Glya

Food for special medical purposes. Without: gluten, , lactose, sugar.
Glìalia is to be used under medical control in subjects with disorders sustained by neuroinflammatory processes associated with: transitional ischemic events (TIA); post-hyptic states on ischemic basis; post-traumatic SNC states; cognitive decline states (Mild Neurocognitive Disorder - Mild-NCD); initial dementia; parkinsonisms in the initial phase; demyelinating inflammatory diseases; diseases of the motorboat; mood alterations.
Palmitoilethanolamide
It is a natural endogenous substance of a lipid nature with N-acilethanolamydic structure that in the organism has the function of physiological intervention in order to maintain intersistemic tissue homeostasis.
Luteolina
It is also a natural substance belonging to the family of flavones, equipped with considerable and peculiar antioxidant effects.
The Palmitoiletanolamide and Luteolina association in co-ultramicronized form (ultramicrocomposito PEALUT) allows the two active ingredients to explicate a synergistic effect in the control of neuroinflammation induced by different endogenous and hexogeneous noxes to the Central Nervous System; such control is expressed through the inhibition modulation of non-neuronal cells - astrocytes, microglia, mastocytes - normally used to guarantee the homeodynamic balance of the central nervous tissue.

Ingredients

	for 1 envelope
Palmitoilethanolamide	700 mg
Luteolin in co-ultramicronized form (Ultramicrocomposito PEALUT®)	70 mg
Mixture of excipients (Sorbitol, Polysorbate 80, Palmitato sucrose	50 mg

Mode of use
Microgranules for sublingual use must be used under medical control following acute events associated with neuroinflammation in the SNC (post-ictal, post-traumatic situations) or, as an attack therapy, in the initial states of neurodegenerative diseases promptly diagnosed; it is recommended to take 2 sachets per day for cycles of 20-30 days possibly repeated using, when possible, the sublingual route.

Notices and precautions of employment
Use under medical control.
The product cannot be the only source of nutrition.
Keep away from the reach of children under 3 years.
Interactions: not highlighted.
Pregnancy: we do not recommend the administration of the product during the period of pregnancy ascertained or presumed, due to inadequate data regarding the use of the Palmitoiletanolamide and Luteolina association in these situations.
Effects on driving vehicles and the use of machinery: Palmitoiletanolamide and Luteolina do not interfere with the ability to drive vehicles and the use of machinery.
Undesirable effects: undesirable effects have not been reported also following long-term administration and high doses of Palmitoilethanolamide, nor have cases of addiction or addiction been reported. In man the administration for 4 months of 100 mg/die of Luteolina proved to be very well tolerated and safe.
Overdose: no known clinical cases of overdose.

Pharmacological properties
Category of Health Authorization (Ministry of Health): Food at Fini Medici Speciali.
Pharmacodynamic properties
Palmitoilethanolamide is an endogenous N-acilethanolamide, without psychotropic effects. Preclinical studies have shown that Palmitoilethanolamide acts pleiotropicly on the mechanisms of neuroinflammation by explicating an effective neuroprotective effect. The use of translational experimental models has clearly shown that Palmitoilethanolamide is able to act on central neuroinflammation through the synchronic modulation of non-neuronal cells (astrocyc, microglia, mastocita) thus effectively determining neuroprotection.
Luteolina explicates a high normalization of the local oxidative state associated with neuroinflammation in the SNC. The available data shows that the association between Palmitoiletanolamide and Luteolina, administered in the form of ultramicrocomposed. Pealut obtained by co-ultramicronization, is highly synergistic on the mechanisms of neuroinflammation in SNC.
Mechanisms of action
Recent studies have shown that the administration of Palmitoiletanolamide + Luteolina, in the form of ultramicro-composed Pealut obtained by co-ultramicronization in the mass ratio 10:1, increases the cellular vitality of both macrophagesic and astrociers subjected to oxidative stress. Pealut ultramicro composite synergistically inhibits lipid peroxidation, mitochondrial dysfunctions associated with cell apoptosis, nitric oxide production (NO) and the expression of inducible enzymes (NO-sintase and oxygenase-2 cycle). Analogue results have been observed in organotypical hippocampus crops damaged by amiloid protein fragment Ab1-42. In hischemy models, the ultra-composed Pealut has proven to completely protect neurons from cell death by confirming the synergistic effect of the two molecules in the co-ultramicronized form. Pealut has demonstrated its effectiveness in vivo in SNC trauma patterns and mood alteration.

Pharmactical properties
Palmitoilethanolamide's temporal profile in human plasma after individual oral intake of quantities between 300 and 1200 mg, shows a dose-dependent increase in the molecule. The plasma peak of Palmitoiletanolamide is observed at an hour from intake; later plasma levels begin to decrease and reach basal value within six hours. At one hour, plasma levels of Palmitoiletanolamide double compared to basal ones after taking 300 mg, while increasing seven times after taking 1200 mg. Experimental studies have shown that after oral administration Palmitoilethanolamide is distributed evenly in tissues; a percentage of the dose administered crosses the blood barrier and reaches the brain tissues. The free Luteolina was found in plasma both in the experimental animal and in man, after oral administration, demonstrating that a part of the luteoline escapes degradation due to the first hepatic passage, in any case avoided for sublingual administration. In the rat, after oral administration the maximum peak of Luteolina in the plasma is reached after 1 hour, while the peak of maximum excretion in the feces and urine takes place around 8 hours.

Toxicology and Tolerance
Toxicology studies have shown that the LD/50 of Palmitoylethanolamide administered by injection (intraperitoneal) in dogs is greater than 400 mg/kg, and in rats, after a single administration by gastric tube, it exceeds 5000 mg/kg, while after repeated administration by gastric tube, it exceeds 500 mg/kg/day.
Clinical studies carried out on a large number of patients demonstrate the excellent tolerability of Palmitoilethanolamide also for very high doses and the absence of clinically relevant variations of blood and blood tests performed. Toxicological studies in rats have shown that administration up to 1 g/kg of Luteolin does not induce toxic effects. Chronic administration of Luteolina at the dose of 23, 48 and 87 mg/kg for 26 weeks, showed no toxic effect on body weight, hematologic, hematochemical and histopathological examinations.
Palmitoiletanolamide and embryotoxicity: no Palmitoilethanolamide teratogenic or embryotoxic effect has been highlighted after pregnancy administration of 50 mg/kg body weight for 12 days. In addition, infants from mothers who received PEA before childbirth and up to 10 days after childbirth were more resistant to Shigella Shigae toxin. Similarly, newborns of mothers who received PEA after childbirth, have demonstrated an increasing resistance already 5 days after birth: these data suggest that mothers may have transferred PEA to infants through milk.
Mutagenicity: although a potential mutagenic effect of Palmitoiletanolamide can be excluded as already present ?lìalia® in the mammals organism, the mutagenicity of PEA has been verified using the Ames test, using 5 mutant species of S. typhimurium (TA 1535-TA1537-TA1538-TA98 and TA 100). With the Ames test, Palmitoiletanolamide, used for dosages between 10,000 and 1,000 μg/ml did not significantly alter the number of revertants. Luteolina at the Ames test also showed no mutagenic effects.
Palmitoiletanolamide and gastric tolerance: oral administration of Palmitoilethanolamide at the dose of 50mg/kg (approximately 5 times higher than the active dose), and at the dose of 10 mg/kg in repeated administrations for 5 days does not induce ulcer formation. In addition, if administered to the dose of 50 mg/kg at the same time as diclofenac 15 mg/kg, a dosage known to induce gastric lesions, PEA decreases the ulcerative potential of NSAIDs, lowering the number of animals that develop ulcerations and mitigating any damage.

Conservation
Store at room temperature.
Validity of packaging: 36 months.

Format
Pack of 20 thermowelded bags.

Cod. 8060