US4003992A
Expired / Lapsed
US
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Hydrolytic process for the preparation of amino acids
Assignee: Syntex USA LLC
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Filing: 1975-06-16
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Granted: 1977-01-18
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Expires: 1995-06-16
Abstract
Abstract A highly efficient process for preparing a nutritionally acceptable mixture of amino acids from erythrocytes comprises the steps of denaturization, hydrolysis and neutralization, desludging, decolorization, deionization, concentration and sterilization.
Inventors
- 👤 Myron A. Beigler
- 👤 William B. Benken
- 👤 Jorge J. Nassar
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 21:13
CPC Classifications
A; A61; A61K; A61K35/00; A61K35/12; A61K35/14; A61K35/18; A61K31/00; A61K31/185; A61K31/19; A61K31/195; A61K38/00; A61K38/01; A61K38/012; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/829
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
235 words
A process for the preparation of a nutritionally acceptable amino acid mixture suitable for intravenous administration which comprises the steps of: a. heating erythrocytes to denature protein contained therein, followed by separation of the insoluble denatured protein formed thereby from the soluble components; b. hydrolyzing the denatured protein from step (a) with sulfuric acid at a temperature equal to or greater than 200° F to afford a crude amino acid mixture essentially free of peptides, followed by partial neutralization with calcium hydroxide to a final pH of between 2.7 and 3.5, thereby affording a mixture of soluble amino acids and a cake comprising calcium sulfate and humin impurities; c. desludging the mixture formed in step (b) by separating the amino acid solution from the calcium sulfate-humin cake; d. decolorizing the amino acid solution obtained from step (c); e. deionizing the decolorized amino acid solution from step (d) to remove nutritionally objectionable ions by loading the amino acid solution on a column of a strong cationic exchange resin comprising a sulfonated copolymer of styrene cross-linked with approximately 8% divinyl benzene and eluting the amino acids therefrom with dilute sodium hydroxide solution; f. concentration of the amino acid solution obtained from step (e) by removal of water to afford an amino acid solution containing greater than 2% w/w of amino acids; and g. sterilization of the amino acid solution obtained from step (f) to remove microbial contamination.
Claim 2
Dependent Claim
235 words
A process for the preparation of a nutritionally acceptable amino acid mixture suitable for intravenous administration which comprises the steps of: a. heating erythrocytes to denature protein contained therein, followed by separation of the insoluble denatured protein formed thereby from the soluble components; b. hydrolyzing the denatured protein from step (a) with sulfuric acid at a temperature equal to or greater than 200° F to afford a crude amino acid mixture essentially free of peptides, followed by partial neutralization with calcium hydroxide to a final pH of between 2.7 and 3.5, thereby affording a mixture of soluble amino acids and a cake comprising calcium sulfate and humin impurities; c. desludging the mixture formed in step (b) by separating the amino acid solution from the calcium sulfate-humin cake; d. decolorizing the amino acid solution obtained from step (c); e. deionizing the decolorized amino acid solution from step (d) to remove nutritionally objectionable ions by loading the amino acid solution on a column of a strong cationic exchange resin comprising a sulfonated copolymer of styrene cross-linked with approximately 8% divinyl benzene and eluting the amino acids therefrom with dilute sodium hydroxide solution; f. concentration of the amino acid solution obtained from step (e) by removal of water to afford an amino acid solution containing greater than 2% w/w of amino acids; and g. sterilization of the amino acid solution obtained from step (f) to remove microbial contamination.
Claim 3
Dependent Claim
12 words
The process of claim 1 wherein the erythrocytes used are bovine erythrocytes.
Claim 4
Dependent Claim
27 words
The process of claim 1 wherein, in step (b), the acid hydrolysis is effected by means of 8N sulfuric acid at a temperature 258° F or greater.
Claim 5
Dependent Claim
17 words
The process of claim 1 wherein, in step (d), decolorization is accomplished by means of activated charcoal.
Claim 6
Dependent Claim
26 words
The process of claim 8 wherein the activated charcoal is utilized in a ratio of from about 1 to 2% w/w relative to amino acid solution.
Claim 7
Dependent Claim
49 words
The process of claim 1 wherein, in step (d), decolorization is accomplished by passage of the hydrolysate from step (c) through a column of a strong cationic exchange resin of the type used in step (e) followed by passage through a column of a weak anionic macroreticular phenolformaldehyde resin.
Claim 8
Dependent Claim
16 words
The process of claim 1 wherein, in step (e), the cationic exchange resin is 40-80 mesh.
Claim 9
Dependent Claim
23 words
The process of claim 1 wherein, in step (e), the ion exchange column is washed sulfate-free with water after loading with amino acids.
Claim 10
Dependent Claim
18 words
The process of claim 1 wherein, in step (e), the sodium hydroxide solution used for elution is ≦0.1N.
Claim 11
Dependent Claim
50 words
The process of claim 1 wherein, in step (f), the concentration is effected by loading the amino acid solution obtained from step (e) on a cationic exchange column of the type utilized in step (e), and eluting with sodium hydroxide solution of higher concentration than that utilized in step (e).
Claim 12
Dependent Claim
16 words
The process of claim 10 wherein the sodium hydroxide solution used for elution is approximately 0.5N.
Claim 13
Dependent Claim
16 words
The process of claim 10 wherein, prior to elution, the column is washed sulfate-free with water.
Claim 14
Dependent Claim
18 words
The process of claim 1 wherein, in step (g), residual volatiles are substantially removed during the sterilization process.
Claim 15
Dependent Claim
20 words
The process of claim 13 wherein sterilization and removal of residual volatiles are accomplished by means of steam injection-flash evaporation.
Claim 16
Dependent Claim
20 words
The process of claim 1 wherein the amino acid solution produced contains between about 2 and 4% w/w amino acids.
Claim 17
Dependent Claim
17 words
The process of claim 1 wherein the amino acid solution produced has an ammonia content of ≦0.02%.
Claim 18
Dependent Claim
24 words
The process of claim 1 wherein the amino acid solution produced is additionally spray dried to afford a dried mixture of crystalline amino acids.
References Cited (Backward Citations)
US3579495A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-01-18 | 1980-07-19 | 1981-01-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-01-18 | 1984-07-19 | 1985-01-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-01-18 | 1988-07-19 | 1989-01-18 | $7700.00 | Window Closed / Lapsed |