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Responsible Pain Management

•Amino Acid Based Formula•No Severe Side Effects•Reduce Pain, Inflammation & Numbness•Alternative and Complimentary Therapy to Commonly Prescribed Medications

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Indication & Dosing

Percura™ for the dietary management of pain, inflammation and loss of sensation due to peripheral neuropathy.

DOSAGE AND ADMINISTRATION

Recommended Dosing: 1 or 2 capsules taken 1 to 2 times daily or as directed by physician.

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Targeted Amino Technology

The efficacy of Percura is driven by a unique ingredient technology that stimulates the production of specific progenitor cells and neurotransmitters with specific roles in pain management and cell to cell signaling.

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1. Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K. Serum amino acids in fibrositis/fibromyalgia syndrome. J Rheumatol Suppl 1989;19:158-1632. Shell, et al., “A Double-Blind Controlled Trial of a Single Dose Ibuprofen and an Amino Acid Medical Food Theramine for the Treatment of Low Back Pain; Publication

pending, 2010.

There are well documented amino acid deficiencies in patients with chronic pain syndromes. These deficiencies can alter the metabolic processes associated with neurotransmitter synthesis. For example, in one double blind study, subjects with chronic back pain who improved low levels of the amino acids required for production of pain modulating neurotransmitters using a medical food reported a significant improvement in pain.

Amino Acid Levels and Chronic Pain

Arginine Serine Histidine Tryptophan0

5

10

15

20

25

30

35

Change in Blood Concentration of Amino Acids2

Day 1Day 28Normal

Ug/m

l

N=25

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Clinical Response Data

In a clinical outcomes study of Percura, patients with peripheral neuropathy experienced a reduction in pain and numbness over a 56 day period as measured by a 10 point Physician Global Assessment Visual Analog Scale.

Baseline 28 560

1

2

3

4

5

6

7

8

9

Physician Global Assessment Visual Analog Scale

PainNumbness

DAYS

VAS

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Clinical Response Data

Pain Numbness

-35

-30

-25

-20

-15

-10

-5

0

-29.5

-23.1

Physician Global Assessment Visual Analog Scale

% Change in Endpoints after 21 Days

In a clinical outcomes study of Percura, patients with peripheral neuropathy experienced a reduction in pain and numbness over a 21 day period as measured by a 100 point Physician Global Assessment Visual Analog Scale.

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Nerve Impulse and Activation

Inflammation

Pain & Numbness

GABA, Serotonin, Dopamine, Acetylcholine, Nitric Oxide

and D-serine

Histamine, Nitric Oxide, Acetylcholine

Inositol Creatine

Improve Clinical Outcomes

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• Patients who are contraindicated for NSAIDs (High BP, Over 65, CVD, Taking Aspirin)

• Patients who experience severe side effects from Pregabalin or Gabapentin

• Percura can be used as an adjunct therapy to a low dose of a drug

Alternative to NSAIDs & Anti-Epileptics

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• Percura can be used as an adjunct therapy to a low dose opioid pain medication

• Percura can be used as a replacement therapy for other ineffective or dangerous pain medications

Alternative to Narcotic Pain Medications

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Percura is a source of amino acids, biogenic amines,

and botanicals that promote the production of

neurotransmitters responsible for reducing signals

along the ascending and descending pain pathways

and inflammatory pathways.

Pain and inflammatory conditions increase the

turnover rate of arginine, choline, GABA, glutamine,

histidine, 5-hydroxytryptophan, and serine. Simple

dietary modifications are not sufficient to satisfy

cellular demand and restore homeostasis to the

ascending and descending pain pathways and

inflammatory processes.

Neurotransmitter Pathways

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Progenitor cells are developmentally committed to a cell line but are undifferentiated or immature in comparison to those cells that have differentiated and matured into specialized cells. Progenitor cells are multipotent or unipotent.

Activation of neuronal progenitor cells through growth factors such as creatine can lead to increased cell division important for the repair process in peripheral sensory nerves.*

Progenitor Cell Pathways

*Murakami, et al. Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair. Brain Research, 2003.

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PRECAUTIONS AND CONTRAINDICATIONSPercura is contraindicated in an extremely small number of patients with hypersensitivity to any of the nutritional components of Percura.

ADVERSE REACTIONSOral supplementation with L-arginine at high doses up to 15 grams daily is generally well tolerated. The most common adverse reactions of higher doses - from 15 to 30 grams daily - are nausea, abdominal cramps, and diarrhea. Percura contains less than 1 gram per dose of amino acids however, some patients may experience these sympotoms at lower doses. The total combined amount of amino acids in each Percura capsule does not exceed 500mg.

Safety Information

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DRUG INTERACTIONSPercura does not directly influence the pharmacokinetics of prescription drugs.

OVERDOSEThere is a negligible risk of overdose with Percura as the total amount of amino acids in a one month supply (120 capsules) is less than 60 grams. Overdose symptoms may include diarrhea, weakness, and nausea.

Safety Information Cont.

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2006;21:482-493.10. Turek FW, Dugovic C, Zee PC. Current understanding of the circadian clock and the clinical implications for neurological disorders. Arch Neurol

2001;58:1781-1787.11. Belousov AB, O'Hara BF, Denisova JV. Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate

excitation. J Neurosci 2001;21:2015-2027.12. Farber L, Haus U, Spath M, Drechsler S. Physiology and pathophysiology of the 5-HT3 receptor. Scand J Rheumatol Suppl 2004;2-8.13. Dickenson AH, Chapman V, Green GM. The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of

pain in the spinal cord. Gen Pharmacol 1997;28:633-638.14. Ernberg M, Lundeberg T, Kopp S. Pain and allodynia/hyperalgesia induced by intramuscular injection of serotonin in patients with fibromyalgia and healthy

individuals. Pain 2000;85:31-39.15. Furst DE, Manning DC. Future directions in pain management. Clin Exp Rheumatol 2001;19:S71-S76. 16. Linderoth B, Stiller CO, Gunasekera L et al. Release of neurotransmitters in the CNS by spinal cord stimulation: survey of present state of knowledge and

recent experimental studies. Stereotact Funct Neurosurg 1993;61:157-170.17. Hogg RC, Raggenbass M, Bertrand D. Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol 2003;147:1-46.18. Abbadie C, Brown JL, Mantyh PW, Basbaum AI. Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of

persistent pain. Neuroscience 1996;70:201-209.19. Thomas RJ. Excitatory amino acids in health and disease. J Am Geriatr Soc 1995;43:1279-1289.20. Dickenson AH. Plasticity: implications for opioid and other pharmacological interventions in specific pain states. Behav Brain Sci 1997;20:392-403.21. Dickenson AH. NMDA receptor antagonists: interactions with opioids. Acta Anaesthesiol Scand 1997;41:112-115.22. Oliverio A, Castellano C, Puglisi-Allegra S. Psychobiology of opioids. Int Rev Neurobiol 1984;25:277-337.23. Ono T, Inoue M, Rashid MH, Sumikawa K, Ueda H. Stimulation of peripheral nociceptor endings by low dose morphine and its signaling mechanism.

Neurochem Int 2002;41:399-407.24. Ribeiro JA, Sebastiao AM, de MA. Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 2002;68:377-392.25. Gallowitsch-Puerta M, Pavlov VA. Neuro-immune interactions via the cholinergic anti-inflammatory pathway. Life Sci 2007;80:2325-2329.26. Hancock CM, Riegger-Krugh C. Modulation of pain in osteoarthritis: the role of nitric oxide. Clin J Pain 2008;24:353-365.27. Holthusen H, Arndt JO. Nitric oxide evokes pain at nociceptors of the paravascular tissue and veins in humans. J Physiol 1995;487 ( Pt 1):253-258.28. Wahl SM, McCartney-Francis N, Chan J, Dionne R, Ta L, Orenstein JM. Nitric oxide in experimental joint inflammation. Benefit or detriment? Cells Tissues

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Select References

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