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US4100160A
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Therapeutic compositions comprising alpha-hydroxy analogs of essential amino acids and their administration to humans for promotion of protein synthesis and suppression of urea formation
Assignee: Johns Hopkins University
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Filing: 1976-03-23
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Granted: 1978-07-11
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Expires: 1996-03-23
Abstract
Abstract Compositions containing the hydroxy analogs of certain essential amino acids are formulated for therapeutic use, particularly in the treatment of renal disorders, hepatic failure and conditions of protein wasting in human subjects. In preferred embodiments, keto analogs of certain essential amino acids are used in combination with hydroxy analogs of other essential amino acids.
Inventors
- 👤 Mackenzie Walser
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 15:04
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/185; A61K31/19
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
106 words
A composition capable of promoting protein synthesis and conserving nitrogen in a patient in need thereof, said composition being in the form of a mixture adapted for oral or parenteral administration to subjects on a protein-restricted diet, said composition being substantially devoid of non-essential amino acids, and said composition comprising a mixture of effective quantities of hydroxy-acid and/or keto-acid analogs of the essential amino acids valine, phenylalanine, isoleucine, leucine and methionine, at least one of said analogs of essential amino acids being hydroxy-acid analogs, said hydroxy-acid or keto-acid analogs being present in the form of the acid analogs per se or salts of the acid analogs.
Claim 2
Dependent Claim
106 words
A composition capable of promoting protein synthesis and conserving nitrogen in a patient in need thereof, said composition being in the form of a mixture adapted for oral or parenteral administration to subjects on a protein-restricted diet, said composition being substantially devoid of non-essential amino acids, and said composition comprising a mixture of effective quantities of hydroxy-acid and/or keto-acid analogs of the essential amino acids valine, phenylalanine, isoleucine, leucine and methionine, at least one of said analogs of essential amino acids being hydroxy-acid analogs, said hydroxy-acid or keto-acid analogs being present in the form of the acid analogs per se or salts of the acid analogs.
Claim 3
Dependent Claim
30 words
A composition as defined in claim 1 wherein the hydroxy-acid analogs are present as the L-hydroxy form, except the hydroxy-acid analog of methionine which is present as the D, L-form.
Claim 4
Dependent Claim
27 words
A composition as defined in claim 1 wherein the mixture does not contain both the hydroxy-acid analog and the keto-acid analog of the same essential amino acid.
Claim 5
Dependent Claim
24 words
A composition as defined in claim 1 containing the hydroxy-acid analogs of methionine, phenylalanine and isoleucine and the keto-acid analogs of valine and leucine.
Claim 6
Dependent Claim
21 words
A composition as defined in claim 1 wherein said analogs are present as calcium or sodium salts of the acid analogs.
Claim 7
Dependent Claim
26 words
A composition as defined in claim 5 wherein said composition also contains in effective quantities in amino acid form L-lysine hydrochloride or acetate, L-threonine and L-tryptophan.
Claim 8
Dependent Claim
13 words
A composition as defined in claim 6 further containing in effective quantity L-histidine.
Claim 9
Dependent Claim
13 words
A composition as defined in claim 6 further containing in effective quantity L-arginine.
Claim 10
Dependent Claim
31 words
A composition as defined in claim 1 wherein the recited analogs are present in amounts to afford dosages constituting at least the minimum daily requirement of the corresponding essential amino acid.
Claim 11
Dependent Claim
32 words
A composition as defined in claim 1 wherein the quantities of the analogs of valine, leucine and isoleucine are each present in approximately 2 to 3 times that of phenylalanine and methionine.
Claim 12
Dependent Claim
23 words
A composition as defined in claim 1 wherein tryptophan is also present in effective quantity in the form of its alpha-keto acid analog.
Claim 13
Dependent Claim
23 words
A composition as defined in claim 1 wherein histidine is also present in effective quantity in the form of its alpha-keto acid analog.
Claim 14
Dependent Claim
49 words
A composition as defined in claim 1 wherein the five recited analogs are present as salts in the weight proportions: 2 to 4 parts valine analog, 3 to 5 parts leucine analog, 2.5 to 3.5 parts isoleucine analog, 1.5 to 2.5 parts each of methionine analog and phenylalanine analog.
Claim 15
Dependent Claim
21 words
A composition as defined in claim 13 wherein said components are present in a sterilized isotonic aqueous solution for parenteral administration.
Claim 16
Dependent Claim
96 words
A composition for treatment of uremia resulting from renal disorders comprising a mixture in form for oral or parenteral administration to subjects on a protein-restricted diet, said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenylpyruvate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate; 1.5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; 2.5-3.5 parts racemic sodium or calcium alpha-keto-beta-methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 17
Dependent Claim
96 words
A composition for treatment of uremia resulting from renal disorders comprising a mixture in form for oral or parenteral administration to subjects on a protein-restricted diet, said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenylpyruvate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate; 1.5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; 2.5-3.5 parts racemic sodium or calcium alpha-keto-beta-methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 18
Dependent Claim
70 words
A composition for treatment of uremia resulting from renal disorders comprising a mixture in form for oral or parenteral administration to subjects on a protein-restricted diet, said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium L-phenyllacetate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 2.5-3.5 parts sodium or calcium alpha keto or L-alpha hydroxy-beta-methylvalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate;
Claim 19
Dependent Claim
70 words
A composition for treatment of uremia resulting from renal disorders comprising a mixture in form for oral or parenteral administration to subjects on a protein-restricted diet, said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium L-phenyllacetate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 2.5-3.5 parts sodium or calcium alpha keto or L-alpha hydroxy-beta-methylvalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate;
Claim 20
Dependent Claim
29 words
5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 21
Dependent Claim
29 words
5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 22
Independent Claim
98 words
A method for promoting protein synthesis and conserving nitrogen in a patient in need thereof which method comprises orally or parenterally administering in effective dosages to subjects on a protein-restricted diet a composition substantially devoid of non-essential amino acids, said composition comprising a mixture of effective quantities of hydroxy-acid and/or keto-acid analogs of the essential amino acids valine, phenylalanine, isoleucine, leucine and methionine, at least one of said analogs of essential amino acids being hydroxy-acid analogs, said hydroxy-acid or keto-acid analogs being present in the form of the acid analogs per se or salts of the acid analogs.
Claim 23
Independent Claim
98 words
A method for promoting protein synthesis and conserving nitrogen in a patient in need thereof which method comprises orally or parenterally administering in effective dosages to subjects on a protein-restricted diet a composition substantially devoid of non-essential amino acids, said composition comprising a mixture of effective quantities of hydroxy-acid and/or keto-acid analogs of the essential amino acids valine, phenylalanine, isoleucine, leucine and methionine, at least one of said analogs of essential amino acids being hydroxy-acid analogs, said hydroxy-acid or keto-acid analogs being present in the form of the acid analogs per se or salts of the acid analogs.
Claim 24
Dependent Claim
25 words
A method as defined in claim 17 wherein said composition also contains in effective quantities in amino form: L-lysine hydrochloride or acetate, L-threonine and L-tryptophan.
Claim 25
Dependent Claim
20 words
A method as defined in claim 18 wherein said composition also contains in effective quantity in amino acid form L-histidine.
Claim 26
Dependent Claim
16 words
A method as defined in claim 18 wherein said composition also contains in effective quantity L-arginine.
Claim 27
Dependent Claim
34 words
A method as defined in claim 17 wherein the recited 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 28
Dependent Claim
35 words
A method as defined in claim 17 wherein the quantities of the analogs of valine, leucine and isoleucine are each present in said composition in approximately two to three times that of phenylalanine and methionine.
Claim 29
Dependent Claim
48 words
A method as defined in claim 17 wherein the five recited analogs are present in the weight proportions: 2 to 4 parts valine analog, 3 to 5 parts leucine analog, 2.5 to 3.5 parts isoleucine analog, 1.5 to 2.5 parts each of the analogs of methionine and phenylalanine.
Claim 30
Dependent Claim
19 words
A method as defined in claim 17 wherein said composition is parenterally administered as a sterilized isotonic aqueous solution.
Claim 31
Independent Claim
74 words
A method for treatment of uremia resulting from renal disorders which comprises oral or parenteral administration in effective dosages to a subject on a diet of restricted amounts of protein of a therapeutic composition substantially devoid of non-essential amino acid; said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenylpyruvate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate;
Claim 32
Independent Claim
74 words
A method for treatment of uremia resulting from renal disorders which comprises oral or parenteral administration in effective dosages to a subject on a diet of restricted amounts of protein of a therapeutic composition substantially devoid of non-essential amino acid; said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenylpyruvate; 2.0-4.0 parts sodium or calcium alpha-keto isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate;
Claim 33
Dependent Claim
37 words
5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; 2.5-3.5 parts sodium or calcium racemic alpha-keto-beta methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 34
Dependent Claim
37 words
5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate; 2.5-3.5 parts sodium or calcium racemic alpha-keto-beta methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 35
Dependent Claim
37 words
The method as defined in claim 25 wherein the defined composition is intravenously administered to patients suffering from severe uremic syndrome for the purpose of diminishing the rate of urea formation in the liver of such patients.
Claim 36
Dependent Claim
14 words
The method as defined in claim 25 wherein the defined composition is orally administered.
Claim 37
Independent Claim
79 words
A method for treatment of uremia resulting from renal disorders which comprises oral or parenteral administration in effective dosages to a subject on a diet of restricted amounts of protein or a therapeutic composition substantially devoid of non-essential amino acid; said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenyllactate; 2.0-4.0 parts sodium or calcium alpha-keto-isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate; 1.5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate;
Claim 38
Independent Claim
79 words
A method for treatment of uremia resulting from renal disorders which comprises oral or parenteral administration in effective dosages to a subject on a diet of restricted amounts of protein or a therapeutic composition substantially devoid of non-essential amino acid; said composition consisting essentially of the components in the following ranges of proportions by weight: 1.5-2.5 parts sodium or calcium phenyllactate; 2.0-4.0 parts sodium or calcium alpha-keto-isovalerate; 3.0-5.0 parts sodium or calcium alpha-keto-isocaproate; 1.5-2.5 parts sodium or calcium D,L-alpha-hydroxy-gamma-methyl-thiobutyrate;
Claim 39
Dependent Claim
28 words
5-3.5 parts L-(R,S)-alpha-hydroxy- or R,S-alpha-keto-beta-methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 40
Dependent Claim
28 words
5-3.5 parts L-(R,S)-alpha-hydroxy- or R,S-alpha-keto-beta-methylvalerate; about 0.5 parts of L-histidine; about 0.8 parts of L-lysine hydrochloride or acetate; about 0.5 parts of L-threonine; about 0.25 parts of L-tryptophan.
Claim 41
Dependent Claim
14 words
The method as defined in claim 28 wherein the defined composition is intravenously administered.
Claim 42
Dependent Claim
14 words
The method as defined in claim 28 wherein the defined composition is orally administered.
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 |