AU2021286756A1 - A novel medicament for immune modulation and treating chronic or hyper inflammation - Google Patents
A novel medicament for immune modulation and treating chronic or hyper inflammation Download PDFInfo
- Publication number
- AU2021286756A1 AU2021286756A1 AU2021286756A AU2021286756A AU2021286756A1 AU 2021286756 A1 AU2021286756 A1 AU 2021286756A1 AU 2021286756 A AU2021286756 A AU 2021286756A AU 2021286756 A AU2021286756 A AU 2021286756A AU 2021286756 A1 AU2021286756 A1 AU 2021286756A1
- Authority
- AU
- Australia
- Prior art keywords
- use according
- medicament
- anabasine
- treatment
- immune
- 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.)
- Abandoned
Links
- 239000003814 drug Substances 0.000 title claims abstract description 18
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 15
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 15
- 230000001684 chronic effect Effects 0.000 title claims abstract description 7
- 230000008102 immune modulation Effects 0.000 title claims abstract description 5
- MTXSIJUGVMTTMU-JTQLQIEISA-N (S)-anabasine Chemical group N1CCCC[C@H]1C1=CC=CN=C1 MTXSIJUGVMTTMU-JTQLQIEISA-N 0.000 claims abstract description 16
- 229930014345 anabasine Natural products 0.000 claims abstract description 8
- 208000006673 asthma Diseases 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 230000006378 damage Effects 0.000 claims abstract description 4
- 230000001404 mediated effect Effects 0.000 claims abstract description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 3
- 230000001681 protective effect Effects 0.000 claims abstract description 3
- 208000015181 infectious disease Diseases 0.000 claims abstract 6
- 201000010099 disease Diseases 0.000 claims abstract 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract 2
- 102000004877 Insulin Human genes 0.000 claims abstract 2
- 108090001061 Insulin Proteins 0.000 claims abstract 2
- 239000008280 blood Substances 0.000 claims abstract 2
- 210000004369 blood Anatomy 0.000 claims abstract 2
- 229940125396 insulin Drugs 0.000 claims abstract 2
- 230000009885 systemic effect Effects 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 210000002660 insulin-secreting cell Anatomy 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 230000002458 infectious effect Effects 0.000 claims 2
- 206010050685 Cytokine storm Diseases 0.000 claims 1
- 208000024777 Prion disease Diseases 0.000 claims 1
- 208000010362 Protozoan Infections Diseases 0.000 claims 1
- 206010052015 cytokine release syndrome Diseases 0.000 claims 1
- 244000078703 ectoparasite Species 0.000 claims 1
- 230000007614 genetic variation Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000000813 microbial effect Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 abstract description 2
- 208000025721 COVID-19 Diseases 0.000 abstract description 2
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 244000052769 pathogen Species 0.000 abstract description 2
- 231100001261 hazardous Toxicity 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- 108090000695 Cytokines Proteins 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 12
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 10
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 7
- 239000000556 agonist Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 230000001713 cholinergic effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000000586 desensitisation Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 210000001428 peripheral nervous system Anatomy 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 210000001186 vagus nerve Anatomy 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 102000047725 alpha7 Nicotinic Acetylcholine Receptor Human genes 0.000 description 2
- 108700006085 alpha7 Nicotinic Acetylcholine Receptor Proteins 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 102100028115 Forkhead box protein P2 Human genes 0.000 description 1
- 241000948258 Gila Species 0.000 description 1
- 102100037907 High mobility group protein B1 Human genes 0.000 description 1
- 101001059881 Homo sapiens Forkhead box protein P2 Proteins 0.000 description 1
- 101001025337 Homo sapiens High mobility group protein B1 Proteins 0.000 description 1
- 206010052341 Impaired insulin secretion Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000004047 hyperresponsiveness Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001002 parasympathetic nervous system Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229930000732 piperidine alkaloid Natural products 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229930002371 pyridine alkaloid Natural products 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000378 teratogenic Toxicity 0.000 description 1
- 230000003390 teratogenic effect Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (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
Present invention is a designation of a novel medicament for immune modulation and treating chronic or hyper inflammation. Its active ingredient is anabasine or its salt. It was designed for example to treat some of auto immune diseases permanently such as asthma and atopic dermatitis by one medication course, to stop the progression and development of diabetes type 2 in diabetics and restoring their blood sugar to normal with respect to administration in the disease early stages, to prevent the incidence and development of autoimmune Diabetes Type 1 resulted from T cell-mediated damage of pancreatic β-cells and loss of insulin production. Further, it plays a pivotal and protective role in treating hazardous infections caused by diverse pathogens to promote and accelerate recovery, including COVID -19 with its variants.
Description
Title Of The Invention
A novel medicament for immune modulation and treating chronic or hyper inflammation .
Technical Field
Therapeutic drugs discovery .
Background Art
In continuation to the filed patent application in the Egyptian office in June,
9 , 2020. serial number 768 / 2020 .
Disclosure Of The Invention
1- Present medicament comprises of (-)-anabasine as an active ingredient at 0.1: 0.15 mg/kg of body weight and a pharmacologically acceptable excipient , diluent or carrier .
2- (-)-Anabasine is pyridine and piperidine alkaloid . Alkaloids are a class of natural products known to have wide pharmacological activity and have great potential for the development of new drugs for several pathologies .
3- (-)-Anabasine has a full agonist action on a7 nicotinic acetylcholine receptors {Perspective in molecular toxinology - page 302 {which are pharmacological targets for inflammation , they are also widely expressed by cells of the immune system and by cells with a secondary role in pathogen defense.
4- The principal therapeutic effects of current medicament are supposed to be obtained from targeting alpha7 nicotinic acetylcholine receptor (a7nAChR {-mediated anti-inflammatory effects through modulation of pro-inflammatory cytokines. This “cholinergic anti-inflammatory pathway” (CAP) modulates the immune system through cholinergic mechanisms that act on alpha7 receptors expressed on macrophages and immune cells. (CAP), which is composed of efferent vagus nerve, acetylcholine and al subunit of the nicotinic acetylcholine receptor (a7nAchR), has been reported to attenuate excessive inflammation in critical settings{l}. Activated by peripheral or central stimuli, the brain cholinergic neurons deliver the information to efferent vagus nerves which innervate peripheral organs and release acetylcholine that can
inhibit the production of pro-inflammatory cytokines by interacting with a7nAchR on inflammatory cells {2} . (CAP) could be implemented by activation of the macrophage a7 receptor by acetylcholine, nicotine, or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed . Clinical studies have also reported negative correlation between concentrations of a7nAChR agonists and pro-inflammatory mediators' levels {3} .
Additionally, a7nAchR activation showed benefits for septic conditions by improving bacterial clearance of macrophages (4) . It also appeared to maintain integrity of pulmonary endothelium {5} . Furthermore ,cx7nAChR was also identified expressed in mitochondria, and it could regulate cytokines production and cellular apoptosis after being activated by intracellular acetylcholine (Ach) (6).
On the other hand , cx7nAChR cascades might evoke multiple antiinflammatory mechanisms of T cells to maintain immune homeostasis as a7nAChR activation augmented the suppressive effects of CD4+CD25+ Tregs by up-regulating expressions of cytotoxic T- lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3), and decreasing IL-2 levels {7} . Activating cx7nAchR effectively diminished the production of pro- inflammatory cytokines and restored disturbed function of immune cells {8} .
Consequently , a7 nAChRs activation by specific agonists or positive allosteric modulators is emerging to have a key role in preventing or controlling inflammatory cytokines storm , that common complication not only of covid-19 and flu but of other respiratory diseases caused by coronaviruses such as SARS and MERS. but also associated with some non-infectious diseases such as chronic systemic inflammation and systemic inflammation . That strategy could be the key in preventing the coronavirus-19’s deadly effects , Besides, antecedent protective characteristics , pursuing to save lives until immune system can destroy it .
On the other hand , systemic inflammation, via an increase in proinflammatory cytokines, plays an important role in the pathogenesis of type 2 diabetes and metabolic syndrome, mostly by promoting insulin resistance; however, pancreatic beta cell function may also be affected via cytokine-induced apoptosis . And under a strong cytokine
“pressure” by long-time of systemic inflammation and/or high concentration exposure to cytokines , islet can develop dysfunctional responses, which result in both impaired insulin secretion and insulitis development. In this perspective, cytokines pathways could represent potential therapeutic targets to control efficiently glucose metabolism and to prevent autoimmune damage.
In a study using NOD mice, it was demonstrated that the neurons innervating pancreatic b-cells were lost before any damage in the islets could be detected {9} . - Current medicament at mentioned doses is described to be administered, for example by oral route twice per day for a period from 30 : 45 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 . - 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 . 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(-)- 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 bv phosphorylation beside the induced conformational changing in them particularly in alpha7 ligand binding domain . Receptors function modulation also may last longlv after removal of (L) anabasine due to the permanent loss of functional channels within prolonged desensitizationf S imasko 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 mechanisms((permanentlvi) 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 x7 nAChR 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 in last involved cells in the pathophysiology of asthma and (AD) 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 from prolonged nAChRs exposure to low concentration of a 7nAChR agonist (-)-anabasine .
References
1 -Pavlov VA, Tracey KJ. Controlling inflammation: the cholinergic antiinflammatory pathway. BiochemSoc Trans. 2006;34:1037-40
Su X, Lee JW, Matthay ZA, Mednick G, Uchida T, Fang X. et at. Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and rats. Am J Respir Cell Mol Biol. 2007;37:186-92
2-Rosas-Ballina M, Tracey KJ. Cholinergic control of inflammation. J Intern Med. 2009;265:663-79 r> - :i - I \/ Q 7h ann M Yann H Rotchkina Gl. Watkins LR. et
al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature . 2000;405:458-62
Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 2007; 117:289-96
3- Kox M, Porripe JC, Gordinou De Gouberville MC, Van Der Hoeven JG, Hoedemaekers CW, Pickkers P. Effects of the alpha7 nicotinic acetylcholine receptor agonist GTS-21 on the innate
immune response in humans. Shock. 2011;36:5-11
4-Su X, Matthay MA, Malik AB. Requisite role of the cholinergic alpha7 nicotinic acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung inflammatory injury. J Immunol. 2010;184:401-10
Sitapara RA, Antoine DJ, Sharma L, Patel VS, Ashby CR Jr, Gorasiya S. et al: The alpha7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function. Mol Med. 2014;20:238-47
5-Costantini TW, Krzyzaniak M, Cheadle GA, Putnam JG, Hageny AM, Lopez N. et al. Targeting alpha-7 nicotinic acetylcholine receptor in the enteric nervous system: a cholinergic agonist prevents gut barrier failure after severe burn injury. Am J Pathol. 2012;181 :478-86
Roman J, Koval M. Control of lung epithelial growth by a nicotinic acetylcholine receptor: the other side of the coin. Am J Pathol. 2009; 175:1799-801
6-Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Chernyshov V, Kryukova E. et al. Mitochondria express alpha7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria. PLoS One. 2012;7:e31361
Lu B, Kwan K, Levine YA, Olofsson PS, Yang H, Li J. et al. alpha7 nicotinic acetylcholine receptor signaling inhibits inflammasome activation by preventing mitochondrial DNA release. Mol Med. 2014;20:350-8
7- Wang DW, Zhou RB, Yao YM, Zhu XM, Yin YM, Zhao GJ. et al. Stimulation of alpha7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. J PharmacolExp Ther. 2010;335: 553-61
8-Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas- Ballina M. et al. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med. 2007;35:2762-8
Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X. et al. Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 2007;35:1139-44
9- Saravia F, Homo-Delarche F. Is innervation an early target in autoimmune diabetes? Trends Immunol. (2003) 24:574-9. doi: 10.1016/j.it.2003.09.010
Claims (1)
- Claims1- Use of anabasine in the preparation of a human medicament for immune modulation and treating chronic or hyper inflammation .2- Use of anabasine in the preparation of a human medicament for the innate immune modulation and treating chronic or hyper inflammation .3- The use according to either claim 1 or 2 is for the treatment of auto immune diseases and as an immune modulator medicament for these diseases .4- The use according to either claim 1 or 2 is for the treatment of all infections types as microbial infections , protozoan infections , prion disease and other infections including those caused by ectoparasites , as an immune modulator and pivotal / protective treatment .5- The use according to either claim 1 or 2 is for inhibiting or controlling hypercytokinemia induced by infectious or non-infectious etiologies as an immune modulator .6- The use according to either claim 1 or 2 is for the therapeutic treatment of diabetes type 2 , stopping the progression and development of diabetes type 2 in diabetics and restoring their blood sugar to normal with respect to the administration in disease first / early stages as an immune modulator .7- The use according to either claim lor 2 is a treatment for preventing the incidence and development of autoimmune Diabetes Type 1 , particularly which resulted from T cell- mediated damage of pancreatic b-cells and loss of insulin production as an immune modulator .8- The use according to either claim 1 or 2 is for the therapeutic treatment of asthma types, chest allergy and atopic dermatitis permanently .9- The use according to either claim 1 or 2 is for the therapeutic treatment of chronic systemic inflammation , systemic inflammation or systemic inflammation response syndrome particularly which due to internal (genetic mutations/variations) factors and as an immune modulator medicament .10- The use according to claim 1 or 2 or 3 or 4 or 5 or 9 wherein subject in need to such treatment is an animal .11- The pharmaceutical composition of the said medicament according to any preceding claim is comprising of anabasine as an active ingredient or its salt and a pharmacologically acceptable excipient , diluent or carrier.12- The pharmaceutical composition of the said medicament according to claims from 1 to 10 is comprising of anabasine as an active ingredient at concentration of anabasine from 0.01 mg /kg : 3.5 mg / kg of body weight or its salt and a pharmacologically acceptable excipient , diluent or carrier.13- The use according to any preceding claim wherein said medicament with said pharmaceutical composition is for systemic , local or topical administration .14- The use according to any preceding claim wherein said medicament with said pharmaceutical composition further comprises or may be co-administered with an existing therapeutic agent for achieving , treating or managing any said purposes , diseases or conditions in claims 1 to 9 .
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EG2020060768 | 2020-06-09 | ||
| EG2020060768 | 2020-06-09 | ||
| PCT/EG2021/000016 WO2021249608A2 (en) | 2020-06-09 | 2021-06-07 | A novel medicament for immune modulation and treating chronic or hyper inflammation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2021286756A1 true AU2021286756A1 (en) | 2023-03-23 |
Family
ID=78845336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2021286756A Abandoned AU2021286756A1 (en) | 2020-06-09 | 2021-06-07 | A novel medicament for immune modulation and treating chronic or hyper inflammation |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2021286756A1 (en) |
| GB (1) | GB2612481A (en) |
| WO (1) | WO2021249608A2 (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5977144A (en) * | 1992-08-31 | 1999-11-02 | University Of Florida | Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines |
| KR100272614B1 (en) * | 1992-08-31 | 2000-11-15 | 엠. 잭 오해니언 | Anabaseine derivatives useful in the treatment of degenerative diseases of the nervous system |
| WO2005123075A2 (en) * | 2004-06-08 | 2005-12-29 | University Of Florida Research Foundation, Inc. | Controlling angiogenesis with anabaseine analogs |
| US7662965B2 (en) * | 2006-01-26 | 2010-02-16 | Cornerstone Therapeutics, Inc. | Anabaseine derivatives, pharmaceutical compositions and method of use thereof |
| JP5934796B2 (en) * | 2011-08-29 | 2016-06-15 | アールシーピー ディベロップメント インコーポレイテッド | Anti-inflammatory products |
| US10667515B2 (en) * | 2016-11-20 | 2020-06-02 | Iowa State University Research Foundation, Inc. | (S)-5-ethynyl-anabasine, derivatives thereof, and related compositions and methods of making and using |
| MX2020010908A (en) * | 2018-04-16 | 2021-03-25 | Poviva Corp | Compositions infused with nicotine compounds and methods of use thereof. |
-
2021
- 2021-06-07 GB GB2300774.3A patent/GB2612481A/en active Pending
- 2021-06-07 WO PCT/EG2021/000016 patent/WO2021249608A2/en active Application Filing
- 2021-06-07 AU AU2021286756A patent/AU2021286756A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021249608A3 (en) | 2022-02-03 |
| WO2021249608A2 (en) | 2021-12-16 |
| WO2021249608A4 (en) | 2022-04-07 |
| GB2612481A (en) | 2023-05-03 |
| GB202300774D0 (en) | 2023-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11344545B2 (en) | Use of levocetirizine and montelukast in the treatment of autoimmune disorders | |
| US20210128504A1 (en) | Autoimmune disorder treatment using rxr agonists | |
| US20200101067A1 (en) | Use of levocetirizine and montelukast in the treatment of anaphylaxis | |
| US9421187B2 (en) | Phytocannabinoids for use in the treatment of intestinal inflammatory diseases | |
| WO2021249608A2 (en) | A novel medicament for immune modulation and treating chronic or hyper inflammation | |
| Änggård et al. | Orally administered decongestant drugs in disorders of the upper respiratory passages: a survey of clinical results | |
| AU2017261680B2 (en) | Sultiame for the treatment of sleep apnea | |
| Kopec et al. | Opioid-Induced Hearing Loss | |
| US9415064B2 (en) | Prevention or treatment of painful polyneuropathies by administration of an aluminosilicate | |
| Andrews et al. | Efficacy and safety of once-daily and twice-daily olopatadine/mometasone nasal spray treatment in seasonal allergic rhinitis | |
| Rafe et al. | Targeting NMDA receptors with an antagonist is a promising therapeutic strategy for treating neurological disorders | |
| RU2020126396A (en) | USE OF CARRIMYCIN OR ITS ACTIVE INGREDIENTS | |
| Falières | Do we really need opioids in anesthesia? | |
| Gupta et al. | Comparative study of ondansetron, granisetron and ramosetron for prevention of postoperative nausea and vomiting (PONV) in surgeries under general anaesthesia | |
| Wagenlehner et al. | Safety and efficacy of finafloxacin versus ciprofloxacin in the treatment of hospitalized patients with complicated urinary tract infections and pyelonephritis determined in a phase 2 clinical study | |
| Takahama et al. | Anaphylaxis due to levofloxacin. | |
| Calarge et al. | Electroconvulsive therapy in myasthenia gravis | |
| Sharma et al. | Influence of honey on adverse reactions due to anti-tuberculosis drugs in pulmonary tuberculosis patients | |
| Javaheri et al. | 0568 Phrenic Nerve Stimulation to Treat Idiopathic Central Sleep Apnea | |
| Bolay et al. | Advances in Migraine Treatment. | |
| Li et al. | The Relative Mechanism of Tetrodotoxin: From Poison to Drug | |
| US20120077883A1 (en) | Treatment of tinnitus and associated auditory dysfunctions | |
| Kaur et al. | Comparative evaluation of granisetron versus palonosetron to prevent postoperative nausea and vomiting after open cholecystectomy | |
| WO2021028005A1 (en) | A medicament comprising anabasine for treatment of asthma, chest allergy and atopic dermatits | |
| TW200838534A (en) | Treatment for irritable bowel syndrome |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NB | Applications allowed - extensions of time section 223(2) |
Free format text: THE TIME IN WHICH TO ENTER THE NATIONAL PHASE HAS BEEN EXTENDED TO 09 FEB 2023 |
|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted | ||
| NB | Applications allowed - extensions of time section 223(2) |
Free format text: THE TIME IN WHICH TO GAIN ACCEPTANCE HAS BEEN EXTENDED TO 17 MAY 2024 |
|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |