Leucine-enriched ketogenic formulations

Patent metadata

Field	Value
Publication number	US-12257221-B2
Application number	US-202117301076-A
Country	US
Kind code	B2
Filing date	Mar 24, 2021
Priority date	Oct 4, 2018
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

Described herein are nutritional compositions, such as ketogenic compositions, leucine-enriched amino acid mixtures, etc., useful, for example, for dietary management of intractable epilepsy. In some embodiments, the disclosure relates to methods of inhibiting epileptic seizures in a subject comprising administering to the subject a leucine-enriched amino acid mixture.

First claim

The invention claimed is:

1. A ketogenic composition comprising: fat, a protein source, and carbohydrate, wherein: (a) the fat provides 60-90% of total calories of the composition and medium chain triglycerides (MCTs) provide between 10-40% of total calories of the composition; (b) the protein source comprises a non-casein protein and a leucine-enriched amino acid mixture; (c) and the ratio of calories fat to calories combined protein and net carbohydrate ranges from about 2:1 to about 4:1,
wherein the leucine-enriched amino acid mixture comprises L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, and comprises leucine at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture.

2. The ketogenic composition of claim 1 , wherein the protein source comprises a non-casein protein isolate, non-casein protein concentrate, non-casein protein hydrolysate, or a combination of the foregoing, optionally wherein the protein source is nutritionally complete.

3. The ketogenic composition of claim 1 , wherein the leucine-enriched amino acid mixture comprises leucine at a molar ratio between 35% and 60% with respect to total essential amino acids in the mixture.

4. The ketogenic composition of claim 1 , wherein each of the amino acids in the composition is present at the following molar composition ratio (%) with respect to total of essential amino acids in the composition: 0.1% to 5% of L-histidine, 5.0% to 15% of L-isoleucine, 30% to 70% of L-leucine, 8.0% to 25% of L-lysine, 2.0% to 10% of L-methionine, 2.5% to 8.0% of L-phenylalanine, 7.0% to 20% of L-threonine, 5.0% to 15% of L-valine, and 0.1% to 4.0% of L-tryptophan.

5. The ketogenic composition of claim 1 , wherein the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1, the ratio of leucine to valine ranges from about 1:1 to about 4:1, or a combination of the foregoing.

6. The ketogenic composition of claim 1 , wherein the fat comprises about 40% to about 50% MCTs by weight.

7. The ketogenic composition of claim 1 further comprising one or more vitamins and one or more minerals, optionally wherein the one or more vitamins comprise vitamin D, vitamin K1, and/or vitamin K2, and/or wherein the one or more minerals comprise calcium, magnesium and/or phosphorous.

8. The ketogenic composition of claim 1 , wherein the composition is a solid, optionally wherein the solid is a powder.

9. The ketogenic composition of claim 1 , wherein the composition is a liquid, optionally wherein the liquid is an aqueous liquid.

10. The ketogenic composition of claim 1 , wherein the composition is nutritionally complete.

11. A method for dietary management of a disease or condition associated with clinical improvement after Ketogenic diet administration, the method comprising administering to the subject an effective amount of the composition of claim 1 .

12. The method of claim 11 , wherein the disease or condition is intractable epilepsy.

13. The method of claim 11 , wherein the subject is following or has previously followed a ketogenic diet.

14. The method of claim 11 , wherein the subject has been determined to be refractory to treatment with anti-epileptic drugs (AEDs).

15. The method of claim 11 , wherein the subject is determined to have an improvement in clinical outcomes after administration of the ketogenic diet.

16. A method for treating intractable epilepsy in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.

17. A method for reducing epileptic seizures in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.

18. The method according to claim 16 , wherein the intractable epilepsy is the epilepsy that is refractory to treatment with one or more anti-epileptic drugs (AEDs).

19. The method according to claim 16 , wherein the subject has previously been administered a ketogenic formula or is currently following a ketogenic diet.

20. The method according to claim 16 , wherein the subject is in a state of ketosis.

21. The method according to claim 16 , wherein the leucine-enriched amino acid mixture accounts for between 1.0% and 6.0% of the subject's daily caloric intake.

22. A method for clinical dietary management of a disease or disorder of a subject on a ketogenic diet, comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.

23. A method for inducing ketogenesis in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.

24. The method according to claim 23 , wherein the method further comprises administering a ketogenic diet to the subject.

25. A non-therapeutic method of inducing ketogenesis in a subject comprising administering to the subject a leucine-enriched amino acid mixture comprising L-leucine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, and L-valine, wherein
(i) the leucine is present at a molar ratio between 30% and 70% with respect to total essential amino acids in the mixture; and
(ii) the molar ratio of leucine to isoleucine ranges from about 1:1 to 4:1 or the ratio of leucine to valine ranges from about 1:1 to about 4:1.

26. The method according to claim 25 , further comprising administering a ketogenic diet to the subject.

27. The method according to claim 25 , wherein the non-therapeutic method is cosmetic or athletic performance-enhancing.

28. A method for treating disease or disorder in a subject selected from traumatic brain injury (TBI), neurodegenerative disease, cancer, obesity, diabetes, and diseases related to certain inborn errors of metabolism, comprising administering to the subject a mixture

Assignees

• Ajinomoto Kk

Inventors

• Gingrich Susan
• Reed Robert
• Nagao Kenji
• Nishikata Natsumi

Classifications

• A61K2800/92

  Oral administration · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K8/44

  Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A23L33/29

  Mineral substances, e.g. mineral oils or clays · CPC title