EP-4504155-B1 - DELAYED-RELEASE GRANULATES OF MELATONIN, COMBINATIONS COMPRISING MELATONIN, PHARMACEUTICAL COMPOSITIONS AND DIETARY SUPPLEMENTS CONTAINING THEM, AND THEIR USE IN THE TREATMENT OF INSOMNIA AND FOR THE REDUCTION OF THE TIME REQUIRED TO FALL ASLEEP

Inventors

• Costa, Andrea Domizio
• MADARO, ELENA
• MERICO, ROBERTO

Dates

Publication Date

20260506

Application Date

20230404

Claims (10)

1. A slow-release granulate that comprises or, alternatively, consists of melatonin, sodium alginate, and calcium lactate.
2. The granulate according to claim 1, characterized by the fact that said granulate comprises from 1% to 20% by weight of melatonin with respect to the total weight of the granulate, preferably from 1.5% to 15%, more preferably from 2% to 10%; from 20% to 60% by weight of sodium alginate with respect to the total weight of the granulate, preferably from 40% to 55%, more preferably from 45% to 50%; and from 30 to 60% by weight of calcium lactate with respect to the total weight of the granulate, preferably from 40% to 55%, more preferably from 45% to 50%.
3. A process for preparing a granulate according to claim 1 or 2, wherein said process comprises the following steps: a. a wet granulation of a mixture comprising or, alternatively, consisting of melatonin, sodium alginate and calcium lactate to form granules intended to be coated; b. a coating of the granules obtained from step (a) through two sequential steps: b' a granulation of the granules obtained from passage (a) with calcium lactate; and b" a granulation of the granules obtained from passage (b') with sodium alginate.
4. A process for preparing a granulate according to claim 1 or 2, wherein said process comprises a granulation of a mixture comprising or, alternatively, consisting of melatonin, sodium alginate and calcium lactate and subsequent coating with a mixture comprising or, alternatively, consisting of sodium alginate and calcium lactate.
5. A combination consisting of melatonin, sodium alginate and calcium lactate.
6. A pharmaceutical and/or food composition comprising the granulate according to claim 1 or 2, or the combination of claim 5, together with one or more conventional excipients and/or vehicles.
7. The composition according to claim 6, characterized by the fact that it is in the form of a composition for oral use.
8. The composition according to claim 7, characterized by the fact that it is in the form of gummy candies, chewable tablets, capsules or chewing gum.
9. The composition according to any one of claims 6 to 8, characterized by the fact that it comprises from 0.5 to 5 mg of melatonin, preferably from 1 to 3 mg of melatonin.
10. The granulate according to claim 1 or 2, the combination of claim 5, or the composition according to any one of claims 6 to 9, for use in a method of treatment of sleep disorders, preferably primary insomnia, for the reduction of the time required to fall asleep and for the maintenance of the state of falling asleep.

Description

It is an object of the present invention a delayed-release melatonin granulate, pharmaceutical compositions and dietary supplements comprising said granulate and their use in the treatment of sleep disorders and for the reduction of the time required to fall asleep, particularly of primary insomnia. It is also an object of the present invention to a combination consisting of melatonin, sodium alginate and calcium lactate and its use in the treatment of sleep disorders, particularly primary insomnia. Technical Background The International Classification of Sleep Disorders defines insomnia as the subjective perception of difficulty falling asleep, duration, consolidation, or quality of sleep that occurs despite adequate opportunity for sleep and results in some form of daytime disturbance (e.g., fatigue, decreased energy, daytime sleepiness, and mood disordes). Insomnia disorders can be primary or secondary. Primary insomnias may have both intrinsic and extrinsic factors involved in their etiology, but they are not considered secondary to another disorder. Secondary forms occur when insomnia is a symptom of a medical or psychiatric disease, another sleep disorder, or results from substance abuse. The term primary insomnia (used in both the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)) is a disorder identified as chronic when it persists for at least three months with a frequency of at least three times a week. When the disorder meets the symptom criteria but persists for less than three months, it is considered acute short-term insomnia. Different manifestations of insomnia can occur at different times during the sleep period. By way of example: sleep onset insomnia (or initial insomnia) involves difficulty initiating sleep before bedtime;sleep maintenance insomnia (or medium insomnia) involves frequent or prolonged awakenings during the night;late insomnia involves early morning awakening with an inability to return to sleep;non restorative sleep, a disorder of poor sleep quality that does not leave the individual refreshed upon awakening despite adequate duration, is a common sleep disorder that usually occurs in association with difficulty initiating or maintaining sleep; this disorder can also occur in association with other sleep disorders (e.g., breathing-related sleep disorder). Impairment of cognitive performance may include difficulties with attention, concentration, and memory, and may even impair the performance of simple manual skills. Associated mood disorders, are generally described as irritability or mood lability and less commonly as depressive or anxious symptoms. Not all individuals with nighttime sleep disorders are anxious or have functional impairment. For example, sleep continuity is often disrupted in healthy elderly people who nevertheless identify as good sleepers. A diagnosis of insomnia disorder should be reserved for those individuals with significant daytime discomfort or impairment related to their nighttime sleep difficulties. An insomnia disorder is diagnosed if insomnia presents as an independent condition or is in comorbidity with another mental disorder (e.g., major depressive disorder), a medical condition (e.g., pain) or another sleep disorder (e.g., a breathing-related sleep disorder). The onset of insomnia symptoms can occur at any time in life, but the first episode is most common in young adulthood. Less frequently, insomnia begins in childhood or adolescence. Insomnia is a more prevalent disorder among females than males, with first onset often associated with the birth of a new baby or menopause. Despite a higher prevalence among older females, polysomnographic studies suggest better preservation of sleep continuity and slow-wave sleep in older females than in older males. Short-term insomnia affects 30% to 50% of the population. It is estimated that the prevalence of chronic insomnia disorder in industrialized nations is at least 5% to 10%. Chronic insomnia is associated with numerous adverse effects on function, health, and quality of life. Increased rates of absenteeism from work, and work and motor vehicle accidents have also been widely reported. Persistent insomnia has been identified in numerous studies as a significant risk factor for the development of psychiatric disorders, particularly mood disorders. This condition is also associated with an increased risk of relapse for depression and alcoholism, as well as adverse effects in populations with chronic pain. More recent investigations suggest that chronic insomnia is associated with an increased risk of cardiovascular disease. In particular, insomnia with objectively short sleep times is a significant risk factor for the development of hypertension. Regulation (EU) 432/2012 established the list of health claims authorized under Article 13.1 of Regulation (EC) 1924/2006 for vitamins, minerals and other substances. S