US4100293A
Expired / Lapsed
US
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Treatment of hepatic disorders with therapeutic compositions comprising keto analogs of essential amino acids
Assignee: Johns Hopkins University
•
Filing: 1976-03-23
•
Granted: 1978-07-11
•
Expires: 1996-03-23
Abstract
Abstract Treatment of hepatic disorders, such as are characterized by hyperammonemia and portal-systemic encephalopathy, is advocated using compositions comprising keto analogs of certain essential amino acids. In the preferred embodiments, such compositions comprise the keto analogs of valine, phenylalanine, methionine, leucine and isoleucine.
Inventors
- 👤 Mackenzie Walser
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 03:26
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/41; A61K31/415; A61K38/00; A61K38/01
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
115 words
A composition for improving nitrogen balance in patients having hepatic disorders comprising a mixture in form for oral or parenteral administration to adults suffering from such disorders, said composition consisting essentially of the components in the following approximate proportions by weight: ______________________________________
0.0 to 3.0
grams phenylpyruvic acid; sodium or calcium
salt
4.0 to 8.0
grams alpha-ketoisovaleric acid; sodium
or calcium salt
3.0 to 5.0
grams alpha ketoisocaproic acid; sodium or
calcium salt
0.0 to 3.0
grams alpha-keto-gamma-methylthiobutyric
acid; sodium or calcium salt
2.0 to 4.0
grams alpha-keto-beta-methylvaleric acid;
sodium or calcium salt
˜0 to 0.1
gram L-tryptophan
˜0 to 0.4
gram L-threonine
˜0 to 0.4
gram L-lysine monohydrochloride
1.0 to 4.0
grams L-arginine.
______________________________________
Claim 2
Dependent Claim
115 words
A composition for improving nitrogen balance in patients having hepatic disorders comprising a mixture in form for oral or parenteral administration to adults suffering from such disorders, said composition consisting essentially of the components in the following approximate proportions by weight: ______________________________________
0.0 to 3.0
grams phenylpyruvic acid; sodium or calcium
salt
4.0 to 8.0
grams alpha-ketoisovaleric acid; sodium
or calcium salt
3.0 to 5.0
grams alpha ketoisocaproic acid; sodium or
calcium salt
0.0 to 3.0
grams alpha-keto-gamma-methylthiobutyric
acid; sodium or calcium salt
2.0 to 4.0
grams alpha-keto-beta-methylvaleric acid;
sodium or calcium salt
˜0 to 0.1
gram L-tryptophan
˜0 to 0.4
gram L-threonine
˜0 to 0.4
gram L-lysine monohydrochloride
1.0 to 4.0
grams L-arginine.
______________________________________
Claim 3
Dependent Claim
14 words
A composition as defined in claim 1 which further includes about 0.54 grams L-histidine.
Claim 4
Dependent Claim
23 words
A composition as defined in claim 2 in form for parenteral administration, said composition being in form of a sterilized isotonic aqueous solution.
Claim 5
Independent Claim
59 words
A method for improving nitrogen balance in patients having hepatic disorders which method comprises oral or parenteral administration in effective dosages to subjects on a low protein diet of a composition comprising a mixture of the keto analogs of the branched-chain essential amino acids valine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity.
Claim 6
Independent Claim
59 words
A method for improving nitrogen balance in patients having hepatic disorders which method comprises oral or parenteral administration in effective dosages to subjects on a low protein diet of a composition comprising a mixture of the keto analogs of the branched-chain essential amino acids valine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity.
Claim 7
Independent Claim
111 words
A method for improving nitrogen balance in patients having hepatic disorders which comprises oral or parenteral administration in effective dosage to a subject on a diet of small amounts of protein, a therapeutic composition consisting essentially of the components in the following ranges of proportions by weight: ______________________________________
0.0 to 2.0 parts
phenylpyruvic acid; calcium salt
4.0 to 8.0 parts
alpha-ketoisovaleric acid; calcium salt
3.0 to 5.0 parts
alpha ketoisocaproic acid; calcium salt
0.0 to 3.0 parts
alpha-keto-gamma-methylthiobutyric
acid; calcium salt
2.0 to 4.0 parts
alpha-keto-beta-methylvaleric acid;
calcium salt
˜0 to 0.1 parts
L-tryptophan
˜0 to 0.4 parts
L-threonine
˜0 to 0.4 parts
L-lysine monohydrochloride
1.0 to 4.0 parts
L-arginine
______________________________________
Claim 8
Independent Claim
111 words
A method for improving nitrogen balance in patients having hepatic disorders which comprises oral or parenteral administration in effective dosage to a subject on a diet of small amounts of protein, a therapeutic composition consisting essentially of the components in the following ranges of proportions by weight: ______________________________________
0.0 to 2.0 parts
phenylpyruvic acid; calcium salt
4.0 to 8.0 parts
alpha-ketoisovaleric acid; calcium salt
3.0 to 5.0 parts
alpha ketoisocaproic acid; calcium salt
0.0 to 3.0 parts
alpha-keto-gamma-methylthiobutyric
acid; calcium salt
2.0 to 4.0 parts
alpha-keto-beta-methylvaleric acid;
calcium salt
˜0 to 0.1 parts
L-tryptophan
˜0 to 0.4 parts
L-threonine
˜0 to 0.4 parts
L-lysine monohydrochloride
1.0 to 4.0 parts
L-arginine
______________________________________
Claim 9
Dependent Claim
16 words
A method as defined in claim 5 wherein said composition further includes about 0.54 parts L-histidine.
Claim 10
Dependent Claim
23 words
A method as defined in claim 6 in form for parenteral administration, said composition being in form of a sterilized isotonic aqueous solution.
Claim 11
Dependent Claim
13 words
The method as defined in claim 5 wherein said composition is orally administered.
Claim 12
Independent Claim
74 words
A method for treatment of hyperammonemia which comprises oral or parenteral administration in effective dosages to subjects on a low protein diet of a composition comprising a mixture of the keto analogs of the essential amino acids valine, phenylalanine, methionine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity, said keto analogs being present in the form of the alpha-keto acids per se or salts of the alpha-keto acids.
Claim 13
Independent Claim
74 words
A method for treatment of hyperammonemia which comprises oral or parenteral administration in effective dosages to subjects on a low protein diet of a composition comprising a mixture of the keto analogs of the essential amino acids valine, phenylalanine, methionine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity, said keto analogs being present in the form of the alpha-keto acids per se or salts of the alpha-keto acids.
Claim 14
Dependent Claim
23 words
The method as defined in claim 9 wherein each of the recited analogs is in the form of its calcium or sodium salt.
Claim 15
Dependent Claim
25 words
A method as defined in claim 10 wherein said composition also contains in effective quantities in amino acid form: L-arginine, L-lysine hydrochloride, L-threonine and L-tryptophan.
Claim 16
Dependent Claim
16 words
A method as defined in claim 11 wherein said composition further contains in effective quantity L-histidine.
Claim 17
Dependent Claim
37 words
A method as defined in claim 10 wherein the five recited keto acid analogs are present in said composition in amounts to afford dosages constituting at least the minimum daily requirement of the corresponding essential amino acid.
Claim 18
Dependent Claim
41 words
A method as defined in claim 10 wherein the quantities of the keto acids of valine, leucine and isoleucine are each present in said composition in approximately one and a half to three times by weight that of phenylalanine and methionine.
Claim 19
Dependent Claim
27 words
A method as defined in claim 9 wherein histidine is also present in said composition in effective quantity in the form of its alpha keto acid analog.
Claim 20
Dependent Claim
53 words
A method as defined in claim 9 wherein the five recited keto analogs are present as salts in the weight proportions: 4 to 8 parts valine analog, 3 to 5 parts leucine analog, 2 to 4 parts isoleucine analog, 0.0 to 3.0 parts of methionine analog and 0 to 3 parts phenylalanine analog.
Claim 21
Dependent Claim
19 words
A method as defined in claim 16 wherein said composition is parenterally administered as a sterilized isotonic aqueous solution.
Claim 22
Independent Claim
84 words
A method for treatment of congenital hyperammonemia in children having deficiency of enzymes of the Krebs-Henseleit urea cycle, which method comprises oral or parenteral administration to such patient in effective dosage of a therapeutic composition comprising a mixture of the keto analogs of the essential amino acids valine, phenylalanine, methionine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity, said keto analogs being present in the form of the alpha-keto acids per se or salts of the alpha-keto acids.
Claim 23
Independent Claim
84 words
A method for treatment of congenital hyperammonemia in children having deficiency of enzymes of the Krebs-Henseleit urea cycle, which method comprises oral or parenteral administration to such patient in effective dosage of a therapeutic composition comprising a mixture of the keto analogs of the essential amino acids valine, phenylalanine, methionine, leucine and isoleucine, each of said recited keto analogs being present in effective quantity, said keto analogs being present in the form of the alpha-keto acids per se or salts of the alpha-keto acids.
Claim 24
Dependent Claim
26 words
A method as defined in claim 18 wherein the administration composition also contains in effective quantities in amino acid form: L-arginine, L-lysine hydrochloride, L-threonine, and L-tryptophan.
Claim 25
Dependent Claim
17 words
A method as defined in claim 19 wherein the administration composition further contains in effective quantity L-histidine.
Claim 26
Dependent Claim
68 words
A method as defined in claim 18 wherein the composition is intravenously administered and consists essentially of the following components in proportions by weight: ______________________________________
sodium or calcium alpha-keto-
isovalerate 0.9
sodium or calcium alpha-keto-
isocaproate 1.2
sodium or calcium alpha-keto-beta-
methylvalerate 0.8
sodium or calcium phenylpyruvate
1.2
sodium or calcium alpha-keto-gamma-
methyl thiobutyrate 1.2
L-arginine hydrochloride
2.0
L-histidine 0.2
L-tryptophan 0.1
L-lysine hydrochloride 0.3
L-threonine 0.2
______________________________________
Claim 27
Dependent Claim
67 words
A method as defined in claim 18 wherein the composition is orally administered and consists essentially of the following components in proportions by weight: ______________________________________
sodium or calcium alpha-keto-
isovalerate 0.68
sodium or calcium alpha-keto-
isocaproate 0.94
sodium or calcium alpha-keto-beta-
methylvalerate 0.69
sodium or calcium phenylpyruvate
0.47
sodium or calcium alpha-keto-gamma-
methylthiobutyrate 0.50
lysine hydrochloride 0.20
histidine 0.12
threonine 0.15
tryptophan 0.10
arginine hydrochloride 1.0
______________________________________
Claim 28
Dependent Claim
70 words
The method as defined in claim 18 wherein the composition is intravenously administered to patients having a deficiency in arginase, and consists essentially of the following components in proportions by weight: ______________________________________
sodium or calcium alpha-keto-
isovalerate 0.9
sodium or calcium alpha-keto-
isocaproate 1.2
sodium or calcium alpha-keto-beta-
methylvalerate 0.8
sodium or calcium phenylpyruvate
1.2
sodium or calcium-alpha-keto-gamma-
methylthiobutyrate 1.2
L-histidine 0.2
L-tryptophan 0.1
L-lysine hydroclhoride 0.3
L-threonine 0.2
______________________________________
Claim 29
Dependent Claim
71 words
The method as defined in claim 18 wherein the composition is orally administered to patients having a deficiency in arginase, and consists essentially of the following components in proportions by weight: ______________________________________
sodium or calcium alpha-keto-
0.68
isovalerate
sodium or calcium alpha-keto-
isocaproate 0.94
sodium or calcium alpha-keto-beta-
methylvalerate 0.69
sodium or calcium phenylpyruvate
0.47
sodium or calcium alpha-keto-gamma-
methylthiobutyrate 0.50
lysine hydrochloride 0.20
histidine 0.12
threonine 0.15
tryptophan 1.0
______________________________________
Claim 30
Independent Claim
47 words
A method for treatment of congenital hyperammonemia in children having deficiency of enzymes of the Krebs-Henseleit urea cycle, which method comprises oral or parenteral administration to such patient in effective dosage a therapeutic composition comprising the calcium salts of the keto analogs of valine, leucine and isoleucine.
Claim 31
Independent Claim
47 words
A method for treatment of congenital hyperammonemia in children having deficiency of enzymes of the Krebs-Henseleit urea cycle, which method comprises oral or parenteral administration to such patient in effective dosage a therapeutic composition comprising the calcium salts of the keto analogs of valine, leucine and isoleucine.
References Cited (Backward Citations)
US2457820A
Cited
US3764703A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-07-10 | 1982-01-09 | 1982-07-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-07-10 | 1986-01-09 | 1986-07-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-07-10 | 1990-01-09 | 1990-07-11 | $7700.00 | Window Closed / Lapsed |