, lyxose, ribose, allose, altrose, idose, talose, deoxyribose, 2-deoxyribose, quinovose, and abequose may be cited. As concrete examples of the oligosaccharide residues, such sugar residues as maltose, lactose, cellobiose, raffinose, xylobiose, and sucrose which are formed by the union of two to four such monosaccharides as mentioned above. Among other monosaccharide residues mentioned above, glucose, galactose, fucose, xylose, rhamnose, mannose, and fructose prove particularly advantageous. The hydrogen atom of the hydroxyl group in the saccharide residue of X may be substituted for a lower alkyl group, preferably a lower alkyl group of 1-8 carbon atoms, or for a lower acyl group, preferably a lower acyl group of 1-10 carbon atoms. Then, n denotes an integer of 0-6, preferably 1-4, and m denotes an integer of 1-6, preferably 1-3. As preferred examples of the chromanol glycoside represented by the general formula (1), 2-(&agr;-
D
-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, 2-(&bgr;-
D
-galactopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol, 2-(&bgr;-L-fucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol, 2-(&agr;-L-rhamnopyranosyl)-methyl-2,5,7,8-tetramethylchroman-6-ol, 2-(&bgr;-D-xylopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-cl, 2-(&bgr;-
D
-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, 2-(&bgr;-
D
-fructofuranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, and 2-(&agr;-D-mannopyranosyl)methyl-2,
Murase Hironobu
Yoshida Norimasa
Yoshikawa Toshikazu
CCI Corporation
Krass Frederick
Mathews, Collins Shepherd & McKay, P.A.
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