Compositions and methods for increasing energy metabolism

• US 9,943,517 B2
• Filed: 11/13/2013
• Issued: 04/17/2018
• Est. Priority Date: 11/13/2012
• Status: Active Grant

• Current Assignee: Nusirt Sciences, Inc.
• Original Assignee: Nusirt Sciences, Inc.
• Inventors: Zemel, Michael, Bruckbauer, Antje, Baggett, Brooke
• Primary Examiner(s): Shiao, Yih-Horng
• Application Number:
  US14/442,711
• Publication Number:
  US 20160279130A1
• Time in Patent Office: 1,616 Days
• Field of Search: 514 27
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/4415 Pyridoxine, i.e. Vitamin B6 pyridoxal phosphate A61K31/675
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions comprise a combination of a PDE 5 inhibitor, such as sildenafil or icariin, and resveratrol, and a branched amino acid such as leucine, or its metabolite.

Claims

1. A composition comprising:

(a) a synergistically effective amount of a phosphodiesterase 5 (PDE

     5) inhibitor; and

(b) at least 500 mg of leucine and/or at least 200 mg of a leucine metabolite, wherein the PDE 5 inhibitor comprises sildenafil.

2. The composition of claim 1, wherein the amount of phosphodiesterase 5 (PDE 5) inhibitor is a sub-therapeutic amount.

3. The composition of claim 1, wherein the composition is formulated as a unit dosage.

4. The composition of claim 3, wherein the unit dosage comprises a sub-therapeutic amount of component (a) that is between 0.1 and 20 mg of sildenafil.

5. The composition of claim 3, wherein the unit dosage comprises a sub-therapeutic amount of component (a) that is between 0.1 and 10 mg of sildenafil.

6. The composition of claim 2, wherein the sub-therapeutic amount of component (a) further comprises between 0.5-50 mg of avanafil, 0.05-10 mg of iodenafil, 0.25-25 mg of mirodenafil, 0.01-1.25 mg of tadalafil, 0.01-1.25 mg of vardenafil, 0.5-50 mg of udenafil, 0.5-50 mg of zaprinst, or 0.05-100 mg of icariin.

7. The composition of claim 1, wherein the component (b) is free leucine.

8. The composition of claim 1, wherein the component (b) comprises between 500 to 2000 mg of free leucine.

9. The composition of claim 1, wherein the component (b) comprises at least 200 mg of a leucine metabolite comprising beta-hydroxymethylbutyrate (HMB).

10. The composition of claim 1, further comprising an anti-diabetic agent.

11. The composition of claim 1, further comprising a sub-therapeutic amount of an anti-diabetic agent.

12. The composition of claim 10, wherein the anti-diabetic agent is a biguanide or thiazoladinedione.

13. The composition of claim 10, wherein the anti-diabetic agent is metformin or rosiglitazone.

14. The composition of claim 10, wherein the anti-diabetic agent comprises at least 25 mg of metformin.

15. The composition of claim 1, further comprising resveratrol.

16. The composition of claim 10, wherein component (a) comprises between 0.1 and 10 mg of sildenafil, component (b) comprises between 500 and 2000 mg of free leucine, and the anti-diabetic agent comprises at least 250 mg of metformin.

17. The composition of claim 1, further comprising a pharmaceutically active agent other than the PDE 5 inhibitor and the leucine and/or the leucine metabolite.

18. The composition of claim 1, wherein the composition further comprises less than 1% by weight of an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in free amino acid form.

19. The composition of claim 1, wherein the composition further comprises less than 1% by weight of isoleucine and valine.

20. The composition of claim 1, wherein the composition is free of isoleucine and valine.

21. The composition of claim 1, wherein the composition is formulated in tablets or capsules.