WO2020260506A1

WO2020260506A1 - Combination product for helping maintain the natural defenses of the organism

Info

Publication number: WO2020260506A1
Application number: PCT/EP2020/067914
Authority: WO
Inventors: Estelle CHANU
Original assignee: Urgo Recherche Innovation Et Developpement
Priority date: 2019-06-28
Filing date: 2020-06-25
Publication date: 2020-12-30
Also published as: EP3989995A1; FR3097744A1; FR3097744B1

Abstract

The invention relates to a combination product comprising, as active substances, at least echinacea, propolis, vitamin C and vitamin D3 in a liquid form to help maintain the natural defenses of the organism. The invention further relates to the use of a combination product as defined above for the prevention and/or treatment of infectious viral and bacterial diseases.

Description

Title of the invention: Combination product to help maintain the body's natural defenses

[0001] TECHNICAL FIELD

The present invention relates to a combination product comprising as active substances, at least echinacea, propolis, vitamin C and vitamin D3 in a liquid form to help maintain defenses natural body. The invention finally relates to the use of a combination product as defined above for the prevention and / or treatment of infectious pathologies, whether of viral or bacterial origin.

[0003] BACKGROUND

[0004] A viral disease, or virosis, is a disease triggered by a virus and its spread in the body (and at the expense of the body).

[0005] RNA viruses can transform very quickly and thwart the

host defenses as shown by influenza (influenza). Viral illnesses are all illnesses, mild or severe, caused by a virus. They can be transmitted and take the form of an epidemic. There are many, many viral diseases. Among them, the common cold, angina, influenza, chickenpox, measles, smallpox, hepatitis B, AIDS ...

[0006] Viral diseases are transmitted from person to person through saliva, promiscuity or sexual intercourse. More rarely, a viral disease can be contracted from the consumption of food of animal origin. Each virus attacks a specific part of the body. It is this action that will identify the viral disease.

[0007] A viral disease does not develop immediately upon exposure. A period

incubation can be noticed. This incubation lasts a few hours for a flu and a few months for other viruses.

[0008] The manifestations of a viral disease are fever, headaches, muscle stiffness, fatigue and lack of tone. Depending on the severity of the pathology, the general state of fatigue can be disabling. Some viral diseases have skin lesions as symptoms, such as chickenpox, measles, rubella or herpes.

[0009] Other viral diseases such as the AIDS virus or polio do not

cannot be cured. Early treatment of the patient ensures an optimized life expectancy and quality of life.

[0010] A bacterial disease (or bacteriosis) is an infectious disease caused by a bacterium. Bacterial diseases are very numerous in human pathology.

[001 1] Among the infectious pathologies, mention may be made, by way of example, of tonsillitis, nasopharyngitis, gastroenteritis, seasonal flu, colds, sinusitis, cough, bronchitis, sore throats, etc. ...

[0012] The immune system is a complex system which protects the body from external attacks, whether they are viruses, bacteria or parasites. For this, it involves thousands of cells produced mainly in the bone marrow which then specialize in the thymus, spleen, lymph nodes, then circulate in the blood.

Located behind the breastbone, the thymus is an extremely important gland in the development of the immune system: it positively selects cells (T lymphocytes) capable of recognizing what is foreign to the body (the non-self ), while it removes those that could react against our own constituents (the self).

[0014] Good natural immunity makes it possible to eliminate many of these pathologies without treatment. In order to help the body maintain these natural defenses, the Applicant has developed a combination product comprising, as active substances, at least echinacea, propolis, vitamin C and vitamin D .

[0015] There are a number of products on the market to help maintain the body's natural defenses. Among these products, mention may be made, by way of example, of Immunité, from Bio Ponroy which contains: extract of astragalus, eleutherococcus and echinacea. Strong Immunity of Nutrigée, which contains: Andrographis, cat's claw, grapefruit seeds, maca, cola nuts and eleutherococcus, natural Vitamin C and D3, Copper and zinc. The product Defatyl Energy Plus Energy And Immunity (from Defatyl) is based on L-carnitine, taurine, vitamin B6, vitamin B12, vitamin B1, vitamin B2, vitamin B9. Merck's Bion 3 Defense product contains ferments (Lactobacillus gasseri PA 16/8, Bifidobacterium bifidum MF 20/5, Bifidobacterium longum SP 07/3), vitamins: A, B1, B2, B3, B5, B6 , B8, B9, B12, C, D, E and minerals: iodine, iron, zinc, selenium, chromium, manganese, magnesium.

[0016] None of the products offered contain the combination which is the subject of the present invention.

[0017] These products, although containing vitamin C or vitamin D or propolis and / or echinacea, are not entirely satisfactory in terms of helping to maintain the body's natural defenses. In addition, the taste and galenic are not necessarily suitable for children. Echinacea in particular, has a bitter taste and can cause stinging, which is not appreciated by all people. Propolis, on the other hand, has a very strong and sour taste that is not appreciated by children and adults.

[0018] The combination product of the present invention helps to maintain

the body’s natural defenses by stimulating and strengthening the immunity of individuals. The product of the present invention further tastes good and is popular with children. It is without side effects or addiction.

[0019] The product according to the present invention also has the advantage of containing, preferably, no artificial coloring, allergens and of being,

preferably, lactose or gluten free and is without added preservatives.

[0020] The product of the present invention has a dosage form suitable for the child, preferably in the form of a syrup.

[0021] SUMMARY OF THE INVENTION

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

(i) echinacea, (ii) propolis,

(iii) vitamin C, and

(iv) vitamin D3

in liquid form to help maintain the body's natural defenses.

[0023] The present invention also relates to a combination product, comprising as active substances at least:

(i) echinacea,

(ii) propolis,

(iii) vitamin C, and

(iv) vitamin D3

for its use in the prevention and / or treatment of infectious pathologies.

[0024] In some embodiments, the combination product according to

the invention includes, in addition to echinacea, vitamin C propolis and vitamin D3, as active substances:

[0025] Plants or plant extracts, such as for example astragalus or

the eleutherococcus

Vitamins and minerals, such as for example the vitamins of group B, such as vitamin B6 and / or zinc, iron or selenium

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

(i) echinacea,

(ii) propolis,

(iii) vitamin C, and

(iv) vitamin D3

in liquid form in a physiologically acceptable medium. In certain embodiments, the combination product of the invention is characterized in that echinacea, propolis, vitamin C and vitamin D3 are administered in the form of a solution containing:

- 1 to 15% by weight, preferably 2 to 10% by weight of echinacea

- from 1 to 10% by weight, preferably 2 to 6% by weight of propolis

- from 0.1 to 1.5% by weight, preferably 0.2 to 1% by weight of vitamin C

- from 1 ^* 10-7 to 1 ^* 10-4% by weight, preferably 1 ^* 10-6 to 1 ^* 10-5% by weight of vitamin D3

in percentage by weight relative to the total weight of the composition.

[0029] According to a particular embodiment of the invention, the product of

combination 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 liquid medium. Preferably, the combination product is a syrup or a capsule containing said syrup.

When used for the treatment or prevention of pathologies

infectious diseases, the combination product according to the present invention is intended in particular for children or adults with swallowing problems.

[0031] The various embodiments of the invention are particularly

described in the detailed description below. These embodiments can be taken separately or in combination with each other.

[0032] DETAILED DESCRIPTION OF THE INVENTION:

In the present invention, the applicant has demonstrated that

the combination of at least (i) echinacea, (ii) propolis, (iii) vitamin C, and (iv) vitamin D3, exhibited a synergistic effect to help maintain natural defenses of the body.

By synergistic effect, it is understood according to the present invention that

the combination of at least (i) echinacea, (ii) propolis, (iii) vitamin C, and (iv) vitamin D3 has an effect on helping to maintain natural defenses of the body, during the treatment which is greater than the effects cumulative treatment (a) comprising the administration of echinacea, not associated with propolis, vitamin C and vitamin D3, and vice versa of a treatment (b) comprising the administration of propolis, not associated echinacea, vitamin C and vitamin D or a treatment (c) comprising administration of vitamin C, not associated with echinacea, propolis and vitamin D3 or a treatment (d) comprising administration of vitamin D3, not associated with echinacea, propolis and vitamin C.

[0035] Echinacea

Echinacea (coneflower, term derived from the Greek echino, "thorn", because of the central "thorny" disc of the flower) is a genus of plants of the Asteraceae family native to North America. Three species are well known for their reputation in herbalism and their ethnobotanical use: Echinacea angustifolia, Echinacea purpurea and Echinacea pallida.

The Echinacea genus includes plants of about 1 m in height with a yellow, pink and sometimes white flower. The center of the flower is covered with prickly tips.

[0038] It is mainly Echinacea purpurea which is used as a plant.

medicinal. The rhizome of Echinacea was used by the Plains Indians of North America, perhaps more than any other plant, in the development of medicinal remedies. In the 1930s, Echinacea became popular both in Europe and in the United States as a people's medicine. Echinacea has been credited with the ability to strengthen the body's immune system defenses and help prevent infections. Depending on the species used, medicinal compositions can be prepared from the stem and the flower, or from the root. In the context of the present invention, the aerial part of Echinacea purpurea and the root of Echinacea angustifolia will preferably be used.

[0039] In the context of the present invention, echinacea is present in an amount of 1 to 15% by weight, preferably 2 to 10% by weight percentage relative to the total weight of the composition.

[0040] Echinacea is preferably present in the form of a plant extract. In the context of the present invention, Echinacea purpurea plant extracts will preferably be used in combination with Echinacea angustifolia in the proportions of 1: 2 to 1: 10, preferably from 1: 5 to 1: 7.

[0042] Propolis

[0043] Propolis designates both a resinous material produced by certain plants and a complex material produced by bees from this plant resin and wax

[0044] Vegetable propolis designates a series of resinous substances,

gummy and balsamic present on plants. The main tree species producing propolis are conifers (bark of pines, firs, spruces) 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.

Bee propolis is a complex produced by the bee from its secretions and from the vegetable propolis that it has collected.

The propolis collected in the hive consists overall of:

resins and balms: 50 to 55%

wax: 30 to 40%

volatile or essential oils: 5 to 10%

pollen: 5%

various materials: 5%

[0047] This propolis also contains many other elements such as organic acids, many flavonoids, trace elements, many vitamins. It also contains paraben, the antibacterial and antifungal properties of which help fight pathogens in the hive.

In the hive, propolis has multiple uses. It is a mortar which is used to seal cracks or interstices, to seal against humidity and the development of mold, to strengthen spokes or parts defective hive and protection of the colony by reducing entry to the hive. It is also a sanitizing varnish deposited in a thin layer inside the cells before the queen is laid, or to smooth the interior walls of the hive. It is also used to mummify dead intruder animals (rats and mice for example), too large to be evacuated by bees, thus preventing their decomposition.

Crude propolis or in the form of a mother tincture is an anti-infectious agent.

(antifungal, antiseptic, antibiotic). It also has an anesthetic, healing and anti-inflammatory power and increases cell metabolism.

In internal use, it would be used in the form of mother tincture or in

dry extract form in otorhinolaryngology against voice extinctions, hoarseness, tonsillitis, 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 vegetable propolis and wax.

The composition according to the present invention comprises from 1 to 10%, of

preferably 2 to 6% of propolis as a percentage by weight relative to the total weight of the composition.

[0053] Vitamin C

[0054] Vitamin C is a water-soluble vitamin sensitive to heat and to

light playing 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, the ascorbates. The most common are sodium ascorbate and calcium ascorbate.

[0055] Vitamin C is an enzymatic cofactor involved in a certain 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 an 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 0.1 to 1, 5%, of

preferably from 0.2 to 1% of vitamin C as a percentage by weight relative to the total weight of the composition.

[0058] Vitamin D3

[0059] Cholecalciferol is a form of vitamin D, also called vitamin D3. Vitamin D3 is a secosteroid rather related to testosterone, cholesterol and cortisol.

Vitamin D has a dual origin: it is provided by

food and synthesized by the body in the skin under the action of UVB rays from the sun.

Subjects exposing themselves very little to the sun may have more or less significant deficiencies in vitamin D. People with fair skin synthesize vitamin D faster than those with dark skin, and therefore need a period of time. shorter exposure to convert vitamin D precursors produced by the liver into vitamin D. The amount of vitamin D that the skin can produce is limited; prolonged exposure to sunlight (more than 30 minutes for a fair-skinned person, up to three hours for

people with dark skin) does not increase the amount of cholecalciferol produced in the body. For a person with fair skin, an exposure of 10 to 15 minutes a few times a week is enough to cover the needs in vitamin D3. Vitamin D produced by the skin is stored in the liver, muscle and fatty tissue and used on demand during winter periods.

Two forms of vitamin D exist: vitamin D2 or ergocalciferol produced by plants and vitamin D3 or cholecalciferol produced by animals, as well as by certain lichens. In humans, these two forms are converted to 1,25-dihydroxyvitamin D (commonly referred to as vitamin D), their main active metabolite. [0063] The essential function of vitamin D is to increase the capacity

absorption of the intestine for calcium and phosphorus which allows:

[0064] 1. to ensure optimal mineralization of mineralized tissues, in particular bone, cartilage and teeth;

2. to contribute to the maintenance of the plasma concentrations of calcium and phosphorus.

[0066] The clinical signs of vitamin D deficiency are: osteomalacia and

rickets in the bones, decreased muscle tone, attacks of tetany and convulsions (related to hypocalcaemia) and sometimes anemia. In the elderly, vitamin D deficiency constitutes a favorable ground for bone loss (therefore osteoporosis), and depression (as confirmed by a Dutch study mentioned in Archives of General Psychiatry (May 2008)) .

Several age groups constitute populations at risk of vitamin D deficiency: these are newborns, infants, pregnant women and the elderly, particularly those placed in institutions, who

have little sun exposure and / or have increased needs. Other factors may worsen these risks of deficiency, the strong skin pigmentation, specific diets (vegetarian, macrobiotic), pathologies inducing intestinal malabsorption.

The recommended nutritional intakes of vitamin D have been defined in

whereas endogenous production covers 50 to 70% of the needs

daily in this vitamin.

A limited number of foods contain significant amounts of vitamin D. In fact, these contents are closely linked to the presence of fat in the foods. The best sources of vitamin D are fatty sea fish, whatever their method of preparation and conservation (boiling, smoking, canning, grilling): herring, salmon, sardines, mackerel for example. Egg yolks, dairy products, soy and its derivatives (tofu and soy milk for example) and certain mushrooms (with great differences depending on the variety) are also sources of vitamin D. Low amounts of vitamin D are also provided by meats, offal and pâtés. The lean fish (ray, sole, hake ...) do not have it. Some lichens also produce cholecalciferol (vitamin D3), and are used to produce plant food supplements with this vitamin.

The composition according to the present invention comprises from 1 ^* 10-7 to 1 ^* 10-4%, preferably 1 ^* 10-6 to 1 ^* 10-5% of vitamin D3 in 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 can, for example, comprise different adjuvants according to its therapeutic or cosmetic purpose, such as, without limitation, flavors, colorants, fillers, diluents, wetting or suspending agents, etc. Such media can also allow immediate, modified or delayed release of one or other of the active ingredients.

[0073] The physiologically acceptable medium can be composed of water, mash and / or fruit juice, texturizers, emulsifiers, colorants, flavors, sugar or sugars.

By "texturizers" is meant the compounds which modify the texture of the

products in which they are incorporated. Examples of texturizers are: guar and carob flour; gum arabic, xanthan and gellan; carrageenans; starches (native or modified); cellulose

microcrystalline; 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 interesting if it is desired to add, for example, liposoluble active agents such as liposoluble 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. The term “dyes” is understood to mean compounds of natural or synthetic origin capable of conferring on themselves a coloring on the composition. Examples of food colors are known in Europe under the codes E100 to E180.

The term “aromas” is understood to mean compounds of natural or synthetic origin capable of themselves alone of modifying the taste of the composition. 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.

[0077] Preferably the flavor used in the present invention is the tutti frutti flavor combined with the natural orange flavor.

By sugar or sugars is meant, within the meaning of the present invention, any

sweetening carbohydrate, preferably glucose syrup, sucrose, glucose, fructose, invert sugar, honey, maltose, or mixtures thereof. In the context of the present invention, the sugars used are a mixture of sorbitol syrup and glucose syrup.

In the context of the present invention, the combination product is in liquid form. For the purposes of the present invention, the term “liquid form” means a syrup, an emulsion, a juice or a solution.

[0080] Advantageously, the composition according to the present invention, no preservative is added to the composition.

[0081] Additional asset (s)

Any additional active having a nutritional interest and / or helping to

maintenance of the body's natural defenses can 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, fatty acids essential, trace elements, various plant extracts, fibers,

antioxidants, flavonoids.

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

Of course, a person skilled in the art will take care to choose the additional active agents as well as their quantity in such a way that the advantageous properties of the composition in accordance with the invention are not, or substantially not, altered by the addition envisaged. .

As an additional active ingredient, there may be mentioned:

- 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) and vitamin B12 (cobalamin). Examples of fat-soluble vitamins present in the syrupy product prepared according to the invention are in particular: vitamin A (retinol), 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 (procyanidol oligomers); ubiquinones; coffee extracts containing polyphenols and / or diterpenes; chicory extracts; extracts of ginkgo biloba; grape extracts rich in

proanthocyanidins; chilli extracts; soy extracts; Cocoa ; the grenade ; the Emblica; CoenzymeQI O; selenium,

- minerals, such as zinc, calcium, copper, iron, iodine, manganese, selenium, chromium (III), - amino acids, in particular sulfur-containing amino acids, such as precursors of glutathione, amino acids of selenium, citrulline,

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

In a particularly advantageous embodiment of the invention,

the combination of active ingredients comprises, as additional active ingredient, a liposoluble vitamin, in particular vitamin D3, minerals such as potassium.

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, lyophilizates, drinkable solutions and syrups. Tablets, powders, granules, lyophilizates, drinkable solutions and syrups constitute the form

pharmaceutical or cosmetic suitable for the currently preferred oral route.

Example 1 of composition according to the invention

[0089] [Table 1]

^* Cholecalciferol (intake form of vitamin D3) is present at 0.007% by weight relative to the total weight of the composition corresponds to 0.0000166% of vitamin D3.

[0091] Manufacturing process:

The glucose syrup is heated between 30 ° C and 40 ° C then all of the

other compounds are added (after sieving for compounds in powder form) then mixed and heated between 40 ° C and 50 ° C until a homogeneous composition is obtained.

[0093] Example 2: perception survey in adults of two compositions

The composition according to Example 1 was compared with the product Alvityl Defenses from Laboratoires Urgo.

61 people (adults) tasted the two syrups. The syrup according to Example 1 is preferred by 93% of people. Its taste (7.3 out of 10 against 4.3 out of 10 for the product Alvityl Défenses), its texture, its color are more appreciated. It is less bitter and its texture is more fluid.

[0096] Example 3: perception survey in the child of three compositions

The composition according to Example 1 was compared with the Alvityl Defense product from Laboratoires Urgo and the product Pediakid Immunoconfort from Laboratoires Ineldea.

127 children aged 6 to 8 tested the products

For the sequential monadic taste, the composition according to Example 1 (6.7 out of 10) performs better than the product Pediakid Immunoconfort (5.7 out of 10) and the product Alvityl Défenses (4.3 out of 10).

[0100] The taste "which remains at the end" of the composition according to Example 1 is appreciated by 63% of the children.

Claims

[Claim 1] Combination product comprising as active substances at least:

i. echinacea

ii. propolis,

iii. vitamin C, and

iv. vitamin D3

in liquid form to help maintain the body's natural defenses.

[Claim 2] Combination product according to claim 1,

characterized in that it is in the form of a single composition containing at least:

i. echinacea

ii. propolis,

iii. vitamin C, and

iv. vitamin D3

in a physiologically acceptable medium.

[Claim 3] Combination product according to the claims

above characterized in that it comprises echinacea, propolis, vitamin C and vitamin D3 in an amount:

from 1 to 15% by weight, preferably 2 to 10% by weight of echinacea

from 1 to 10% by weight, preferably 2 to 6% by weight of propolis

from 0.1 to 1.5% by weight, preferably 0.2 to 1% by weight of vitamin C from 1 ^* 10-7 to 1 ^* 10-4% by weight, preferably 1 ^* 10-6 to 1 ^* 10-5% by weight of vitamin D3

in percentage by weight relative to the total weight of the composition.

[Claim 4] Combination product according to one of the preceding claims, characterized in that the physiologically acceptable medium is suitable for oral administration.

[Claim 5] Combination product according to one of the preceding claims, characterized in that it is in the form of a syrup or a capsule comprising a syrup.

[Claim 6] Combination product according to one of the preceding claims, characterized in that the echinacea is in the form of a plant extract.

[Claim 7] Combination product according to claim 6

characterized in that the echinacea plant extracts are derived from Echinacea purpurea in combination with Echinacea angustifolia in the proportions of 1: 2 to 1: 10, preferably 1: 5 to 1: 7.

[Claim 8] Combination product according to at least one of

preceding claims, for the prevention and / or treatment of infectious pathologies.