EP3672589A1

EP3672589A1 - Combination product for relieving the symptoms associated with upper respiratory tract infections

Info

Publication number: EP3672589A1
Application number: EP18750212.5A
Authority: EP
Inventors: Séverine HERTLEIN
Original assignee: Urgo Recherche Innovation et Developpement
Current assignee: Urgo Recherche Innovation et Developpement
Priority date: 2017-08-23
Filing date: 2018-08-09
Publication date: 2020-07-01
Also published as: FR3070261A1; WO2019038100A1

Abstract

The subject of the present invention is a combination product comprising, as active substances, at least zinc, eucalyptus and Erysimum or a bioequivalent compound of same, for helping in relieving the symptoms associated with upper respiratory tract infections. Finally, the invention relates to the use of a combination product as defined above for treating the symptoms associated with upper respiratory tract infections.

Description

Combination product to relieve symptoms associated with pathway infections

upper respiratory

TECHNICAL AREA

The present invention relates to a combination product comprising as active substances, at least zinc, eucalyptus and erysimum or a bioequivalent compound thereof to help relieve symptoms related to respiratory tract infections. higher. The invention finally relates to the use of a combination product as previously defined for the treatment of symptoms related to upper respiratory tract infections.

BACKGROUND

Upper respiratory tract infections are a medical term for a specific infection in the nose, throat or sinuses. These types of infections are usually characterized by cold symptoms and are most often caused by viruses. However, in some cases, bacteria are also responsible for triggering these infections.

Although these types of infections can occur in everyone, it is more common in children who tend to have a weak immune system. While children are more susceptible to upper respiratory tract infections, adults are more often affected by lower respiratory tract infections that affect the lungs, throat, and respiratory tract and can cause serious complications.

Upper respiratory tract infections include rhinitis, nasopharyngitis, laryngitis and sinusitis.

Rhinitis is the medical term describing the irritation and inflammation (acute or chronic) of the mucous membranes of the nasal cavity. Rhinitis can be allergic or not. When they are chronic, they strongly affect the quality of life of those who are victims, to the point that the WHO published in 2001 a new classification of the disease.

Rhinitis is often accompanied by other disorders such as asthma and / or sinusitis and is a cause of insomnia and fatigue. Fifty percent (50%) of patients with rhinitis have non-specific bronchial hyperreactivity, and therefore an increased risk of asthma. Inversely, asthmatics almost all have rhinitis (more or less acute) associated with asthma attacks. The symptoms are: - flowing (rhinorrhea);

-Nasal congestion that may lead to nasal obstruction

-irritation of the mucous membranes of the nose, with or without redness, pruritus and lesions (crusts, ulcerations ..) and possibly accompanied by irritation of the eyes, throat and / or ears.

Acute non-allergic rhinitis can be induced by an infection (bacterial or more often viral). In the latter case, acute viral rhinitis can lead to a loss of smell (35% of cases of dysosmia) when an overabundant mucus covers the olfactory epithelium to the point of preventing the recognition of odors by the brain8).

by structural defects of the nasal ducts: displaced walls, obstructive nasolabial polyposis (nasal duct more or less closed by polyps).

by pathological or pregnancy-related hormonal changes ("pregnancy rhinitis" or "pregnancy rhinitis" occurring in about 30% of pregnant women with a "stuffy nose" sensation). This usually occurs after the first trimester and worsens during the third trimester and disappears most often two weeks after delivery.

by abuse of certain drugs (nasal decongestant, aspirin, certain antihypertensives, erectile dysfunction drugs), it will be called in this case privinism or rhinitis medicamentosa.

Rhinopharyngitis

Rhinopharyngitis is a very common infection of the respiratory tract, specifically the nasopharynx, the cavity that extends from the nasal cavity to the pharynx. The symptoms of rhinopharyngitis, similar to those of colds, usually persist between 7 and 10 days. Very common in young children from the age of 6 months, it appears mostly in autumn and winter. A child may have between 7 and 10 episodes of nasopharyngitis per year.

Laryngitis Laryngitis is often infectious laryngeal inflammation of viral or bacterial origin. Laryngitis can be more or less dangerous depending on the seat of the condition. There are also chronic irritating laryngitis due to tobacco or the misuse of his voice.

The diagnosis of laryngitis is clinical and associates a dysphonic syndrome (hoarseness of the voice, gradual extinction of the voice) and a dyspneic syndrome (especially in the child because of the narrowness of the laryngeal die, inspiratory bradypnea with draw, or whirling). In case of subglottic obstruction, the dyspnoeic syndrome dominates. In case of glottic obstruction, the dysphonic syndrome dominates.

There are different types of laryngitis: chronic laryngitis, acute subglottic laryngitis of the child, striatal laryngitis, pseudo-myxomatous laryngitis.

Sinusitis

Sinusitis is an inflammation or infection of one or more of the four sinuses (maxillary, frontal, sphenoidal or ethmoidal) that the human body has.

When a virus, fungus (fungal), bacterium or allergy affects the mucous membranes of the L5 nose, these react by igniting and swelling, causing sinus obstruction. As a result, mucus is no longer drained normally, and viruses or bacteria can grow quickly. Sinusitis therefore begins, in most cases, with a viral rhinopharyngitis which causes an alteration of the purifying capacities of the ciliated nasal-sinus apparatus and can evolve towards an authentic bacterial sinusitis. The sensations of pressure that the patient may feel are due to the overpressure caused by the obstruction of the sinuses.

The main viruses involved are: Rhinovirus, Myxovirus and Adenovirus.

The main bacteria responsible for sinus superinfections are: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus.

Mushrooms: Aspergillus

Sinusitis can be of two types:

Acute: in most cases caused by a viral infection of the cold type, it is treated between 7 and 12 days. It can also be caused by allergies or dental abscesses. Chronic: they can be the consequence of insufficiently treated infectious episodes and are often favored by anatomical or allergic factors. Sinusitis is described as chronic when it lasts beyond 2 weeks and up to 4-8 weeks. However, acute sinusitis can be described as chronic if it is repeated 2 to 4 times during the same year.

In order to relieve the symptoms associated with upper respiratory infections, there are different products on the market. These products generally contain paracetamol, pseudoephedrine, chlorphenamine, diphenhydramine. By way of example, such products are marketed by Laboratoires URGO under the trade name HUMEX®

L0 Day and Night Cold, by the SANOFI-AVENTIS Laboratories under the trade name DOLIRHUMEPRO, or by Johnson & Johnson under the trade name ACTIFED®Rhume Jour et Nuit. These compositions, because of the presence of active molecules such as paracetamol, pseudoephedrine, chlorphenamine, diphenhydramine, ibuprofen have the disadvantage of not being able to be used by the entire population. Indeed,

L5 these products should not be used in the following cases: liver failure; risk of closed angle glaucoma; risk of blockage of urine (adenoma of the prostate); arterial hypertension not controlled by a specific treatment; severe coronary heart disease; history of seizures, history of stroke; in combination with a non-selective MAOI antidepressant or for at least 15 days after taking it; in association with

Another decongestant vasoconstrictor or a vasoconstrictor containing one of the following substances: bromocriptine, pergolide, lisuride, cabergoline, ergotamine or dihydroergotamine; child under 15 years; breastfeeding.

In addition, consumers are increasingly opting for natural solutions and are reluctant to use active ingredients such as those described above.

Among the existing natural solutions, for example Arkopharma Duoflash® Respiratory Comfort product which contains sunflower oil, Ravintsara leaf essential oil (Cinnamomum Camphora), essential oil. Thymol Thyme (Thymus Vulgaris) thymus aerial part, Eucalyptus leaf extract (Eucalyptus Globulus), and Pelargonium root extract (Pelargonium Sidoides). The Efirub® product of Laboratoires

50 3 Oaks that contains echinacea extract, N-acetyl-L-cysteine, Andrographis extract, Astragalus extract, thyme extract, extract of glitches grapefruit, vitamin C, white willow extract, uncaria tomantosa extract, licorice extract, black elder extract, and zinc.

There may also be mentioned Actirub® product marketed by the Green Health Laboratory which contains echinacea dry extract (Echinacea purpurea) titrated with 4% echinacosides, dry extract

Andrographis (Angrographis paniculata) titrated to 6% of andrographolides, astragalus dry extract (Astragalus membranaceus) titrated to 16% polysaccharides, N-acetylcysteine, vitamin C, dry extract white broth (Verbascum thapsus), dry extract of thyme (Thymus vulgaris), dry extract of White willow (salix alba) titrated with 25% of salicin, dry extract of camomillie (Tanacetum) parthenium) titrated with 0.5% parthenolides, dry extract of elderberry

L0 black (Sambucus nigra) titrated with 4.5% rutin, zinc.

None of the products proposed contains the association object of the present invention.

The Applicant has developed, and it is the object of the present invention, a combination product comprising as active substances, at least zinc, eucalyptus and erysimum or a bioequivalent compound thereof. last to help relieve L5-related symptoms to upper respiratory infections.

By "relieving the symptoms associated with upper respiratory tract infections" is meant in the context of the present invention, a product that makes it possible to soften the throat, to provide tone for the day, to clear the upper respiratory tract, especially the nose, bringing a feeling of freshness, but also to facilitate falling asleep at bedtime.

Such a product thus makes it possible to relieve the symptoms associated with upper respiratory tract infections with products of natural origin and to treat a greater number of people.

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

The product of the present invention has a galenic adapted to the adult, preferably in the form of a tablet to be sucked or swallowed.

The product according to the present invention, although containing products of natural origin has a pleasant taste and smell.

SUMMARY OF THE INVENTION The present invention relates to a combination product comprising, as active substances, at least zinc, eucalyptus and erysimum or a bioequivalent compound of eucalyptus and erysimum to help relieve symptoms related to to infections of the upper respiratory tract.

The present invention also relates to a combination product comprising as active substances at least zinc, eucalyptus and erysimum or a bioequivalent compound of eucalyptus and erysimum for its use. in the treatment of symptoms related to upper respiratory tract infections.

In certain embodiments, the combination product according to the invention comprises, in addition to zinc, eucalyptus and erysimum, as active substances:

(i) Plants or plant extracts, such as, for example, poppies

(ii) vitamins and minerals, such as for example vitamin C,

(iii) Propolis

In certain embodiments, the combination product of the invention is characterized in that L5 eucalyptus and erysimum are in the form of plant extracts in a tablet comprising: from 3 to 15%, preferably from 6 to 10% % of eucalyptus solids of 3 to 10, preferably 4 to 8%, of erysimum solids of 0.01 to 0.2%, preferably 0.05 to 0.1% of zinc

10% by weight relative to the total weight of the composition

In certain embodiments, the combination product of the invention is characterized in that the tablet comprises, according to a first alternative: from 3 to 15%, preferably from 6 to 10%, of eucalyptus solids of 3 to 10%. preferably 4 to 8% of dry extracts of erysimum

From 0.01 to 0.2%, preferably from 0.05 to 0.1% zinc, from 1 to 10, preferably from 2 to 5%, of dry poppy extracts. in percentage by weight relative to the total weight of the composition

In this alternative, the composition will be taken, preferably, before the sleep phase of the subject having an infection of the upper respiratory tract.

In some embodiments, the combination product of the invention is characterized in that the tablet comprises, according to a second alternative: from 3 to 15%, preferably 6 to 10%, of eucalyptus solids of 3 to 10%. %, preferably 4 to 8% of dry extracts of erysimum of 0.01 to 0.2%, preferably 0.05 to 0.1% of zinc of 0.01 to 2%, preferably 0.05 to 0.5% of 1% propolis of 1 to 20%, preferably 5 to 10% of vitamin C as a percentage by weight relative to the total weight of the composition

In this alternative, the composition will be taken, preferably during the "active" phase, that is to say at least 4 hours before the sleep phase of the subject having an infection of the upper respiratory tract. In some 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) zinc,

(ii) eucalyptus,

(iii) erysimum,

(iv) poppy

(v) propolis

(vi) Vitamin C physiologically acceptable medium. According to a particular embodiment of the invention, the combination product is characterized in that the active ingredients (i), (ii), (iii), (iv), (v) and (vi) or a bioequivalent compound of these are in a medium suitable for oral administration. Preferably, the suitable medium is a solid medium. Preferably, the combination product is in the form of a tablet.

The eucalyptus, the erysimum, and the poppy may be present as ingredients (ii), (iii) or (iv) in a combination product of the invention in more or less purified form, especially in the form of vegetable extract.

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

DETAILED DESCRIPTION OF THE INVENTION

In the present invention, the Applicant has demonstrated that the combination of zinc, eucalyptus and erysimum has a synergistic effect to help relieve symptoms related to upper respiratory tract infections.

By synergistic effect, it is understood according to the present invention that the combination of zinc, eucalyptus and erysimum has an effect on the relief of symptoms related to upper respiratory tract infections, during treatment which is superior the cumulative effects of a treatment (a) comprising the administration of zinc, not associated with eucalyptus, with erysimum, and conversely with a treatment (b) comprising the administration of eucalyptus, not associated with zinc and erysimum or a treatment (c) including the administration of erysimum, not associated with zinc and eucalyptus.

Eucalyptus

Native to Australia, the genus Eucalyptus has given over 600 species ranging from simple shrubs to very large trees. Several tree species have long been cultivated in the Mediterranean and in all subtropical regions, both in the East and the West.

European aromatherapy mainly uses the essential oil of four species of eucalyptus. • Lemon eucalyptus (E. citriodora). Preferred for topical applications (arthritis, tendonitis, itching, mosquito repellent, etc.).

• Mentulized eucalyptus {E. Clives). Preferred for respiratory conditions, but the use of its essential oil is not recommended in children under 6 years and in pregnant or breastfeeding women.

• Eucalyptus radish (E. radiata). Better tolerated by the mucous membranes and the skin; good for children Not recommended during the first three months of pregnancy.

• Eucalyptus with multiple bracts {E. cryptoned CT polybractea). Preferred for parasitic diseases (tropical diseases in particular) and for gynecological or urinary infections of viral origin. The essential oil is not recommended for children under 6 years and pregnant or breastfeeding.

Researchers believe that the medicinal properties of eucalyptus are mainly attributable to eucalyptol (also called 1,8-cineole) contained in its leaves. That's why we generally agree that to be effective, the essential oil must contain from 70% to 85%

Recognized Use: The European Commission has approved the use of the leaves (internal route) and the essential oil (internal and external route) of Eucalyptus globulus, to treat inflammation of the respiratory tract.

The World Health Organization recognizes the traditional use of eucalyptus leaves (E. globulus) to relieve fever and symptoms of asthma, inflammation of the airways, bronchial tubes or throat.

The composition according to the present invention comprises from 3 to 15%, preferably from 6 to 10%, of dry extracts of eucalyptus in percentage by weight relative to the total weight of the composition.

The Erysimum

Erysimum (velars) is a genus of dicotyledonous plants of the family Brassicaceae. This genus includes wallflowers, which include both cultivated ornamental species and various wild forms. Erysimum has pain-canceling effects as well as active principles similar to those of promethazine. With expectorant properties, velar leaves can calm coughs and inflammation of the larynx. They are therefore recommended in hoarseness of the voice. Since these same leaves are mucolytic, they can also facilitate the expulsion of mucus. They also prevent the disease called scurvy and stimulates the whole body. The flowering tops of this plant have the same properties as these leaves.

The composition according to the present invention comprises from 3 to 10, preferably from 4 to 8% of dry extracts of erysimum in percentage by weight relative to the total weight of the composition.

Zinc

Zinc is a trace element essential for low doses to animal and human life

In very small quantities, zinc in assimilable form is an important trace element, essential for plant and animal organisms. Duly assimilated by the organisms, it activates in particular the enzymes, influences the growth, favors the reactions and biochemical controls on the level of the pulmonary surfaces. The human body contains 2 g to 4 g. Daily requirements can be estimated at a minimum of 15 mg for a normal man, and up to twice as much for a breastfeeding woman.

Zinc is contained in various yeasts (up to 100 mg per kilogram) and in red meat (in the range of 50 mg to 120 mg per kilogram), but also in a multitude of marketed foods.

A deficit, even a slight one, has an impact on certain functions, including immunity responsible for the defense against certain infections.

The composition according to the present invention comprises from 0.01 to 0.2%, preferably from 0.05 to 0.1%, of zinc as a percentage by weight relative to the total weight of the composition.

The poppy

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

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

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

In herbal medicine, one uses its dried petals, which take a color wine-wine to the desiccation 5 and of which one makes most often herbal teas. Its soothing effects are felt on the adult, but especially on young children (we used to mix poppy with children's porridge to help them sleep). With its emollient, mild sedative and bicicidal properties, the poppy is a calming agent for coughs and irritation of the throat. It is then used in the form of lozenges to suck.

The composition according to the present invention comprises from 1 to 10, preferably 2 to 5% dry L0 extracts of poppy in percentage by weight relative to the total weight of the composition.

Propolis

Propolis refers to both a resinous material produced by certain plants and a complex material made by bees from this plant resin and wax

Plant propolis refers to a series of resinous, gummy and balsamic L5 substances present on plants. The main tree species producing propolis are conifers (pine bark, fir, spruce) and the buds of several species of alder, willow, birch, plum, ash, oak and elm. , poplars (which seem to be the most important source) and horse chestnut.

Bees propolis is a complex made by the bee from its secretions and the plant propolis that it has harvested.

The propolis collected in the hive is composed of: resins and balms: 50 to 55% wax: 30 to 40% volatile or essential oils: 5 to 10% 15 pollen: 5% various materials: 5% This propolis also contains many other elements such as organic acids, many flavonoids, trace elements, many vitamins. It also contains paraben, whose antibacterial and antifungal properties help fight pathogens in the hive.

In the hive, propolis has multiple uses. It is a mortar used to seal cracks or gaps, to seal against moisture and mold growth, to reinforce racks or defective parts of the hive and to protect the colony by reducing entrance to the hive. It is also a sanitizing varnish deposited in a thin layer inside the cells before the laying of the queen, or to smooth the inner walls of the hive. It also serves to mummify dead intruder animals (rats and mice for example), too big to be evacuated by the bees, thus avoiding their decomposition.

Raw propolis or in the form of mother tincture is an anti-infective (antifungal, antiseptic, antibiotic). It also has anesthetic, healing and anti-inflammatory power and increases cellular metabolism.

In internal use, it would be used in the form of mother tincture or in the form of dry extract in otorhinolaryngology against the extinction of voice, hoarseness, angina, sore throat, cough, colds, bronchitis, pharyngitis, ear infections and sinusitis.

In the context of the present invention, propolis is a complex material made by bees from plant propolis and wax

The composition according to the present invention comprises 0.01 to 2%, preferably 0.05 to 1% of propolis as a percentage by weight relative to the total weight of the composition.

Vitamin C

Vitamin C is a water-soluble, heat-sensitive vitamin and light that plays an important role in the metabolism of humans and many other mammals. Chemically speaking, it is L-ascorbic acid, one of the stereoisomers of ascorbic acid, and its salts, ascorbates. The most common are sodium ascorbate and calcium ascorbate. Vitamin C is an enzymatic cofactor involved in a number of physiological reactions (hydroxylation). It is required in the synthesis of collagen and red blood cells and contributes to the immune system. It also plays a role in the metabolism of iron as a promoter of its absorption; its use is therefore not recommended in patients with iron overload and particularly hemochromatosis. In oxidized form (dehydroascorbic acid), it crosses the blood-brain barrier to access the brain and several organs with a high concentration of vitamin C.

This vitamin is widely used in self-medication in the common cold. It seems to shorten the duration of symptoms and improve them in adults.

The composition according to the present invention comprises from 1 to 20%, preferably from 5 to 10% of vitamin C as a percentage by weight relative to the total weight of the composition.

Physiologically acceptable medium

A physiologically acceptable medium is a medium 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, comprise various adjuvants according to its therapeutic or cosmetic purpose, such as, but not limited to, flavors, dyes, fillers, preservatives, diluents, wetting or suspending agents, etc. Such media may also allow immediate, modified or delayed release of either active ingredient.

The physiologically acceptable medium may be water, mash and / or fruit juice, texturizers, emulsifiers, colorants, preservatives, flavorings, sugar or sugars.

By "mash and / or fruit juice" is meant a more or less liquid preparation, in particular according to the nature of the fruit and / or the fineness of the grinding, prepared by grinding, pressing or other extraction process of one or more several fruits and optionally the concentration of the ground material obtained and / or the separation (in particular filtration) of the seeds, achenes and / or all or part of the pulp, and / or flash pasteurisation.

The fruits can be chosen from: apple, banana, strawberry, peach, raspberry, blackberry, mango, kiwi, blueberry, blackcurrant, currant, orange, cherry, fig, pear, apricot, coconut, passion fruit, guava, papaya, melon, lychee, pineapple, lemon, mandarin, plum, grapefruit, grape, rhubarb and their mixtures, without this list being exhaustive.

"Texturizers" means compounds that modify the texture of the products in which they are incorporated. Examples of texturants are: guar and carob flour; the erasers

Arabic, xanthan and gellan; carrageenans; starches (native or modified); microcrystalline cellulose; gelatin; pectin; alginates (E400 to E405); agar-agar; and their mixtures. By "emulsifiers" is meant amphiphilic compounds characterized by their HLB (Hydrophilic Lipophilic Balance) value, in particular capable of stabilizing oil-in-water emulsions (particularly advantageous if it is desired to add, for example, liposoluble active agents).

L0 such 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" is meant compounds of natural or synthetic origin capable of conferring on their own a coloration to the composition. Examples of food colorants are L5 known in Europe under the codes E100 to E180.

"Preservatives" means compounds that inhibit 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), sulfites and derivatives (E220 to E228), natamycin, nisin; Preferably, the composition according to the invention does not comprise any preservative.

By "flavors" is meant compounds of natural or synthetic origin capable alone to change the taste of the composition. Examples of flavors are apricots, pineapples, bananas, blackcurrants, cherries, lemons, lime, strawberries, raspberries, passion fruits, tangerines, peppermint, mint orange, pistachio, pear, licorice, rose, anise, blueberry, cinnamon, ginger, grapefruit, apple, kiwi, lychee, melon, coconut, peach, currant, guava, grenadine, mango, blackberry, papaya, tea, vanillin, natural vanilla extract, essential oils and mixtures thereof.

For the purposes of the present invention, sugar or sugar is understood to mean any sweetening carbohydrate, preferably glucose syrup, sucrose, glucose, fructose, invert sugar, honey, maltose, polyol or mixtures thereof. In the context of the present invention, the sugar used is a polyol, preferably sorbitol.

Additional asset (s)

Any additional active ingredient of nutritional interest and / or helping to relieve the symptoms associated with upper respiratory tract infections may also be added to the combination products of the invention. 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, flavonoids.

Advantageously, such additional asset may be intended to enhance the desired effect as described above.

Of course, those skilled in the art will take care to choose the additional assets and their amount so that the advantageous properties of the composition according to the invention are not, or not substantially impaired by the addition envisaged.

As additional assets that can be used, mention may be made of:

- 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 (preventive pellagra), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B8 or H (biotin), vitamin B9 (folic acid) and vitamin B12 (cobalamin). Examples of liposoluble 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, especially 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 extracts; soy extracts; Cocoa ; the grenade ; the Emblica; CoenzymeQ10; selenium, minerals, such as magnesium, calcium, copper, iron, iodine, manganese, selenium, chromium (III),

amino acids, especially sulfur-containing amino acids, such as glutathione precursors, the amino acids of selenium, citrulline,

phytosterols, resveratrol, hesperidin, neohesperidin, orthosilicic acid, monomethylsilanetriol, and mixtures thereof.

Preferably, a combination product according to the invention is administered orally. Suitable forms for the oral route are, for example, tablets, capsules, lozenges, powders, granules, lyophilisates, oral solutes and syrups. Tablets, powders, granules, lyophilisers, oral solutes and syrups are the currently preferred oral pharmaceutical form. In the case of the preparation of a solid composition in tablet form, it is possible for example to mix the main active ingredients (i), (ii), (iii), (iv), (v) or (vi) with a Physiologically acceptable vehicle such as gelatin, starch, magnesium stearate, calcium stearate, talc, gum arabic or analogies. The tablets may be varied in nature, immediate release, controlled or delayed and optionally in effervescent or orodispersible form.

A tablet preparation is obtained by mixing the active ingredient (i), (ii), (iii), (iv), (v) or (vi) as a powder.

Example 1 Composition According to the Invention (Table 1)

This composition is obtained by mixing the various compounds according to the methods conventionally used for this type of preparation. The composition is then preferably in the form of a tablet. This tablet will be taken, preferably, by the subjects presenting an infection of the upper respiratory tracts, before the phase of sleep (at the time of the bedtime).

Example 2 Composition According to the Invention (Table 2)

This composition is obtained by mixing the various compounds according to the methods conventionally used for this type of preparation. The composition is then preferably in the form of a bilayer tablet. This tablet will be taken, preferably, by the subject having an infection of the upper respiratory tract, during the "active" phase, preferably the subject will take 2 tablets during this "active" phase.

Example 3: Tablet perception survey according to Examples 1 and 2

A panel of 60 (men-women) over 18 years old tested the tablets according to Examples 1 and 2. These people had to decide on the smell, the taste and the immediate perceived effectiveness.

The evaluation of the smell of the tablet according to Example 1: 18% of these people gave the tablet a score of 9 to 10, 65% a score of 6 to 8, or 83% gave a score of 6 or more.

The evaluation of the smell of the tablet according to Example 2:

5% of these people scored 9 to 10 on this tablet, 76% a score of 6 to 8, or 81% gave a rating greater than or equal to 6.

The taste assessment of the tablet according to Example 1:

18% of these people gave the tablet a score of 9 to 10, 65% a score of 6 to 8, or 83% gave a score of 6 or more.

The taste assessment of the tablet according to example 2: 7% of these people gave a rating of 9 to 10 to this tablet, 40% a score of 6 to 8, or 47% gave a score greater than or equal to 6.

The perceived immediate effectiveness for the throat softening of tablet 1: 50% of people were "in agreement" or "strongly agree" The immediate perceived effectiveness for the throat softening of tablet 2 63% of people were "in agreement" or "strongly agree"

The immediate perceived effectiveness for nose clearance of tablet 2: 73% of people were "agree" or "strongly agree"

Example 4: Observational study evaluating the efficacy of the tablets according to Examples 1 and 2 The study was proposed to men and women, aged 18 to 65, with discomfort in the nose and / or throat characterized by symptoms such as runny nose, stuffy nose, sore throat or sneezing. The primary endpoint is the evolution of the Wisconsin upper respiratory symptom survey. It is an internationally validated questionnaire for assessing cold symptoms and their impact on quality of life. It has 21 questions rated from 0 to 7 and ranges from 0 to 147, the higher the score, the more severely ill the patient is. The particularity of the study is to document every day, from very accurately, the evolution of their symptoms by asking these people to describe them on a secure data collection system. This study also highlights the perceived improvement over inclusion in the criteria of respiratory comfort, throat softening, sleep, and fatigue. On the other hand, the overall satisfaction of the people at the end of the study is also evaluated.

The results of the study include 93 people, 92 of whom completed the elements daily to assess the evolution of their symptoms. They are on average 38 years old and 81.5% female. At baseline, nose or throat symptoms and their impacts on daily life are relatively high with a Wurss score of 63 on average. The persons taking the study take two tablets each day following example 2 (one in the morning and one at midday) and one tablet according to example 1 in the evening. Under the effect of the product, from the first day, the overall inconvenience decreases rapidly and regularly as shown in Figure 1 with reductions reaching 45% from the second day, 65.4% on the 3rd day and disappear gradually thereafter. It is the same when we specifically analyzes the evolution of the score of clinical symptoms of the common cold (-42.4% on the second day) and improving the quality of life (-40.8% from the ^2nd day).

From the first day, on a scale of 1 (greatly improved) to 7 (greatly aggravated), the study shows the concomitant reduction of respiratory discomfort (4.2 to 3.5) and fatigue (4.7 to 4.1). ) and improvement of sleep disorders (4.2 to 3.8). At the end of the 6 days of follow-up, 9 out of 10 people say they are satisfied or very satisfied with the effectiveness of the product on cold symptoms.

On the other hand, it is important to note that more than 8 out of 10 patients are satisfied with the effectiveness of the "night" tablet on the quality of sleep and that 88% of people are satisfied with the effectiveness of the treatment on the softening of the throat. As a result, more than 9 out of 10 patients say they would definitely or probably recommend the product to a loved one.

The effectiveness and speed of action of the food supplement tested in the study on the reduction of symptoms and the improvement perceived by the people are related to the specific and adapted combination of the various ingredients.

Claims

1. A combination product comprising, as active substances, at least zinc, eucalyptus and erysimum or a bioequivalent compound of eucalyptus and erysimum to help relieve symptoms of upper respiratory infections:

Combination product according to Claim 1, characterized in that the active substances consist of:

(i) zinc, (ii) eucalyptus,

(iii) erysimum,

(vii) poppy

(viii) Propolis

(ix) vitamin C

3. Combination product according to one of claims 1 or 2, characterized in that it is in the form of a single composition containing at least:

from 3 to 15%, preferably from 6 to 10%, of eucalyptus solids

from 3 to 10, preferably from 4 to 8% of dry extracts of erysimum

from 0.01 to 0.2%, preferably from 0.05 to 0.1% of zinc

in percentage by weight relative to the total weight of the composition in a physiologically acceptable medium.

4. Combination product according to claim 1 characterized in that it is in the form of a single composition containing at least:

from 3 to 15%, preferably from 6 to 10%, of eucalyptus solids

from 3 to 10, preferably from 4 to 8% of dry extracts of erysimum

from 0.01 to 0.2%, preferably from 0.05 to 0.1% of zinc

from 1 to 10, preferably from 2 to 5% of poppy solids

Combination product according to claim 1, characterized in that it is in the form of a single composition containing at least:

from 3 to 15%, preferably from 6 to 10%, of eucalyptus solids

from 3 to 10%, preferably from 4 to 8% of dry extracts of erysimum, of from 0.01 to 0.2%, preferably 0.05 to 0.1% of zinc;

from 0.01 to 2%, preferably from 0.05 to 1% of propolis

from 1 to 20%, preferably from 5 to 10% of vitamin C as a percentage by weight relative to the total weight of the composition in a physiologically acceptable medium.

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

7. Combination product according to one of the preceding claims characterized in that it is in the form of a tablet.

8. Combination product according to one of the preceding claims, characterized in that eucalyptus, erysimum and poppy are in the form of plant extracts 9. Combination product according to at least one of the preceding claims, for relieving the symptoms of subjects with upper respiratory infection.