WO2020201920A1

WO2020201920A1 - Product for the prevention and treatment of motion sickness

Info

Publication number: WO2020201920A1
Application number: PCT/IB2020/052801
Authority: WO
Inventors: Marilyn GENTILHOMME; Tiphaine BRICOUT
Original assignee: Urgo Recherche Innovation Et Developpement
Priority date: 2019-04-05
Filing date: 2020-03-25
Publication date: 2020-10-08
Also published as: FR3094638A1; FR3094638B1

Abstract

The invention relates to a product comprising at least dandelion and ginger as active substances for the prevention and/or treatment of motion sickness. The product of the present invention is a galenical formulation suitable for children, preferably in the form of boiled sugars and particularly in the form of confectionery to be sucked.

Description

Title of the invention: Product for the prevention and

treatment of motion sickness

[0001] Technical field

The present invention relates to a product comprising as

active substances, at least from dandelion and ginger for the prevention and / or treatment of motion sickness.

[0003] State of the art

[0004] Motion sickness or motion sickness is a disorder which manifests itself in a situation of discordance between visual perception and the vestibular system. Depending on the cause, it can also be called car sickness, air sickness or seasickness.

[0005] Dizziness, fatigue and nausea are the most common symptoms

frequent motion sickness. Sopite syndrome, in which the individual experiences fatigue, is also associated with motion sickness. If the causes of the nausea are not resolved, the patient will vomit frequently. Unlike a common illness, vomiting during motion sickness does not relieve nausea.

[0006] The stimuli at the origin of motion sickness can be real or virtual.

Motion sickness is due to a central conflict between perceptions

somesthetic, visual and vestibular due to the discrepancy on the one hand between this information and on the other hand with what is expected at the central level due to experience and acquired patterns.

[0007] In motion sickness, the digestive symptoms could correspond to a

defense mechanism against neurotoxins, eg spoiled food. The postrema area of the brainstem is responsible for the emesis reflex when the nervous and sensory systems detect sensory conflicts in order to eliminate the neurotoxic agent responsible for these conflicts. When we feel movement without seeing it (for example in a windowless boat), the inner ear transmits to the brain that it is feeling movement but the eye tells the brain that everything is stable. As a consequence of this disagreement, the brain concludes that one of the two hallucinated and that the hallucination is due to the ingestion of poison. The brain responds by commanding vomiting in order to remove the supposed toxin.

[0008] A theory, known as the nystagmus hypothesis, has been proposed which is based on stimulation of the vagus nerves, which results from stretching or pulling extraocular muscles simultaneously with the movements of the vagus. eyes caused by vestibular stimulation. There are three critical aspects to the theory: first, the remarkably close links between activity in the vestibular system and the otholith organs as well as a change in tone between the various six extraocular muscles. Even though, with the exception of voluntary eye movements, the vestibular oculomotor systems are intimately linked. Second is Sherrington's law describing the reciprocal inhibitions between agonist and antagonist muscle pairs and by implication the stretching of the extraocular muscle which must occur when Sherrington's law fails, in this case causing stretching of the muscle. 'a contracted muscle. Finally, the critical presence of afferent outputs from the vagus nerves as a direct result of stretching or pulling an eye muscle. The theory explains why individuals with defective labyrinths never experience motion sickness, why the symptoms appearing when one experiences accelerations of the body / head, why combinations of voluntary movements and reflexes of the eye can oppose each other. to Sherrington's Law Operation and why many eye movement suppressing drugs are also used to suppress symptoms of motion sickness.

[0009] Motion sickness can be divided into three categories:

1. Kinetosis caused by movement felt but not seen

2. motion sickness caused by movement seen but not felt

3.Kinetosis caused when the two systems detect mismatched movements

[0010] The movement is felt but not visualized

[001 1] In these cases, movement is felt by the vestibular system and therefore the movement is felt, but no movement is detected by the visual system. [0012] Car sickness

Car sickness is a specific form of motion sickness that is rather common and often evidenced by the inability to read a map or a book while traveling. Car sickness results from sensory contact rising in the brain by several non-corresponding sensory sensors. The eyes mostly see the interior of the car which is not moving while the vestibular system of the inner ear senses movement when the vehicle is driven around a bend, over a hill or over small bumps. The effect is worse when looking down but can be inferior when looking outside the vehicle.

It is also felt in some high speed tilting trains.

[0014] Air sickness

[0015] Air sickness is a sensation induced by air travel, it is a specific form of motion sickness, considered a normal response for healthy individuals. It is essentially the same as car sickness but transposed to an airplane. With, however, some significant differences, which are that an airplane can pitch and shake abruptly, and that due to the small size of the windows (except if the passenger is in a seat glued to a window) it is very likely he can only see the inside of the plane. Another factor is that in flight, the view outside the windows can be blocked by clouds, which would prevent a passenger in the window from seeing the ground or clouds lower in motion.

[0016] Seasickness

Seasickness is a form of motion sickness characterized by a feeling of nausea, and in extreme cases, dizziness when spending time in a boat at sea. It is, again, essentially the same as car sickness, even though the movements of a sea craft tend to be more constant. It is typically caused by the movement of

rocking of the boat. As with air sickness, it can be difficult to visually detect movement even when looking outside the boat since the water does not offer fixed points with which to visually judge. movement. Impaired visibility conditions, such as fog, can make seasickness worse.

[0017] Centrifuges

[0018] Rotating devices such as centrifuges used for training astronauts and in amusement parks can cause motion sickness in many people. While the interior of the centrifuge seems not to move, the person experiences a sensation of movement. In addition, the centrifugal force can cause the vestibular system to feel that the bottom is in the direction away from the center of the centrifuge rather than in its true direction.

[0019] Dizziness due to rotation

[0020] When a person turns and suddenly stops, the fluid in his inner ear continues to rotate, causing an impression of continued rotation while the visual system no longer detects rotation.

[0021] The movement is seen but not felt

[0022] In these cases, the movement is detected by the visual system and therefore the movement is seen, but no movement is felt by the vestibular system. Motion sickness resulting from such situations has been referred to as Visually Induced Motion Sickness (CVI).

[0023] Motion sickness due to films and other videos

[0024] This type of disease is particularly widespread when people

Sensitive people watch movies on large screens like IΊMAC but can also take place in full sized cinemas or even while watching TV. The IMAX and other types of panoramic cinemas often show dramatic movements such as flying over a landscape or riding a roller coaster. This type of motion sickness can be avoided if the person closes their eyes during scenes of this type.

[0025] Motion sickness due to simulation Simulation disease, or simulator disease, is a form where the person exhibits symptoms similar to motion sickness caused by playing computer / simulator / video games.

[0027] Symptoms are often described as rather similar to motion sickness and include headache, nausea, vomiting, sweating, drowsiness, dizziness.

[0028] Motion sickness due to virtual reality

[0029] Motion sickness due to virtual reality is very similar to the disease of

simulation as well as motion sickness due to films. In virtual reality, however, the effect is more acute as all external reference points are removed from vision, the simulated images being three-dimensional and in some cases the stereo sound can also give the impression of movement.

[0030] Movements felt and seen but which do not correspond

[0031] The Coriolis effect

[0032] During movement in a rotating frame reference such as a centrifuge or an environment where gravity is simulated with centrifugal force, the Coriolis effect causes a sensation of movement in the vestibular system which does not correspond to the movement seen.

Sometimes, during a long driving of a vehicle on a poorly maintained road at a very low speed (10-20 km / h) the two directions do not correspond. Due to the poor quality of the road, the vehicle will bump too much, giving a feeling of strong movement to the inner ear, but due to the low speed the eye does not feel a proportional movement.

Unexpectedly, the Applicant has found that the use of a product comprising, as active substances, at least ginger and dandelion or extracts thereof for the prevention and / or treatment of motion sickness was found to be particularly effective, especially in children.

[0035] There are a number of products on the market to overcome the

motion sickness problems.

[0036] The majority of drugs used in motion sickness have antiemetic activity. In the therapeutic arsenal available, molecules such that scopolamine and H1 antihistamines are benchmarks. Scopolamine is one of the oldest remedies known to prevent motion sickness but remains a molecule of choice today from the point of view of its effectiveness. In France, only transdermal scopolamine is marketed in motion sickness

(SCOPODERM TTS ^® ), and only on medical prescription (list I of poisonous substances, not reimbursed). However, due to a relatively high price, its use remains limited. Antihistamines and scopolamine have common atropine or

anticholinergics: dry mouth, constipation,

accommodation, risk of urinary retention in the event of urethro-prostatic obstruction, risk of glaucoma flare by closing the angle, possible psychological disorders especially at extreme ages of life (excitement or mental confusion). Drowsiness, however, remains the major side effect common to these drugs.

As an alternative to these allopathic medicines, “soft” medicines can be used. Homeopathy, despite the lack of scientific studies establishing its effectiveness is used in motion sickness because it does not cause the side effects of allopathic drugs, mainly the decrease in alertness, drug interactions and counter- indications and can be used without restriction in children and pregnant women. In the fields of herbal medicine and aromatherapy, the essential oil of peppermint and the essence of lemon can relieve nausea and vomiting. Ginger, meanwhile, has benefited from several specific studies in motion sickness establishing its effectiveness. The pharmacist can combine other plants such as lemon balm, passionflower and lavender, which act, in particular on the anxiogenic component of motion sickness. In addition, parsley has not shown proven efficacy to date, despite its reputation with the general public in this area. Finally, the impact in the prevention of motion sickness of anti-nausea bracelets, based on the principle of acupressure, remains controversial. For people looking for more naturalness, there are products, such as, for example, the products marketed by Ineldea Laboratories under the trade name Pediakid transport sickness which contains extract of mint, sage , milk thistle, ginger, orange and lemon as well as magnesium or the product Nauséflash in the form of a syrup from the Densmore laboratory which contains extract of the ginger rhizome in a capsule. Minnesium Nausea

Laboratoires Ortis which contains extracts of ginger, marshmallow and essential oil of peppermint or Vagaline® products (spray or tablets) from Laboratoires 3 Chênes, which contain extracts of ginger, sage, lemon balm as well as essential oils of peppermint and caraway.

[0039] None of the products offered contain the combination object of the present invention.

[0040] These products are not entirely satisfactory, especially when it comes to treating children. Indeed, products in syrup form are not necessarily well suited for transport, products containing essential oil can cause seizures, and Nauséflash-type products in capsule form are intended for adults only.

The product according to the present invention has no side effects or

habituation.

More specifically, the invention relates to a product comprising, as active substances, at least dandelion and ginger for the prevention and / or treatment of motion sickness.

The product of the present invention has a galenic suitable for the child, preferably in the form of boiled sugars, in particular in the form of confectionery to suck.

Thus, the product according to the present invention, by virtue of its composition, has improved efficacy, is suitable for both adults and children, is, from a taste point of view, appreciated, thus resulting in better compliance.

[0045] SUMMARY OF THE INVENTION The present invention relates to a product, comprising as active substances, at least:

(i) ginger,

(ii) dandelion,

for the prevention and / or treatment of motion sickness.

In certain embodiments, the product according to the invention comprises, in addition to ginger and dandelion, as active substances:

- Plants or plant extracts, such as, for example, mint, sage, milk thistle, orange, lemon, marshmallow, passionflower, lavender or lemon balm

- Vitamins and minerals, such as for example vitamin C, vitamin D, vitamins of group B, such as vitamin B6, magnesium, potassium and / or calcium

[0048] In some embodiments, the product of the invention comprises ginger as a fluid root extract and dandelion as an aqueous root extract.

In this case, the product according to the invention is characterized in that it comprises: from 200 to 2000 mg, preferably 300 to 600 mg of ginger root extract, from 50 to 500 mg, preferably 100 to 200 mg dandelion extract

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

(i) ginger,

(ii) dandelion

in a physiologically acceptable medium. According to a particular embodiment of the invention, the product is characterized in that the active ingredients (i) and (ii) are in a medium suitable for oral administration. Preferably, the suitable medium is a solid medium. Preferably, the product is in the form of boiled sugars, such as a candy or a lollipop.

When used for the treatment of motion sickness, the product according to the

the present invention is particularly intended for children.

[0053] Ginger and dandelion may be present as ingredients (i) or (ii) in a product of the invention in more or less purified form, in particular in the form of a plant extract obtained from ginger roots and of dandelion.

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.

[0055] DETAILED DESCRIPTION OF THE INVENTION:

In the present invention, the Applicant has demonstrated that

the combination of at least (i) ginger and (ii) dandelion, exhibited a synergistic effect to help relieve motion sickness.

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

the combination of at least (i) ginger and (ii) dandelion has an effect on the treatment and prevention of motion sickness which is greater than the cumulative effects of a treatment (a) comprising the administration of ginger , not associated with dandelion.

[0058] Ginger

Ginger (Zingiber officinale) is a species of plants native to India, of the Zingiber genus and of the Zingiberaceae family, the rhizome of which is used in cooking and in traditional medicine.

[0060] Ginger root is commonly known as an anti-emetic agent. Ginger is often advocated as beneficial for nausea and vomiting. A systematic review of evidence from trials Randomized controlled trials for or against the effectiveness of ginger for nausea and vomiting was performed. Six studies met all inclusion criteria and were reviewed. Three on postoperative nausea and vomiting were identified and two of them suggested that ginger was superior to placebo and as effective as metoclopramide. One study was found for each of the following conditions: seasickness, morning sickness, and chemotherapy-induced nausea. These studies collectively favored ginger over placebo.

[0061] Ginger is reported to calm the pyloric valve located at the base of the stomach, to suppress gastric contractions and to stimulate gastrointestinal motility and peristalsis. This relaxation of the valve allows the stomach to behave normally so the contents will enter the small intestine instead of being retained in the stomach. It is this undesirable retention effect in the stomach which results in possible vomiting. No acute or chronic toxicity is reported when ginger is used as a condiment in reasonable doses. On the other hand, in high doses (greater than 4 to 6 g), it can lead to heartburn. Ginger is contraindicated for gallstones and as a precaution during pregnancy and breastfeeding, although it is used in traditional Chinese medicine for nausea and vomiting, especially during pregnancy.

In the context of the present invention, ginger has

preferably in the form of a plant extract, in an amount ranging from 200 to 2000 mg, preferably 300 to 600 mg of plant extract of ginger.

[0063] The dandelion

[0064] True "dandelions" belong to the genus Taraxacum.

Dandelions have long been renowned for their virtues

therapeutic, being supposed to treat liver disease, gout, dermatosis, obesity. Among these medicinal virtues, we can mention:

[0066] Dandelion roots contain inulin, tannins and a latex

containing a bitter principle (lactupicrin). The green leaves are very rich in vitamin A: 700 times more than the pear,

70 times more than oranges and twice as much as spinach. They also contain vitamins B1, B2, C and E, and most mineral salts: Ca, Mg, P, K, Na, Cl, S, Fe, Mn, Si, in significant proportions, as well as other substances .

Were isolated in the common dandelion also: carotene,

phytoxanthins, choline, flavonoids (Taraxine), mucilages, fatty acids and a phytosterol: Triterpene.

[0069] Dandelion is a bitter tonic, endowed with stomachic, cholagogue, depurative and eupeptic properties. The diuretic effect of dandelion, which gives it its name, is real. More generally, the dandelion allows the elimination of toxins.

[0070] In the context of the present invention, the dandelion is preferably provided in the form of a liquid extract, in an amount of 50 to 500 mg, preferably 100 to 200 mg of dandelion.

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 product. Such a medium can, for example, comprise different adjuvants according to its therapeutic or cosmetic purpose, such as, without limitation, flavors, colorants, fillers, preservatives, diluents, wetting or suspending agents, etc. Such media can also allow immediate, modified or delayed release of one or other of the active ingredients. In the context of the present invention, the physiologically acceptable medium contains at least one sugar chosen from sucrose, glucose, fructose, glucose syrup, isoglucose, dextrose, maltose, invert sugar, dextrin, maltodextrin and / or at least one sweetener chosen from acesulfame, aspartame, erythritol, glycerol, isomalt, maltitol, maltose, mannitol, sorbitol, sucralose, trehalose or xylitol.

[0073] In the context of the present invention, the physiologically

acceptable preferably comprises a combination of sugar and glucose syrup. [0074] The physiologically acceptable medium preferably also comprises an acidifier and an aroma.

[0075] This preferred physiologically acceptable medium has the advantage of

making the composition according to the invention satisfactory from a taste point of view. Thus, the subject presenting motion sickness will consume the product in full, but will also have better compliance.

[0076] Additional asset (s)

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

treatment and / or prevention of motion sickness can also be added to the products of the invention. The product may include, by way of example, vitamins, mineral salts, essential amino acids, essential fatty acids, trace elements, various plant extracts such as plant extracts of mint, sage, milk thistle, orange, lemon, marshmallow, passionflower, lavender or lemon balm, fiber, antioxidants, flavonoids.

Advantageously, such an additional active can be intended to enhance 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, we can cite:

- water-soluble vitamins and fat-soluble vitamins. Examples of water-soluble vitamins present in the product prepared according to the invention are in particular: vitamin C, 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 product prepared according to the invention are in particular: vitamin A (retinol), vitamin D3 (cholecalciferol), vitamin E and vitamin K (phylloquinone). - antioxidants, such as bioflavonoids, curcuminoids; carotenoids, in particular chosen from beta-carotene, astaxanthin, zeaxanthin, lutein or compounds containing them, such as goji berries; polyphenol compounds, flavonoids such as catechins; proanthocyanidins, anthocyanins, OPCs (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 potassium, magnesium, 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.

The product according to the invention is administered orally and contains

cooked sugars.

[0082] Example 1 of composition according to the invention (Table 1)

[Table 1]

Comparative Example 2 of Composition (Table 2)

[Table 2]

The compositions according to Examples 1 and 2 are obtained by mixing the various compounds according to the methods conventionally used for this type of preparation. The composition is then preferably packaged in the form of lollipops. Example 3: Observational study evaluating the perceived effectiveness of the composition according to Example 1 on the symptoms of motion sickness in children

The main objective of this study was to evaluate the effect of the consumption of the composition according to Example 1 on the evolution of the intensity of the symptoms of motion sickness in children and the occurrence and the time to onset of possible vomiting

The secondary objectives were:

- to assess the effect of consuming the composition according to Example 1 on the occurrence, the time to onset and the time to relief from motion sickness in children;

- assess the overall perceived improvement and the satisfaction of parents / children;

- assess the tolerance of the product;

- to evaluate the methods of consumption of the composition according to Example 1.

The composition according to Example 1 is in the form of a confectionery to suck (lollipop) and available according to three tastes: cola, strawberry and orange.

[0089] The child was invited to suck on a whole confectionery 30 minutes before departure. For long journeys, the confectionery can be taken up to 5 times in a day.

[0090] The study was offered to a panel of volunteers, men or women, having a child (ren) between 6 and 14 years old who were subject to motion sickness in the car during the last 16 months.

The primary endpoint was the change in severity of motion sickness symptoms assessed by the parent and using:

-the Motion Sickness Assessment Questionnaire (MSAQ) scale

The scale goes from 1 to 9, where 1 means that the declaration does not apply at all and 9 means the declaration occurs very severely:

1. I felt uncomfortable in my stomach (G ^* )

2. I felt weak (C) 3. I felt annoyed / irritated (S)

4. I felt sweaty (P)

5. I felt smeared (G)

6. I felt dizzy (C)

7. I felt asleep (S)

8. I was cold (cold sweat) (P)

9. I felt disturbed (C)

10. I felt tired (S)

1 1. I felt nauseous (G)

12. I was hot (P)

13. I felt dizzy (C)

14. My head was spinning (C)

15. I felt like I was going to throw up (G)

16. I didn't look well (S)

^* G: Gastrointestinal; C: Central; P: Peripheral; S: Sopite-related

The overall motion sickness score is obtained by calculating the percentage of the total points obtained: (sum of points of all items / 144) x 100.

The subscale scores are obtained by calculating the percentage of points obtained on each factor:

Gastrointestinal: (sum of Gastrointestinal items / 36) x 100;

Central (sum of items Central / 45) x 100;

Peripheral (sum of items Peripheral / 27) x100;

Sopite-related (sum of Sopite-related items / 36) x 100.

-a questionnaire describing the occurrence and the time of occurrence of

possible vomiting. The data were collected retrospectively during the inclusion visit on D1 and during the study after each trip / transport by car for which the composition according to Example 1 was consumed by the child (3 evaluations will be collected maximum).

The secondary endpoints were evaluated by the parent in

using:

- a questionnaire describing the occurrence, the time to onset and the time to relief from motion sickness in children;

- the Patient Global Impression of Improvement (PGM) to assess

the overall improvement after at least 2 post-transport assessments completed by the parent or on D60;

- 5-point Lickert scales assessing the satisfaction of parents and children after at least 2 post-transport reports completed by the parent or on D60;

- the collection of any undesirable effects evaluating the tolerance of the product after at least 2 post-transport assessments completed by the parent or on D60;

- the count of the lollipops consumed during each trip, evaluating the methods of consumption of the composition according to Example 1.

[0095] 58 children were therefore included in the statistical analysis. These 58 children made 185 trips by car. For each of these 185 trips at least one pacifier was consumed, whether before or after the start of the trip. The 58 children are part of the tolerance analysis.

[0096] 58 children, mostly female (58.6%) and aged 9.2 ± 2.4 years on average, were included in the statistical analysis. They all reported having felt sick several times in the car, 32.8% of which were frequent and almost three quarters of them (74.1%) were also sick in one or more situations other than the car.

The symptoms most severely felt by children during car trips made before inclusion in the study are mainly digestive with nausea, desire to vomit and general malaise. The overall motion sickness score assessed by the MSAQ for these trips is 51.9 ± 13.7 with a predominance of gastrointestinal signs (75.3 ± 16.5) but also a strong dimension component. fatigue (49.6 ± 16.7), peripheral (42.3 ± 19.3) and central (40.8 ± 18.8) signs.

51 (87.9%) children vomit during travel / transport by car, more than half (56.5%) frequently or systematically and 41.2% repeatedly.

[0100] In 60.0% of cases, vomiting occurs before an hour and a half of the journey and in a third of cases from the first hour.

[0101] Childhood motion sickness causes parents to stop more

frequently than desired in one in two cases and on average 2 additional stops are necessary due to the occurrence of nausea (44.8%), vomiting (27.6%) or general malaise (24.1%).

[0102] The last trip made by the children dates back on average to 1.7 months and lasted 2.4 hours on average. On this journey, the first symptoms of motion sickness occurred on average after 56 minutes and 31% of children vomited at least once and up to 3 times with an average time to onset of the first vomiting of 1.4 hours .

[0103] During the study, the 58 children made 185 trips, or 3.6

journeys / child on average which lasted 4.2 hours on average. These long travel times are linked to the fact that parents were encouraged to carry out the study on trips they considered significant and which, in large part, corresponded to summer vacation trips.

[0104] Analysis by trip

[0105] A pacifier was consumed as recommended before the start of the journey by 94.1% of the children. During 11 trips out of the 185, the children did not take the pacifier as recommended before the trip but during the trip, which does not seem to have an influence on the occurrence or no of vomiting or signs of illness transports. During half of the 185 trips (50.3%), an additional one to 7 lollipops were consumed after the trip began. For 92.0% of children, consuming another pacifier improves symptoms, considerably or a lot in 54.0% and slightly in 38.0% of them.

[0106] Almost two-thirds (63.2%) of the 185 trips took place without any sign of motion sickness being presented by the child and 94.1% of trips did not result in any vomiting. . Over the 68 trips some children experienced motion sickness, it started on average 2.0 hours after the trip started.

[0107] The overall average motion sickness severity score explored by the MSAQ over the 185 trips decreased significantly by 75.1% (p <0.0001) when compared to the average overall score for trips made in the months preceding the trip. 'study. The gastrointestinal, central, peripheral and fatigue dimensions decreased by 73.9% (p <0.0001), 76.7% (p <0.0001), 74.5% (p <0.0001) and 70.3% (p <0.0001). The symptoms most severely felt by children, namely nausea, the urge to vomit and general malaise, decreased the most with 62.8%, 64.0% and 60.8% reduction, respectively.

[0108] Stops were more frequent than desired in only a third of cases (33.8%) versus one in two trips usually with on average, 1.3 additional stops versus 2 usually.

[0109] When comparing the time to onset of symptoms of sickness

transport, these appear on average in less than an hour before inclusion versus almost 2 hours during the first journey made during the study with the composition according to example 1 being taken.

[01 10] If half of the children vomited from the first hour during the last trip before inclusion in the study, out of the 3 children who vomited during the first trip after inclusion, one vomited in the first half hour and the other 2 after more than 3 hours of travel.

[01 1 1] Analysis by child

[01 12] All the children made at least one trip without vomiting and 51 (87.9%) children did not present any vomiting on all the trips. achieved while the same percentage, 87.9% of the children presented vomiting, frequent or systematic for more than half of them.

[01 13] We note that 94.4% of children who vomited frequently during

trips taken in the months prior to study inclusion never vomited during study trips with pacifier. More than half (55.6%) of the children who vomited systematically before the study showed no vomiting when they had taken one or more pacifiers and 73.7% of the children who had vomited during the last trip before inclusion never vomited during the study.

[01 14] 79.3% of the children made at least one trip without showing any signs of motion sickness and 22 (37.9%) experienced no signs of motion sickness on all the trips made.

[01 15] For all the dimensions explored by the MSAQ as well as for the overall score, the severity presented on average per child over all the 185 journeys decreases significantly (p <0.0001) when compared to the severity score presented in average during journeys made in the months preceding the study. The same is true if we compare the first trip made during the study to the average per child of the MSAQ score of trips made in the months preceding the study since the overall average motion sickness score decreases significantly by 80, 0% (p <0.0001) and the gastrointestinal, central, peripheral and fatigue dimensions decrease respectively by 79.7% (p <0.0001), 80.2% (p <0.0001), 78.6% (p <0 , 0001) and 74.7% (p <0.0001).

[01 16] Analysis of the factors likely to influence the response

[01 17] An analysis was performed to explore the factors likely

to influence a so-called total response, either no vomiting or no signs of motion sickness presented by the child.

[01 18] The occurrence of vomiting before or during the last journey before inclusion in the study is significantly inversely correlated (p <0.05) with the total disappearance of vomiting or signs of motion sickness during the course of the study. study, the total response rate being higher when the child did not show vomiting. However, we note that 94.4% of children who vomited frequently and more than half (55.6%) of the children who vomited systematically during trips made in the months prior to inclusion in the study never vomited during trips taken during the study when they had taken one or more lollipops. If, during the last trip before inclusion in the study, almost a third (31.0%) of the children had vomited, only 5.2% vomited during the first trip and 12.1% after vomiting during all the journeys made during the study after taking the pacifier.

[01 19] On the other hand, the effectiveness of pacifiers in preventing vomiting and signs of motion sickness appears to be comparable regardless of the sex of the children and their age and independent of whether or not they are also sick in d 'other situations than the car.

[0120] Evaluation of satisfaction data

[0121] 81.0% of parents are satisfied with the action of this product on the prevention of motion sickness and its action on the digestive comfort of the child during car trips. Indeed, 96.6% of parents consider that their child's symptoms in the car after using the product have improved, of which 62.1% "considerably" or "a lot". The same goes for digestive comfort considered to be improved by 88.0% of parents, including 53.5%

"Considerably" or "a lot".

[0122] 86.2% of the children are themselves satisfied with the effect of the product on their symptoms and 86.2% appreciate the taste of lollipops with a clear preference for the cola taste (53.4%), ahead of the strawberry (25.9%) and orange (10.3%).

[0123] Corroborating their high degree of satisfaction, 93.1% of parents

would recommend this product to a loved one whose children suffer from motion sickness.

[0124] Example 4: Observational study evaluating the perceived effectiveness of the composition according to Example 2 on the symptoms of motion sickness in children

An observational study was carried out under the same conditions as in Example 3 with the lollipop according to Example 2 (containing only ginger). [0126] Analysis by trip

[0127] Just over half (55%) of trips were completed without any sign of motion sickness being presented by the child, and 85% of trips did not result in vomiting.

[0128] The overall average motion sickness severity score explored by the

MSAQ on trips was significantly reduced by 70% (p <0.0001) when compared to the average overall score for trips taken in the months prior to the study. The gastrointestinal, central, peripheral and fatigue dimensions also decrease. The symptoms most severely felt by children, namely nausea, the urge to vomit and general malaise, decrease the most with a decrease of 52.3%, 54.5% and 50.2% respectively.

[0129] Analysis by child

[0130] All the children made at least one trip without vomiting and 75% of the children did not experience any vomiting on all the trips made.

[0131] It is noted that 83% of the children who vomited frequently during trips made in the months preceding inclusion in the study never vomited during trips made during the study with the pacifier.

[0132] It therefore follows from the studies of Examples 3 and 4 that the association of

Dandelion ginger improves results in the prevention and / or treatment of motion sickness.

[0133] Example 5: Quantitative study of the composition according to Example 1

[0134] The composition according to the invention comprises ginger, known to have a very strong taste and to provide pseudo-heat when ingested, and dandelion, known for its bitter taste. As the tastes of these two plants are not unanimous, in particular among children, it was important to verify that the composition according to the invention had a satisfactory taste in order, in particular, to improve compliance.

[0135] The three fragrances (Cola, Strawberry and Orange) were tested on children in order to: - Make sure these lollipop scents are loved by children,

-Check that the flavors offered are sufficiently appreciated so that the lollipops are consumed whole,

-Determine which fragrance is preferred.

[0136] Phase 1: Indoor test

Step 1: Evaluation of the 3 flavors of lollipops (Cola, Strawberry, Orange) in terms of:

Overall assessment after 2 minutes of tasting (smiley scale),

Intention to consume the whole lollipop, if not, reason for multiple choice,

Evocation of taste in MCQ,

Appreciation of sweetness and acidity intensity,

Step 2: Preference between the three flavors.

[0137] During the indoor phase, each child blindly evaluated the 3 flavors of lollipops. They were presented in sequential monadic, following a balanced complete experimental design that controlled for presentation order effects.

For this phase, the children answered the self-administered product questionnaire after tasting each lollipop for 2 minutes. The youngest children (primary) were assisted by an investigator. The questionnaire was adapted to their cognitive ability and was the subject of a specific formulation of the questions.

[0138] Phase 2: Home use test: Evaluation of the 3 scents by the children + evaluation of the concept by the parents

Evaluation of pacifiers by children:

Use: full consumption of the pacifier: yes / no

If not: reasons?

Overall assessment (smiley scale),

Intentions to re-use. Concept evaluation by parents:

Global appeal,

Purchase intentions at the appropriate price,

Reasons and obstacles to buying (spontaneously),

[0139] At the end of the indoor phase, each parent was given 3 pacifiers (one for each scent studied) so that their child could participate in the second phase of the home test.

[0140] In order to guarantee good mastery of the field, the parents received the necessary elements for the test in person (instructions, 3 pacifiers, 1 copy of the paper questionnaire). The anonymity of the products has been guaranteed thanks to the packaging in neutral containers. An experiment plan made it possible to counterbalance the order of evaluation of the 3 formulas.

[0141] The children had 6 days to test the 3 pacifiers. They were invited to test at home, imperatively in the presence of their parents, the 3 pacifiers on separate days. After complete consumption of each pacifier, the children in the presence of their parents completed the self-administered questionnaire.

[0142] Following the evaluation of the 3 pacifiers, the parent who most often buys pharmacy products for their child was invited to give their opinion on the concept of herbal pacifiers.

[0143] The 3 pacifiers tested in phase 1 performed satisfactorily in terms of overall assessment as well as in terms of consumption intentions as a whole.

[0144] Based on these 2 criteria as well as in a situation of forced choice, the Cola perfume

overall performs better than Strawberry and Orange scents.

[0145] The 3 lollipops tested in phase 2 performed satisfactorily in terms of overall assessment and consumption intentions, and were consumed entirely by almost all of the children, in particular the Cola perfume which performs slightly better. than Strawberry and Orange scents on these criteria. [0146] Evaluation of the concept by the parents:

[0147] The “Pacifiers” concept is well appreciated by parents and generates

very high purchase intentions. The main reasons for buying mentioned relate to the ease of administration to children, the original and attractive side of the concept and the tastes offered, as well as the reassuring composition.

Claims

[Claim 1] Product comprising, as active substances, at least:

(i) ginger,

(ii) dandelion

for the prevention and / or treatment of motion sickness.

[Claim 2] Product according to claim 1, characterized in that it comprises:

200 to 2000 mg, preferably 300 to 600 mg of ginger extract, 50 to 500 mg, preferably 100 to 200 mg of dandelion extract.

[Claim 3] Product according to one of claims 1 or 2, characterized in that it is in the form of a single composition containing at least:

(i) ginger,

(ii) dandelion

in a physiologically acceptable medium.

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

[Claim 5] Product according to one of the preceding claims, characterized in that it is in the form of a confectionery to be sucked on.

[Claim 6] Product according to one of the preceding claims characterized in that the ginger and dandelion are in the form of plant extracts.

[Claim 7] Product according to at least one of the preceding claims, for the treatment of subjects exhibiting motion sickness. |