Compositions and methods for pain relief
View Patent ↗The invention provides pharmaceutical compositions having improved effects and synergistic efficacy against pain, and provides methods for their use to treat pain, wherein the composition comprises: a sulfur-containing amino acid; a carnitine compound; and at least one compound that is a L-citrulline compound or a beta-alanine compound.
1. A pharmaceutical composition consisting of:
a) a sulfur-containing amino acid selected from the group consisting of at least one of L-methionine, L-homocysteine, L-cystathionine, L-cysteine, L-cysteine sulfinic acid, hypotaurine, taurine, lower alkyl esters of the sulfur-containing amino acid, and pharmaceutically acceptable salts of the sulfur-containing amino acid;
b) a carnitine compound selected from the group consisting of L-carnitine, a lower alkyl ester of L-carnitine, and a pharmaceutically acceptable salt of L-carnitine;
c) at least one of a beta-alanine compound and a citrulline compound, wherein the beta-alanine compound is selected from the group consisting of beta-alanine, a lower alkyl ester of beta-alanine, and a pharmaceutically acceptable salt of beta-alanine, and the citrulline compound is selected from the group consisting of L-citrulline, a lower alkyl ester of L-citrulline, and a pharmaceutically acceptable salt of L-citrulline;
d) optionally at least one of vitamins selected from the group consisting of B 1 , B 2 , B 6 and B 12 ;
e) optionally a lipoic acid compound; and
f) optionally an excipient, a binding agent, an adjuvant, a lubricant, a gliding agent, a sweetening agent, a flavoring agent, or a liquid carrier.
2. The composition of claim 1 , wherein the weight ratio of the sulfur-containing amino acid to the beta-alanine compound is from 1:1 to 7.5:1.
3. The composition of claim 1 , wherein the weight ratio of the sulfur-containing amino acid to the beta-alanine compound is from 2.5:1 to 6:1.
4. The composition of claim 1 , wherein the composition is a unit dose form, wherein the sulfur-containing amino acid is present in the unit dose form in an amount from 20 milligrams to 2 grams; the carnitine compound is present in the unit dose form in an amount from 20 milligrams to 2 grams; and the beta-alanine compound is present in the unit dose form in an amount from 5 milligrams to 500 milligrams.
5. The composition of claim 1 , wherein the sulfur-containing amino acid is taurine in an amount of from 25 mg to 800 mg.
6. The composition of claim 1 , wherein the carnitine compound is L-carnitine or the pharmaceutically acceptable salt thereof in an amount of from 25 mg to 800 mg.
7. The composition of claim 1 , wherein the beta-alanine compound is beta-alanine in an amount of from 2 mg to 200 mg.
8. The composition of claim 1 , wherein a beta-alanine compound and a citrulline compound are present in the composition.
9. The composition of claim 8 , wherein the citrulline compound is L-citrulline in an amount of from 25 mg to 800 mg.
10. The composition of claim 1 , wherein the composition consists of taurine in an amount of from 35 mg to 400 mg; L-carnitine or the pharmaceutically acceptable salt thereof in an amount of from 35 mg to 400 mg; L-citrulline in an amount of from 35 mg to 400 mg; and beta-alanine in an amount of from 2 mg to 100 mg.
11. The composition of claim 1 , wherein at least one of vitamins B 1 , B 2 , B 6 and B 12 is present in the composition.
12. The composition of claim 1 , wherein vitamin B12 is present in the composition in an amount of from 0.30 mcg to 625 mcg.
13. The composition of claim 1 , wherein the lipoic acid compound is present in the composition, wherein the lipoic acid compound is selected from the group consisting of alpha-lipoic acid, a lower alkyl ester of alpha lipoic acid, and a pharmaceutically acceptable salt of alpha-lipoic acid.
14. The composition of claim 1 , wherein the lipoic acid compound is present in the composition in an amount of from 2 mg to 1 g.
15. The composition of claim 1 , wherein the composition comprises taurine in an amount of from 35 mg to 400 mg; L-carnitine or the pharmaceutically acceptable salt thereof in an amount of from 35 mg to 400 mg; L-citrulline in an amount of from 35 mg to 400 mg; and beta-alanine in an amount of from 2 mg to 100 mg; vitamin B12 in an amount of from 7.5 mcg to 250 mcg; and alpha-lipoic acid in an amount of from 2 mg to 800 mg.
16. The composition of claim 1 , wherein the composition is in the form of a tablet, a powder, a capsule, a liquid, a gel or a spray.
17. A method for treating pain comprising providing to a patient in need thereof a therapeutically effective amount of the composition of claim 1 .
18. The method of claim 17 , wherein the pain comprises acute pain, chronic pain, nociceptive pain, or incident pain.
19. The method of claim 17 , wherein the pain comprises a feeling of burning or coldness, stabbing tingling, numbness, or itching.
20. The method of claim 17 , wherein the pain comprises neuropathic pain.
21. The method of claim 20 , wherein the neuropathic pain is associated with a nerve selected from the group consisting of: peripheral nervous system; cranial nerves; auditory nerve; optic nerve; giant axonal neuropathy; autonomic nerves; sensory nerves; motor nerves; and autosomal dominant familial amyloid neuropathy.
22. The method of claim 20 , wherein the neuropathic pain is associated with a disorder selected from the group consisting of: diabetic neuropathy; hereditary neuropathy with liability to pressure palsy; neuropathy target esterase; “neuropathy, ataxia, and retinitis pigmentosa” (NARP); delayed neuropathy induced by organophosphate poisoning; and polyneuropathy.
23. The method of claim 20 , wherein the neuropathic pain arises from a cause selected from one of the following: aberrant regeneration after formation of a lesion at a peripheral nerve; hyper-sensitized spinothalamic tract due to ongoing spontaneous activity in the peripheral system; central nerve pain arising from the spinothalamic tract (STT, from the spinal cord dorsal horn neurons) representing the major ascending nociceptive pathway; central neural hypersensitization following peripheral nerve damage; loss of afferent inhibition due to a drop in input of large fiber lowering interneuron activity inhibiting nociceptive neurons; loss of afferent inhibition due to reduced activity of the descending antinociceptive systems or loss of descending inhibition; deafferentation hypersensitivity; central neuron hypersensitivity due to release of proinflammatory cytokines and glutamate by glial cells induced by peripheral nerves; and alteration of gene expression or expression of ion channels, causing changes in neurotransmitters and response to neural input.