Combination product to aid relaxation and sleep

Abstract

The present invention relates to a combination product comprising, as active substances, at least valerian, lemon balm, California poppy, and common poppy to aid relaxation and / or sleep onset. The invention also relates to the use of a combination product as defined above for the treatment of sleep disorders.

Description

Title of the invention: Combination product to aid relaxation and sleep technical field

[0001] The present invention relates to a combination product comprising, as active substances, at least valerian, lemon balm, California poppy, and corn poppy to aid relaxation and / or sleep onset. The invention also relates to the use of a combination product as defined above for the treatment of sleep disorders.

[0002] BACKGROUND

[0003] 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.

[0004] Sleep disturbances can be caused by a variety of problems, from teeth grinding (bruxism) to night terrors. When an individual experiences difficulty falling asleep without an apparent cause, this is referred to as insomnia. In addition, sleep disorders can lead the individual to sleep excessively, a condition known as hypersomnia. Other sleep disorder conditions may be related to substantial abuse.

[0005] Sleep disorders include:

[0006] -primary insomnia - chronic difficulty falling asleep and / or maintaining sleep when no other symptomatic cause can be perceived;

[0007] - bruxism, involuntary grinding or clicking of the teeth during sleep;

[0008] -delayed sleep phase syndrome, inability to fall asleep or wake up during socially acceptable hours but not causing any problems in sleep maintenance, a circadian rhythm disorder (similar symptom -hypernycthemeral syndrome);

[0009] -hypopnea, respiratory or cardiac abnormality during sleep;

[0010] -narcolepsy, sudden sleep often spontaneous at any time of day;

[0011] -cataplexy, sudden weakness of the motor muscles which can result in a fall to the ground;

[0012] -night terror, pavor nocturnus, a nocturnal disorder characterized by intense fear and anxiety;

[0013] - sleepwalking, an activity undertaken physically and unconsciously during sleep;

[0014] -somniphobia, fear of sleeping;

[0015] -sleep apnea.

[0016] Following the evolution of knowledge about sleep in the 20th century, including the discovery of hypnology and sleep apnea, the medical importance of sleep has been recognized. The clinical community has taken a closer interest in sleep disorders, such as sleep apnea, and in the role and quality of sleep under different conditions. During the 1970s in the United States, clinics and laboratories dedicated themselves to the study of sleep and its disorders.

[0017] 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 (average age in the study, 74.9 years plus or minus 5.6 years).

[0018] Sleep medicine is now adapted in internal medicine, family medicine, pediatrics, otolaryngology, psychiatry and neurology.

[0019] The present invention relates to a composition to aid relaxation and falling asleep in adults as well as children.

[0020] Indeed, a study published in the journal Paediatrica (vol. 14, no. 3, 2003) reviews sleep disorders in children. 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. Some sleep disorders are more frequent at a certain age and linked to particular situations, while others can occur at any age (for example: sleep apnea syndrome, sleep-related epilepsy). A sleep disorder is not only a problem for parents. Disturbed sleep also implies risks for the child's cognitive development with the occurrence of behavioral disorders. As with adults, there appears to be an association between obstructive sleep apnea and a higher prevalence of metabolic syndrome in children and adolescents.

[0021] The duration and organization of sleep are subject to changes during development. Basic knowledge allows one to distinguish true sleep disorders from variations in the norm. As a guide, the approximate values ​​for sleep duration per 24 hours are: 16 hours for a full-term newborn, 13 hours for a 2-year-old, 11 hours at age 5, 10 hours at age 9, and approximately 9 hours for a 14-year-old adolescent. Young adults still need about 8 hours, a fact often overlooked. The variability of these values ​​is quite significant and corresponds to the distribution of genetic traits in the population. Individual sleep requirements are more easily established during weekends and holidays, when the body is allowed to sleep as much as necessary.

[0022] During the night, three states are observed: wakefulness, rapid eye movement (REM) sleep, and non-REM sleep. A sleep cycle includes a transition through all three states. Various parasomnias (non-REM parasomnias) can originate during deep sleep: for example, night terrors in young 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 common to observe these parasomnias during the first few hours after falling asleep.

[0023] A number of products are available on the market to address problems with falling asleep or relaxing. Among these products, we can cite, for example, Passiflore, a homeopathic preparation from Boiron which contains: Passiflore incamata, Ignatia amara, Coffea cruda, Nyckterinia, Tellurium metallicum, Phosphoricum acidum, Palladium metallicum, Magnesium metallicum. Quiétude, also a homeopathic preparation from Boiron, contains: Chamomilla vulgaris, Gelsemium, Hyoscyamus niger, Kalium bromatum, Passiflore incamata, Stramonium. The Pediakid Sommeil product from Ineldea is based on magnesium, manganese, phosphorus, orange blossom extract, lavender extract, chamomile extract, lemon balm extract, marjoram extract, and hawthorn extract. The Pediakid Nervousness product from Ineldea contains hydroglycerin extracts of plants (hops, lemon balm, orange blossom, passionflower, gentian), magnesium, vitamin B6, and phosphate.Bayer's Euphytocalm product contains a dry extract of lemon balm and magnesium. Merlin Santé Sommeil, on the other hand, contains melatonin, valerian, and California poppy. Other options include Noverg's Complexe Sommeil, based on melatonin, California poppy, passionflower, and corn poppy, and Laboratoires Santarom's SommeilBio, based on California poppy, passionflower, linden, lemon balm, and valerian.

[0024] None of the proposed products contain the combination that is the subject of the present invention.

[0025] These products, although containing valerian in combination with lemon balm, do not provide complete satisfaction in terms of calming, relaxation, and / or aiding sleep. The combination product of the present invention provides a calming effect to facilitate falling asleep and helps to naturally restore restful sleep without waking up during the night. The product according to the present invention has no side effects or risk of addiction. The combination product according to the present invention helps to aid falling asleep, calms, relaxes, and helps to maintain healthy sleep.

[0026] The product according to the present invention also has the advantage of preferably containing no artificial coloring, allergens and of being preferably lactose-free or gluten-free.

[0027] The product of the present invention has a galenic form suitable for adults, preferably in the form of a tablet. Summary of the invention

[0028] The present invention relates to a combination product comprising, as active substances, at least:

[0029] (i) of valerian,

[0030] (ii) lemon balm,

[0031] (iii) of the California poppy, and

[0032] (iv) of the poppy

[0033] to aid relaxation and / or falling asleep.

[0034] The present invention also relates to a combination product comprising, as active substances, at least:

[0035] (i) of valerian,

[0036] (ii) lemon balm,

[0037] (iii) of the California poppy, and

[0038] (iv) of the poppy

[0039] for its use in the treatment of sleep disorders.

[0040] In certain embodiments, the combination product according to the invention comprises, in addition to valerian, lemon balm, California poppy and corn 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 tryptophan

[0041] In certain embodiments, the combination product of the invention is characterized in that valerian, lemon balm, California poppy and corn poppy are in the form of plant extracts.

[0042] 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 the following active substances:

[0043] (i) of valerian,

[0044] (ii) lemon balm,

[0045] (iii) of the California poppy, and

[0046] (iv) of the poppy

[0047] in a physiologically acceptable environment.

[0048] In certain embodiments, the combination product of the invention is characterized in that valerian, lemon balm, California poppy, and corn poppy are administered in the form of a tablet containing:

[0049] - 100 to 500 mg, preferably 200 to 300 mg of valerian

[0050] - 50 to 300 mg, preferably 100 to 200 mg of lemon balm

[0051] - 10 to 200 mg, preferably 30 to 100 mg of California poppy

[0052] - from 2 to 100 mg, preferably from 10 to 50 mg of poppy

[0053] per unit of dry form.

[0054] 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.

[0055] When used for the therapeutic treatment of sleep disorders, the combination product according to the present invention is particularly intended for adults or children.

[0056] The various embodiments of the invention are particularly described in the detailed description below. These embodiments can be considered separately or in combination with each other. Description of the implementation methods

[0057] In the present invention, the applicant has demonstrated that the combination of at least (i) valerian, (ii) lemon balm, (iii) California poppy, and (iv) corn poppy had a synergistic effect to aid relaxation and / or falling asleep.

[0058] 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 helping with relaxation and / or falling asleep, during 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 of a treatment (b) comprising the administration of lemon balm, not associated with valerian, California poppy and poppy or of a treatment (c) comprising the administration of California poppy, not associated with valerian, lemon balm and poppy or of a treatment (d) comprising the administration of poppy, not associated with valerian, lemon balm and California poppy.

[0059] Valerian

[0060] Valerian officinalis or hill valerian or small-leaved valerian ( Valeriana officinalis L., also known by the common names Catnip, St. George's Herb, or Woundwort, is a perennial herbaceous plant in the Valerianaceae family. In the West, its roots are traditionally used for their sedative and anxiolytic effects. They are believed to promote sleep and reduce anxiety, and are therefore considered a natural alternative to sleeping pills and chemical anxiolytics.

[0061] 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. The amount of valerian represents, in plant equivalent, 400 to 2000 mg, preferably 800 to 1200 mg.

[0062] Valerian is preferably present in the form of a plant extract.

[0063] Lemon balm

[0064] Lemon balm (Melissa officinalis) is a perennial herbaceous plant in the mint family (Lamiaceae). Its name comes from the Greek word melissophullon, meaning "bee leaf." It is also called lemon balm or simply lemon balm, not to be confused with lemongrass (Cymbopogon citratus) used in Asian cuisine. Native to the eastern Mediterranean basin, it spread throughout Europe in antiquity. Lemon balm has been cultivated in gardens since ancient times. Native to Europe, it was introduced to North America. The stems and leaves are still used as a mild tonic and stimulant. It has an astringent taste and a light aroma. Alcohol is obtained by distilling its fresh leaves; lemon balm water has antispasmodic properties. Lemon balm can also be consumed in the form of herbal teas.

[0065] 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). As an infusion, lemon balm has a mild sedative effect and also promotes sweating; this is why it is recommended in cases of insomnia, or in hot weather for infants and the elderly.

[0066] 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. The amount of lemon balm represents, in plant equivalent, 300 to 1800 mg, preferably 600 to 1200 mg.

[0067] Lemon balm is preferably present in the form of a plant extract.

[0068] The California poppy

[0069] The California poppy or American poppy (Eschscholzia califomica Chain.) is a herbaceous plant of the Papaveraceae family commonly cultivated in the Ornamental gardens. This plant is native to California and the Southwestern United States, where it covers vast areas near redwood forests. Thanks to the californidine and protopine (isoquinolines with sleep-inducing properties) it contains, as well as its lack of habit-forming properties, the California poppy is used as a gentle alternative to barbiturate, benzodiazepine, and first-generation H1 antihistamine sleep aids.

[0070] California poppy acts on the different phases of sleep. First, it helps to fall asleep more quickly during the sleep onset phase. Second, it helps to improve the quality of sleep.

[0071] In addition to its qualities for good sleep, the poppy also helps to cope with stress and contributes to relaxation, maintaining physical and mental relaxation.

[0072] 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. The amount of California poppy represents, in plant equivalent, 50 to 1000 mg, preferably 150 to 500 mg.

[0073] California poppy is preferably present in the form of a plant extract.

[0074] The poppy

[0075] The poppy (Papaver rhoeas) is a species of dicotyledonous plant in the family Papaveraceae, native to Eurasia.

[0076] This is an annual herbaceous plant, very abundant in freshly disturbed soil from spring onwards, distinguished by the red color of its flowers and by the fact that it often forms large, colorful carpets visible from a great distance. It belongs to the group of so-called cornfield weeds because it has been associated with agriculture since ancient times, thanks to its life cycle adapted to cereal crops, with flowering and seed production occurring before harvest.

[0077] Like all poppies, the corn poppy has narcotic effects due to the alkaloids it contains.

[0078] In herbal medicine, its dried petals, which turn a deep red color when dried, are used and are most often used to make herbal teas. Its soothing effects are felt by adults, but especially by young children (poppy was once mixed into children's porridge to help them sleep). Due to its emollient, mildly sedative, and cough-relieving properties, the poppy is used to soothe coughs and throat irritations. It is then used in the form of lozenges.

[0079] 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, 10 to 500 mg, preferably 50 to 250 mg.

[0080] Poppy is preferably present in the form of a plant extract.

[0081] Physiologically acceptable environment

[0082] A physiologically acceptable medium is one that has no toxic or harmful effects under the conditions of use and is inert with respect to the active ingredients of the combination product. Such a medium may, for example, include various adjuvants depending on its therapeutic or cosmetic purpose, such as, but not limited to, flavorings, colorants, fillers, preservatives, diluents, wetting or suspending agents, texturizers, etc. Such media may also allow for the immediate, modified, or delayed release of one or more of the active ingredients.

[0083] By "texturizers" is meant compounds that modify the texture of the products in which they are incorporated. Examples of texturizers are: guar and locust bean gums; arabic, xanthan and gellan gums; carrageenans; starches (native or modified); microcrystalline cellulose; gelatin; pectin; alginates (E400 to E405); agar-agar; and mixtures thereof. The term "emulsifiers" refers to amphiphilic compounds characterized by their HLB (Hydrophile Lipophilic Balance) value, particularly those capable of stabilizing oil-in-water emulsions (especially useful when adding, for example, fat-soluble active ingredients such as fat-soluble vitamins). Examples of food emulsifiers include lecithin and its derivatives, found notably in egg yolks; mono- and diglycerides of fatty acids; and polysorbate 80.

[0084] The term "colorants" means compounds of natural or synthetic origin capable of imparting color to the composition on their own. Examples of food colorings are known in Europe under the codes El00 to El80.

[0085] By "preservatives" is meant compounds that inhibit the growth 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); sulfites and derivatives (E220 to E228); natamycin; nisin; and mixtures thereof. Preferably, the composition according to the invention does not contain any preservatives.

[0086] The term "flavorings" means compounds of natural or synthetic origin capable of altering the taste of the composition on their own. Examples of flavorings include apricot, pineapple, banana, blackcurrant, cherry, lemon, lime, strawberry, raspberry, passion fruit, mandarin, mint, orange, pistachio, pear, licorice, rose, anise, blueberry, cinnamon, ginger, grapefruit, apple, kiwi, lychee, melon, coconut, peach, redcurrant, guava, grenadine, mango, blackberry, papaya, vanillin, natural vanilla extract, essential oils, and mixtures thereof.

[0087] For the purposes of this invention, sugar or sugars means any hydrate of sweetening carbon, preferably glucose syrup, sucrose, glucose, fructose, invert sugar, honey, maltose, polyol or mixtures thereof.

[0088] Additional asset(s)

[0089] Any additional active ingredient with nutritional value and / or that aids relaxation or sleep may also be added to the combination products of the invention in pharmaceutical or cosmetic form. The combination product may include, by way of example, vitamins, mineral salts, essential amino acids, essential fatty acids, trace elements, various plant extracts, fibers, antioxidants, and flavonoids.

[0090] Advantageously, such an additional active ingredient may be intended to enhance the desired effect as described above.

[0091] Of course, a person skilled in the art will take care to choose the additional assets and 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 envisaged addition.

[0092] As an additional usable asset, one can cite:

[0093] - water-soluble vitamins and fat-soluble vitamins. Examples of Examples of water-soluble vitamins present in the syrupy product prepared according to the invention include: vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid), also known as 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 include: vitamin A (retinol), vitamin D3 (cholecalciferol), vitamin E (a mixture of tocopherols and tocotrienols), and vitamin K (phylloquinone).

[0094] - antioxidants, such as curcuminoids; carotenoids, in particular selected among beta-carotene, astaxanthin, zeaxanthin, lutein, or compounds containing them such as goji berries; polyphenol compounds, flavonoids such as catechins; proanthocyanidins, anthocyanins, OPCs (oligomeric procyanidins); ubiquinones; coffee extracts containing polyphenols and / or diterpenes; chicory extracts; ginkgo biloba extracts; grape extracts rich in proanthocyanidins; chili pepper extracts; soy extracts; cocoa; pomegranate; Emblica; Coenzyme Q10; selenium,

[0095] - minerals, such as zinc, calcium, copper, iron, iodine, manganese, the magnesium, selenium, chromium (III),

[0096] - amino acids, in particular sulfur-containing amino acids, such as precursors of glutathione, selenium amino acids, citrulline,

[0097] -phytosterols, resveratrol, hesperidin, neohesperidin, orthosilicic acid, monomethylsilanetriol, and mixtures thereof.

[0098] Preferably, a combination product according to the invention is administered orally. Suitable oral dosage forms include, for example, tablets, capsules, lozenges, powders, granules, lyophilized powders, oral solutions, and syrups. Tablets, powders, granules, lyophilized powders, oral solutions, and syrups constitute the currently preferred pharmaceutical or cosmetic dosage form suitable for oral administration. In the case of preparing a solid composition in tablet form, the main active ingredients (i), (ii), (iii), or (iv) may, for example, be mixed with a physiologically acceptable vehicle such as gelatin, starch, magnesium stearate, microcrystalline cellulose, talc, acacia gum, or similar substances. The tablets may be of various types, including immediate-release, controlled-release, or delayed-release, and optionally effervescent or orally dispersible.

[0099] A tablet preparation is obtained by mixing the active ingredient (i), (ii), (iii) or (iv) in powder form and forming tablets.

[0100] Example 1 of a composition according to the invention [Tables 1] Ingredients Unit Quantity (in mg) Valerian (root extract 4:1) 250 Lemon Balm (dry leaf extract) 128 California Poppy (aerial parts extract 5:1) 64 Common Poppy (petal extract 5:1) 22.4 Microcrystalline Cellulose 349.6 Tricalcium Citrate 175 Magnesium Stearate 6 Coating: Hydroxypropyl Methylcellulose 3 Microcrystalline Cellulose 1.25 Magnesium Stearate 0.45

[0101] Manufacturing process:

[0102] This composition is obtained by mixing the different compounds according to the processes classically used for this type of preparation. The composition is preferably presented in tablet form.

Claims

Demands

1. A combination product in the form of a single composition comprising, as active substances, at least: (i) 100 to 500 mg, preferably 200 to 300 mg, of valerian, (ii) 50 to 300 mg, preferably 100 to 200 mg, of lemon balm, (iii) 10 to 200 mg, preferably 30 to 100 mg, of California poppy, and (iv) 2 to 100 mg, preferably 10 to 50 mg, of common poppy per unit of dry form, in a physiologically acceptable medium

2. Combination product according to any one of the preceding claims characterized in that the physiologically acceptable medium is in a form suitable for oral administration.

3. Combination product according to any one of the preceding claims characterized in that it is in the form of a tablet or a capsule.

4. Combination product according to any one of the preceding claims characterized in that valerian, lemon balm, California poppy and corn poppy are in the form of plant extract.

5. Produced according to claim 6 for its use in the treatment of sleep disorders.