Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-07-19
1998-04-14
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
A61K 3170
Patent
active
057391173
DESCRIPTION:
BRIEF SUMMARY
TECHNOLOGICAL ASPECT
This invention provides an agent for improving cerebral metabolism, including glucose ester derivatives (glucose pyranose derivatives), which is excellent in penetrating activity across the blood-brain barrier.
BACKGROUND
Transport from blood to the cerebral tissue of substances necessary for the maintenance of cerebral function is extremely impeded by the blood-brain barrier. Glucose, which is a sole and very important energy source for the cerebral tissue, is therefore, no exception as reported by Goldstein (Scientific America., 254:74-83, 1986). The supply of glucose from blood to inside of brain is controlled by carrier proteins which are specific for the blood-brain barrier, through their selective and active transport from the outside of the barrier to the cerebral tissue. Glucose transported to the cerebral tissue, is metabolized by hexokinase to glucose-6-phosphate, which is a very important intermediate in glucose catabolism system, and then entered into a metabolic pathway where it is degraded up to an end product of the energy generating system while generating simultaneously with high energy-phosphoric compounds such as ATP through its linked phosphorylation reaction under influence of oxidation, decarboxylation and other reactions.
Approximately 20% of the total oxygen consumption in the body takes place in the brain where a large amount of glucose is concomitantly consumed. In the cerebral tissue, however, there is no sugar storage in the form of glycogen, and therefore, the brain is liable to fall into a state of energy metabolism dysfunction within a short time when glucose supply is disturbed due to blood hypoglycemia or to a decrease in the capacity of the blood-brain barrier transport, the conditions of which are just similar to those of respiratory or circulation disorders.
In an acute situation, disorders appear first in an metabolically active tissue site with the highest sugar consumption, then to the next site in an order of sugar consumption degrees. A cerebrum dysfunction starts at a blood sugar level lower than 60 mg/dl, and hypoglycemic coma may be caused when its level becomes lower than 20 mg/dl. In this case, 50% of human subjects will die unless they get an improvement in the cerebral energy metabolic disorder within 5 minutes. Even if survived, they may suffer from sequela such as dementia and a vegetable state depend on the degree of disorder. Similar to brain hypoxia, an irreversible neuronal symptom is known to progress in some cases even afer revival from coma as a result of regressive degeneration due to delayed cell death following excess release of glutamic acid and elicitation of a calcium concentration increase in neuronal cells, particularly when the coma state prolonged or spasm occurred repeatedly.
The current treatment that has been considered best for cerebral disorders resulting from hypoglycemic shock and disturbance in consciousness associated with diabetic hypoglycemia is oral or intravenous administration of glucose. This therapy method has been widely exercised. This treatment can raise a blood sugar level immediately. However, since glucose per se cannot cross the barrier, glucose needs to be captured first by carrier proteins and then subjected to an active and selective transport together with its carrier through the blood-brain barrier into cerebral tissues. Because of this fact, a time-lag of a few minutes is inevitable between administration of glucose and attainment of a sufficient concentration of glucose at a site of the cerebral tissue. This detriment in glucose administration has remained to be solved, since supply of energy source at a sufficient level to the cerebral tissue of these patients must be carried out as urgently as possible.
In the same token as above, a decreased capacity in the active transport of glucose at the blood-brain barrier due to aging or cerebral disorders can result in reducing cerebral metabolic functional competence and causing necrosis of the cerebral tissue. Thereby, the administration of
REFERENCES:
patent: 5374716 (1994-12-01), Biermann et al.
Yokoyama Akira
Yoneda Fumio
Fujimoto Pharmaceutical Co., Ltd.
Peselev Elli
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