EP2379110A1 - Formulierung zur bukkalen transmukosalen verabreichung von setronen - Google Patents

Formulierung zur bukkalen transmukosalen verabreichung von setronen

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Publication number
EP2379110A1
EP2379110A1 EP09805726A EP09805726A EP2379110A1 EP 2379110 A1 EP2379110 A1 EP 2379110A1 EP 09805726 A EP09805726 A EP 09805726A EP 09805726 A EP09805726 A EP 09805726A EP 2379110 A1 EP2379110 A1 EP 2379110A1
Authority
EP
European Patent Office
Prior art keywords
active ingredient
formulation according
formulation
alcohol
until
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09805726A
Other languages
English (en)
French (fr)
Inventor
Philippe Perovitch
Marc Maury
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP2379110A1 publication Critical patent/EP2379110A1/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • 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 formulation for the instantaneous oral mucosal systemic delivery of at least one active ingredient belonging to the family of Sperins.
  • the invention also relates to a process for the preparation of this formulation and its use for the treatment and prevention of major nausea and / or emetic syndromes, as well as for the treatment and prevention of disabling spastic disorders of the digestive tract.
  • Tetrons are pharmaceutical active ingredients mainly used for the prevention or treatment of nausea and vomiting syndromes related to anti-cancer therapies. They are potent lipophilic and low molecular weight anti-emetic molecules that act at the level of the central nervous system as 5-hydroxytryptamine-3 (5-HT3) receptor antagonists to serotonin.
  • 5-HT3 5-hydroxytryptamine-3
  • the best known Tetrons are Ondansetron, Tropisetron and Ranisetron respectively marketed as Zophren®, Navoban® and Kytril®.
  • Dolasetron and Itasetron whose indications are similar, or Alosetron, Azasetron, Benesetron, Cilansetron, Ramosetron or Zatosetron, whose indications of Market introduction are rather turned towards the treatment of irritable bowel syndrome.
  • Tetron have proven anti-emetic activity, but their administration to prevent or treat a nausea and / or emetic syndrome major related to the administration of chemotherapy or physical therapy anti-cancer, presents many difficulties.
  • Tetrons The fastest and most effective route of administration of Tetrons is intravenous infusion. However this mode of administration requires dedicated personnel and the use of specific materials. It is expensive and its implementation is cumbersome for the patient who is already subject to very many infusion treatments, particularly for the administration of chemotherapy. In order to preserve the patient's venous capital, to facilitate drug intake and to reduce costs, it is therefore preferable to avoid the intravenous route and to administer oral Tetrons.
  • the most commonly known oral form is enteral administration with the aid of tablets, but this mode of administration is not adapted to the administration of Sozons. Indeed, the target patients are extremely sensitive to any oral medication and often reject them instantly. Thus the anti-emetics administered orally can already by themselves induce the syndrome that they are supposed to fight.
  • the Sommens administered are suitably ingested, their time of action is between one and three hours after the taking, a disproportionate delay compared to waiting for a patient in pain.
  • the molecules of Létons of lipophilic nature suffer the so-called effect of "first digestive passage", alterations and losses related to the stomach environment or to variations in intestinal physiology. They are then subjected to an effect called “first pass liver” which causes their metabolism and / or their more or less intense degradation, with constitution of many metabolites, mostly inactive or toxic causing side effects.
  • the dose of active ingredients truly bioavailable is therefore low: only a residual part that does not exceed, in the best case, 60% of the quantity administered, is effectively distributed to the central nervous system and reaches the brain receptors 5-HT3 to produce the pharmacologically expected effect.
  • the first problem is that we must succeed in having a product absorbed by an already weakened subject, burdened with important nauseating reflexes.
  • the drug intake should not be rejected once swallowed and the active ingredient must be sufficiently absorbed despite the patient's digestive disorders.
  • a second difficulty lies in the administration of a sufficient dose of Strins to the patient, taking into account the weight status of the subject, the dilution and the dispersion of this active principle in the body, so that the only significantly active part which reaches the brain receptors 5-HT3 is effective.
  • Tetron digestive is not appropriate.
  • Other possible routes of administration of Tetron are known, such as the transdermal route.
  • Transdermal administration is generally performed using semi-solid gel systems or solid systems with reservoirs.
  • the application US-2007/0225379 which describes in its examples J and K, gels based on ⁇ 9ranisetron or Ondansetron and their administration through the skin.
  • these are complex systems intended for prolonged administration over time, which do not allow the instantaneous passage into the blood of a therapeutic dose of active principle, therefore incompatible with immediate treatment of nausea and / or emetic syndrome.
  • the per-sublingual route is used to administer medications by passive crossing of sublingual, jugal, gingival, lingual, palatal or pharyngeal mucosa, then passing into the sub-lingual veins and distribution to the general circulation, thereby bypassing the digestive tract. and hepatic metabolism.
  • the use of this route is not obvious because the Tetron molecules are all lipophilic and therefore virtually insoluble in the oral mucosa atmosphere exclusively aqueous and hydrophilic.
  • Patent applications WO-2008/079295 and WO-2005/032520 describe per / sublingual formulations to be administered in the form of sprays.
  • these products have characteristics which are unsatisfactory in terms of the accuracy of administration, the absorption efficiency and the bioavailability of the dosages administered.
  • These are complex liquid formulations that involve a combination of multiple ingredients to solubilize and stabilize Ondansetron salts, and create a very specific viscosity state for a particle size distribution determined by spray.
  • the distribution in the oral cavity remains diffuse and random and upon receipt of the particles propelled spray, they are instantly mixed with the saliva produced reflexively and mechanically in the oral cavity.
  • hydroalcoholic solution consisting of water and ethanol, containing at least 30 degrees of alcohol, wherein said active ingredient is present in a stable and complete dissolution state
  • the pH of the formulation is between 5.0 and 9.0.
  • the invention also provides a method of preparation and the use of this formulation for the treatment or prevention of major nausea and / or emetic syndromes, as well as for the treatment or prevention of disabling spastic disorders of the digestive tract.
  • the formulation according to the invention is very simple to manufacture and use and allows the passage immediate mucosa and complete of a therapeutic preparation based on
  • the subject of the invention is therefore a formulation for the oral transmucosal administration of at least one active anti-nausea, anti-emetic and / or antispasmodic digestive active ingredient of the family of the Sriadns.
  • This formulation is a solution having a pH of between 5.0 and 9.0, consisting of:
  • hydroalcoholic solution consisting of water and ethanol, containing at least 30 degrees of alcohol
  • a pH-correcting agent optionally, a pH-correcting agent.
  • the active ingredient is present in a stable and complete dissolution state in the hydroalcoholic solution of less than 2 mL volume, so as to allow rapid absorption of said active ingredient through the mucous membranes of the oral cavity.
  • transmucosal route means any passive crossing of a lipophilic or amphiphilic molecule presented in a state of stable dissolution through the lingual, sublingual, gingival, palatal, jugal, or any other mucous membranes constituting the oral cavity.
  • stable and complete dissolution state is meant a state of dissolution restoring the active ingredient to the molecular state and weakly ionized in its medium of dissolution, state of dissolution preventing any eventuality of an inopportune recrystallization.
  • This stable and complete dissolution state can be controlled as soon as the formulation according to the invention is used by evaluating the visual appearance of the solution obtained (measurement of the degree of clarity) and then at the level of the filtration residues (appearance or no crystals), and finally in the medium and long term during stability monitoring tests at varying temperatures and degrees of hygrometry.
  • hydroalcoholic solution titrating X degrees of alcohol is meant a solution having an alcohol degree of X, corresponding to the ratio between the volume of pure alcohol (100 °) contained in the hydroalcoholic solution and the total volume of this alcoholic solution. solution.
  • the degree of alcohol in the hydroalcoholic solution varies depending on the degree of alcohol used to form the solution and the water / alcohol ratio of the solution. For example for an initial alcohol at 100 degrees and a 50/50 water / alcohol ratio, the hydroalcoholic solution titrates 50 degrees alcohol.
  • pH corrector agent is meant any acidic agent or any basic agent that does not alter the physicochemical characteristics of the active ingredient (s).
  • the pH-correcting agent is chosen from sodium carbonates and bicarbonates, monosodium or disodium phosphates, triethanolamine, sodium hydroxide (NaOH) and potassium hydroxide (KOH), but also hydrochloric, sulphuric acid agents.
  • the active substance in the family Sommens is present in base form and / or in salt form.
  • the formulation according to the invention comprises a pH correcting agent, acid.
  • the formulation according to the invention comprises a basic pH corrector agent.
  • the distribution gradient between base and salt is determined extemporaneously according to the specific physicochemical characteristics of each principle. active ingredient and its salt, as well as the dosage, that is to say the concentration of active ingredient relative to the volume of solution.
  • the active ingredient is present in base form.
  • Cetron in base form of lower molecular weight than the salt-form Tetron, dissolve and stabilize more easily in the formulation according to the invention and have a better ability to pass through the mucosa at a higher velocity.
  • the active ingredient may be selected from Ondansetron, Tropisetron, Ranisetron, Dolasetron, Itasetron, Alosetron, Azasetron, Benesetron, Cilansetron, Ramosetron or Zatosetron.
  • the active ingredient is Ondansetron, ⁇ 9ranisetron or Tropisetron. Even more preferentially, the active ingredient is Ondansetron base.
  • the formulation according to the invention is in the form of a hydroalcoholic solution comprising between 30 and 95% of alcohol by volume and a water content of between 5 and 70%. Even more preferably, the formulation according to the invention is in the form of a hydroalcoholic solution comprising between 40 and 85% of ethanol by volume and a water content of between 15 and 60%.
  • the hydroalcoholic solution has a variable degree of alcohol of at least 30 °, preferably between 30 and 70 °, even more preferably between 40 ° and 70 °, and ideally around 50 °.
  • the hydroalcoholic solution is the only solvent used in the formulation according to the invention.
  • the ethanol of the hydroalcoholic solution not only acts as a diluent, but also as a promoter of an accelerated peri-mucous absorption, whose speed increases as a function of the elevation of the degree of alcohol used.
  • the degree of alcohol in the formulation should not exceed 70 °, however, because a higher degree would be incompatible with a pharmaceutical product for oral application due to mucosal burn.
  • the dissolution coefficient of ondansetron in ethanol makes it possible to obtain a complete dissolution of said active ingredient at a level of 2 mg, of ondansetron for 0.75 ml of ethanol at approximately 50.degree. This coefficient can be modulated according to the degree of alcohol and the water / ethanol ratio used.
  • the pH of the formulation according to the invention is between 5.0 and 9.0, preferably between 5.5 and 7.5. These pHs are favorable for optimal absorption of the solution.
  • the formulation according to the invention allows the active ingredient passively pass through the oral mucosa in less than 6 seconds after administration.
  • This very fast absorption time makes it possible to prevent any stagnation of the solution and of the active principle in the oral atmosphere, as well as their untimely mixing with saliva which can alter them, which would introduce a break in the continuity and stability of the dissolution of the active ingredient (s).
  • This short delay also makes it possible to prevent any reflex swallowing of the solution and of the active principle that it contains.
  • the trans-mucosal passage of the active principle presented in the state of dissolution according to the invention on the side of the external epithelial membrane, consisting of phospholipidic structures which passively absorb, by elective affinity, the lipophilic molecules presented in a stable and complete dissolution state, is based on an osmotic call to the other side of said membrane, in which together the concentration of dissolved active ingredient and that of the alcoholic solution considered.
  • the osmotic appeal is all the more perennial and powerful as the degree of alcohol that serves as an absorption promoter is high.
  • a suitable degree of alcohol is between 40 ° and 70 °, preferably between 45 ° and 60 °.
  • a particularly suitable embodiment corresponds to 0.75ml of hydroalcoholic solution with an alcohol degree of about 50 ° for 2mg or 4mg of ondansetron.
  • the mucous membranes of the mouth possess a very dense, quasi-spongy network of micro-vessels, so that the molecules, both of alcohol solvent and of dissolved active principle, which cross the lipophilic pores of the epithelial membrane, are instantly captured by the micro-circulation and collected towards the sublingual veins, then the jugular veins towards the heart.
  • This phenomenon is accentuated by the presence of alcohol which causes vasodilation and an increase in the local microvascular flow of the mucous membranes. Because of this locally high circulatory flow, increased by alcohol, there is never equilibrium on either side of the epithelial membrane: the concentration in the mouth is always greater, until exhaustion. the default mechanism of molecules to absorb.
  • the use of the dosage form according to the invention makes it possible to passively administer a dose of Tetron immediately absorbed as soon as deposited in contact with the mucosa, to be distributed in the instant by vascular route, without any delay for its pharmacological action and without undergoing the prior destructive effects of digestive and hepatic passage.
  • the galenic form according to the invention thus allows an immediacy of complete tissue absorption of the Sozon molecules, then their distribution in the central circulation of the organism, generating a rapid pharmacological response of "flash" type.
  • the hydroalcoholic solution according to the invention containing at least 30 degrees of alcohol, also has the advantage of solubilizing the Sozons molecules, although they are lipophilic, which allows their spontaneous per-mucous absorption and to protect the pharmaceutical formulation. against microbiological contamination without having to introduce antimicrobial preservative (s).
  • the hydroalcoholic solution according to the invention has a quadruple competence:
  • the degree of alcohol doubly increases the rate of mucosal absorption, by osmotic effect and by causing reflex microvascular vasodilatation, which accelerates the local micro-circulatory flow, and - It is its own stability agent which avoids the use of conventional additives.
  • the present invention offers a great simplicity of realization and a very good galenic stability: the solution water / ethanol extremely simplified guarantees the solubilization of the active principle and makes it possible to disregard the excipients usually used for the conventional pharmaceutical preparations, including the preservatives . Only a pH corrector may be added to adjust the pH of the solution to between 5.0 and 9.0. It thus makes it possible both to reduce manufacturing costs and to reduce the risks of intolerance and the possible interactions between active ingredient and excipients.
  • the pharmacodynamic action time of the galenic form according to the invention is very short, compared to the absorption delays of drugs based on existing Tetrons that require a waiting time of 45 minutes to 2 hours between taking the drug and starting the pharmacological action anti-nausea, anti-emetic or anti-spasmodic.
  • the quasi-instantaneous pharmacological delivery can allow a patient to self-administer a product for an effect equivalent to the efficacy of an intravenous injection of Sozons flash into the circulation, without the disadvantages associated with this type of administration, in particular the risks of nosocomial infections.
  • the gain in terms of dose / effect ratio is at least 40 to 50%.
  • the formulation according to the invention uses at least 40 to 50% less dose for a therapeutic effect obtained without delay.
  • the molecules of Shuntns do not encountering no significant obstacle to their instantaneous carotid arterial distribution to the central nervous system 5-HT3 target receptors, which they gain in a few seconds, the basic dose administered is reduced, comparable to the bioavailable dose required to exercise the pharmacological activity required.
  • the dose of active ingredient contained in the formulation according to the invention is therefore lower than the doses conventionally administered. This dose is of course dependent on the administered Tetron and the desired effect. It is preferably between 2 mg and 8 mg of active ingredient, for volumes of hydroalcoholic solution ranging from 0.5 ml to 2 ml.
  • the oral mucosa having a total surface of extremely broad absorption, multiplied by its character of pleated villous tissue
  • the administration of the dosage form according to the invention is devoid of any risk of inadvertent swallowing or wrong way. Indeed, it allows an extremely fast peri-mucous passage that prevents any salivary dissolution or swallowing of the active ingredient administered, with the advantage of not destabilizing the mucous membranes, bone / ec of various elements or excipients, as is the case.
  • the formulation according to the invention is particularly suitable for patients suffering from major nausea or emetic syndromes, because it avoids any possible vomiting of the ingested medicine.
  • the effects of alcohol are insignificant.
  • an aqueous alcohol solution of 0.75 ml ethanol at 50 ° can only produce a circulating blood alcohol content of less than 0.005 g per liter of blood, according to Widmark's official reference formula, ie one hundredth of the legal tolerance in France established at 0.5g per liter of blood.
  • the initial passage of the alcoholic solution by pulmonary route must allow the near complete elimination of ethanol in the form of vapor extracted by breathing and exhaled, before Ethanol can be distributed in the body.
  • the alcoholic vector is eliminated almost completely through the respiratory parenchyma.
  • the invention relates to a process for preparing the formulation.
  • a method of manufacturing the galenic form according to the invention, particularly adapted, comprises the following steps:
  • the method comprises the following steps:
  • the method according to the invention comprises the following steps:
  • the method according to the invention comprises the following steps:
  • the method according to the invention comprises the following steps: - mix ethanol and water and introduce into this mixture an active ingredient of the family of Sriadns in base form and in salt form,
  • the present invention can be used for instantaneous, reduced-dose and useful systemic administration of Sriadns, including ondansetron.
  • the formulation according to the present invention may be used for producing a medicament for the treatment and / or prevention of major nausea and / or emetic syndromes, in particular related to anti-cancer treatment.
  • Such a drug has an anti-emetic therapeutic activity in a very short time and at very small doses compared to traditional doses.
  • the formulation according to the present invention may also be used for producing a medicament for the treatment and / or prevention of digestive spasms.
  • the formulation according to the invention corresponding to a very small fluid volume, is very easy to administer. A patient can easily place it in his mouth in direct contact with a specific mucosal area of reduced surface, buccal, para-gingival or sublingual.
  • the formulation according to the invention requires a specific industrial packaging, in order to allow its safe, simple and ergonomic use and to prevent degradation of the active ingredient in contact with the air.
  • a particular embodiment consists of using a packaging, preferably of small size, of flexible plastic or metalloplastic or of glass, opaque filled under an inert atmosphere such as nitrogen, for the protection of the stability of the composition and the impermeability to oxygen and radiation.
  • a packaging preferably of small size, of flexible plastic or metalloplastic or of glass, opaque filled under an inert atmosphere such as nitrogen, for the protection of the stability of the composition and the impermeability to oxygen and radiation.
  • these packages comprise a cannula allowing the precise deposition of the solution according to the invention in contact with a suitable mucosal area.
  • the dosage form according to the invention is packaged in single-dose packages of 0.5 to 2 ml, capable of providing an adequate dose of active ingredient.
  • this packaging is easy to transport and allows easy use of the dosage form at any time of the day.
  • This first example of formulation can be obtained by the implementation of the method described in the following for a batch of 1000 doses, or 0.75 L.
  • a stainless steel tank add 0.375 L of 95% V / V ethanol and 0.150 L of purified water.
  • Ondansetron Continue agitation until complete dissolution of Ondansetron. Complement with the purified water to obtain a solution of a volume of 0.75L and shake the preparation for 10 to 30 minutes to ensure homogeneity. Filter the preparation on a polypropylene filter or equivalent of 5 ⁇ m porosity and distribute the preparation in single dose vials of 0.75mL.
  • This formulation example can be obtained by carrying out the method described below for a batch of 1000 doses, ie 1 L.
  • Formulation 4 Granisetron 3mq, 1.0ml at 50 ° alcohol

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Organic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP09805726A 2008-12-19 2009-12-17 Formulierung zur bukkalen transmukosalen verabreichung von setronen Withdrawn EP2379110A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0807258A FR2940120B1 (fr) 2008-12-19 2008-12-19 Formulation pour l'administration par voie trans-muqueuse de setrons
PCT/FR2009/052590 WO2010070236A1 (fr) 2008-12-19 2009-12-17 Formulation pour l'administration par voie trans-muqueuse buccale de setrons

Publications (1)

Publication Number Publication Date
EP2379110A1 true EP2379110A1 (de) 2011-10-26

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP09805726A Withdrawn EP2379110A1 (de) 2008-12-19 2009-12-17 Formulierung zur bukkalen transmukosalen verabreichung von setronen

Country Status (8)

Country Link
US (1) US20110251233A1 (de)
EP (1) EP2379110A1 (de)
JP (1) JP5811404B2 (de)
CN (1) CN102245209A (de)
BR (1) BRPI0923379A2 (de)
CA (1) CA2747846C (de)
FR (1) FR2940120B1 (de)
WO (1) WO2010070236A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102552124B (zh) * 2011-01-12 2014-07-02 韩斌 雷莫司琼的液体药物组合物
FR3031668A1 (fr) 2015-01-20 2016-07-22 Philippe Perovitch Dispositif d'administration d'un principe actif par voie per-muqueuse buccale.
FR3053244A1 (fr) 2016-07-01 2018-01-05 Philippe Perovitch Dispositif d'administration d'au moins un principe actif par voie per-muqueuse buccale.

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040136914A1 (en) 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
DE19929197A1 (de) * 1999-06-25 2000-12-28 Novosis Pharma Ag Transdermalsysteme zur Abgabe von 5-HT3-Rezeptor-Antagonisten und ihre Verwendung zur antiemitischen Behandlung
US20070225379A1 (en) * 2001-08-03 2007-09-27 Carrara Dario Norberto R Transdermal delivery of systemically active central nervous system drugs
WO2006089082A2 (en) * 2005-02-17 2006-08-24 Velcera Pharmaceuticals Transmucosal administration of drug compositions for treating and preventing disorders in animals
FR2906140B1 (fr) * 2006-09-22 2008-12-05 Philippe Perovitch Forme galenique pour l'administration par voie trans-muqueuse de principes actifs
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
None *
See also references of WO2010070236A1 *

Also Published As

Publication number Publication date
FR2940120B1 (fr) 2012-07-13
WO2010070236A1 (fr) 2010-06-24
CA2747846A1 (en) 2010-06-24
RU2011129781A (ru) 2013-01-27
CN102245209A (zh) 2011-11-16
FR2940120A1 (fr) 2010-06-25
US20110251233A1 (en) 2011-10-13
CA2747846C (en) 2017-03-07
JP5811404B2 (ja) 2015-11-11
BRPI0923379A2 (pt) 2015-07-21
JP2012512851A (ja) 2012-06-07

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