Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof

Definitions

• the present invention has as the object to provide a new therapeutic use of a known drug, namely pyridoxine 5-oxo-2-pyrrolidone carboxylate, also known as 5-hydroxy-6-methyl-3,4-pyridinemethanol 5-oxo-2-pyrrolidone carboxylate of the formula:
• Pyridoxine known also under the name of B6 vitamin, finds several therapeutic uses, among which the treatment of acute alcoholic intoxication states has been proposed in the past. However, this therapeutic indication has been subsequently abandoned, since it did not receive experimental confirmation.
• the compound of the present invention finds also application in treating acute alcoholic intoxication caused by ethyl alcohol (Italian Patent No.
• the object of this invention is a novel therapeutic use of the same compound, i.e. pyridoxine 5-oxo-2-pyrrolidone carboxylate.
• Free fatty acids and esters thereof have important effects in the human organism and, particularly, several negative or harmful effects, due to their accumulation in tissues, such as heart, brain, kidney, liver and plasma, have been noted.
• liver As far as liver is concerned, for example, they are responsible of the so-called steatosis.
• the ethyl esters of free fatty acids are, in turn, one of the main metabolites of the acids themselves and tend to accumulate in concentrations that might reach levels up to 100 micromoles in the myocardium, with a half life of nearly 16 hrs. This means that they persist at tissue level even after the factors promoting these accumulations are eliminated, as, for example, the ethyl alcohol action.
• the free fatty acids esterification represents a vehicle of toxic states.
• 5-oxo-2-pyrrolidone carboxylate as active principle for inhibiting the free fatty acid ethyl esters, the therapeutic treatment including the active principle administration in oral dosages from 250 mg/day to 2500 mg/day, and in parenteral dosages from 250 mg/day to 1500 mg/day.
• Wistar rats of 250-300 g weight have been randomly divided in groups of six animals each.
• the first group of animals was orally administered with a 20% ethanol solution at a
• the second group was administered as the first group, except that each day, for all the seven days of the parenteral treatment, received 60 mg/kg of pyridoxine pyrrolidone carboxylate in crystalline form, 30 minutes before the ethanol solution was administered.
• the third group was used as a control group and was administered with a physiological solution.
• Tables 1 and 2 report the measuring data of fatty acid ethyl ester, obtained in vivo. in the heart, plasma, liver, kidney and brain, respectively.
• the heart is the organ showing the highest levels of ethyl esters (6.96 nmoles of total esters/mg of proteins).
• Stearate, linoleate, linolenate and arachidonate are the mostly present chemical species of ethanol esterified fatty acids.
• the analyzed organs showed the following sequence: heart - kidney - brain - plasma - liver
• the treatment with the active principle of the invention produces a significant reduction of the contents of total esters formed, particularly in the kidney, brain, heart and plasma (80-60%).
• Table 3 shows the effect of ethanol solution administration on the
• the activity of this enzyme appears to be strengthened by the ethanol administration in the liver, kidney, heart and, particularly, in the • brain
• DCNB-GSH TRASFERASE nmoles / min / mg protein
• Table 4 illustrates the effect of the ethanol administration on the activity decrease of the GSH reductase, which occurs in all tested organs, except for brain, where it is found to be strengthened.
• the administration of this active principle by the normal administration means and known dosages for normal uses is to be suggested, when the free fatty acid ester formation, accumulation of the acids themselves and alteration of enzymatic functions bound to said free fatty acid action, such as GSH-S-transferase and GSH-reductase, must be controlled and compensated for.
• the preparation of the pharmaceutical compositions using the active principle of this invention and dosages thereof reference is made to the already known pharmaceutical compositions for the control and therapy of acute alcoholic intoxication.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Pyridine Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=11365120

Family Applications (1)

Country Status (3)

Cited By (13)

Citations (1)

• 1993
  • 1993-02-23 IT ITMI930341A patent/IT1263957B/it active IP Right Grant
  • 1993-05-22 TW TW082104060A patent/TW230749B/zh not_active IP Right Cessation
• 1994
  • 1994-02-19 WO PCT/EP1994/000518 patent/WO1994018965A1/en not_active Ceased

Patent Citations (1)

Non-Patent Citations (7)

Also Published As

Similar Documents

Legal Events