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WO2021014370A1 - Pharmaceutical composition for use in the treatment and prevention of motion sickness - Google Patents

Pharmaceutical composition for use in the treatment and prevention of motion sickness Download PDF

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Publication number
WO2021014370A1
WO2021014370A1 PCT/IB2020/056881 IB2020056881W WO2021014370A1 WO 2021014370 A1 WO2021014370 A1 WO 2021014370A1 IB 2020056881 W IB2020056881 W IB 2020056881W WO 2021014370 A1 WO2021014370 A1 WO 2021014370A1
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Prior art keywords
pharmaceutical composition
drug
motion sickness
composition according
treatment
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French (fr)
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Eros ZANOTTI
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics

Definitions

  • the present invention relates to a pharmaceutical composition and the use thereof in the treatment and prevention of motion sickness.
  • the invention relates to an association of at least a first pharmaceutically active ingredient with anti-gastric secretion properties and at least a second pharmaceutically active ingredient with anti-vertigo and antiemetic properties for use in the treatment and prevention of motion sickness.
  • the invention relates to an association of at least a proton-pump inhibitor (PPI) or, alternatively, a histamine H2 receptor antagonist, and at least a third-generation or second-generation antihistamine for use in the treatment of motion sickness.
  • PPI proton-pump inhibitor
  • histamine H2 receptor antagonist at least a histamine H2 receptor antagonist for use in the treatment of motion sickness.
  • Motion sickness is a disorder/series of neuro- vegetative disorder (s) which some individuals experience as a result of rhythmic or irregular body movements during motion (e.g. on a swing, on a carousel, or during travel on transport means such as ships, cars, planes, etc.) and which is mostly characterized by nausea, vomiting and dizziness .
  • motion sickness is mainly attributable to a disturbance of the subject's vestibular apparatus and parasympathetic nervous system.
  • This disorder can also be increased by visual and/or olfactory stimuli/ impulses , or by gastrointestinal developments.
  • these impulses go to stimulate the vomiting center in the medulla oblongata, causing nausea and vomiting, often accompanied by general malaise, asthenia, pallor, cold sweat, anxiety, yawns, and increased salivation.
  • nausea and vomiting often accompanied by general malaise, asthenia, pallor, cold sweat, anxiety, yawns, and increased salivation.
  • other symptoms may also be present, such as headache and diarrhea.
  • the symptoms generally disappear at the end of the triggering cause (for example, travel).
  • Motion sickness is not an inflammatory disease.
  • the drugs normally used in motion sickness syndromes have a possible protective effect against dizziness, nausea, and vomiting.
  • scopolamine which has only a preventive action
  • some old-generation antihistamine drugs such as dimenhydrinate, promethazine, cyclizine and meclonazine, may be mentioned.
  • these drugs are not able to ensure, on average, a rapid, long-term effect.
  • they cause a series of side effects, well known in the literature, among which the most significant is drowsiness; for this reason, driving vehicles after their ingestion is strongly advised against .
  • the prior art document CN 1 709 509 describes the association between promethazine, cimetidine, meclofenoxate, calcium gluconate (or lactate) , chlorpheniramine and diphenhydramine for use in motion sickness and there is no mention of a possible association between a proton-pump inhibitor and a second or third- generation antihistamine. This association has drowsiness as a side effect.
  • WO 2016/011254 describes an association of an anti-Hl antihistamine with an anti-leukotriene in the treatment of allergic and/or inflammatory conditions.
  • the patent document WO 2005/074536 describes an association between a proton-pump inhibitor and an NSAID or antibiotics or anti-kinetics or drugs for the treatment of cystic fibrosis, in the prevention or treatment of gastro-intestinal disorders, including motion sickness. Such an association does not comprise a second or third- generation antihistamine.
  • the document WO 96/20708 describes an association between descarboethoxyloratadine, an NSAID, non-narcotic analgesics, decongestants, antitussives and expectorants in the treatment of allergies, dizziness, motion sickness, flu-like symptoms and diabetic retinopathy; not comprising a proton-pump inhibitor, it causes the well-known side effects .
  • the US patent document 2002/137768 describes an association between astemizole metabolites, NSAIDs or other non-narcotic or decongestant or antitussive or expectorant analgesics; it does not comprise proton-pump inhibitors. Due to serious cardiotoxic effects, astemizole was withdrawn from commerce in 1999.
  • the present invention relates to a pharmaceutical composition comprising the above-indicated association, as described in the appended independent claim.
  • the present invention also relates to the above pharmaceutical composition for medical use.
  • the pharmaceutical composition detailed above is described for medical use in the treatment or prevention of motion sickness, as described in the appended independent claim.
  • said anti-gastric secretion drug A is selected from the group of drugs belonging to the family of proton- pump inhibitors (PPIs), or from the group of drugs belonging to the family of histamine H2 receptor antagonists; and
  • said anti-vertigo, and also antiemetic, drug B) is selected from the group of drugs belonging to the family of so-called third-generation antihistamines and/or those belonging to the family of second-generation antihistamines; both families, and in particular the first, group compounds which are provided with rapid functioning onset and prolonged half-life, and cause very low or no sleepiness .
  • said drug A) is selected from the group consisting of Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole and/or Rabeprazole (sodium) and/or Ilaprazole and/or Tenatoprazole and/or Dexlansoprazole, or from the group consisting of Ranitidine and/or Famotidine and/or Cimetidine and/or Nizatidine; and
  • said drug B) is selected from the group consisting of Levocetirizine and/or Desloratadine ; and/or selected from the group consisting of Cetirizine and/or Loratadine and/or Fexofenadine.
  • said drug A) is selected from Esomeprazole and/or Omeprazole;
  • said drug B) is selected from Levocetirizine and desloratadine .
  • the proton-pump inhibitors are administered in an average amount from 5 mg to 180 mg, and the histamine H2 receptor antagonists are administered in an average amount from 20 mg to 2000 mg;
  • the third-generation antihistamines are administered in an average amount from 5 mg to 250 mg per dose.
  • the drug A) and the drug B) are taken simultaneously or one immediately after the other.
  • the pharmaceutical composition introduced above may further comprise excipients commonly used in preparative pharmaceutical techniques, selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; pharmaceutical polymers.
  • excipients commonly used in preparative pharmaceutical techniques selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; pharmaceutical polymers.
  • said excipients may be selected from the group consisting of lactose, glucose, saccharose, sweeteners, aspartame, acesulfame K, saccharin, cyclamate, stevioside, glycyrrhizin, xylitol, sorbitol, mannitol, mannite, kaolin, talc, bentonite, titanium dioxide .
  • said pharmaceutical composition may further comprise adjuvant additives, such as natural extracts having soothing and/or digestive action: chamomile and/or valerian and/or althea extracts, and/or the like.
  • adjuvant additives such as natural extracts having soothing and/or digestive action: chamomile and/or valerian and/or althea extracts, and/or the like.
  • said pharmaceutical composition may be prepared in a common pharmaceutical form adapted for oral administration; in the form of a tablet, a lozenge, a pill, a comfit, a soft or hard capsule, a sachet to be reconstituted in water upon ingestion, a chewing gum, a transdermal patch, drops, even in gastro-resistant form, as well as in controlled release form.
  • the complete resolution of the motion sickness symptoms occurs after about 10-60 minutes from the ingestion of said composition.
  • the present invention also relates to a process for preparing the aforesaid pharmaceutical composition, as described in the appended independent claim.
  • a kit is also described herein, comprising separate dosages of the drugs A) and B) in accordance with the description, to be taken when necessary, simultaneously or one immediately before the other.
  • a method for the treatment or prevention of motion sickness comprising the administration of the composition of the invention is further described.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a suitable association of:
  • said anti-gastric secretion drug A) is preferably selected from the group of drugs belonging to the family of proton-pump inhibitors (PPIs), or from the group of drugs belonging to the family of histamine H2 receptor antagonists.
  • PPIs proton-pump inhibitors
  • the proton-pump inhibitors are selected from the group comprising: Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole and/or Rabeprazole (sodium) and/or Ilaprazole and/or Tenatoprazole and/or Dexlansoprazole ; more preferably, Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole ; even more preferably, Esomeprazole.
  • the histamine H2 receptor antagonists are selected from the group consisting of Ranitidine and/or Famotidine and/or Cimetidine and/or Nizatidine; more preferably Ranitidine and/or Famotidine; even more preferably, Ranitidine.
  • said drug A) is preferably represented by a proton-pump inhibitor.
  • said drug A) is more preferably represented by Esomeprazole or Omeprazole, where Esomeprazole is more preferred.
  • said drugs are preferably administered within dosage limits similar to those already known and commonly used in therapy for the diseases usually treated with these drugs.
  • said drugs are comprised in the combination of the invention and, therefore, are administered, in an average amount from 5 mg to 180 mg, approximately.
  • Esomeprazole is preferably administered in an amount from 10 mg to 160 mg; preferably, from 20 mg to 40 mg; more preferably, 20 mg per dose;
  • - Omeprazole is preferably administered in an amount from 5 mg to 120 mg; preferably, from 10 mg to 40 mg; more preferably, 20 mg per dose;
  • Lansoprazole is preferably administered in an amount from 10 mg to 180 mg; preferably, from 15 mg to 30 mg; more preferably, 30 mg per dose;
  • Pantoprazole is preferably administered in an amount from 10 mg to 160 mg; preferably, from 20 to 40 mg; more preferably, 40 mg per dose;
  • - Rabeprazole sodium is preferably administered in an amount from 5 mg to 120 mg; preferably, from 10 to 20 mg; more preferably, 20 mg per dose.
  • said drugs are comprised in the combination of the invention and, therefore, are administered, in an average amount from 20 mg to 2000 mg.
  • - Ranitidine is preferably administered in an amount ranging from 100 mg to 900 mg; preferably, from 150 to 300 mg; more preferably at 300 mg per dose;
  • - Famotidine is preferably administered in an amount from 30 to 800 mg; preferably, from 40 mg to 80 mg; more preferably 40 mg per dose;
  • Cimetidine is preferably administered in an amount from 400 mg to 2000 mg; preferably, from 400 mg to 1000 mg; more preferably, 200, 400 or 800 mg per dose;
  • - Nizatidine is preferably administered in an amount from 100 mg to 600 mg; preferably, from 200 mg to 400 mg; more preferably, 300 mg per dose.
  • Said anti-vertigo and antiemetic drug B) is preferably selected from the group of drugs belonging to the family of so-called third-generation antihistamines, but also, possibly, from a suitably selected group of drugs belonging to the family of so-called second- generation antihistamines; both families, especially the first, are characterized by a rapid functioning onset and prolonged half-life and cause very low or no sleepiness.
  • said third-generation antihistamines are selected from the group comprising: Levocetirizine, Desloratadine ; while the second-generation antihistamines are selected from the group comprising: Cetirizine, Loratadina, Fexofenadine.
  • said drugs are preferably administered within dosage limits similar to those already known and commonly used in therapy for the diseases usually treated with these drugs.
  • said drugs are administered in an average amount from 5 mg to 250 mg per dose.
  • said drugs are administered in an average amount from 5 mg to 250 mg per dose.
  • - Levocetirizine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 5 mg per dose;
  • Desloratadine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 5 mg per dose.
  • any preferred second-generation antihistamines are any preferred second-generation antihistamines :
  • - Cetirizine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 10 mg per dose;
  • - Loratadine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 10 mg per dose;
  • Fexofenadine is preferably administered in an amount from 50 mg to 250 mg; preferably, from 100 mg to 200 mg; more preferably, from 120 mg to 180 mg per dose.
  • the administration of the amounts described above, in the association of the invention may take place in a single daily dose, or divided into separate dosages, or in whole doses repeated throughout the day, according to needs .
  • the treatment may be carried out preventively, before the onset of the motion sickness, or once the motion sickness symptoms have started.
  • the association of the present invention is taken, in single daily administration, for the entire exposure period to the motion sickness inducing noxa (for example, in the case of a week's travel by boat, it must be taken once a day for all 7 days) .
  • the pharmaceutical composition of the present invention is preferably prepared in a common pharmaceutical form adapted for oral administration; for example, in the form of a tablet, a lozenge, a pill, a comfit, a capsule (soft or hard), a sachet to be reconstituted in water upon ingestion, a chewing gum, a transdermal patch, drops, possibly even in gastro- resistant form, possibly in controlled release form as well to ensure a gradual and long-lasting release of the composition itself.
  • the pharmaceutical composition of the present invention may further comprise a number of excipients commonly and notoriously used in the preparative pharmaceutical technique; for example, selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; polymers (for prolonged-release or gastro-resistant preparations) .
  • excipients commonly and notoriously used in the preparative pharmaceutical technique
  • the most common excipients used to dilute the powders of the association of the active ingredients are selectable from the group consisting of lactose, glucose, saccharose, sweeteners (aspartame, acesulfame K, saccharin, cyclamate, stevioside, glycyrrhizin, xylitol, sorbitol, mannitol), mannite, kaolin, talc, bentonite, titanium dioxide.
  • the pharmaceutical composition of the present invention may further comprise adjuvant additives, such as natural extracts having a soothing and/or digestive action; for example, chamomile, valerian, althea extracts and the like .
  • adjuvant additives such as natural extracts having a soothing and/or digestive action; for example, chamomile, valerian, althea extracts and the like .
  • the preparation of the pharmaceutical composition of the present invention is carried out using any well-known mixing process of the powders of the desired active ingredients and of any selected excipients and/or adjuvants, using known and commonly used mixing devices (for example, dry, wet, in turbo-mixer, and so on) .
  • the final mixed powder is then subjected to the known techniques for preparing the final products; for example, the same is subjected to suitable compression (by means of a known compactor with loading hopper) to prepare tablets or other similar solid forms; or it is used to fill pre dosed sachets, to be reconstituted with water at the time of use, or capsules of various types; or it is used to prepare dosed solutions (for example pediatric), and so on
  • kits prepared with the desired separate dosages of the drugs A) and B) to be taken with the time and quantitative methods described above is also an object of the invention.
  • the present patent application further describes a method for the treatment or prevention of motion sickness, comprising the step of administering to a patient in need thereof a pharmaceutically effective amount of the pharmaceutical composition in accordance with the above description.
  • said method for the treatment or prevention of motion sickness comprises the step of administering the composition of the invention once a day, possibly in a single dose.
  • a capsule for oral use is filled (using a normal pharmaceutical encapsulating machine) with an association of :
  • said capsule is filled with the above association, but further comprises any known mixture of excipients commonly used in the preparation of hard capsules.
  • a sachet the content of which is to be reconstituted in water before ingestion, is filled with an association of:
  • said sachet is filled with the above association, but further comprises a suitable known mixture of excipients commonly used in the preparation of reconstitutable sachets, containing, for example, disintegrating agents/solubilizers, sweeteners (stevia), flavorings (mandarin and citrus aroma) and coloring (orange) , in the quantities notoriously used in the art.
  • An oval, divisible tablet is produced (using a normal pharmaceutical pressing machine) with an association of:
  • Levocetirizine 5 mg to give the desired pharmaceutical composition in oral tablets against seasickness, car sickness and plane sickness .
  • said tablet is produced with the above association, but further comprising a mixture of excipients commonly used in the preparation of tablets .
  • said tablet is also coated on the surface (with techniques well known in the field) to give it the desired gastro-resistance .
  • a chewing gum in the form of a round tablet is produced (using a normal pharmaceutical pressing machine provided with pistons, which are suitable for the production of chewable gums) with an association of:
  • the granules of the powder of the composition are pre-micro encapsulated in a gastro- resistant polymer (such as an Eudragit® for food use adapted to the need) to ensure a gastric-level passage which is not harmful to the stomach.
  • a gastro- resistant polymer such as an Eudragit® for food use adapted to the need
  • the pharmaceutical composition of the present invention has proven to be extremely effective in the treatment of the disabling symptoms of the various forms of motion sickness, as well as in the prevention of the same.
  • the ingestion of the formulation of the present invention resulted in the complete resolution of the motion sickness symptoms, after about 10-60 minutes; preferably, after about 15-50 minutes; more preferably, after about 20-40 minutes, or after about 30 minutes (in this case, the word approximately means ⁇ 1 or 2 minutes with respect to the indicated period of time) .
  • the symptoms no longer occurred.
  • the administration is preferably carried out in single daily administration, for the entire duration of the exposure to the noxa inducing motion sickness (e.g. in the case of a week's vacation on a boat, it must be taken once a day for all 7 days) .
  • the combination therapy of the present invention has been applied to several subjects, also to children, both in the preventive phase and during more or less pronounced episodes of motion sickness, obtaining a success rate substantially equal to 100% (i.e., 100% or slightly less) .
  • the activity of the composition has proved to be of rapid onset, long lasting, and free of the side effects (for example, sleepiness) typical of the known anti-motion sickness drugs.
  • the pharmaceutical composition/ formulation of the present invention has proven to be able to treat or prevent the forms of motion sickness caused by the most varied reasons, such as, for example, caused by seasickness, car sickness and plane sickness, with considerable success.
  • the activity of the composition has proven to be of rapid onset, long-lasting and greater than the anti-motion sickness drugs on the market, and free of the side effects, represented for example by drowsiness, nausea and/or vomiting, vertigo, asthenia, central nervous system depressive activity and habituation, typical of the already known drugs.
  • the therapy suggested by the present invention may comprise the use of two independent drugs, the treatment can exhibit greater manageability and practicality of use.

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Abstract

The present invention relates to a pharmaceutical composition for use in the treatment and prevention of motion sickness. In particular, the invention relates to an association of at least a first pharmaceutically active ingredient with anti-gastric secretion properties and at least a second pharmaceutically active ingredient with anti-vertigo and antiemetic properties for use in the treatment and prevention of motion sickness. Specifically, the invention relates to an association of at least one proton-pump inhibitor (PPI) or, alternatively, one histamine H2 receptor antagonist, and at least one third-generation antihistamine for use in the treatment and prevention of motion sickness.

Description

" PHARMACEUTICAL COMPOSI TION FOR USE IN THE TREATMENT AND
PREVENTION OF MOTION SICKNESS"
Technical field of the invention
The present invention relates to a pharmaceutical composition and the use thereof in the treatment and prevention of motion sickness.
In particular, the invention relates to an association of at least a first pharmaceutically active ingredient with anti-gastric secretion properties and at least a second pharmaceutically active ingredient with anti-vertigo and antiemetic properties for use in the treatment and prevention of motion sickness.
Specifically, the invention relates to an association of at least a proton-pump inhibitor (PPI) or, alternatively, a histamine H2 receptor antagonist, and at least a third-generation or second-generation antihistamine for use in the treatment of motion sickness.
Background art
Motion sickness is a disorder/series of neuro- vegetative disorder (s) which some individuals experience as a result of rhythmic or irregular body movements during motion (e.g. on a swing, on a carousel, or during travel on transport means such as ships, cars, planes, etc.) and which is mostly characterized by nausea, vomiting and dizziness .
In general, motion sickness is mainly attributable to a disturbance of the subject's vestibular apparatus and parasympathetic nervous system. This disorder can also be increased by visual and/or olfactory stimuli/ impulses , or by gastrointestinal developments.
In turn, these impulses go to stimulate the vomiting center in the medulla oblongata, causing nausea and vomiting, often accompanied by general malaise, asthenia, pallor, cold sweat, anxiety, yawns, and increased salivation. In particular, in the case of seasickness, other symptoms may also be present, such as headache and diarrhea. The symptoms generally disappear at the end of the triggering cause (for example, travel).
Motion sickness is not an inflammatory disease.
The drugs normally used in motion sickness syndromes have a possible protective effect against dizziness, nausea, and vomiting. Among these, scopolamine (which has only a preventive action) and some old-generation antihistamine drugs, such as dimenhydrinate, promethazine, cyclizine and meclonazine, may be mentioned. However, these drugs are not able to ensure, on average, a rapid, long-term effect. Furthermore, they cause a series of side effects, well known in the literature, among which the most significant is drowsiness; for this reason, driving vehicles after their ingestion is strongly advised against .
The prior art document CN 1 709 509 describes the association between promethazine, cimetidine, meclofenoxate, calcium gluconate (or lactate) , chlorpheniramine and diphenhydramine for use in motion sickness and there is no mention of a possible association between a proton-pump inhibitor and a second or third- generation antihistamine. This association has drowsiness as a side effect.
The document US 2014/275116 describes an association between cetirizine and famotidine for use in the treatment of diarrhea.
The document US 2015/132410 describes an association between sodium naproxen, loratadine, ranitidine, vitamins Bl, B2, B6 and B12, magnesium citrate, magnesium aspartate and magnesium hydroxide for the prevention and treatment of acute ethylism syndrome.
The document WO 2016/011254 describes an association of an anti-Hl antihistamine with an anti-leukotriene in the treatment of allergic and/or inflammatory conditions.
The patent document WO 2005/074536 describes an association between a proton-pump inhibitor and an NSAID or antibiotics or anti-kinetics or drugs for the treatment of cystic fibrosis, in the prevention or treatment of gastro-intestinal disorders, including motion sickness. Such an association does not comprise a second or third- generation antihistamine.
The prior art document US 2013/131026 describes an association between caffeine and an antihistamine, also third generation, for the treatment of symptoms related to inflammation; a proton-pump inhibitor is not comprised.
The US patent document 2002/183241 describes the association between descarboethoxyloratadine, ephedrine, amphetamines and psychostimulants in the treatment of urinary incontinence, vertigo and motion sickness; this association, however, does not comprise a proton-pump inhibitor and can therefore cause gastrointestinal disturbances .
The prior art document EP 1.769.797 describes the association between cetirizine, an antileukotriene and possibly a decongestant, an NSAID, an antitussive and an expectorant in the treatment of inflammation, asthma, allergic disorders and motion sickness; this association, which does not include a proton-pump inhibitor, causes drowsiness as a significant side effect.
The document WO 96/20708 describes an association between descarboethoxyloratadine, an NSAID, non-narcotic analgesics, decongestants, antitussives and expectorants in the treatment of allergies, dizziness, motion sickness, flu-like symptoms and diabetic retinopathy; not comprising a proton-pump inhibitor, it causes the well-known side effects . The US patent document 2002/137768 describes an association between astemizole metabolites, NSAIDs or other non-narcotic or decongestant or antitussive or expectorant analgesics; it does not comprise proton-pump inhibitors. Due to serious cardiotoxic effects, astemizole was withdrawn from commerce in 1999.
Therefore, the demand for new drugs which can cure and prevent the disorders associated with the onset of motion sickness remains well felt in the sector, one which acts quickly, for a prolonged period of time, without exhibiting the known harmful and dangerous side effects presented by the traditional anti-motion sickness drugs.
Summary
Therefore, it is an object of the present invention to provide a suitable pharmaceutical composition which solves the aforesaid technical problems.
Said object was achieved by the inventor of the present patent application, who unexpectedly found that a suitable association of at least two drugs, well known for being provided with other pharmacological properties (such as anti-gastric secretion, anti-vertigo and antiemetic properties) is able to provide the desired response to the technical problem described above.
Therefore, the present invention relates to a pharmaceutical composition comprising the above-indicated association, as described in the appended independent claim.
The present invention also relates to the above pharmaceutical composition for medical use.
According to a preferred aspect of the present invention, the pharmaceutical composition detailed above is described for medical use in the treatment or prevention of motion sickness, as described in the appended independent claim. These and other objects are thus achieved by the present pharmaceutical composition comprising at least an association of:
A) an anti-gastric secretion drug;
B) an anti-vertigo, and also antiemetic drug.
Advantageously, for use in the treatment, also preventive, of motion sickness.
Advantageously, in said pharmaceutical composition :
- said anti-gastric secretion drug A) is selected from the group of drugs belonging to the family of proton- pump inhibitors (PPIs), or from the group of drugs belonging to the family of histamine H2 receptor antagonists; and
- said anti-vertigo, and also antiemetic, drug B) is selected from the group of drugs belonging to the family of so-called third-generation antihistamines and/or those belonging to the family of second-generation antihistamines; both families, and in particular the first, group compounds which are provided with rapid functioning onset and prolonged half-life, and cause very low or no sleepiness .
Advantageously, in said pharmaceutical composition:
- said drug A) is selected from the group consisting of Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole and/or Rabeprazole (sodium) and/or Ilaprazole and/or Tenatoprazole and/or Dexlansoprazole, or from the group consisting of Ranitidine and/or Famotidine and/or Cimetidine and/or Nizatidine; and
- said drug B) is selected from the group consisting of Levocetirizine and/or Desloratadine ; and/or selected from the group consisting of Cetirizine and/or Loratadine and/or Fexofenadine.
Even more advantageously, in said pharmaceutical composition :
said drug A) is selected from Esomeprazole and/or Omeprazole; and
said drug B) is selected from Levocetirizine and desloratadine .
Advantageously, in said pharmaceutical composition:
- regarding drug A) , the proton-pump inhibitors are administered in an average amount from 5 mg to 180 mg, and the histamine H2 receptor antagonists are administered in an average amount from 20 mg to 2000 mg; and
regarding drug B) , the third-generation antihistamines are administered in an average amount from 5 mg to 250 mg per dose.
Advantageously, the drug A) and the drug B) are taken simultaneously or one immediately after the other.
Advantageously, the pharmaceutical composition introduced above may further comprise excipients commonly used in preparative pharmaceutical techniques, selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; pharmaceutical polymers.
For example, advantageously, said excipients may be selected from the group consisting of lactose, glucose, saccharose, sweeteners, aspartame, acesulfame K, saccharin, cyclamate, stevioside, glycyrrhizin, xylitol, sorbitol, mannitol, mannite, kaolin, talc, bentonite, titanium dioxide .
Advantageously, said pharmaceutical composition may further comprise adjuvant additives, such as natural extracts having soothing and/or digestive action: chamomile and/or valerian and/or althea extracts, and/or the like. Advantageously, said pharmaceutical composition may be prepared in a common pharmaceutical form adapted for oral administration; in the form of a tablet, a lozenge, a pill, a comfit, a soft or hard capsule, a sachet to be reconstituted in water upon ingestion, a chewing gum, a transdermal patch, drops, even in gastro-resistant form, as well as in controlled release form.
Advantageously, the complete resolution of the motion sickness symptoms occurs after about 10-60 minutes from the ingestion of said composition.
Therefore, the present invention also relates to a process for preparing the aforesaid pharmaceutical composition, as described in the appended independent claim.
A kit is also described herein, comprising separate dosages of the drugs A) and B) in accordance with the description, to be taken when necessary, simultaneously or one immediately before the other.
A method for the treatment or prevention of motion sickness comprising the administration of the composition of the invention is further described.
Detailed description of the invention
The present invention relates to a pharmaceutical composition comprising a suitable association of:
A) an anti-gastric secretion drug;
B) an anti-vertigo and also antiemetic drug.
For the purposes of the present invention, said anti-gastric secretion drug A) is preferably selected from the group of drugs belonging to the family of proton-pump inhibitors (PPIs), or from the group of drugs belonging to the family of histamine H2 receptor antagonists.
Preferably, the proton-pump inhibitors (PPIs) are selected from the group comprising: Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole and/or Rabeprazole (sodium) and/or Ilaprazole and/or Tenatoprazole and/or Dexlansoprazole ; more preferably, Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole ; even more preferably, Esomeprazole.
Preferably, the histamine H2 receptor antagonists are selected from the group consisting of Ranitidine and/or Famotidine and/or Cimetidine and/or Nizatidine; more preferably Ranitidine and/or Famotidine; even more preferably, Ranitidine.
For the purposes of the present invention, said drug A) is preferably represented by a proton-pump inhibitor.
In particular, said drug A) is more preferably represented by Esomeprazole or Omeprazole, where Esomeprazole is more preferred.
As regards the dosage, said drugs are preferably administered within dosage limits similar to those already known and commonly used in therapy for the diseases usually treated with these drugs.
Regarding the proton-pump inhibitors, said drugs are comprised in the combination of the invention and, therefore, are administered, in an average amount from 5 mg to 180 mg, approximately.
Specifically, for example:
Esomeprazole is preferably administered in an amount from 10 mg to 160 mg; preferably, from 20 mg to 40 mg; more preferably, 20 mg per dose;
- Omeprazole is preferably administered in an amount from 5 mg to 120 mg; preferably, from 10 mg to 40 mg; more preferably, 20 mg per dose;
Lansoprazole is preferably administered in an amount from 10 mg to 180 mg; preferably, from 15 mg to 30 mg; more preferably, 30 mg per dose;
Pantoprazole is preferably administered in an amount from 10 mg to 160 mg; preferably, from 20 to 40 mg; more preferably, 40 mg per dose;
- Rabeprazole sodium is preferably administered in an amount from 5 mg to 120 mg; preferably, from 10 to 20 mg; more preferably, 20 mg per dose.
Regarding the histamine H2 receptor antagonists, said drugs are comprised in the combination of the invention and, therefore, are administered, in an average amount from 20 mg to 2000 mg.
Specifically, for example:
- Ranitidine is preferably administered in an amount ranging from 100 mg to 900 mg; preferably, from 150 to 300 mg; more preferably at 300 mg per dose;
- Famotidine is preferably administered in an amount from 30 to 800 mg; preferably, from 40 mg to 80 mg; more preferably 40 mg per dose;
- Cimetidine is preferably administered in an amount from 400 mg to 2000 mg; preferably, from 400 mg to 1000 mg; more preferably, 200, 400 or 800 mg per dose;
- Nizatidine is preferably administered in an amount from 100 mg to 600 mg; preferably, from 200 mg to 400 mg; more preferably, 300 mg per dose.
Said anti-vertigo and antiemetic drug B) , it is preferably selected from the group of drugs belonging to the family of so-called third-generation antihistamines, but also, possibly, from a suitably selected group of drugs belonging to the family of so-called second- generation antihistamines; both families, especially the first, are characterized by a rapid functioning onset and prolonged half-life and cause very low or no sleepiness.
Preferably, said third-generation antihistamines are selected from the group comprising: Levocetirizine, Desloratadine ; while the second-generation antihistamines are selected from the group comprising: Cetirizine, Loratadina, Fexofenadine. As regards the dosage, said drugs are preferably administered within dosage limits similar to those already known and commonly used in therapy for the diseases usually treated with these drugs.
Regarding the third-generation antihistamines, said drugs are administered in an average amount from 5 mg to 250 mg per dose. Specifically, for example:
- Levocetirizine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 5 mg per dose;
Desloratadine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 5 mg per dose.
Regarding, in turn, any preferred second-generation antihistamines :
- Cetirizine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 10 mg per dose;
- Loratadine is preferably administered in an amount from 5 mg to 50 mg; preferably, from 5 mg to 20 mg; more preferably, 10 mg per dose;
Fexofenadine is preferably administered in an amount from 50 mg to 250 mg; preferably, from 100 mg to 200 mg; more preferably, from 120 mg to 180 mg per dose.
The administration of the amounts described above, in the association of the invention, may take place in a single daily dose, or divided into separate dosages, or in whole doses repeated throughout the day, according to needs .
The treatment may be carried out preventively, before the onset of the motion sickness, or once the motion sickness symptoms have started.
In a preferred embodiment, the association of the present invention is taken, in single daily administration, for the entire exposure period to the motion sickness inducing noxa (for example, in the case of a week's travel by boat, it must be taken once a day for all 7 days) .
The pharmaceutical composition of the present invention is preferably prepared in a common pharmaceutical form adapted for oral administration; for example, in the form of a tablet, a lozenge, a pill, a comfit, a capsule (soft or hard), a sachet to be reconstituted in water upon ingestion, a chewing gum, a transdermal patch, drops, possibly even in gastro- resistant form, possibly in controlled release form as well to ensure a gradual and long-lasting release of the composition itself.
The pharmaceutical composition of the present invention may further comprise a number of excipients commonly and notoriously used in the preparative pharmaceutical technique; for example, selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; polymers (for prolonged-release or gastro-resistant preparations) . By way of non-limiting example, the most common excipients used to dilute the powders of the association of the active ingredients are selectable from the group consisting of lactose, glucose, saccharose, sweeteners (aspartame, acesulfame K, saccharin, cyclamate, stevioside, glycyrrhizin, xylitol, sorbitol, mannitol), mannite, kaolin, talc, bentonite, titanium dioxide.
The pharmaceutical composition of the present invention may further comprise adjuvant additives, such as natural extracts having a soothing and/or digestive action; for example, chamomile, valerian, althea extracts and the like . The preparation of the pharmaceutical composition of the present invention is carried out using any well-known mixing process of the powders of the desired active ingredients and of any selected excipients and/or adjuvants, using known and commonly used mixing devices (for example, dry, wet, in turbo-mixer, and so on) . The final mixed powder is then subjected to the known techniques for preparing the final products; for example, the same is subjected to suitable compression (by means of a known compactor with loading hopper) to prepare tablets or other similar solid forms; or it is used to fill pre dosed sachets, to be reconstituted with water at the time of use, or capsules of various types; or it is used to prepare dosed solutions (for example pediatric), and so on
All these final preparations, as well as similar ones which are suitable for oral administration, are made by using traditional machinery well known in the preparative pharmaceutical technique and, therefore, do not require further description here, fully falling within the common knowledge of the preparation technician skilled in the art .
In any case, for example in case of need or in particular urgency, it will also be possible to directly take a single dose of a drug A) and a single dose of a drug B) (in one embodiment, selecting them, for example, from those directly obtainable on the market) , taking them simultaneously or one immediately before the other.
In this regard, a kit prepared with the desired separate dosages of the drugs A) and B) to be taken with the time and quantitative methods described above is also an object of the invention.
According to a further aspect of the invention, the present patent application further describes a method for the treatment or prevention of motion sickness, comprising the step of administering to a patient in need thereof a pharmaceutically effective amount of the pharmaceutical composition in accordance with the above description.
In particular, said method for the treatment or prevention of motion sickness comprises the step of administering the composition of the invention once a day, possibly in a single dose.
Description of some preferred embodiments
The following section describes, purely by way of non-limiting example of the applicative potential of the present invention, some particularly preferred embodiments of the same.
Example 1
Preparation of a two-tone hard capsule containing Esomeprazole and Levocetirizine
A capsule for oral use is filled (using a normal pharmaceutical encapsulating machine) with an association of :
Esomeprazole : 40 mg
Levocetirizine 5 mg
to give the desired pharmaceutical composition against seasickness, car sickness and plane sickness.
In another embodiment, said capsule is filled with the above association, but further comprises any known mixture of excipients commonly used in the preparation of hard capsules.
Example 2
Preparation of a sachet containing Esomeprazole and
Desloratadine
A sachet, the content of which is to be reconstituted in water before ingestion, is filled with an association of:
Esomeprazole : 40 mg
Desloratadine : 5 mg
to give the desired pharmaceutical composition which is reconstitutable before use against seasickness, car sickness and plane sickness.
In a particularly preferred embodiment, said sachet is filled with the above association, but further comprises a suitable known mixture of excipients commonly used in the preparation of reconstitutable sachets, containing, for example, disintegrating agents/solubilizers, sweeteners (stevia), flavorings (mandarin and citrus aroma) and coloring (orange) , in the quantities notoriously used in the art.
Example 3
Preparation of a tablet containing Ranitidine and
Levocetirizine
An oval, divisible tablet is produced (using a normal pharmaceutical pressing machine) with an association of:
Ranitidine: 300 mg
Levocetirizine 5 mg to give the desired pharmaceutical composition in oral tablets against seasickness, car sickness and plane sickness .
In a preferred embodiment, said tablet is produced with the above association, but further comprising a mixture of excipients commonly used in the preparation of tablets .
In another preferred embodiment, said tablet is also coated on the surface (with techniques well known in the field) to give it the desired gastro-resistance .
Example 4
Preparation of a chewing gum containing Ranitidine and Desloratadine
A chewing gum in the form of a round tablet is produced (using a normal pharmaceutical pressing machine provided with pistons, which are suitable for the production of chewable gums) with an association of:
Ranitidine: 300 mg
Desloratadine: 5 mg
and of the excipients known and commonly used in the pharmaceutical technique for preparing chewing gums to give the desired pharmaceutical composition in the form of chewable gum against seasickness, car sickness and plane sickness .
Preferably, the granules of the powder of the composition are pre-micro encapsulated in a gastro- resistant polymer (such as an Eudragit® for food use adapted to the need) to ensure a gastric-level passage which is not harmful to the stomach.
The pharmaceutical composition of the present invention has proven to be extremely effective in the treatment of the disabling symptoms of the various forms of motion sickness, as well as in the prevention of the same. In particular, after the onset of symptoms, the ingestion of the formulation of the present invention, resulted in the complete resolution of the motion sickness symptoms, after about 10-60 minutes; preferably, after about 15-50 minutes; more preferably, after about 20-40 minutes, or after about 30 minutes (in this case, the word approximately means ± 1 or 2 minutes with respect to the indicated period of time) . Subsequently, even in the presence of persistent unfavorable environmental conditions, the symptoms no longer occurred.
The administration is preferably carried out in single daily administration, for the entire duration of the exposure to the noxa inducing motion sickness (e.g. in the case of a week's vacation on a boat, it must be taken once a day for all 7 days) .
However, other methods of administration can also be adopted (as already explained above) depending on the judgment of the attending physician.
By way of absolutely non-limiting example of the scope of the invention, the case of a young patient (male, aged 35 years) is reported here, who, during a sailing cruise suffered a violent episode of motion sickness caused by particularly unfavorable sea conditions. The person, who experienced dizziness and especially intense asthenia, general malaise and languor with a strong sense of nausea and vomiting, was treated with the formulation described in Example 1 in one administration during the day, obtaining the complete resolution of the motion sickness symptoms, after about 30-40 minutes. In the following days, despite the unfavorable weather and sea conditions, said subject, treated with the formulation described in Example 1, administered as a preventive measure, in single daily administration, no longer exhibited dizziness or nausea, being able to fully enjoy the cruise.
The combination therapy of the present invention has been applied to several subjects, also to children, both in the preventive phase and during more or less pronounced episodes of motion sickness, obtaining a success rate substantially equal to 100% (i.e., 100% or slightly less) . The activity of the composition has proved to be of rapid onset, long lasting, and free of the side effects (for example, sleepiness) typical of the known anti-motion sickness drugs.
From the above description the advantages offered by the present invention will be immediately clear.
In particular, the pharmaceutical composition/ formulation of the present invention has proven to be able to treat or prevent the forms of motion sickness caused by the most varied reasons, such as, for example, caused by seasickness, car sickness and plane sickness, with considerable success.
Furthermore, it has been noted that the success rate was 100% or almost, as all subjects benefited from the treatment; therefore, the efficacy was greater than the currently available anti-motion sickness drugs.
Furthermore, the activity of the composition has proven to be of rapid onset, long-lasting and greater than the anti-motion sickness drugs on the market, and free of the side effects, represented for example by drowsiness, nausea and/or vomiting, vertigo, asthenia, central nervous system depressive activity and habituation, typical of the already known drugs.
Since the therapy suggested by the present invention may comprise the use of two independent drugs, the treatment can exhibit greater manageability and practicality of use.

Claims

1. A pharmaceutical composition comprising at least an association of:
A) an anti-gastric secretion drug;
B) an anti-vertigo, and also antiemetic drug.
2 . A pharmaceutical composition according to claim
1, wherein:
- said anti-gastric secretion drug A) is selected from the group of drugs belonging to the family of proton- pump inhibitors (PPIs), or from the group of drugs belonging to the family of histamine H2 receptor antagonists; and
- said anti-vertigo, and also antiemetic, drug B) is selected from the group of drugs belonging to the family of so-called third-generation antihistamines and/or those belonging to the family of second-generation antihistamines; both families, in particular the first, have rapid functioning onset and prolonged half-life, and cause very low or no sleepiness.
3 . A pharmaceutical composition according to claim
2, wherein:
- said drug A) is selected from the group consisting of Esomeprazole and/or Omeprazole and/or Lansoprazole and/or Pantoprazole and/or Rabeprazole (sodium) and/or Ilaprazole and/or Tenatoprazole and/or Dexlansoprazole, or from the group consisting of Ranitidine and/or Famotidine and/or Cimetidine and/or Nizatidine; and
- said drug B) is selected from the group consisting of Levocetirizine and/or Desloratadine ; and/or selected from the group consisting of Cetirizine and/or Loratadine and/or Fexofenadine .
4. A pharmaceutical composition according to any one of the preceding claims, wherein:
- regarding drug A) , the proton-pump inhibitors are in an average amount from 5 mg to 180 mg, and the histamine H2 receptor antagonists are in an average amount from 20 mg to 2000 mg; and
regarding drug B) , the third-generation antihistamines are in an average amount from 5 mg to 250 mg per composition dose.
5. A pharmaceutical composition according to any one of the preceding claims, wherein said drug A) is represented by Esomeprazole or Ranitidine and said drug B) is represented by Levocetirizine or Desloratadine .
6. A pharmaceutical composition according to any one of the preceding claims, further comprising pharmaceutically acceptable excipients, selected from one or more diluents; absorbents; adsorbents; lubricants, antiadhesives, glidants; ligands; disintegrating agents; surfactants; colorants; sweeteners; flavorings; antioxidants; antimicrobials; fillers; pharmaceutical polymers, preferably said excipients being selected from the group consisting of lactose, glucose, saccharose, sweeteners, aspartame, acesulfame K, saccharin, cyclamate, stevioside, glycyrrhizin, xylitol, sorbitol, mannitol, mannite, kaolin, talc, bentonite, titanium dioxide.
7. A pharmaceutical composition according to any one of the preceding claims, further comprising adjuvant additives, such as natural extracts having soothing and/or digestive action: chamomile and/or valerian and/or althea extracts, and/or the like.
8. A pharmaceutical composition according to any one of the preceding claims, prepared in a pharmaceutical form which is suitable for oral administration; in the form of a tablet, a lozenge, a pill, a comfit, a soft or hard capsule, a sachet to be reconstituted in water upon ingestion, a chewing gum, a transdermal patch, drops, even in gastro-resistant form, as well as in controlled release form.
9. A pharmaceutical composition according to any one of the preceding claims for medical use.
10. A pharmaceutical composition according to the preceding claim for use in the treatment or prevention of motion sickness.
11. A pharmaceutical composition according to the preceding claim for use in the treatment or prevention of motion sickness, wherein:
- regarding drug A) , the proton-pump inhibitors are administered in an average amount from 5 mg to 180 mg, and the histamine H2 receptor antagonists are administered in an average amount from 20 mg to 2000 mg; and
regarding drug B) , the third-generation antihistamines are administered in an average amount from 5 mg to 250 mg per dose.
12. A pharmaceutical composition according to the preceding claim 9 or 10 or 11 for use in the treatment or prevention of motion sickness, wherein said drug A) and said drug B) are taken simultaneously or one immediately before the other.
13. A pharmaceutical composition for use in the treatment or prevention of motion sickness according to any one of the preceding claims 9 to 12, wherein said composition is administered once a day.
14. A kit comprising an amount of each of the drugs A) and B) according to any one of the preceding claims 1 to 8.
15. A method for the treatment or prevention of motion sickness, comprising the step of administering to a patient in need thereof a pharmaceutically effective amount of the pharmaceutical composition according to any one of the preceding claims 1 to 8.
16. A method for the treatment or prevention of motion sickness according to the preceding claim, wherein said amount is administered once a day.
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