Amino acid solutions for parenteral nutrition and methods of formulation and use

Claim 3

A method according to claim 1, wherein said amino acid content consists essentially of ______________________________________ 1.34-2.19 mM/dl L-threonine 3.03-3.61 " L-valine 3.62-7.04 " L-leucine 2.12-4.12 " L-isoleucine 0.78-4.82 " L-lysine 0.62-1.66 " L-methionine 0-3.00 " L-cysteine 0.59-2.63 " L-histidine 1.07-1.83 " L-phenylalanine 0.33-1.32 " L-tyrosine 0.25-0.98 " L-tryptophan 1.75-5.25 " L-arginine 0.91-2.71 " L-serine 1.48-4.42 " L-proline 1.92-2.88 " glycine 1.50-4.50 " L-alanine 0-2.40 " L-aspartic acid 0.85-2.55 " L-glutamic acid. ______________________________________

Claim 4

A method according to claim 1, wherein said amino acid content consists essentially of ______________________________________ 1.03-1.69 mM/dl L-threonine 3.45-4.13 " L-valine 5.47-10.63 " L-leucine 1.76-3.42 " L-isoleucine 1.07-6.55 " L-lysine 0.58-1.58 " L-methionine 0-3.00 " L-cysteine 0.43-1.85 " L-histidine 1.10-1.88 " L-phenylalanine 0-0.44 " L-tyrosine 0.20-0.80 " L-trypotophan 1.46-4.36 " L-arginine 0.88-2.62 " L-serine 1.12-3.38 " L-proline 2.96-4.44 " glycine 1.56-4.66 " L-alanine 0-1.36 " L-aspartic acid 0.37-1.11 " L-glutamic acid. ______________________________________

Claim 5

A method according to claim 1, wherein said amino acid content consists essentially of ______________________________________ 2.02-3.30 mM/dl L-threonine 3.17-3.79 " L-valine 4.17-8.09 " L-leucine 1.83-3.55 " L-isoleucine 0.41-2.51 " L-lysine 0.55-1.49 " L-methionine 0-3.00 " L-cysteine 1.28-5.48 " L-histidine 1.23-2.09 " L-phenylalanine 0.35-0.75 " L-tyrosine 0.20-0.80 " L-tryptophan 2.26-6.76 " L-arginine 0.81-2.43 " L-serine 1.06-3.18 " L-proline 2.46-3.70 " glycine 1.30-3.90 " L-alanine 0-1.20 " L-aspartic acid 0.31-0.93 " L-glutamic acid. ______________________________________

Claim 6

A method according to claim 1, wherein said solution has a molar ratio of total essential amino acids to total amino acids between about 0.58 and about 0.65.

Claim 9

An amino acid solution for parenteral nutrition comprising an aqueous solution of amino acids wherein the amino acid content consists essentially of ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 mM/dl L-valine 3.62-10.63 mM/dl L-leucine 1.76-4.12 mM/dl L-isoleucine 0.41-6.55 mM/dl L-lysine 0.55-1.66 mM/dl L-methionine 0-3.00 mM/dl L-cysteine 0.43-5.48 mM/dl L-histidine 1.07-2.09 mM/dl L-phenylalanine 0-1.32 mM/dl L-tyrosine 0.20-0.98 mM/dl L-tryptophan 1.46-6.76 mM/dl L-arginine 0.81-2.71 mM/dl L-serine 1.06-4.42 mM/dl L-proline 1.92-4.44 mM/dl glycine 1.30-4.66 mM/dl L-alanine 0-2.40 mM/dl L-aspartic acid 0.31-2.55 mM/dl L-glutamic acid. ______________________________________

Claim 10

An amino acid solution for parenteral nutrition comprising an aqueous solution of amino acids wherein the amino acid content consists essentially of ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 mM/dl L-valine 3.62-10.63 mM/dl L-leucine 1.76-4.12 mM/dl L-isoleucine 0.41-6.55 mM/dl L-lysine 0.55-1.66 mM/dl L-methionine 0-3.00 mM/dl L-cysteine 0.43-5.48 mM/dl L-histidine 1.07-2.09 mM/dl L-phenylalanine 0-1.32 mM/dl L-tyrosine 0.20-0.98 mM/dl L-tryptophan 1.46-6.76 mM/dl L-arginine 0.81-2.71 mM/dl L-serine 1.06-4.42 mM/dl L-proline 1.92-4.44 mM/dl glycine 1.30-4.66 mM/dl L-alanine 0-2.40 mM/dl L-aspartic acid 0.31-2.55 mM/dl L-glutamic acid. ______________________________________

Claim 11

A solution as defined in claim 7, wherein said amino acid content consists essentially of ______________________________________ 1.34-2.19 mM/dl L-threonine 3.03-3.61 " L-valine 3.62-7.04 " L-leucine 2.12-4.12 " L-isoleucine 0.78-4.82 " L-lysine 0.62-1.66 " L-methionine 0-3.00 " L-cysteine 0.59-2.63 " L-histidine 1.07-1.83 " L-phenylalanine 0.33-1.32 " L-tyrosine 0.25-0.98 " L-tryptophan 1.75-5.25 " L-arginine 0.91-2.71 " L-serine 1.48-4.42 " L-proline 1.92-2.88 " glycine 1.50-4.50 " L-alanine 0-2.40 " L-aspartic acid 0.85-2.55 " L-glutamic acid. ______________________________________

Claim 12

A solution as defined in claim 7, wherein said amino acid content consists essentially of ______________________________________ 1.03-1.69 mM/dl L-threonine 3.45-4.13 " L-valine 5.47-10.63 " L-leucine 1.76-3.42 " L-isoleucine 1.07-6.55 " L-lysine 0.58-1.58 " L-methionine 0-3.00 " L-cysteine 0.43-1.85 " L-histidine 1.10-1.88 " L-phenylalanine 0-0.44 " L-tyrosine 0.20-0.80 " L-trypotophan 1.46-4.36 " L-arginine 0.88-2.62 " L-serine 1.12-3.38 " L-proline 2.96-4.44 " glycine 1.56-4.66 " L-alanine 0-1.36 " L-aspartic acid 0.37-1.11 " L-glutamic acid. ______________________________________

Claim 13

A solution as defined in claim 7, wherein said amino acid content consists essentially of ______________________________________ 2.02-3.30 mM/dl L-threonine 3.17-3.79 " L-valine 4.17-8.09 " L-leucine 1.83-3.55 " L-isoleucine 0.41-2.51 " L-lysine 0.55-1.49 " L-methionine 0-3.00 " L-cysteine 1.28-5.48 " L-histidine 1.23-2.09 " L-phenylalanine 0.35-0.75 " L-tyrosine 0.20-0.80 " L-tryptophan 2.26-6.76 " L-arginine 0.81-2.43 " L-serine 1.06-3.18 " L-proline 2.46-3.70 " glycine 1.30-3.90 " L-alanine 0-1.20 " L-aspartic acid 0.31-0.93 " L-glutamic acid. ______________________________________

Claim 14

A solution as defined in claim 7, having a molar ratio of total essential amino acids to total amino acids between about 0.58 and about 0.65.

Claim 15

An amino acid solution for parenteral nutrition comprising an aqueous solution of amino acids having an amino acid content consisting essentially of essential and non-essential amino acids in proportions for producing and maintaining, in an infant to whom the same is administered, a steady-state plasma amino acid pattern within established ranges for the normal infant two-hour post-prandial plasma amino acid pattern, said content including the following amino acids in the following ranges: ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 mM/dl L-valine 3.62-10.63 mM/dl L-leucine 1.76-4.12 mM/dl L-isoleucine 0.41-6.55 mM/dl L-lysine 0.55-1.66 mM/dl L-methionine 0-3.00 mM/dl L-cysteine 0.43-5.48 mM/dl L-histidine 1.07-2.09 mM/dl L-phenylalanine 0-1.32 mM/dl L-tyrosine 0.20-0.98 mM/dl L-tryptophan 1.46-6.76 mM/dl L-arginine 0.81-2.71 mM/dl L-serine 1.06-4.42 mM/dl L-proline 1.92-4.44 mM/dl glycine 1.30-4.66 mM/dl L-alanine 0-2.40 mM/dl L-aspartic acid 0.31-2.55 mM/dl L-glutamic acid. ______________________________________

Claim 16

An amino acid solution for parenteral nutrition comprising an aqueous solution of amino acids having an amino acid content consisting essentially of essential and non-essential amino acids in proportions for producing and maintaining, in an infant to whom the same is administered, a steady-state plasma amino acid pattern within established ranges for the normal infant two-hour post-prandial plasma amino acid pattern, said content including the following amino acids in the following ranges: ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 mM/dl L-valine 3.62-10.63 mM/dl L-leucine 1.76-4.12 mM/dl L-isoleucine 0.41-6.55 mM/dl L-lysine 0.55-1.66 mM/dl L-methionine 0-3.00 mM/dl L-cysteine 0.43-5.48 mM/dl L-histidine 1.07-2.09 mM/dl L-phenylalanine 0-1.32 mM/dl L-tyrosine 0.20-0.98 mM/dl L-tryptophan 1.46-6.76 mM/dl L-arginine 0.81-2.71 mM/dl L-serine 1.06-4.42 mM/dl L-proline 1.92-4.44 mM/dl glycine 1.30-4.66 mM/dl L-alanine 0-2.40 mM/dl L-aspartic acid 0.31-2.55 mM/dl L-glutamic acid. ______________________________________

Claim 17

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the essential amino acid content consists essentially of ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 " L-valine 3.62-10.63 " L-leucine 1.76-4.12 " L-isoleucine 0.41-6.55 " L-lysine 0.55-1.66 " L-methionine 0-3.00 " L-cysteine 0.43-5.48 " L-histidine 1.07-2.09 " L-phenylalanine 0-1.32 " L-tyrosine 0.20-0.98 " L-tryptophan ______________________________________ and wherein said non-essential amino acids include one or more of the group consisting of L-arginine, L-serine, L-proline, glycine, L-alanine, L-aspartic acid, and L-glutamic acid.

Claim 18

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the essential amino acid content consists essentially of ______________________________________ 1.03-3.30 mM/dl L-threonine 3.03-4.13 " L-valine 3.62-10.63 " L-leucine 1.76-4.12 " L-isoleucine 0.41-6.55 " L-lysine 0.55-1.66 " L-methionine 0-3.00 " L-cysteine 0.43-5.48 " L-histidine 1.07-2.09 " L-phenylalanine 0-1.32 " L-tyrosine 0.20-0.98 " L-tryptophan ______________________________________ and wherein said non-essential amino acids include one or more of the group consisting of L-arginine, L-serine, L-proline, glycine, L-alanine, L-aspartic acid, and L-glutamic acid.

Claim 19

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the amino acids are present in the following relative proportions as expressed in terms of moles: ______________________________________ L-threonine 2.60 8.25 L-valine 7.58 10.32 L-leucine 9.05 26.58 L-isoleucine 4.40 10.30 L-lysine 1.02 16.40 L-methionine 1.38 4.15 L-cysteine 0 7.50 L-histidine 1.08 13.70 L-phenylalanine 2.68 5.22 L-tyrosine 0 3.30 L-tryptophan 0.50 2.45 L-arginine 3.65 16.90 L-serine 2.02 6.80 L-proline 2.65 11.05 glycine 4.80 11.10 L-alanine 3.25 11.65 L-aspartic acid 0 6.00 L-glutamic acid 0.78 6.38 ______________________________________

Claim 20

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the amino acids are present in the following relative proportions as expressed in terms of moles: ______________________________________ L-threonine 2.60 8.25 L-valine 7.58 10.32 L-leucine 9.05 26.58 L-isoleucine 4.40 10.30 L-lysine 1.02 16.40 L-methionine 1.38 4.15 L-cysteine 0 7.50 L-histidine 1.08 13.70 L-phenylalanine 2.68 5.22 L-tyrosine 0 3.30 L-tryptophan 0.50 2.45 L-arginine 3.65 16.90 L-serine 2.02 6.80 L-proline 2.65 11.05 glycine 4.80 11.10 L-alanine 3.25 11.65 L-aspartic acid 0 6.00 L-glutamic acid 0.78 6.38 ______________________________________

Claim 21

An amino acid solution according to claim 14 wherein one or more of said amino acids is present in the same relative mole proportions in the form of one or more of their pharmaceutically acceptable salts, keto acid analogs, dipeptides or N-acetyl derivatives.

Claim 22

An amino acid solution according to claim 14 wherein said amino acids are present in pharmaceutically acceptable amounts.

Claim 23

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the essential amino acids are present in the following relative proportions as expressed in terms of moles: ______________________________________ L-threonine 2.60 8.25 L-valine 7.58 10.32 L-leucine 9.05 26.58 L-isoleucine 4.40 10.30 L-lysine 1.02 16.40 L-methionine 1.38 4.15 L-cysteine 0 7.50 L-histidine 1.08 13.70 L-phenylalanine 2.68 5.22 L-tyrosine 0 3.30 L-tryptophan 0.50 2.45 ______________________________________ and wherein the molar ratio of total essential amino acids to total amino acids is in the range from 0.50 to 0.70.

Claim 24

An amino acid solution for parenteral nutrition comprising an aqueous solution of essential and non-essential amino acids wherein the essential amino acids are present in the following relative proportions as expressed in terms of moles: ______________________________________ L-threonine 2.60 8.25 L-valine 7.58 10.32 L-leucine 9.05 26.58 L-isoleucine 4.40 10.30 L-lysine 1.02 16.40 L-methionine 1.38 4.15 L-cysteine 0 7.50 L-histidine 1.08 13.70 L-phenylalanine 2.68 5.22 L-tyrosine 0 3.30 L-tryptophan 0.50 2.45 ______________________________________ and wherein the molar ratio of total essential amino acids to total amino acids is in the range from 0.50 to 0.70.

Claim 25

An amino acid solution according to claim 17 wherein one or more of said amino acids is present in the same relative mole proportions in the form of one or more of their pharmaceutically acceptable salts, keto acid analogs, dipeptides or N-acetyl derivatives.

Claim 26

An amino acid solution according to claim 18 wherein said solution further comprises sufficient non-specific nonessential amino acids to provide adequate nitrogen for nutrition.

Claim 29

An amino acid solution according to claim 20 wherein one or more of said amino acids is present in the same relative mole proportions in the form of one or more of their pharmaceutically acceptable salts, keto acid analogs, dipeptides or N-acetyl derivatives.

Claim 30

An amino acid solution according to claim 20 wherein said amino acids are present in pharmaceutically acceptable amounts.