EP2846771A1 - Composition à usage nasal - Google Patents

Composition à usage nasal

Info

Publication number
EP2846771A1
EP2846771A1 EP13732077.6A EP13732077A EP2846771A1 EP 2846771 A1 EP2846771 A1 EP 2846771A1 EP 13732077 A EP13732077 A EP 13732077A EP 2846771 A1 EP2846771 A1 EP 2846771A1
Authority
EP
European Patent Office
Prior art keywords
substances
pharmaceutical composition
nervous system
central nervous
acting
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Withdrawn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
EP13732077.6A
Other languages
German (de)
English (en)
Inventor
Dimitry TERTEROV
Sergei TERTEROV
Alexandr TERTEROV
Naum Goldstein
Roman Goldstein
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.)
BBU-VITA Corp
Original Assignee
BBU-VITA Corp
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 BBU-VITA Corp filed Critical BBU-VITA Corp
Publication of EP2846771A1 publication Critical patent/EP2846771A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • 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
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs

Definitions

  • composition for nasal application Composition for nasal application
  • the invention relates to a pharmaceutical composition for a nasal application, in which substances act on the central nervous system, and substance-assistants, which act on the structures of the mucous membrane of the nasal cavity and are intended for an active action on the regulatory centers of the brain.
  • This invention is intended for stationary and private use and at the same time is easy to use.
  • Many biologically active molecules from the external environment and from the internal environment of the organism are useful and necessary for maintaining the physiological functions of organs and tissues, including the brain and the central nervous system (CNS) as a whole. These include, for example, the majority of medications and many biochemical compounds - products of metabolism that arise in the organism through metabolism.
  • the biologically active molecules including regulatory substance metabolites, are said to penetrate the structures of the brain through the multiple biological membranes, the least permeable of which are the brain-blood barrier complexes.
  • Ming Ming Wen (201 1) describes the delivery of drugs from the nasal cavity to the brain using a variety of techniques, in particular the use of mucoadhesive agents to enhance the drug's contact with the nasal mucus, as well as the use of penetrating enhancers , Liposomes, Nanoparticles and Other Methods (Ming Ming Wen (2011) Intranasal Delivery - Physicochemical and Therapeutic Aspects, International Journal of Pharmaceutics 337, 1-24). Although the proposed methods allow small molecules of drugs to penetrate into the brain, these methods are not universally suitable for delivery to the brain for a wide range of drug substances.
  • Known nasally introduced drugs reach the brain from the nasal cavity thanks to both the anatomical connections of the elements of the olfactory system and the trigeminal nerve. Nevertheless, despite direct connection of peripheral elements of an olfactory system with a brain, efficiency of delivery to a brain of nasally administered drugs is very limited, that is connected in particular with the limited surface of the olfactory epithelium, which is less than 8% of the surface of nasal cavity mucous membrane forms.
  • a modern approach to solving the problem of delivery of drugs to the brain is the use of some low molecular weight substances of a free radical nature.
  • the inhaled application of active oxygen radicals is known for increasing the analgesic pain-killing effects introduced into the body by one of the traditional routes, such as oral or by injection ⁇ Goldstein, N., Lewin, T., Kamensky, A., Dubinin V., Baumann, S., Konstantinova, O. (1996) Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents. Inflamm. Res., 5, 473-478).
  • Patent DE 19514 522 describes a pharmaceutical composition for the treatment of pain consisting of an analgesic for the treatment of severe pain, as well as Oxygen radicals and / or products of their transformations or decay.
  • a deficiency in the patent DE 195 14 522 is the limited therapeutic effectiveness.
  • Another deficiency is the limited clinical applicability associated with difficulties of separate oral or injection administration of a drug and nasal induction of SAR.
  • Patent RU N ° 2253461 describes the enhancement of the therapeutic efficacy of medicinal substances by a pharmaceutical combination in which the function of the CNS is influenced, whereby at least one substance is contained which has a healing effect on the CNS and differs in that as the substance contributing to penetration through the brain blood barrier acts via reflector-preferential neuro- and vasodilatory action on the structures and receptors of the nasal cavity mucosa, mainly the receptors of the vomeronasal organs and the trigeminal nerve.
  • experience has shown that increasing the effectiveness of the drugs for various biological substances is substantially different in the pharmaceutical combination described in patent RU Na 2253461, which makes the practical application considerably more complicated.
  • Eurasian patent .No. 10692 describes the pharmaceutical agent for nasal application for the treatment of diseases and disorders of the central nervous system using a mixture containing biologically active substances acting on the central nervous system and such substances, which act on the mucosa of the nose using the oxygen anion radicals and / or the active products of the nitric oxide.
  • the use of the described spray (see item 14 of the formula) consists of a mixture of biologically active substances which act on the central nervous system and consist of substances which are concentrated on the nasal mucosa such as oxygen anion. Radical and / or active products of the nitrogen oxide act.
  • the object of the invention is to increase the effectiveness of the medicaments, metabolites and / or other previously described types of active substances that are used for the treatment of diseases and disorders of the central nervous system and the reduction of the usual dosage of the drugs used, as well as the achievement of a faster and prolonged effect.
  • substances refers to one or more medicinal substances, metabolites and / or previously described types of biologically active substances which are used for the treatment of diseases and disorders of the CNS.
  • Assistants are meant to be used alone or together with the other active oxygen radicals (SAR) and their conversion or other applied products such as superoxide ion (0 2 * ⁇ ), singlet oxygen ( ⁇ 2 ), hydroxyl radical (HO ' ) , perhydroxyl radical ( ⁇ 0 2 '), hydrogen peroxide (H 2 0 2), individually or together with nitrogen sources (NO- products) as the sources of active nitrogen oxide nO enumerated but not limited L- arginine, isosorbide mononitrate, nitroprusside, Penthaerythril tetranitrate or glycerol tetranitrate.
  • SAR active oxygen radicals
  • NO- products nitrogen sources
  • the pharmaceutical composition described in the invention contains biologically active substances which are biologically active substances and metabolites, for example from the classes of the agonists dopaminergic receptors, narcotic and non-narcotic analgesics, antiepileptic drugs from the group of barbiturates, as well as from a helper, containing free radical forms of anion radicals of oxygen or their conversion products (ROS), for example hydrogen peroxide, and pharmacologically acceptable active nitrogen oxide (NO) products.
  • ROS free radical forms of anion radicals of oxygen or their conversion products
  • NO active nitrogen oxide
  • IEE IEE Index
  • composition-1 dopamine-containing pharmaceutical composition
  • Dopamine / hydrogen peroxide / L-arginine Group IV
  • dopamine-containing pharmaceutical agent according to the Eurasian patent N ° 010692 (group III)
  • the studied feature is the duration of catalepsy caused by intraperitoneal (ip) injection of the haloperidol.
  • Example 1 Table 1
  • Eurasian Patent O 10692 the higher effectiveness of the application of the composition explained here from the assistant and the dopamine according to the formula has been demonstrated.
  • Insufficient effectiveness of the pharmaceutical agent according to Eurasian Patent O 10692 could be caused by a cross-interaction of the substances contained in the spray.
  • the characteristics studied are based on the intensity of the critical pressure (IKD) on the hind paws of the rats and the duration of the analgesic action.
  • the number of animals in each group 10.
  • composition-2 The positive effects of the declared pharmaceutical "Composition-2" are also valid for the substances found in the brain in the usual ways of use as well penetrating, in which case the increase of efficiency is expressed in significant reduction of a dose of biologically active substances (Example 4).

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Inorganic Chemistry (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne une composition pharmaceutique et son système pour un usage nasal. L'invention vise à renforcer l'efficacité des médicaments, des métabolites et/ou d'autres types de principes actifs décrits antérieurement, s'utilisant dans le traitement de maladies et de troubles du système nerveux central, ainsi qu'à diminuer le dosage habituellement utilisé des médicaments et à obtenir un effet plus rapide et plus prolongé. Ladite composition pharmaceutique, composée de substances à activité biologique et de substances agissant sur la muqueuse nasale, qui sont en interaction, est placée et conservée dans un aérosol, dans des emballages étanches séparés les uns des autres, les contenus desdits emballages n'étant réunis qu'au moment de l'utilisation de l'aérosol. L'invention qui est simple à utiliser convient à un usage en milieu hospitalier et à un usage privé.
EP13732077.6A 2012-05-09 2013-05-06 Composition à usage nasal Withdrawn EP2846771A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102012009570A DE102012009570A1 (de) 2012-05-09 2012-05-09 Komposition für nasale Anwendung
PCT/DE2013/000261 WO2013167112A1 (fr) 2012-05-09 2013-05-06 Composition à usage nasal

Publications (1)

Publication Number Publication Date
EP2846771A1 true EP2846771A1 (fr) 2015-03-18

Family

ID=48700230

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13732077.6A Withdrawn EP2846771A1 (fr) 2012-05-09 2013-05-06 Composition à usage nasal

Country Status (8)

Country Link
US (1) US20150165033A1 (fr)
EP (1) EP2846771A1 (fr)
JP (1) JP2015519332A (fr)
CN (1) CN104582690A (fr)
DE (1) DE102012009570A1 (fr)
EA (1) EA201492045A1 (fr)
SG (1) SG11201505178VA (fr)
WO (1) WO2013167112A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102012015248A1 (de) * 2012-08-05 2014-02-06 Naum Goldstein Verfahren zur Einbringung biologisch aktiver Substanzen ins Gehirn

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4969579A (en) * 1987-02-09 1990-11-13 Societe Francaise D'aerosol Et De Bouchage Aerosol sprayer device and method of using same
US5437267A (en) * 1993-08-03 1995-08-01 Weinstein; Allan Device for delivering aerosol to the nasal membranes and method of use
DE60111494T2 (de) * 2000-02-04 2006-05-18 Pherin Pharmaceuticals, Inc., Mountain View Verfahren zur erhöhung der wachsamkeit durch verabreichung von vomeropherin und vomeropherin emittierende alarmvorricthung
WO2014023288A1 (fr) * 2012-08-05 2014-02-13 Naum Goldstein Procédé permettant l'apport de substances à activité biologique au cerveau

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69535607T2 (de) * 1994-05-27 2008-07-10 Strakan International Ltd. Zusammensetzung enthaltend Stickstoffoxid-donatoren und Methode zur Behandlung analer Krankheiten
DE19514522C1 (de) 1995-04-12 1996-06-13 Goldstein & Lewin Tech Gmbh Sauerstoffanionradikale enthaltende therapeutische Mittel und deren Verwendung zur Schmerzbehandlung
DE10248601B4 (de) 2002-10-17 2006-05-24 Goldstein, Naum, Dr.habil.nat. Pharmazeutisches Mittel zur endonasalen Applikation bei der Behandlung von Krankheiten und Störungen des zentralen Nervensystems
BRPI0414970A2 (pt) 2003-06-24 2012-12-11 Baxter Int método para transporte de drogas ao cérebro
RU2253461C1 (ru) 2004-04-30 2005-06-10 Общество с ограниченной ответственностью "Паркинфарм" Фармацевтическая комбинация, оказывающая влияние на функционирование цнс, способ коррекции состояний, связанных с нарушениями функционирования цнс; фармацевтический набор; средство, способствующее проникновению через гематоэнцефалический барьер лекарственных субстанций и метаболитов; фармацевтическое средство для эндоназального применения
KR100632458B1 (ko) * 2004-04-30 2006-10-11 아이치 세이코우 가부시키가이샤 가속도 센서
AU2008345034A1 (en) * 2007-12-27 2009-07-09 Aires Pharmaceuticals, Inc. Aerosolized nitrite and nitric oxide - donating compounds and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4969579A (en) * 1987-02-09 1990-11-13 Societe Francaise D'aerosol Et De Bouchage Aerosol sprayer device and method of using same
US5437267A (en) * 1993-08-03 1995-08-01 Weinstein; Allan Device for delivering aerosol to the nasal membranes and method of use
DE60111494T2 (de) * 2000-02-04 2006-05-18 Pherin Pharmaceuticals, Inc., Mountain View Verfahren zur erhöhung der wachsamkeit durch verabreichung von vomeropherin und vomeropherin emittierende alarmvorricthung
WO2014023288A1 (fr) * 2012-08-05 2014-02-13 Naum Goldstein Procédé permettant l'apport de substances à activité biologique au cerveau

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2013167112A1 *

Also Published As

Publication number Publication date
SG11201505178VA (en) 2015-08-28
WO2013167112A1 (fr) 2013-11-14
EA201492045A1 (ru) 2015-04-30
JP2015519332A (ja) 2015-07-09
US20150165033A1 (en) 2015-06-18
CN104582690A (zh) 2015-04-29
WO2013167112A8 (fr) 2014-01-23
DE102012009570A1 (de) 2013-11-14

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Inventor name: TERTEROV, ALEXANDR

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