PREPARATION AND USE OF METHIONYLMETHIONINE AS FEED ADDITIVE FOR FISH AND CRUSTACEANS

• US 20100098801A1
• Filed: 10/16/2009
• Published: 04/22/2010
• Est. Priority Date: 10/17/2008
• Status: Active Grant

• Current Assignee: Evonik Operations GmbH (Rag-Stiftung)
• Original Assignee: Evonik Degussa GmbH (Rag-Stiftung)
• Inventors: Haeussner, Thomas, Kobler, Christoph, Weckbecker, Christoph
• Granted Patent: US 8,968,817 B2
• Time in Patent Office: Days
• US Class Current: 426/2
• CPC Class Codes: A23K 20/142 Amino acids; Derivatives thereof
• CPC Class Codes: A23K 50/80 for aquatic animals, e.g. fish, crustaceans or molluscs
• CPC Class Codes: C07C 319/20 by reactions not involving the formation of sulfide groups
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07D 241/08 with oxygen atoms directly attached to ring carbon atoms
• CPC Class Codes: C07K 5/0606 the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
• CPC Class Codes: Y02A 40/818 Alternative feeds for fish, e.g. in aquacultures
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

An animal feed mixture containing DL-methionyl-DL-methionine and salts thereof for animals kept in aquacultures is provided. Methods for preparing DL-methionyl-DL-methionine of formula (I)

and methods to fractionate the diasteriomeric forms obtained are also provided.

Claims

1. An animal feed mixture, comprising:

a nutrient selected from the group consisting of DL-methionyl-DL-methionine, a salt thereof and a mixture of DL-methionyl-DL-methionine and a salt thereof.

2. The animal feed mixture according to claim 1, wherein the nutrient is a salt of DL-methionyl-DL-methionine and the salt comprises a cation selected from the group consisting of an alkali metal, an alkaline earth metal, ammonium, Cu²⁺, Zn²⁺, Co²⁺and a mixture thereof.

3. The animal feed mixture according to claim 1, wherein a content of the nutrient in the animal feed mixture is from 0.01 to 5% by weight.

4. The animal feed mixture according to claim 1, further comprising:

protein and carbohydrate, based on a meal selected from the group consisting of fish meal, soybean meal, corn meal, and mixtures thereof, and,

optionally, a supplement selected from the group consisting of an essential amino acid, a protein, a peptide, a vitamin, a mineral, a carbohydrate, a fat, an oil and a mixture thereof.

5. The animal feed mixture according to claim 1, wherein the DL-methionyl-DL-methionine or salt thereof comprises one mixture selected from the group consisting of a DD/LL/LD/DL mixture, a DL/LD mixture, and a DD/LL mixture.

6. The animal feed mixture according to claim 1, further comprising 0.01 to 20% by weight DL-methionine.

7. The animal feed mixture according to claim 1, wherein the DL-methionyl-DL-methionine is a DL/LD-methionylmethionine pair of enantiomers.

8. The animal feed mixture according to claim 4, further comprising 0.01 to 20% by weight DL-methionine.

9. The animal feed mixture according to claim 1 which is in the form of a pellet or an extrudate.

10. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 1, wherein the animal is kept in an aquaculture.

11. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 2, wherein the animal is kept in an aquaculture.

12. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 3, wherein the animal is kept in an aquaculture.

13. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 4, wherein the animal is kept in an aquaculture.

14. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 5, wherein the animal is kept in an aquaculture.

15. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 6, wherein the animal is kept in an aquaculture.

16. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 8, wherein the animal is kept in an aquaculture.

17. A method for feeding an animal, comprising feeding the animal the feed mixture according to claim 9, wherein the animal is kept in an aquaculture.

18. The method as claimed in claim 10, where the animal kept in an aquaculture is at least one animal selected from the group consisting of a salt water fish, a salt water crustacean, a fresh water fish and a fresh water crustacean.

19. The method as claimed in claim 10, wherein the animal kept in an aquaculture is an animal selected from the group consisting of a carp, a trout, a salmon, a catfish, a perch, a flatfish, a sturgeon, a tuna, an eel, a bream, a cod, a shrimp, a krill and a prawn.

20. The method as claimed in claim 10, wherein the animal is selected from the group of animals consisting of a silver carp (Hypophthalmichthys molitrix), a grass carp (Ctenopharyngodon idella), a common carp (Cyprinus carpio), a bighead carp (Aristichthys nobilis), a carassius (Carassius carassius), a catla (Catla Catla), a Roho labeo (Labeo rohita), a Pacific salmon (Salmon salar) an Atlantic salmon (Oncorhynchus kisutch), a rainbow trout (Oncorhynchus mykiss), an American catfish (Ictalurus punctatus), an African catfish (Clarias gariepinus), a pangasius (Pangasius bocourti and Pangasius hypothalamus), a Nile tilapia (Oreochromis niloticus), a milkfish (Chanos chanos), a cobia (Rachycentron canadum), a whiteleg shrimp (Litopenaeus vannamei), a black tiger shrimp (Penaeus monodon) and a giant river prawn (Macrobrachium rosenbergii).

21. A process for preparing DL-methionyl-DL-methionine of formula (I), comprising:

22. The process as claimed in claim 21, wherein the urea derivative of formula II is a methioninehydantoin of formula IId.

23. The process as claimed in claim 21, wherein the reacting a urea derivative of formula II to obtain DL-methionyl-DL-methionine, comprises reacting a methioninehydantoin in aqueous solution with methionine under basic conditions.

24. The process as claimed in claim 21, further comprising adjusting a pH of a solution comprising the urea derivative to a range of from 8 to 14.

25. The process as claimed in claim 21, wherein a temperature of the reaction is from 50 to 200°

C.

26. The process as claimed in claim 21, wherein a pressure of the reaction is in the range from 3 to 20 bar.

27. The process as claimed in claim 23, further comprising obtaining the solution comprising methioninehydantoin and water by a reaction of one or more compounds selected from the group consisting of compounds IIa, IIb, IIe, IId, IIe, IIf and IIg.

28. The process as claimed in claim 27, where the solution comprising methioninehydantoin is obtained by reacting the compound IIe or IIf with a nitrogen-containing base, NH₄HCO₃, (NH₄)₂CO₃, a NH₄OH/CO₂ mixture or a carbamate salt.

29. The process as claimed in claim 28, wherein the compound IIe is reacted and a temperature of the reaction is in a range of from 0°

C. to 150°

C.

30. The process as claimed in claim 28, wherein the compound IIf is reacted with CO₂.

31. The process as claimed in claim 30, wherein the reaction of compound IIf and CO₂ further comprises a base, selected from the group consisting of KHCO₃, K₂CO₃, a tertiary amine, a salt of a tertiary amine, an alkali metal base and an alkaline earth metal base.

32. The process as claimed in claim 27, wherein the solution comprising methioninehydantoin is obtained by reacting the compound IIg with a cyanide ion source and a base selected from the group consisting of a nitrogen-containing base, a mixture of an ammonium salt and CO₂, NH₄HCO₃, (NH₄)₂CO₃, a NH₄OH/CO₂ mixture and a carbamate salt.

33. The process as claimed in claim 32, wherein a reaction temperature is from −

20°

C. to 150°

C.

34. The process as claimed in claim 21, comprising:

a) reacting the urea derivative of formulae IIa, IIb, IIc, IId, IIe, IIf or IIg to obtain a diketopiperazine of formula (III); and

35. The process as claimed in claim 34, wherein a temperature of the reaction of the urea derivative to obtain the diketopiperazine is in a range of from 50°

C. to 200°

C.

36. The process as claimed in claim 34, wherein a pressure of the reaction of the urea derivative to obtain the diketopiperazine is in a range of from 3 to 20 bar.

37. The process as claimed in claim 34, wherein the reaction of the urea derivative to give the diketopiperazine further comprises a base.

38. The process as claimed in claim 37, wherein the base is selected from the group consisting of a nitrogen-containing base, NH₄HCO₃, (NH₄)₂CO₃, KHCO₃, K₂CO₃, a NH₄OH/CO₂ mixture, a carbamate salt, an alkali metal base and an alkaline earth metal base.

39. The process as claimed in claim 34, wherein the reaction of the urea derivative to obtain the diketopiperazine comprises methionine.

40. The process as claimed in claim 34, where the hydrolysis of the obtained diketopiperazine to prepare the DL-methionyl-DL-methionine is an acidic hydrolysis.

41. The process as claimed in claim 40, where the acidic hydrolysis comprises an acid selected from the group of mineral acids consisting of HCl, CO₂/H₂O, H₂SO₄, a phosphoric acid, a carboxylic acid and a hydroxy carboxylic acids.

42. The process as claimed in claim 34, wherein the hydrolysis of the obtained diketopiperazine to give DL-methionyl-DL-methionine is a basic hydrolysis.

43. The process as claimed in claim 42, wherein a pH of the basic hydrolysis to obtain DL-methionyl-DL-methionine is in the range of from 7 to 14.

44. The process as claimed in claim 42, wherein the basic hydrolysis comprises one base selected from the group consisting of a nitrogen-containing base, NH₄HCO₃, (NH₄)₂CO₃, an NH₄OH/CO₂ mixture, a carbamate salt, KHCO₃, K₂CO₃, a carbonate, an alkali metal base and an alkaline earth metal base.

45. The process as claimed in claim 42, wherein a temperature of the basic hydrolysis is in a range of from 50°

C. to 200°

C.

46. The process as claimed in claim 34, wherein the hydrolysis of the diketopiperazine to prepare DL-methionyl-DL-methionine comprises introducing CO₂ into a basic solution.

47. The process as claimed in claim 46, wherein the basic solution is one selected from the group consisting of ammonium hydroxide, potassium hydroxide and sodium hydroxide solution.

48. The process as claimed in claim 34, further comprising isolating the diketopiperazine before the hydrolysis.

49. The process as claimed in claim 48, wherein the isolation of the diketopiperazine comprises crystallization of the diketopiperazine from the reaction solution, at a temperature of from −

30 to 120°

C.

50. The process as claimed in claim 42, further comprising isolating the mixture of DD/LL/DL/LD-methionylmethionine diastereomers by crystallization from the basic hydrolysis solution.

51. The process as claimed in claim 50, wherein the isolation of the mixture of DD/LL/DL/LD-methionylmethionine diastereomers comprises adjusting a pH of the basic hydrolysis solution with an acid to a pH of from 5 to 9.

52. The process as claimed in claim 51, wherein the acid is an acid selected from the group consisting of a mineral acid, HCl, H₂CO₃, CO₂/H₂O, H₂SO₄, a phosphoric acid, a carboxylic acid, and a hydroxy carboxylic acid.

53. The process as claimed in claim 40, further comprising isolating the mixture of DD/LL/DL/LD-methionylmethionine diastereomers by crystallization from the acidic hydrolysis solution.

54. The process as claimed in claim 53, wherein the pH of the acidic hydrolysis solution is adjusted to a range of from 5 to 9, with a base.

55. The process as claimed in claim 54, wherein the base is a base selected from the group consisting of NH₄HCO₃, (NH₄)₂CO₃, a nitrogen-containing base, NH₄OH, a carbamate salt, KHCO₃, K₂CO₃, a carbonate, an alkali metal base and an alkaline earth metal base.

56. A process for fractionating the mixture of DD/LL/DL/LD-methionylmethionine diastereomers isolated in claim 53, comprising fractionally crystallizing the mixture to obtain two pairs of enantiomers of DD/LL-methionylmethionine and DL/LD-methionylmethionine.

57. The process as claimed in claim 56, wherein the fractional crystallization comprises:

acidifying the DD/LL/DL/LD-methionylmethionine-containing suspension with an acid until a clear solution is obtained;

adding a base stepwise to the acidic solution until a precipitate of DL/LD-methionylmethionine separates out;

removing the separated precipitate of DL/LD-methionylmethionine from a mother liquor; and

obtaining DD/LL-methionylmethionine from the mother liquor.

58. The process as claimed in claim 57, wherein

a pH of the clear solution obtained upon acidification is from 0.1 to 1.0, and

a pH of the slurry following stepwise addition of the base is from 5 to 6.

59. The process as claimed in claim 57, wherein the acid for the acidification is an acid selected from the group consisting of phosphoric acid, sulfuric acid, hydrochloric acid, carbonic acid and carbon dioxide.

60. The process as claimed in claim 57, wherein the base added stepwise to the acid solution is at least one selected from the group consisting of NH₄HCO₃, (NH₄)₂CO₃, a nitrogen-containing base, NH₄OH, a carbamate salt, KHCO₃, K₂CO₃, a carbonate, an alkali metal and an alkaline earth metal base.

61. The process as claimed in claim 56, wherein the fractional crystallization comprises:

basifying the DD/LL/DL/LD-methionylmethionine-containing suspension with a base until a clear solution is obtained;

adding an acid stepwise to the basic solution until a precipitate of DL/LD-methionylmethionine separates;

removing the separated precipitate of DL/LD-methionylmethionine from a mother liquor; and

obtaining DD/LL-methionylmethionine from the mother liquor.

62. The process as claimed in claim 61, wherein

a pH of the basified clear solution is from 7.5 to 14, and

a pH of the DL/LD-methionylmethionine slurry following acid addition is from 5 to 6.

63. The process as claimed in claim 61, where the base is selected from the group consisting of NH₄HCO₃, (NH₄)₂CO₃, a nitrogen-containing base, NH₄OH, a carbamate salt, KHCO₃, K₂CO₃, a carbonate, an alkali metal base and an alkaline earth metal base.

64. The process as claimed in claim 61, wherein the acid is an acid selected from the group consisting of phosphoric acid, sulfuric acid, hydrochloric acid, carbonic acid and carbon dioxide.

65. The process as claimed in claim 61, wherein a temperature is in a range from 0°

C. to 100°

C.

66. The process as claimed in claim 56, wherein the resulting DD/LL-methionylmethionine is a racemic mixture, and the two pairs of enantiomers DD/LL-methionylmethionine and DL/LD-methionylmethionine are separated from one another.

67. The process as claimed in claim 56, wherein a medium for the process is an aqueous medium.