FR3131195A1 - Combination product to help relaxation and sleep - Google Patents

Abstract

The subject of the present invention is a combination product comprising, as active substances, at least valerian, lemon balm, California poppy and poppy to help relaxation and/or falling asleep. The invention finally relates to the use of a combination product as previously defined for the treatment of somnopathies.

Description

Combination product to help with relaxation and falling asleep

The subject of the present invention is a combination product comprising, as active substances, at least valerian, lemon balm, California poppy and poppy to help with relaxation and/or falling asleep. The invention finally relates to the use of a combination product as previously defined for the treatment of sleep disorders.

BACKGROUND

A sleep disorder (somnipathy) is a disorder related to an individual's sleep habits. Some sleep disorders are serious enough to interfere with physical, mental, and emotional functioning. A commonly used test for sleep disorders is polysomnography.

Sleep dysfunction can be caused by a variety of issues, from teeth grinding (bruxism) to night terrors. When an individual suffers from difficulty falling asleep without any apparent cause, it is called insomnia. In addition, sleep disorders can lead the individual to sleep excessively, a situation known as hypersomnia. Other sleep disorder conditions may be linked to substantial abuse.

Sleep disorders include:

-primary insomnia - chronic difficulty falling asleep and/or maintaining sleep when no other symptomatic cause can be perceived;

-bruxism, involuntary grinding or clicking of the teeth during sleep;

-delayed sleep phase syndrome, inability to fall asleep or wake up during socially acceptable hours but causing no problem in sleep maintenance, circadian rhythm disorder (similar symptom - hypernycthemeral syndrome);

-hypopnea, respiratory or cardiac abnormality during sleep;

-narcolepsy, sudden sleep, often spontaneous at any time of the day;

-cataplexy, sudden weakness of the motor muscles which can result in a fall to the ground;

-night terror, pavor nocturnus , nocturnal disorder characterized by strong fear and anxiety;

-sleepwalking, an activity engaged physically and unconsciously during sleep;

-somniphobia, fear of sleeping;

-sleep apnea.

Following the evolution of knowledge regarding sleep in the 20th century, including the discovery of hypnology and sleep apnea, the medical importance of sleep is recognized. The clinical community is increasingly interested in sleep disorders, such as sleep apnea, and the role and quality of sleep during different conditions. During the 1970s in the United States, clinics and laboratories devoted themselves to the study of sleep accompanied by its disorders.

The impact of sleep disorders on the lives of individuals can be very significant: a study in 2014 established that sleep perceived as being of poor quality is associated with an increased risk of suicide in the elderly ( mean age in the study, 74.9 years plus or minus 5.6 years).

Sleep medicine is now being adapted into internal medicine, family medicine, pediatrics, otolaryngology, psychiatry and neurology.

The present invention relates to a composition for helping relaxation and falling asleep in adults and children.

Indeed, a study published in the journal Paediatrica (vol 14 n°3 2003) takes stock of children's sleep disorders. Up to 25% of young children and almost 50% of school-aged children have sleep disorders that have lasted for at least 6 months. The prevalence is 33% for adolescents. Hedger Archbold et al. differentiated these disorders. Certain sleep disorders are more common at a certain age and linked to particular situations, others can occur at any age (for example: sleep apnea syndrome, epilepsy associated with sleep. A sleep disorder does not is not only a problem for parents. Disturbed sleep also involves risks for the cognitive development of the child with the occurrence of behavioral disorders. As for adults, it seems that there is an association between obstructive apneas sleep and a higher prevalence of metabolic syndrome in children and adolescents.

The duration and organization of sleep are subject to changes during development. Basic knowledge makes it possible to distinguish true sleep disorders from variations in the norm. As an indication, the approximate values of sleep duration per 24 hours are: 16 hours for full-term newborns, 13 hours for 2-year-olds, 11 hours at 5 years, 10 hours at 9 years and approximately 9 hours for a 14 year old. Young adults still need about 8 hours, a fact often forgotten. The variability of these values is quite significant and corresponds to the distribution of genetic traits in the population. Individual sleep needs are most easily established during weekends and vacations, when the body is allowed to sleep as long as needed.

During the night we observe three states: wakefulness, paradoxical sleep (rapid eye movement sleep or REM sleep) and slow-wave sleep (non-REM sleep). A sleep cycle includes a passage through the three states. In deep sleep different parasomnias (non-REM parasomnias) can originate: for example night terrors in small children, which are replaced by sleepwalking in older children. Since sleep cycles with deep phases occur in the first half of the night, it is usual to observe these parasomnias during the first hours after falling asleep.

There are a number of products on the market to overcome problems falling asleep or relaxing. Among these products, we can cite, for example, Passiflora, a homeopathic preparation from Boiron which contains: Passiflora incarnata, Ignatia amara, Coffea cruda, Nyckterinia, Tellurium metallicum, Phosphoricum acidum, Palladium metallicum, Magnesium metallicum. Quietude, which is also a homeopathic preparation from Boiron, which contains: Chamomilla vulgaris, Gelsemium, Hyoscyamus niger, Kalium bromatum, Passiflora incarnata, Stramonium. The Pédiakid Sommeil product from Ineldea is based on magnesium, manganese, phosphorus, orange flower extract, lavender extract, chamomile extract, lemon balm extract, marjoram extract, hawthorn extract. The Pédiakid Nervousness product from Ineldea contains hydroglycerin extracts of plants (hops, lemon balm, orange blossom, passion flower, gentian), magnesium, vitamin B6, and phosphate. Bayer's Euphytocalm product contains dry lemon balm extract and magnesium. The Merlin Santé Sommeil Product contains melatonin, valerian and California poppy. We can also cite the Sleep Complex product from Noverg based on melatonin, California poppy, passionflower and poppy or the SommeilBio product from Laboratoires Santarom based on California poppy, passionflower, tiller, lemon balm and valerian.

None of the products offered contain the association which is the subject of the present invention.

These products, although containing valerian in combination with lemon balm, do not provide complete satisfaction in terms of soothing, relaxation and/or helping to fall asleep. The combination product of the present invention provides a soothing effect to facilitate falling asleep, and helps to naturally return to restful sleep, without waking up at night. The product according to the present invention is without side effects or addiction. The combination product according to the present invention helps to help you fall asleep, soothes, relaxes and helps maintain healthy sleep.

The product according to the present invention also has the advantage of preferably not containing any artificial coloring or allergens and of being, preferably, lactose or gluten-free.

The product of the present invention has a dosage suitable for adults, preferably in the form of a tablet.

The present invention relates to a combination product, comprising as active substances, at least:

(i) valerian,

(ii) lemon balm,

(iii) California poppy, and

(iv) poppy

to help with relaxation and/or falling asleep.

The present invention also relates to a combination product, comprising as active substances, at least:

(i) valerian,

(ii) lemon balm,

(iii) California poppy, and

(iv) poppy

for its use in the treatment of sleep disorders.

• Des plantes ou extraits de plantes, tels que par exemple de la fleur d’oranger, la lavande, l’aubépine, la marjolaine, le houblon, la gentiane, la passiflore, la camomille et/ou la rhodiola,
• Des vitamines et minéraux, tels que par exemple la vitamine D, les vitamines du groupe B, telles que la vitamine B6, le magnésium et/ou le calcium
• Des acides aminés ou dérivés d’acides aminés, tels que par exemple le tryptophane

In certain embodiments, the combination product according to the invention comprises, in addition to valerian, lemon balm, California poppy and poppy, as active substances:

• Plants or plant extracts, such as for example orange blossom, lavender, hawthorn, marjoram, hops, gentian, passionflower, chamomile and/or rhodiola,
• Vitamins and minerals, such as vitamin D, B vitamins, such as vitamin B6, magnesium and/or calcium
• Amino acids or amino acid derivatives, such as for example tryptophan

In certain embodiments, the combination product of the invention is characterized in that valerian, lemon balm, California poppy and poppy are in the form of plant extracts.

In certain embodiments of the invention, the combination product according to the invention may be in the form of a single (or combined) composition containing at least as active substances:

(i) valerian,

(ii) lemon balm,

(iii) California poppy, and

(iv) poppy

in a physiologically acceptable environment.

In certain embodiments, the combination product of the invention is characterized in that valerian, lemon balm, California poppy and poppy are administered in the form of a tablet containing:

- 100 to 500 mg, preferably 200 to 300 mg of valerian

- 50 to 300 mg, preferably 100 to 200 mg of lemon balm

- 10 to 200 mg, preferably 30 to 100 mg of California poppy

- from 2 to 100 mg, preferably from 10 to 50 mg of poppy

per unit in dry form.

According to a particular embodiment of the invention, the combination product is characterized in that the active ingredients (i), (ii), (iii), (iv) are in a medium suitable for oral administration. Preferably, the suitable medium is a solid medium. Preferably, the combination product is in tablet form.

When used for the therapeutic treatment of sleep disorders, the combination product according to the present invention is particularly intended for adults or children.

The different embodiments of the invention are particularly described in the detailed description below. These embodiments can be taken separately or in combination with each other.

In the present invention, the applicant has demonstrated that the combination of at least (i) valerian, (ii) lemon balm, (iii) California poppy, and (iv) poppy presented a synergistic effect for help with relaxation and/or falling asleep.

By synergistic effect, it is understood according to the present invention that the combination of at least (i) valerian, (ii) lemon balm, (iii) California poppy, and (iv) poppy has an effect on the aid in relaxation and/or falling asleep, during the treatment which is greater than the cumulative effects of a treatment (a) comprising the administration of valerian, not associated with lemon balm, California poppy and poppy, and conversely a treatment (b) comprising the administration of lemon balm, not associated with valerian, California poppy and poppy or a treatment (c) comprising the administration of California poppy, not associated with valerian, lemon balm and poppy or a treatment (d) comprising the administration of poppy, not associated with valerian, lemon balm and California poppy.

Valerian

Valerian officinale or Hill Valerian or Small-leaved Valerian ( Valeriana officinalis L. ), also known under the vernacular names of Catnip(s), St. George's Grass, or Bruised grass is a perennial herb in the family Valerianaceae . In the West its roots are traditionally used for their sedative and anxiolytic effects. They help promote sleep and reduce anxiety and are therefore considered a natural alternative to sleeping pills and chemical anxiolytics.

In the context of the present invention, valerian is present in the composition in an amount of 100 to 500 mg, preferably 200 to 300 mg of valerian. Its quantities of valerian represent in plant equivalent from 400 to 2000 mg, preferably 800 to 1200 mg.

Valerian is preferably present in the form of a plant extract.

Lemon balm

Lemon balm or lemon balm (Melissa officinalis) is a perennial herbaceous plant from the Lamiaceae family. Its name comes from the Greek melissophullon which means “bee leaf”. It is also called lemon balm or simply lemongrass, not to be confused with lemongrass (Cymbopogon citratus) used in Asian cuisine. It is a plant native to the eastern Mediterranean basin, which spread throughout Europe since Antiquity. Lemon balm, or lemon balm, has been cultivated in gardens since very ancient times. Originally from Europe, it was introduced to North America. The stems and leaves are still used as a tonic and mild stimulant. The taste is astringent and the aroma light. Alcohol is obtained by distillation of its fresh leaves: lemon balm water has antispasmodic properties. Lemon balm can also be consumed in the form of herbal teas.

Lemon balm is most often used for its calming and relaxing properties. In fact, it regulates nerve impulses, which has a beneficial effect on tachycardia, but also reduces spasms of the stomach and colon (it also has antifungal properties). In infusion, lemon balm has a slightly sedative effect, and also promotes sweating, which is why it is recommended in cases of insomnia, or in extreme heat in infants and the elderly.

In the context of the present invention, lemon balm is present in the composition in an amount of 50 to 300 mg, preferably 100 to 200 mg of lemon balm. Its quantities of lemon balm represent in plant equivalent from 300 to 1800 mg, preferably 600 to 1200 mg.

Lemon balm is preferably present in the form of a plant extract.

The California poppy

The California poppy or American poppy ( Eschscholzia californica Cham .) is a herbaceous plant of the Papaveraceae family commonly cultivated in ornamental gardens. It is a plant native to California and the Southwestern United States where it covers large areas near redwood forests. Thanks to the californidine and protopine (isoquinolines with sleeping properties) that it contains as well as its non-addictiveness, the California poppy is used as a gentle alternative to sleeping pills such as barbiturates, benzodiazepines and first-class H1 antihistamines. generation.

California poppy acts on the different phases of sleep. First, it helps you get to sleep more quickly during the falling asleep phase. Secondly, it helps improve the quality of sleep.

In addition to its qualities for sleeping well, poppy also helps to cope with stress and contributes to relaxation, by maintaining physical and mental relaxation.

In the context of the present invention, California poppy is present in the composition in an amount of 10 to 200 mg, preferably 30 to 100 mg of California poppy. Its quantities of California poppy represent in plant equivalent 50 to 1000 mg, preferably 150 to 500 mg.

California poppy is preferably present in the form of a plant extract.

The poppy

The poppy ( Papaver rhoeas ) is a species of dicotyledonous plant in the Papaveraceae family, native to Eurasia.

It is an annual herbaceous plant, very abundant in freshly disturbed soil from spring, which is distinguished by the red color of its flowers and by the fact that it often forms large colorful carpets visible from very far away. It belongs to the group of so-called messicole plants because it has been associated with agriculture since very ancient times, thanks to its biological cycle adapted to cereal crops, flowering and setting seeds occurring before the harvest.

Like all poppies, the poppy has narcotic effects due to the alkaloids it contains.

In herbal medicine, we use its dried petals, which take on a wine color when dried and from which we most often make herbal teas. Its soothing effects are felt on adults, but especially on young children (poppy was once mixed with children's porridge to help them sleep). With its emollient, mild sedative and soothing properties, poppy is a calming agent for coughs and throat irritations. It is then used in the form of lozenges to suck.

The composition according to the present invention comprises 2 to 100 mg, preferably 10 to 50 mg of poppy. Its quantities of poppy represent in plant equivalent from 10 to 500 mg, preferably 50 to 250 mg.

Poppy is preferably present in the form of a plant extract.

Physiologically acceptable environment

A physiologically acceptable medium is one having no toxic or detrimental effect under the conditions of use and inert with respect to the active ingredients of the combination product. Such a medium may for example include different adjuvants depending on its therapeutic or cosmetic purpose, such as, but not limited to, flavorings, colorings, fillers, preservatives, diluents, wetting or suspending agents, texturizers, etc. Such media can also allow immediate, modified or delayed release of one or other of the active ingredients.

By “texturants”, we mean compounds which modify the texture of the products in which they are incorporated. Examples of texturizers are: guar and carob flours; gums arabic, xanthan and gellan; carrageenans; starches (native or modified); microcrystalline cellulose; gelatin; pectin; alginates (E400 to E405); agar-agar; and their mixtures. By “emulsifiers”, we mean amphiphilic compounds characterized by their HLB (Hydrophilic Lipophilic Balance) value, in particular capable of stabilizing oil-in-water emulsions (particularly interesting if one wishes to add, for example, lipid-soluble active ingredients such as as fat-soluble vitamins. Examples of food emulsifiers are lecithin and its derivatives present in particular in egg yolk; mono- and diglycerides of fatty acids; and polysorbate 80.

By “dyes” we mean compounds of natural or synthetic origin capable of conferring coloring to the composition on their own. Examples of food colorings are known in Europe under the codes E100 to E180.

By “preservatives” is meant compounds inhibiting the proliferation of microorganisms, in particular yeasts and/or molds and/or bacteria, in particular Staphylococcus Aureus, in the composition. Examples of food preservatives are sorbic acid and its salts (E200 to E203: benzoic acid and its salts (E210 to E219); sulphites and derivatives (E220 to E228); natamycin; nisin; and their mixtures Preferably, the composition according to the invention does not include any preservative.

By “flavorings” we mean compounds of natural or synthetic origin capable of modifying the taste of the composition on their own. Examples of flavors are apricot, pineapple, banana, black currant, cherry, lemon, lime, strawberry, raspberry, passion fruit, tangerine, mint, orange , pistachio, pear, licorice, rose, anise, blueberry, cinnamon, ginger, grapefruit, apple, kiwi, lychee, melon, coconut, peach, currant, guava, grenadine, mango, blackberry, papaya, vanillin, natural vanilla extract, essential oils and mixtures thereof.

By sugar or sugars is meant, for the purposes of the present invention, any sweetening carbohydrate, preferably glucose syrup, sucrose, glucose, fructose, invert sugar, honey, maltose, polyol or their mixtures.

Additional asset(s)

Any additional active ingredient of nutritional interest and/or helping with relaxation or falling asleep can also be added to the combination products of the invention in pharmaceutical or cosmetic form. The combination product may include, for example, vitamins, mineral salts, essential amino acids, essential fatty acids, trace elements, various plant extracts, fibers, antioxidants, flavonoids.

Advantageously, such an additional active ingredient may be intended to reinforce the desired effect as described above.

Of course, those skilled in the art will take care to choose the additional active ingredients as well as their quantity in such a way that the advantageous properties of the composition according to the invention are not, or substantially not, altered by the planned addition.

As additional usable assets, we can cite:

- water-soluble vitamins and fat-soluble vitamins. Examples of water-soluble vitamins present in the syrupy product prepared according to the invention are in particular: vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid) also called vitamin PP (Pellagra Preventive), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B8 or H (biotin), vitamin B9 (folic acid), vitamin B12 (cobalamin) and vitamin C (ascorbic acid). Examples of fat-soluble vitamins present in the syrupy product prepared according to the invention are in particular: vitamin A (retinol), vitamin D3 (cholecalciferol), vitamin E (mixture of tocopherols and tocotrienols) and vitamin K (phylloquinone) .

- antioxidants, such as curcuminoids; carotenoids, in particular chosen from beta.-carotene, astaxanthin, zeaxanthin, lutein or compounds containing them such as goji berries; polyphenol compounds, flavonoids such as catechins; proanthocyanidins, anthocyanins, OPCs (procyanidolic oligomers); ubiquinones; coffee extracts containing polyphenols and/or diterpenes; chicory extracts; ginkgo biloba extracts; grape extracts rich in proanthocyanidins; chili pepper extracts; soy extracts; Cocoa ; the grenade ; the Emblica; CoenzymeQ10; selenium,

- minerals, such as zinc, calcium, copper, iron, iodine, manganese, magnesium, selenium, chromium (III),

- amino acids, in particular sulfur-containing amino acids, such as glutathione precursors, selenium amino acids, citrulline,

-phytosterols, resveratrol, hesperidin, neohesperidin, orthosilicic acid, monomethylsilanetriol, and their mixtures.

Preferably, a combination product according to the invention is administered orally. Forms suitable for the oral route are for example tablets, capsules, lozenges, powders, granules, lyophilisates, oral solutions and syrups. Tablets, powders, granules, lyophilisates, oral solutions and syrups constitute the currently preferred pharmaceutical or cosmetic form adapted to the oral route. In the case of the preparation of a solid composition in the form of tablets, it is possible for example to mix the main active ingredients (i), (ii), (iii) or (iv) with a physiologically acceptable vehicle such as gelatin, starch, magnesium stearate, microcrystalline cellulose, talc, gum arabic or the like. The tablets can be of varied nature, immediate, controlled or delayed release and possibly in effervescent or orodispersible form.

A tablet preparation is obtained by mixing the active ingredient (i), (ii), (iii) or (iv) in powder form and forming tablets.

Example 1 of composition according to the invention Compounds Unit quantity (in mg) Valerian (root extract 4:1) 250 Lemon balm (dry extract of leaves) 128 California poppy (extract of aerial parts 5:1) 64 Poppy (petal extract 5:1) 22.4 Microcrystalline cellulose 349.6 Tricalcium citrate 175 Magnesium stearate 6 Coating: Hydroxypropylmethylcellulose 3 Microcrystalline cellulose 1.25 Magnesium stearate 0.45

Manufacturing process :

This composition is obtained by mixing the different compounds according to the processes conventionally used for this type of preparation. The composition is preferably in the form of tablets.

Claims (7)

Combination product comprising, as active substances, at least:
(i) valerian,
(ii) lemon balm,
(iii) California poppy, and
(iv) poppy Combination product according to claim 1, characterized in that it is in the form of a single composition containing at least:
(i) valerian,
(ii) lemon balm,
(iii) California poppy, and
(iv) poppy
in a physiologically acceptable environment. Combination product according to one of the preceding claims, characterized in that valerian, lemon balm, California poppy and poppy are present in a quantity:
- 100 to 500 mg, preferably 200 to 300 mg of valerian
- 50 to 300 mg, preferably 100 to 200 mg of lemon balm
- 10 to 200 mg, preferably 30 to 100 mg of California poppy
- from 2 to 100 mg, preferably from 10 to 50 mg of poppy
per unit dry form Combination product according to one of the preceding claims, characterized in that the physiologically acceptable medium is in a form suitable for oral administration. Combination product according to one of the preceding claims, characterized in that it is in the form of a tablet or capsule. Combination product according to one of the preceding claims, characterized in that the valerian, lemon balm, California poppy and poppy are in the form of a plant extract. Product according to claim 6 for its use in the treatment of sleep disorders.