MPS norm
microgranules for oral use
(sublingually)

MICRONIZED PALMITOYLETHANOLAMIDE (PEA-m)
Ultra-micronized palmitoylethanolamide (PEA-um)

GLUTEN FREE

1) PRODUCT NAME
MPS norm

2) QUALITATIVE-QUANTITATIVE COMPOSITION
2.1) Active ingredient:
normast MPS microgranules: Micronized Palmitoylethanolamide (PEA-m: particle size 2.0÷10.0 µm) 300 mg + Ultra-micronized Palmitoylethanolamide (PEA-um: particle size 0.8÷6.0 µm) 600 mg per sachet.
2.2) Excipients: each sachet of normast MPS microgranules contains 337.5 mg of a mixture of excipients (for the complete list see paragraph 7.1).
3) PRODUCT FORM
normast MPS microgranules: white granules.

4) CLINICAL INFORMATION
4.1) Indications: Palmitoylethanolamide is a nutritional factor that acts as a biological factor in the body, promoting control of physiological tissue reactivity. It is therefore to be used under medical supervision as part of the dietary regimen of individuals with disorders caused by neuroinflammatory processes. In these individuals, it is useful to physiologically counteract the deficit in endogenous production of palmitoylethanolamide, which occurs when the body, subjected to recurrent inflammatory conditions, exhausts its natural synthesis capacity. normast MPS is to be used under medical supervision as part of the dietary regimen of individuals with disorders caused by neuroinflammatory processes.
4.2) Dosage and method of use: as per medical advice, as a guideline: normast MPS microgranules 1-2 sachets per day to be placed directly under the tongue, allowing the microgranules to dissolve in saliva.
4.3) Contraindications: none.
4.4) Warnings and precautions for use: The product is not suitable as a sole source of nutrition. Keep out of reach of children under 3 years of age.
4.5) Interactions: not highlighted.
4.6) Pregnancy: administration of the product during pregnancy is not recommended, due to insufficient adequate data regarding the use of Palmitoylethanolamide in these situations.
4.7) Effects on ability to drive and use machines: Palmitoylethanolamide, at the recommended doses, does not interfere with the ability to drive and use machines.
4.8) Side effects: No side effects have been reported to date, even following long-term administration and high doses. No cases of habituation or dependence have been reported.
4.9) Overdose: No clinical cases of overdose have been known to date.

5) PROPERTY
5.1) Category: Food for Special Medical Purposes.
5.2) Biodynamic properties: Palmitoylethanolamide is an endogenous N-acylethanolamide that plays an important role in resolving neuroinflammatory and pain processes. Palmitoylethanolamide acts on several non-neuronal cellular targets involved in peripheral and central neuroinflammatory processes, which manifest in both acute and chronic pain conditions, as demonstrated in numerous preclinical studies and supported by a growing number of clinical trials.
5.3) Biokinetic properties: After oral administration to humans, ultramicronized palmitoylethanolamide is present in plasma at dose-dependent concentrations in single doses ranging from 300 to 1200 mg. Peak plasma levels of palmitoylethanolamide are observed one hour after ingestion; subsequently, plasma levels begin to decline and reach baseline within six hours. Experimental studies have shown that after oral administration, ultramicronized palmitoylethanolamide is uniformly distributed throughout tissues.
5.4) Mechanisms of action: The anti-inflammatory and analgesic effects of palmitoylethanolamide are attributable to multiple pleiotropic receptor mechanisms of action. At the cellular level, palmitoylethanolamide acts primarily on two non-neuronal cells: mast cells and microglia. The main effects of palmitoylethanolamide are normalized by the normalization of the excessive activation of these cells involved in peripheral, spinal, and central inflammatory processes characterized by chronic pain. At the molecular level, palmitoylethanolamide interacts with multiple receptors, including PPAR-α, CB2, GPR55, etc. Palmitoylethanolamide enhances the activity of endogenous N-acylethylamides through a mechanism called the entourage effect, which allows it to interact indirectly with the endocannabinoid and endovanilloid systems.
5.5) Clinical efficacy: the use of micronized and ultramicronized Palmitoylethanolamide in clinical practice has been shown to induce an improvement in the painful and functional symptoms that occur in many inflammatory, traumatic and neurodegenerative pathologies affecting the Peripheral Nervous System and the Central Nervous System.

6) TOXICOLOGY AND TOLERABILITY
Acute toxicity studies have shown that the LD50 of palmitoylethanolamide in rats and mice is greater than 5000 mg/kg. After subacute and chronic administration, the safe dose has been estimated at 100 mg/kg/day in dogs and greater than 500 mg/kg/day in mice and rats. Clinical studies conducted on a large number of patients demonstrate the excellent tolerability of palmitoylethanolamide even at very high doses and the absence of clinically relevant changes in hematological and blood chemistry tests performed.
6.1) Palmitoylethanolamide and embryotoxicity: no teratogenic or embryotoxic effect of palmitoylethanolamide was observed after administration during pregnancy of 50 mg/kg of body weight for 12 days.
6.2) Palmitoylethanolamide and mutagenicity: although a potential mutagenic effect of Palmitoylethanolamide can be excluded as it is already present in the mammalian organism, the mutagenicity of PEA has been verified using the Amest test: Palmitoylethanolamide, used at doses between 10000 and 1000 µg/ml, did not demonstrate mutagenic effects.
6.3) Palmitoylethanolamide and gastric tolerability: Oral administration of palmitoylethanolamide at a dose of 50 mg/kg (approximately 5 times higher than the active dose) and at a dose of 10 mg/kg in repeated administrations for 5 days does not induce ulcer formation. Furthermore, when administered at a dose of 50 mg/kg simultaneously with diclofenac 15 mg/kg, a dosage known to induce gastric lesions, PEA decreases the ulcerogenic potential of NSAIDs, reducing the number of animals that develop ulcerations and mitigating any damage.

7) PRODUCT INFORMATION
7.1) Excipients: each sachet of normast MPS microgranules contains 337.5 mg of a mixture of excipients (Fructose, Sorbitol, Polysorbate 80, Palmitic esters of sucrose, Cross-linked sodium carboxymethylcellulose).
7.2) Incompatibilities: none known.
7.3) Validity period: 3 years.
7.4) Special precautions for storage: This product does not require any special storage conditions.
7.5) Nature and contents of the container: heat-sealed sachets in paper/aluminium/PE in boxes of 20; bottles in food-grade polyethylene terephthalate (PET) with PE cap
7.6) Special precautions for disposal: no special instructions.
7.7) Gluten: These products do not contain gluten .

8) MARKETING AUTHORISATION HOLDER
EPITECH Group SpA - via Egadi, 7 - 20144 Milan - Italy

Italy 9) TEXT REVISION DATE 01/2016

normast MPS microgranules pack of 20 sachets.

Code 8014