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WO2021028005A1 - A medicament comprising anabasine for treatment of asthma, chest allergy and atopic dermatits - Google Patents

A medicament comprising anabasine for treatment of asthma, chest allergy and atopic dermatits Download PDF

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Publication number
WO2021028005A1
WO2021028005A1 PCT/EG2019/000032 EG2019000032W WO2021028005A1 WO 2021028005 A1 WO2021028005 A1 WO 2021028005A1 EG 2019000032 W EG2019000032 W EG 2019000032W WO 2021028005 A1 WO2021028005 A1 WO 2021028005A1
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WIPO (PCT)
Prior art keywords
medicament
anabasine
chest
allergy
patients
Prior art date
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Ceased
Application number
PCT/EG2019/000032
Other languages
French (fr)
Inventor
Mohamed Fadly Abd el Ghany ELKAZAZ
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Individual
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Individual
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Publication of WO2021028005A1 publication Critical patent/WO2021028005A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • 2- current medicament comprises of (L)(-)Anabasine as an active ingredient at 0.1 : 0.15 mg/kg of body weight and a pharmacologically acceptable excipient , diluent or carrier .
  • 3- Medicament at mentioned doses is described to be administered by oral route twice per day for a period from 30 : 40 days for asthmatics and patients of chest allergy according to severity and condition development and from 21 : 40 days for patients of atopic dermatitis according to severity and condition development .
  • medication is one course only .
  • Receptors function modulation also may last longly after removal of (L) anabasine due to the permanent loss of functional channels within prolonged desensitizationfSimasko et al.,1986;Boyd,1987; Lukas, 1991; Buisson and Bertrand, 2002 ).
  • This administering also negatively adapts signaling pathways .
  • ALL these mutations may lead to a specific cholinergic modulation of allergic effector cells.
  • this desensitization also shapes cholinergic signaling which regulates and drives skeletal muscles contraction including airways smooth muscle, which plays an integral part in the pathophysiology of asthma.
  • nicotinic acetylcholine receptors in the peripheral nervous system transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system , Heterologous desensitization also may thereafter leads these receptors to internalization .
  • Role of receptor-mediated endocytosis is will recognized up take downregulation of transmembrane signal transduction but can also promote sustained signal transduction . It is actively implicated in transducing signals from the cell periphery to the nucleus .

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The current invention relates to a novel oral medicament comprising (L)(-)Anabasine as an active ingredient at a dose concentration of about 0.1:0.15 mg/kg of body weight and a pharmacologically acceptable excipient, diluent or carrier. The medicament normalizes and treats asthma, chest allergies and atopic dermatitis, due to full agonistic action of Anabasine on al nicotinic acetylcholine receptors.

Description

Title Of The Invention
A MEDICAMENT COMPRISING ANABASINE FOR TREATMENT OF ASTHMA, CHEST ALLERGY AND ATOPIC DERMATITS
Technical Field
Therapeutic drugs discovery .
Background Art
All approved drugs which medicate all asthmatics types or patients of chest allergy and atopic dermatitis are symptomatic types , non therapeutic .
Disclosure Of Invention
1- The innovative element in current medicament that, in contrast of related approved types, that it normalizes and treats all asthmatics types and patients of chest allergy and atopic dermatitis permanently and releases them from their chronic pathological phenomenons .
2- current medicament comprises of (L)(-)Anabasine as an active ingredient at 0.1 : 0.15 mg/kg of body weight and a pharmacologically acceptable excipient , diluent or carrier .
3- Medicament at mentioned doses is described to be administered by oral route twice per day for a period from 30 : 40 days for asthmatics and patients of chest allergy according to severity and condition development and from 21 : 40 days for patients of atopic dermatitis according to severity and condition development . Herein medication is one course only .
4 - As fundamental causes of asthma types , chest allergy and atopic dermatitis are not completely understood to date , administering current medicament as described terminates them permanently . In light of publications which are free from binding between anabasine and asthma or allergic diseases and also free from detecting efforts to develop anabasine as a human drug or trials to generate a hope for that , mentioned unique effect is probably elucidated as anabasine has a full agonist action on a7 nicotinic acetylcholine receptors which found in the central and peripheral nervous system, muscle, and many other tissues of human body. At the neuromuscular junction . So repeated ( L ) anabasine administering as described above to patients of same conditions at this minor concentration, for one course , so far from reported toxic dose and also teratogenic dose which was reported at 2.6 mg/kg animals body weight , this administering causes nicotinic acetylcholine receptors heterologous desensitization which may has the pivotal role in normalizing and treating them permanently via the mechanism of nicotinic acetylcholine receptors function modulation by phosphorylation beside the induced conformational changing in them particularly in alpha7 ligand binding domain . Receptors function modulation also may last longly after removal of (L) anabasine due to the permanent loss of functional channels within prolonged desensitizationfSimasko et al.,1986;Boyd,1987; Lukas, 1991; Buisson and Bertrand, 2002 ). This administering also negatively adapts signaling pathways . ALL these mutations may lead to a specific cholinergic modulation of allergic effector cells. mast cells, basophils, and eosinophils. Furthermore this desensitization also shapes cholinergic signaling which regulates and drives skeletal muscles contraction including airways smooth muscle, which plays an integral part in the pathophysiology of asthma. It is responsible for acute bronchoconstriction, which is potentiated by constrictor hyper responsiveness, impaired relaxation and length adaptation .Thus this shaping may modulate or normalize its contractile properties . On the other hand , nicotinic acetylcholine receptors in the peripheral nervous system transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system , Heterologous desensitization also may thereafter leads these receptors to internalization . Role of receptor-mediated endocytosis is will recognized up take downregulation of transmembrane signal transduction but can also promote sustained signal transduction . It is actively implicated in transducing signals from the cell periphery to the nucleus . Herein noteworthy point , After receptors-mediated endocytosis process resulting it has been proposed that there are mechanismsrtpermanentlyf) downregulating incoming all antecedent signals are strong enough to shut down signaling completely without additional signal- transducing mechanisms .Considering that nAChRs are expressed in many regions of central and peripheral nervous system and a7nAChR is present in various non neuronal tissues as lung cells , epithelial cells , fibroblasts , endothelial cells , blood cells , gila and all types of immune cells , antecedent mechanisms which downregulate incoming signals permanently likely have an integral key role in terminating asthma types , chest allergy and atopic dermatitis permanently . These mechanisms sequently are attributed to nAChRs internalization induced by heterologous desensitization resulted in prolonged nAChRs exposure to low concentration of a 7nAChR agonist (L) anabsine . Chemical Structure DepictionAnabasine
Figure imgf000004_0001

Claims

Claims
1) Current medicament normalizes and treats all asthmatics types , patients of chest allergy and patients of atopic dermatitis to have a permanent cure after one medication course .
2) Current medicament is comprising of (L)(-) Anabasine or its salt as an active ingredient and a pharmacologically acceptable excipient , diluent or carrier .
3) Medicament is formulated for administering (L)(-) Anabasine by oral route at about 0.03 mg /kg to 2 mg / kg of body weight
4) Medicament at mentioned doses is described to be administered by oral route twice per day for a period from 30 : 40 days for asthmatics and patients of chest allergy according to severity and condition development and from 21: 40 days for patients of atopic dermatitis according to severity and condition development . Herein medication is one course only .
PCT/EG2019/000032 2019-08-15 2019-12-30 A medicament comprising anabasine for treatment of asthma, chest allergy and atopic dermatits Ceased WO2021028005A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EG2019081276 2019-08-15
EG2019081276 2019-08-15

Publications (1)

Publication Number Publication Date
WO2021028005A1 true WO2021028005A1 (en) 2021-02-18

Family

ID=74571262

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EG2019/000032 Ceased WO2021028005A1 (en) 2019-08-15 2019-12-30 A medicament comprising anabasine for treatment of asthma, chest allergy and atopic dermatits

Country Status (1)

Country Link
WO (1) WO2021028005A1 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992015306A1 (en) * 1991-03-01 1992-09-17 University Of Florida Use of nicotinic analogs for treatment of degenerative diseases of the nervous system
GB2381750A (en) * 2001-10-10 2003-05-14 Inspire Pharmaceuticals Inc Treatment for enhancing joint lubrication

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992015306A1 (en) * 1991-03-01 1992-09-17 University Of Florida Use of nicotinic analogs for treatment of degenerative diseases of the nervous system
GB2381750A (en) * 2001-10-10 2003-05-14 Inspire Pharmaceuticals Inc Treatment for enhancing joint lubrication

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