IL42726A - Composition for promotion of protein synthesis and suppression of urea formation in the body - Google Patents

Composition for promotion of protein synthesis and suppression of urea formation in the body

Info

Publication number
IL42726A
IL42726A IL4272673A IL4272673A IL42726A IL 42726 A IL42726 A IL 42726A IL 4272673 A IL4272673 A IL 4272673A IL 4272673 A IL4272673 A IL 4272673A IL 42726 A IL42726 A IL 42726A
Authority
IL
Israel
Prior art keywords
parts
alpha
sodium
acid
composition
Prior art date
Application number
IL4272673A
Original Assignee
Mackenzie Walser
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mackenzie Walser filed Critical Mackenzie Walser
Publication of IL42726A publication Critical patent/IL42726A/en

Links

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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles

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)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

Composition for promotion of protein synthesis and suppression of urea formation in the body 42726/2 The invention generally relates to a therapeutic composition of matter. Particularly, the several embodiments of the invention provide compositions for treatment of renal disorders, such as uremia, for treatment of hepatic diseases, such as hyperammonemia and portal-systemic encephalopathy, and for alleviating the effects of dietary protein deprivation. . r or art treatrcaa,.
Protein deprivation due to dietary deficiency is most easily treated by introduction of adequate protein to the diet. In instances, either economic or otherwise, where such a course proves impractical, the present invention may be used to reduce protein requirements by diverting nitrogen precursors in the body away from urea formation (urea is excreted, resulting in bodily protein loss) by combination, of these precursors with keto-acid analogs of essential amino acids to form the amino acids.
SUMMARY OF THE INVENTION The present invention provides a composition of matter and a mot4¾od for promoting protein synthesis and suppressing urea formation in the human body, certain embodiments of the composition of matter and of the method being applicable to medicinal treatment of both renal and hepatic disorders and to treatment of dietary protein deficiencies. The present composition of matter comprises keto-acid analogs of certain essential amino acids. Oral or intravenous administration of these keto-acids acts as a treatment for renal failure by promoting protein synthesis in the blood stream, thereby resulting in suppression of urea breakdown which correspondingly reduces the tendency of the liver to form urea. Contrary to the prior art prediction that a high urea breakdown rate would facilitate the use of keto-acids in the body, the present invention demonstrates that urea breakdown actually impedes the use of keto-acids. The reduction of urea breakdown tends to reduce the net rate of urea-nitrogen appearance in the body, thereby pointing to the use of one embodiment of the present composition of matter to reduce urea breakdown in the body so as to minimize the rate of urea formation by the liver. Thus, renal disorders, such as uremia, may be controlled in certain instances without dialysis or as a supplement thereto.
Treatment of hepatic disorders through the use of the compositions of the present invention also calls for the effective suppression of urea formation in the body due to the combination of nitrogen-containing urea precursors, such as ammonia, with the keto-acid analogs of certain essential amino acids. This process results both in the formation of the essential amino acids via synthesis of the keto-acid analogs thereof with ammonia in normal muscle tissue and in the reduction of ammonia in the blood stream, both being highly desirable objects in the treatment of hepatic disorders. This synthesis in normal muscle tissue as now understood provides a basis for use of the present invention as a treatment for hepatic disorders wherein the liver is incapable of performing such a metabolic function.
The invention is further applied to treatment of dietary protein deficiencies by reducing protein requirements. Conversion of the keto-acid analogs of certain essential amino acids in the body suppresses urea formation by diverting nitrogenous precursors of urea away from urea formation through combination of said precursors with the keto-acids to form amino acids. Urea formed in the body is normally excreted, thereby resulting in a systematic loss of elementary protein components. Reduction of this loss of urea coupled with conversion of said nitrogenous ; urea precursors to avialable amino acids allows bodily conservation of protein without toxic effects.
It is therefore an object of the invention to provide a composition of matter for promoting protein synthesis and suppressing urea formation in the human body.
It 1s another object of the Invention to provide a pharmaceutical composition adapted for medicinal treatment of renal and hepatic disorders and treat ment of dietary protein deficiencies. - 4a -

Claims (9)

42726/2 CLAIMS t
1. A composition for promoting protein synthesis and suppressing urea formation in the body and adapted for oral or parenteral administration to human subjects comprising a mixture of (a) the alpha-keto acid analogs of valine, phenylalanine, methionine, leucine and isoleucine or the calcium or sodium salts thereof; (b) the amino acids as such of L-tryptophan, L-threonine and L-lysine or the hydrochloride salt thereof, or the alpha-keto acid analogs of the amino acids, if available, or the calcium or sodium salts of the analogs.
2. The composition of claim 1 wherein said analog of phenylalanine is present as phenylpyruvic acid.
3. The composition of claim 1 further containing L-histidine or the alpha-keto acid analog of L-histidine, if available, or the calcium or sodium salts of the analog,
4. The composition of Claim 1 further containing L-arginine or the alpha-keto acid analog of L-arginine, if available, or the calcium or sodium salts of the analog.
5. The composition of claim 1 wherein the constituents of the mixture are present therein in amounts ranging , between one and one and a half times the minimum daily requirement thereof.
6. The composition of claim 1 wherein the alpha-keto acids are present therein in the form of the sodium salts.
7. The composition of claim 1 wherein the alpha-keto acids are present therein in the form of the calcium salts. 42726/2
8. The composition of Claim 1/adapted for oral or parenteral administration to human subjects in the treatment of renal disorders comprising in admixture by weight: a) about 1.5 2.5 parts phenylpyruvic acid or the sodium or calcium salt thereof; b) about 2.0 4.0 parts alpha-ketoisovaleric acid or the sodium or calcium salt thereof; c) about 3.0 5.0 parts alpha-ketoisocaproic acid or the sodium or calcium salt thereof; d) about 2.5 3.5 parts alpha-keto-beta-methylvaleric acid or the sodium or calcium salt thereof ; e) about 1.5 - 2.5 parts alpha-keto-gamma-methylthiobutyric acid or the sodium or calcium salt thereof ; f) about 0.54 parts L-histidine; g) about 0.8 parts L-lysine monohydrochloride; h) about 0.5 parts L-threonine ; and i) about 0.25 parts L-tryptophan.
9. The composition of claim 1 dapted for oral or parenteral administration to human subjects in the treatment of hepatic disorders, comprising in admixture by weight: a) about 1.0 - 2.0 parts phenylpyruvic acid or the sodium or calcium salt thereof; b) about 4.0 - 8.0 parts alpha-ketoisovaleric acid or the sodium or calcium salt thereof; c) about 3.0 - 5.0 parts alpha-ketoisocaproic acid or the sodium or calcium salt thereof; d) about 4.0 - 6.0 parts alpha-keto-gamma-methylthiobutyric acid or the sodium or calcium salt thereof ; 42726/2 *<» β) about 0.8 - 1.5 parts alpha-keto-beta-methylvaleric acid or the sodium or calcium salt thereof; £) about 0.1 parts L-tryptophan; g) about 0.4 parts L-threonine; h) about 0.4 parts L-lysine monohydrochloride; and i) about 1.0 - 4.0 parts L-arginine.
IL4272673A 1972-07-13 1973-07-12 Composition for promotion of protein synthesis and suppression of urea formation in the body IL42726A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US27098672A 1972-07-13 1972-07-13
US35532773A 1973-04-30 1973-04-30

Publications (1)

Publication Number Publication Date
IL42726A true IL42726A (en) 1977-10-31

Family

ID=26954620

Family Applications (1)

Application Number Title Priority Date Filing Date
IL4272673A IL42726A (en) 1972-07-13 1973-07-12 Composition for promotion of protein synthesis and suppression of urea formation in the body

Country Status (5)

Country Link
JP (1) JPS4950121A (en)
CA (1) CA1027478A (en)
DE (1) DE2335215B2 (en)
FR (1) FR2226993A1 (en)
IL (1) IL42726A (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2530246A1 (en) * 1975-07-07 1977-01-13 Fresenius Chem Pharm Ind L-AMINO ACID MIXTURES FOR PARENTERAL OR ORAL USE
DE2531299A1 (en) * 1975-07-12 1977-01-13 Fresenius Chem Pharm Ind MIXTURES CONTAINING L-AMINO AND HYDROXY AND / OR KETO ACIDS FOR PARENTERAL OR ORAL USE
DE2636828A1 (en) * 1976-08-16 1978-02-23 Fresenius Chem Pharm Ind (L)-Aminoacid mixt. for treating liver insufficiency - contains isoleucine, leucine, lysine, methionine and cysteine or cystine and non-essential aminoacid(s)
SE7806692L (en) * 1977-07-01 1979-01-02 Pfizer USE FOR MEDICAL PURPOSES OF CERTAIN PHENYLGYLOXAL ACIDS, ESTERS AND SALTS THEREOF
US4228099A (en) * 1978-03-17 1980-10-14 The Johns Hopkins University Ornithine and arginine salts of branched chain keto acids and uses in treatment of hepatic and renal disorders
US4320146A (en) 1978-03-17 1982-03-16 The Johns Hopkins University Treatment of hepatic and renal disorders with ornithine and arginine salts of branched chain keto acids
US4296127A (en) * 1979-04-18 1981-10-20 The Johns Hopkins University Mixed salts of essential or semi-essential amino acids and nitrogen-free analogs thereof
US4752619A (en) * 1985-12-23 1988-06-21 The Johns Hopkins University Nutritional supplement for treatment of uremia
SE8803143L (en) * 1988-09-07 1990-03-08 Kabivitrum Ab ALTERNATIVE ENERGY SUBSTRATE
DE3936319C3 (en) * 1989-11-01 1997-05-07 Bartz Volker Phosphate binder for oral administration
DE3940052A1 (en) * 1989-12-04 1991-06-06 Nephro Medica Pharma DIALYSIS AND SPOOL SOLUTION FOR INTRAPERITONEAL ADMINISTRATION
DE3943424A1 (en) * 1989-12-30 1991-07-04 Nephro Medica Pharma Solns. for intravenous nutrition - contg. alpha-keto acids, for patients with kidney conditions, avoids nitrogen cpd. build-up
WO2012143405A1 (en) * 2011-04-18 2012-10-26 Nestec S.A. Nutritional compositions having alpha-hica and alpha-ketoglutarate

Also Published As

Publication number Publication date
DE2335215A1 (en) 1974-01-31
FR2226993A1 (en) 1974-11-22
CA1027478A (en) 1978-03-07
DE2335215B2 (en) 1979-04-05
AU5794173A (en) 1975-01-16
JPS4950121A (en) 1974-05-15
FR2226993B1 (en) 1977-07-08

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