This product contains sodium benzoate. The increase in bilirubin in the blood after its albumin displacement can increase neonatal jaundice, in which it can progress to an unconjugated bilirubin deposit in the brain tissue. Silymarin, an active component of Legalon®, acts as a stabilizer of hepatocyte membranes, protecting its integrity and, consequently, the physiological function of the liver; experimentally protects the liver cell against the harmful influence of endogenous and/or exogenous toxic substances. In this way, Legalon® acts beneficially as an adjuvant in the treatment of chronic inflammatory liver diseases, cirrhosis and hepatotoxic lesions, and promotes the rapid improvement of clinical symptoms such as headache, asthenism, anorexia, indigestion, epigastric severity, etc. In animals, silymarin has been shown to accelerate hepatic parenchyma regeneration and appear to increase RNA synthesis in the liver. Pharmacodynamic properties The antitoxic efficacy of silymarin has been demonstrated in animal experiments in various models of liver injury, e.g. with the poisons of Amanita phalloides, faloid and amanitin, with lanthanides, carbon tetrachloride, galactosamine, thioacetamine and hepatotoxic virus FV3. The therapeutic effect of silymarin is attributed to the different mechanisms of action: due to the ability to remove radicals, silymarin has an antioxidant effect. The pathophysiological process of lipid peroxidation, which is responsible for the destruction of cell membranes, is interrupted or prevented.
In addition, silymarin stimulates protein synthesis in liver cells that already have damage and normalizes phospholipid metabolism. The end result is that the cell membrane is stabilized by reducing and preventing the release of enzymes into the cytoplasm of the liver cell (e.g. transaminases). Silymarin restricts the entry of certain hepatotoxic substances into the cell (phalloides fungal poison of the amanita). The increase in protein synthesis by silymarin is due to the stimulation of RNA polymerase I, an enzyme located in the cell nucleus. This leads to an increase in ribosomal RNA formation with increased synthesis of structural and functional proteins (enzymes). The result is an increase in the liver`s ability to rebuild and regenerate. Pharmacokinetic properties The main component of silymarin is silibinin. Clinical studies show that after ingestion in the digestive tract, it is excreted mainly in bile (> 80% of the absorbed amount). As metabolites, glycosides and sulfates Nabile have been found.
Silibin is thought to be absorbed after deconjugation and then enters the enterohepatic circulation, as animal studies have shown. Since elimination is expected to occur primarily via the biliary route (site of action: liver), blood levels are low and renal elimination is low. The absorption half-life is 2.2 h and the elimination half-life is 6.3 h. When Legalon® is administered at therapeutic doses (140 mg silymarin, 3 times daily), silibin levels in human bile are the same after repeated doses and after single doses. These results show that silibin does not accumulate in the body. After repeated administration of silymarin in doses of 140 mg, 3 times a day, biliary elimination reaches steady state. Preclinical safety data Silymarin is characterized by its exceptionally low toxicity and can therefore be safely administered at therapeutic doses over long periods of time. Acute toxicity When administered orally to rats and mice, silymarin has been shown to be virtually non-toxic and the LD50 can be established > 2000 mg/kg. Chronic toxicity In long-term studies of up to 12 months, rats and dogs were given oral silymarin at maximum doses of 2500 and 1200 mg/kg, respectively. No evidence of toxic effects was demonstrated, either in the laboratory results or in the autopsy results.
Fertility studies in rats and rabbits as well as prenatal, perinatal and postnatal toxicity studies showed no adverse effects at any of the reproductive stages (maximum dose tested: 2500 mg/kg). In particular, silymarin showed no evidence of teratogenic potential. In vitro and in vivo mutagenicity studies with silymarin have shown negative results. Carcinogenicity No appropriate in vivo studies in rodents have been conducted to date. According to the World Health Organization and Commission E herbal monographs, Silybum marianum extract (L.) Gaertn (silymarin) is approved for the treatment of various liver diseases, including cirrhosis, alcoholic hepatitis, hepatitis due to exposure to toxic substances, and acute and chronic viral hepatitis1-4. Before use, observe the appearance of the drug. If it is on its expiry date and you notice a change in appearance, contact your pharmacist to find out if you can use it. In addition, this remedy can also be used in combination with other drugs to improve the symptoms of chronic inflammatory liver disease and cirrhosis.
Storage Care Store the product in its original packaging at room temperature (15? C to 30? C). Legalon is contraindicated for people allergic to any of the components of the formula. Also, its use during pregnancy and lactation should be avoided. Legalon® is a hepatoprotector used to treat digestive disorders associated with liver disease and toxic liver damage, and as a supportive treatment for chronic inflammatory liver disease and cirrhosis. 1. WHO monographs on selected medicinal plants. Fructus mariae silybi. [Online]. 2004.
Vol. 2 [cited 2009 Oct 5]. Available at: URL: apps.who.int/medicinedocs/en/d/Js4927e/29.html#Js4927e.29. 2. Milk thistle fruit. In: M Blumenthal (Hrsg.). The full German Commission and monographs: Therapeutic Guide for Herbal Medicines. Austin: American Botanical Council; 1998.
pp. 169-0;350;563-5. 3. Silymarin. In: MEDITEXT® Medical Managements. [Online]. Available from: Greenwood Village: Thomson Healthcare; regularly updated. [Accessed 13 April 2011]. 4. Milk thistle.
Fashionable. Opinions about AltMedDex®. [Online]. Disponível em: Greenwood Village: Thomson Healthcare; Atualizado periodicamente. [Acesso EM 13 April 2011]. 5. Fintelmann V, et al. The therapeutic activity of Legalon® in toxic liver disease was demonstrated in a double-blind study. Therapy Week 1980;30:5589–94. 6.
Feher J, et al. Hepatoprotective activity of silymarine therapy in patients with chronic alcoholism. Orv Heil 1989;130: 2723 -2727. 7. Ferenci P, et al. Randomized controlled trial of treatment with silymarine in patients with cirrhosis of the liver. J hepatol 1989; 9(1):105-13. 8. Salmi HA, Sarna S. Effect of silymarin on chemical, functional and morphological changes in the liver.
A double-blind controlled study. Scand L Gastroenterol 1982; 17(4):517-21. 9. Trinchet JC et al. Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients. Clinical Gastroenterology and Biology, 1989, 13:120-124. 10. Magliulo E et al. (Results of a double-blind study on the effect of silymarin in the treatment of acute viral hepatitis, conducted in two medical centers. Med Kin 1978;73(28-29):1060-5. 11.
Cavalieri S. Legalon Controlled Clinical Trial. Gazzette Medica Italiana, 1974, 133:628. 12. Plomteux G et al. Hepatoprotective effect of silymarine in acute viral hepatitis in humans. International Research Communications Systems, 1977, 5:259-261. 13.
Kiesewetter E et al. Results of two double-blind studies on the efficacy of silymarine in chronic hepatitis. Liver, stomach, intestines, 1977, 7:318-323. 14. Szilárd S et al. Protective effect of legalon® in workers exposed to organic solvents. Acta Medica Hungarica, 1988, 45:249-256. 15.
Palasciano G et al. The effect of silymarin on plasma malondialdehyde levels in patients receiving long-term treatment with psychotropic drugs. Current Therapeutic Research, 1994, 55:537-545. Patients treated with silymarin for 90 days showed significant improvement in liver function compared to patients in the placebo group15. This product contains sorbitol. The additive effect of drugs containing simultaneously sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
