epitech

Adolene
Micronized PALMITOYLETHANOLAMIDE + trans-POLYDATIN
200 mg + 20 mg

1) PRODUCT NAME
adolene (Food for Special Medical Purposes - AFMS)

2) QUALITATIVE-QUANTITATIVE COMPOSITION
2.1) Active ingredient: adolene tablets Micronized palmitoylethanolamide 200 mg + trans-Polydatin 20 mg per tablet.
2.2) Excipients: Adolene 200 mg + 20 mg single tablets contain 96.48 mg of a mixture of excipients (for the full list see section 7.1).

3) PRODUCT FORM
adolene 200 mg + 20 mg round, pink tablets.

4) CLINICAL INFORMATION
4.1) Palmitoylethanolamide and trans-Polydatin are nutritional factors that act as synergistic biological modulators in the body, promoting control of physiological tissue reactivity even in the presence of elevated oxidative stress. The combination of Palmitoylethanolamide and trans-Polydatin is indicated to counteract chronic, inflammatory, and painful processes in the pelvic area, a region where oxidative stress represents one of the most important stimuli capable of inducing uncontrolled mast cell degranulation, resulting in tissue hyperreactivity and the onset of inflammatory processes characterized by hyperalgesia. In these subjects, 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, simultaneously modulating the production of regulatory cytokines by T lymphocytes due to the presence of trans-Polydatin. adolene should be used under medical supervision, in the control of the tissue mechanisms that induce and sustain dysmenorrhea.
4.2) Directions for use as directed by a doctor, as a guideline: 2-3 tablets per day for 10 days starting from the 20th day of the menstrual cycle.
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 and trans-Polydatin in these situations.
4.7) Effects on ability to drive and use machines: the combination of Palmitoylethanolamide and trans-Polydatin, 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 drug 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, chemically similar to the endocannabinoid anandamide and with a largely shared spectrum of biological activity. The main difference between the two molecules is the inability of palmitoylethanolamide to interact with the CB1 receptor responsible for the endocannabinoid's psychotropic effects; therefore, its intake is not associated with these central effects. Palmitoylethanolamide has anti-inflammatory effects, affecting both peripheral inflammatory processes and central neuroinflammation, and analgesic effects, evident in both acute and chronic neuropathic pain, as evidenced by numerous in vitro and in vivo experimental studies and a growing number of clinical trials. Trans-Polydatin (or Piceid) is a glucoside of resveratrol, a trihydroxystilbene polyphenol. It possesses marked antioxidant activity, both as a scavenger and as an inhibitor of lipid peroxidation. It has also been shown to be able to control cellular oxidative processes that play an important role in the development of pelvic system pathologies.
5.3) Biokinetic properties: Palmitoylethanolamide, after oral administration to humans, in single doses ranging from 300 to 1200 mg, is present in plasma at dose-dependent concentrations. 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 demonstrated that after oral administration, palmitoylethanolamide is uniformly distributed throughout tissues. After oral administration of trans-Polydatin, glucuronide concentrations similar to those detected after administration of trans-Resveratrol have been identified and quantified in the blood. These metabolites disappear from plasma within 24 hours of ingestion.
5.4) Mechanisms of action: Multiple mechanisms of action of palmitoylethanolamide have been described in various pathological conditions. Two main cellular targets of the molecule are known: mast cells and microglia. Normalizing the excessive activation of these immunocompetent cells, involved in peripheral inflammatory processes, central neuroinflammation, and acute and chronic neuropathic pain, is responsible for the main effects of palmitoylethanolamide. At the molecular level, palmitoylethanolamide interacts with multiple receptors, the principal one being the nuclear receptor PPAR-α, a receptor implicated in the control of inflammatory and neuroprotective processes. In certain conditions, palmitoylethanolamide interacts with the cannabinoid receptor CB2, a receptor primarily present on immune cells, including mast cells and microglia, whose expression increases significantly in inflammatory conditions. Palmitoylethanolamide enhances the activity of endogenous N-acylethylamides. The mechanism, called the entourage effect, allows palmitoylethanolamide to interact indirectly with the endocannabinoid and endovanilloid systems. Trans-Polydatin, in addition to its strong antioxidant properties, exerts an anti-inflammatory effect related to its ability to modulate the functions of various immunocompetent cells, such as T lymphocytes, specifically by regulating these cells' production of regulatory and pro-inflammatory cytokines. At low concentrations, it can stimulate an immune response, while at higher concentrations, it inhibits it.
5.5) Clinical efficacy: Palmitoylethanolamide and trans-Polydatin are molecules that exhibit synergistic effects on cells (mast cells and lymphocytes) strongly implicated in inflammatory processes and capable of triggering reciprocal activation. Their combination has proven to be a valid therapeutic intervention targeting chronic, inflammatory, and painful processes in the pelvic system.

6) TOXICOLOGY AND TOLERABILITY
Toxicology studies have shown that the LD50 of palmitoylethanolamide administered intraperitoneally in dogs is greater than 400 mg/kg, and in rats, after a single administration by gavage, it exceeds 5000 mg/kg, while after repeated administration by gavage, it exceeds 500 mg/kg/day. Clinical studies conducted with adolene on a significant number of patients demonstrate the excellent tolerability of the palmitoylethanolamide + trans-Polydatin combination, even at very high doses, and the absence of clinically relevant changes in hematological and blood chemistry tests performed.
6.1) Embryotoxicity: No teratogenic or embryotoxic effects of Palmitoylethanolamide were observed after administration of 50 mg/kg of body weight to pregnant women for 12 days. Furthermore, newborns of mothers who received PEA antepartum were more resistant to Shigella Shigae toxin up to 10 days after birth. Similarly, newborns of mothers who received PEA antepartum showed increasing resistance evident as early as 5 days after birth: these data suggest that mothers may have transferred PEA to their newborns through their milk. No embryotoxic effects of trans-Polydatin are known.
6.2) Mutagenicity: Although a potential mutagenic effect of Palmitoylethanolamide can be excluded since it is already present in mammalian organisms, the mutagenicity of PEA was verified using the Amest test, using 5 mutant species of S. typhimurium (TA 1535-TA1537-TA1538-TA98 and TA 100). With the Ames test, Palmitoylethanolamide, used at doses between 10,000 and 1,000 mcg/ml, did not significantly alter the number of revertants. No mutagenic effects of trans-Polydatin are known.
6.3) Gastric tolerability: Oral administration of Palmitoylethanolamide at a dose of 50 mg/kg (a dose 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 concurrently with diclofenac 15 mg/kg, a dose known to induce gastric lesions, PEA decreases the ulcerogenic potential of NSAIDs, reducing the number of animals that develop ulcerations and mitigating any damage that may occur.

7) PRODUCT INFORMATION
7.1) Excipients: Adolene 200 mg + 20 mg tablets contain 96.48 mg of a mixture of excipients (Microcrystalline cellulose, Magnesium stearate, Vegetable polysorbate, Croscarmellose sodium, Polyvinylpyrrolidone, Colloidal anhydrous silica, Polyvinyl alcohol) and are coated with a film consisting of a total of 9.5 mg of E120, E1521, E171.
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 container: PVC/PVDC/aluminium foil blisters in boxes of 30 tablets.
7.6) Special precautions for disposal: no special instructions.
7.7) Gluten: This product does not contain gluten .

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

9) MARKETING AUTHORISATION NUMBER
adolene 200 mg + 20 mg tablets DGSAN 0011257-P
10) DATE OF FIRST MARKETING AUTHORISATION
adolene 200 mg + 20 mg tablets 04/22/2008
11) TEXT REVISION DATE 04/2014