Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1992-01-29
1993-12-21
Waddell, Frederick E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514574, A61K 3123, A61K 3119
Patent
active
052721779
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of sebacic acid and pharmacologically acceptable sebacic acid derivatives in enteral and parenteral nutrition.
According to the present invention, by "pharmacologically acceptable sebacic acid derivatives" the following compounds are meant: the pharmacologically acceptable salts, particularly the alkaline metal salts, preferably the sodium and potassium salts, the sebacic acid triglyceride and the pharmacologically acceptable salts thereof, preferably the sodium and potassium salts. The sodium and potassium salts of the sebacic acid triglycerides are novel compounds.
In clinical practice, whereas lipid emulsions of triglycerides of long chain monocarboxylic fatty acids have been in general use for total parenteral nutrition for a number of years, only recently the use of some medium chain triglycerides has met with satisfactory results. However, these emulsions suffer from serious drawbacks. Indeed, in some frequently occurring pathological conditions, such as sepsis, conflicting experimental evidences do exist as to the effectively viable utilization of long chain triglycerides. Supposedly, this impaired utilization would be caused by a relative deficiency of carnitine which, in turn, would bring about an impaired mitochondrial oxidation of long chain fatty acids. Further experimental evidences suggest that high doses of medium chain triglycerides administered to experiment animals wherein ketoacidosis had been induced can bring about toxic effects encompassing narcosis. It is, therefore, felt the need of relying on substrates other than those used to-date.
It has now been found that sebacic acid and the afore-said pharmacologically acceptable derivatives thereof are an excellent substrate for manufacturing compositions suitable for enteral and parenteral nutrition, which do not present the drawbacks of the known substrates.
The present invention provides, therefore, pharmaceutical compositions suited for enteral and parenteral administration characterized in that they comprise, as active principle, sebacic acid or a derivative thereof. Particularly, the sebacic acid derivative is selected from the pharmacologically acceptable sebacic acid salts, the sebacic acid triglyceride and the pharmacologically acceptable salts of the sebacic acid triglyceride. Preferably, the pharmacologically acceptable salt of sebacic acid or sebacic acid triglyceride is selected from the sodium and the potassium salts.
The pharmaceutical compositions, when they are formulated as aqueous solutions, comprise from 0.2 to 0.6 moles/liter of a pharmacologically acceptable salt of sebacic acid or from 0.2 to 1 moles/liter of sebacic acid triglyceride or a pharmacologically acceptable salt of sebacic acid triglyceride. Preferably, they comprise 0.5 moles/liter of salt, triglyceride or triglyceride salt of sebacic acid.
The orally administrable compositions in unit dosage form, e.g. capsules, comprise from 0.5 to 1.5 grams of salt, trigliceride or triglyceride salt of sebacic acid.
Sodium and potassium sebacate are prepared by neutralization of sebacic acid (C10) with NaOH or KOH (molar ratio OH-:C10 2:1).
In order to prepare the sodium and potassium salts of sebacic acid triglyceride, sebacic acid is added to thionyl chloride (b.p. 79.degree. C.) in dioxane freshly distilled over lithium and aluminum hydroxide (molar ratio C10:thionyl chloride 1:2), keeping the resulting mixture at the reflux temperature for 5-6 hours in the presence of cesium chloride as catalyst. By removing dioxane under vacuum the acid chloride of sebacic acid is obtained.
The triglyceride is dissolved in distilled water in the presence of small amounts of magnesium as catalyst and NaOH to maintain the solution pH at about 8 and to form, by reacting with HCl that frees from the esterification reaction, NaCl and H.sub.2 O when C10 acid chloride is added to the reaction mixture.
To this aqueous solution, an excess amount of C10 acid chloride dissolved in dioxane (5-8 times the glycerol amount, lest the polymerization of the c
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Henley III Raymond J.
Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.
Waddell Frederick E.
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