FR3144752A1 - USE OF PENTOSAN POLYSULFATE FOR THE TREATMENT OF DRY COUGH - Google Patents
USE OF PENTOSAN POLYSULFATE FOR THE TREATMENT OF DRY COUGH Download PDFInfo
- Publication number
- FR3144752A1 FR3144752A1 FR2300233A FR2300233A FR3144752A1 FR 3144752 A1 FR3144752 A1 FR 3144752A1 FR 2300233 A FR2300233 A FR 2300233A FR 2300233 A FR2300233 A FR 2300233A FR 3144752 A1 FR3144752 A1 FR 3144752A1
- Authority
- FR
- France
- Prior art keywords
- cough
- pentosan polysulfate
- cells
- treatment
- serotonin
- 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.)
- Pending
Links
- 229940043138 pentosan polysulfate Drugs 0.000 title claims abstract description 43
- 206010011224 Cough Diseases 0.000 claims abstract description 66
- 208000017574 dry cough Diseases 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 239000007922 nasal spray Substances 0.000 claims description 3
- 229940097496 nasal spray Drugs 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 23
- 229940076279 serotonin Drugs 0.000 description 22
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 20
- 210000004072 lung Anatomy 0.000 description 19
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 208000003251 Pruritus Diseases 0.000 description 10
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 7
- 230000011514 reflex Effects 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- 208000013116 chronic cough Diseases 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 230000007794 irritation Effects 0.000 description 5
- 238000002483 medication Methods 0.000 description 5
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 239000000739 antihistaminic agent Substances 0.000 description 4
- 229940124584 antitussives Drugs 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 210000001044 sensory neuron Anatomy 0.000 description 4
- 230000001515 vagal effect Effects 0.000 description 4
- 108091005477 5-HT3 receptors Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000003434 antitussive agent Substances 0.000 description 3
- 210000000621 bronchi Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007803 itching Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229940127240 opiate Drugs 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 210000003800 pharynx Anatomy 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 208000023504 respiratory system disease Diseases 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 2
- 102000035037 5-HT3 receptors Human genes 0.000 description 2
- 102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 2
- 101710138093 5-hydroxytryptamine receptor 2C Proteins 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- 206010062717 Increased upper airway secretion Diseases 0.000 description 2
- 208000005615 Interstitial Cystitis Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000000622 irritating effect Effects 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 208000026435 phlegm Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000002416 recurrent laryngeal nerve Anatomy 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001186 vagus nerve Anatomy 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- NTQVODZUQIATFS-WAUHAFJUSA-N (2s)-2-[[(2s)-6-amino-2-[[2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-methylbutanoic acid Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NTQVODZUQIATFS-WAUHAFJUSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- 108091005436 5-HT7 receptors Proteins 0.000 description 1
- 102100039126 5-hydroxytryptamine receptor 7 Human genes 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 239000012109 Alexa Fluor 568 Substances 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101000744211 Homo sapiens 5-hydroxytryptamine receptor 7 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101150013372 Htr2c gene Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010027566 Micturition urgency Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 description 1
- 101710121435 Proteinase-activated receptor 2 Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000003766 afferent neuron Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000009956 central mechanism Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000002322 enterochromaffin cell Anatomy 0.000 description 1
- 235000020650 eye health related herbal supplements Nutrition 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 210000001357 hemopoietic progenitor cell Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 210000001937 intercostal nerve Anatomy 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007230 neural mechanism Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000000631 nonopiate Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960003820 pentosan polysulfate sodium Drugs 0.000 description 1
- 230000009955 peripheral mechanism Effects 0.000 description 1
- 230000001830 phrenic effect Effects 0.000 description 1
- 210000003105 phrenic nerve Anatomy 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 210000004044 posterior horn cell Anatomy 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- QUCDWLYKDRVKMI-UHFFFAOYSA-M sodium;3,4-dimethylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1C QUCDWLYKDRVKMI-UHFFFAOYSA-M 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000022934 urinary frequency Diseases 0.000 description 1
- 230000036318 urination frequency Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 150000003751 zinc Chemical class 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Composition comprenant une quantité efficace de polysulfate de pentosane pour une utilisation comme médicament dans le traitement de la toux sèche.A composition comprising an effective amount of pentosan polysulfate for use as a medicament in the treatment of dry cough.
Description
La présente invention concerne l’utilisation de composition comprenant du polysulfate de pentosane pour la fabrication d’un médicament destiné au traitement de la toux sèche.The present invention relates to the use of composition comprising pentosan polysulfate for the manufacture of a medicament intended for the treatment of dry cough.
La toux est une réaction normale à une irritation des voies respiratoires. La toux est provoquée par une irritation de la gorge, de la trachée et des bronches. La toux n’est pas une maladie mais un symptôme provoqué par une irritation. La toux est donc généralement un mécanisme endogène de protection et de nettoyage.Coughing is a normal reaction to respiratory irritation. Cough is caused by irritation of the throat, trachea and bronchi. Cough is not a disease but a symptom caused by irritation. Cough is therefore generally an endogenous protective and cleansing mechanism.
Les toux peuvent être regroupées en deux familles : les toux grasses et les toux sèches.Coughs can be grouped into two families: wet coughs and dry coughs.
Une toux dite grasse est une toux productive ou encombrée, destinée à l’évacuation des voies aériennes de corps obstruant ces voies, due à la production abondante de glaires et mucosités.A so-called wet cough is a productive or congested cough, intended to evacuate the airways of bodies obstructing these airways, due to the abundant production of phlegm and mucus.
Le réflexe de défense dû aux sécrétions bronchiques ou nasales, d’une toux grasse, s’attenu dès l’expulsion des corps provoquant l’irritation.The defense reflex due to bronchial or nasal secretions, from a wet cough, is reduced as soon as the bodies causing the irritation are expelled.
Une toux dite sèche est une toux non-productive qui se caractérise par des accès de toux spasmodiques et durs dans lesquels aucun flegme n’est expulsé.A so-called dry cough is a non-productive cough which is characterized by spasmodic and harsh coughing attacks in which no phlegm is expelled.
Le réflexe de défense dû aux sensations d’irritations d’une toux sèche est difficile à atténuer.The defense reflex due to the irritating sensations of a dry cough is difficult to alleviate.
La durée d’une toux est variable, il est considéré une toux aiguë, si une personne tousse depuis moins de trois semaines, une toux subaiguë, entre trois et huit semaines, et une toux chronique, si la toux se prolonge au-delà de huit semaines.The duration of a cough is variable; it is considered an acute cough if a person has been coughing for less than three weeks, a subacute cough, between three and eight weeks, and a chronic cough, if the cough continues beyond eight weeks.
Une toux sèche qui ne disparaît pas spontanément peut-être invalidante ou nuire à la qualité de vie.A dry cough that does not go away spontaneously can be disabling or affect quality of life.
En général, des médicaments pour soulager la toux sèche sont des médicaments dits antitussifs. Ils diminuent le réflexe de la toux en agissant via le système nerveux central. Les médicaments antitussifs se divisent en plusieurs catégories, les médicaments antitussifs opiacés, antitussifs antihistaminiques et antitussifs non opiacés et non antihistaminiques.In general, medicines to relieve dry cough are so-called cough medicines. They reduce the cough reflex by acting via the central nervous system. Cough medications are divided into several categories, opiate cough medications, antihistamine cough medications, and non-opiate and non-antihistamine cough medications.
Les médicaments antitussifs opiacés ont un effet sédatif et ne doivent pas être utilisés en cas d’insuffisance respiratoire ou de toux liée à l’asthme. Ils ne peuvent être achetés que sur présentation d’une ordonnance.Opiate cough medicines have a sedative effect and should not be used in cases of respiratory failure or asthma-related cough. They can only be purchased with a prescription.
Les antitussifs antihistaminiques sont recommandés en cas de toux sèche et irritante survenant la nuit, en raison de leur effet sédatif. Ils ont également des effets dits atropiniques, à savoir sécheresse de la bouche, constipation, blocage des urines et troubles visuels.Antihistamine cough suppressants are recommended for dry, irritating coughs occurring at night, due to their sedative effect. They also have so-called atropinic effects, namely dry mouth, constipation, blockage of urine and visual disturbances.
Les antitussifs non opiacés et non antihistaminiques sont indiqués dans le traitement de courte durée des toux sèches. Ils sont généralement des médicaments d’homéopathie traditionnellement proposés lors des affections respiratoires bénignes.Non-opioid, non-antihistamine cough suppressants are indicated for the short-term treatment of dry coughs. They are generally homeopathy medications traditionally offered for benign respiratory conditions.
D’autres alternatives ont été également proposés, tels que des suppléments à base de plantes ou l’utilisation d’anti-inflammatoire non stéroïdien.Other alternatives have also been proposed, such as herbal supplements or the use of nonsteroidal anti-inflammatory drugs.
Le document EP 0 274 845 divulgue la combinaison d’ibuprofène en tant qu’un anti-inflammatoire non stéroïdien avec un antitussif opiacé.EP 0 274 845 discloses the combination of ibuprofen as a non-steroidal anti-inflammatory drug with an opiate cough suppressant.
Le document EP 2 106 258 décrit l’utilisation d’ibuprofène en tant qu’un anti-inflammatoire non stéroïdien, comme antitussif, pour le traitement contre la toux sèche d’origine virale ou bactérienne.Document EP 2 106 258 describes the use of ibuprofen as a nonsteroidal anti-inflammatory, as an antitussive, for the treatment of dry cough of viral or bacterial origin.
Le document WO 2014/161811 divulgue l’utilisation d’une substance astringente et de substance mucilagineuse, telle que la mousse islandaise, pour le traitement des irritations des muqueuses de la bouche et de la gorge, ainsi que de la toux sèche.Document WO 2014/161811 discloses the use of an astringent substance and a mucilaginous substance, such as Icelandic moss, for the treatment of irritations of the mucous membranes of the mouth and throat, as well as dry cough.
Le document EP 3 086 799 décrit le traitement de toux persistantes par un mécanisme de protection physique des muqueuses des voies aériennes supérieures, par l’utilisation d’agents d’origine végétale.Document EP 3 086 799 describes the treatment of persistent coughs by a mechanism of physical protection of the mucous membranes of the upper airways, through the use of agents of plant origin.
Le mécanisme exact d’une toux chronique n’est pas clairement explicité à ce jour.The exact mechanism of a chronic cough is not clearly explained to date.
Cependant, il est largement reconnu qu’une toux chronique est associée à une inflammation des voies aériennes.However, it is widely recognized that chronic cough is associated with airway inflammation.
La toux est engendrée par le reflex de la toux, un stimulus induit par l’activation de nerfs afférents, sensoriels, innervant les voies respiratoires. Ces signaux sont transmis de manière centrale via le nerf vague, qui est connecté aux réseaux du tronc cérébral. De tels réseaux coordonnent l’activation de la production motrice (par exemple, les nerfs phréniques, intercostaux et laryngés récurrents (RLN) et l'expression ultime de la toux) (Taylor-Clark TE. Peripheral neural circuitry in cough. Curr Opin Pharmacol. 2015 Jun;22:9-17.).Cough is generated by the cough reflex, a stimulus induced by the activation of afferent, sensory nerves innervating the respiratory tract. These signals are transmitted centrally via the vagus nerve, which is connected to brainstem networks. Such networks coordinate activation of motor output (e.g., phrenic, intercostal, and recurrent laryngeal nerves (RLN) and the ultimate expression of cough) (Taylor-Clark TE. Peripheral neural circuitry in cough. Curr Opin Pharmacol 2015 Jun;22:9-17.).
La majorité des fibres nerveuses sensorielles innervant les voies respiratoires sont des afférences vagales pulmonaires sensibles à la capsaïcine (CSLV) (Agostoni, E., Chinnock, J. E., De Daly, M. B., and Murray, J. G. (1957). Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J. Physiol. 135, 182–205.), les terminaisons nerveuses sensorielles nociceptives.The majority of sensory nerve fibers innervating the airways are capsaicin-sensitive pulmonary vagal afferents (CSLV) (Agostoni, E., Chinnock, J. E., De Daly, M. B., and Murray, J. G. (1957). Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J. Physiol. 135, 182–205.), nociceptive sensory nerve endings.
Ces fibres sont très chimiosensibles et peuvent être activées par plusieurs médiateurs endogènes dont les libérations sont élevées lors de l'inflammation pulmonaire (Carr, M. J., and Undem, B. J. (2003). Bronchopulmonary afferent nerves. Respirology 8, 291–301.; Hsu, C. C., Lin, R. L., Lee, L. Y., and Lin, Y. S. (2013). Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R769–R779.).These fibers are very chemosensitive and can be activated by several endogenous mediators whose releases are elevated during pulmonary inflammation (Carr, M. J., and Undem, B. J. (2003). Bronchopulmonary afferent nerves. Respirology 8, 291–301.; Hsu , C. C., Lin, R. L., Lee, L. Y., and Lin, Y. S. (2013). 305, R769–R779.).
Anatomiquement parlant, il existe deux types de neurones : les neurones sensoriels à fibres Aδ myélinisées et les neurones sensoriels à fibres C. Les fibres Aδ myélinisées jouent un rôle dans la génération de la toux. Les fibres Aδ sont responsables de la toux violente et soudaine qui survient lors de l'aspiration (Lieu T, Undem BJ: Neuroplasticity in vagal afferent neurons involved in cough. Pulm Pharmacol Ther 2011, 24(3):276–279. ; Canning BJ, Mori N, Mazzone SB: Vagal afferent nerves regulating the cough reflex. Respir Physiol Neurobiol 2006, 152(3):223–242.).Anatomically speaking, there are two types of neurons: myelinated Aδ fiber sensory neurons and C fiber sensory neurons. Myelinated Aδ fibers play a role in cough generation. Aδ fibers are responsible for the violent and sudden cough that occurs during aspiration (Lieu T, Undem BJ: Neuroplasticity in vagal afferent neurons involved in cough. Pulm Pharmacol Ther 2011, 24(3):276–279. ; Canning BJ, Mori N, Mazzone SB: Vagal afferent nerves regulating the cough reflex. Respir Physiol Neurobiol 2006, 152(3):223–242.).
Ces dernières années, d'énormes progrès ont été accomplis dans notre compréhension du mécanisme neuronal des démangeaisons. En tant que neurotransmetteur endogène, la sérotonine s'est imposée comme un acteur clé dans les démangeaisons aiguës comme chroniques (X. Dong (2018): “Peripheral and central mechanisms of itch”. Neuron 98, 482–494.).In recent years, enormous progress has been made in our understanding of the neural mechanism of itch. As an endogenous neurotransmitter, serotonin has emerged as a key player in both acute and chronic itch (X. Dong (2018): “Peripheral and central mechanisms of itch”. Neuron 98, 482–494.).
Dans notre corps, il semble que 95% de la sérotonine soit synthétisée et libérée par les cellules entérochromaffines dans l'intestin, en réponse à une stimulation mécanique ou chimique (Linan-Rico, A., et al. (2016), Front. Neurosci. 10 :564.)In our body, it appears that 95% of serotonin is synthesized and released by enterochromaffin cells in the intestine, in response to mechanical or chemical stimulation (Linan-Rico, A., et al. (2016), Front. Neurosci. 10:564.)
Récemment, la sérotonine et son récepteur 5HT7 ont été identifiés comme l'acteur clé dans la médiation de la sensation de démangeaison aiguë et chronique de la peau (Morita T, McClain SP, Batia LM, et al. 2015: HTR7 Mediates Serotonergic Acute and Chronic Itch. Neuron. 87:124–38).Recently, serotonin and its receptor 5HT7 have been identified as the key player in mediating the sensation of acute and chronic itching of the skin (Morita T, McClain SP, Batia LM, et al. 2015: HTR7 Mediates Serotonergic Acute and Chronic Itch.
Il a été démontré que la sérotonine produit des démangeaisons fortes et robustes chez la souris et le rat, ainsi que chez l'homme (Akiyama et al., 2009: T. Akiyama, A.W. Merrill, M.I. Carstens, et al. Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential role in itch. J Neurosci, 29, pp. 6691-6699 ; Morita T, McClain Shannan P, Batia Lyn M, Pellegrino M, Wilson Sarah R, Kienzler Michael A, Lyman K, Olsen Anne Sofie B, Wong Justin F, Stucky Cheryl L, et al. (2015): “HTR7 Mediates Serotonergic Acute and Chronic Itch”. Neuron. ; 87:124–138.)Serotonin has been shown to produce strong and robust itch in mice and rats, as well as in humans (Akiyama et al., 2009: T. Akiyama, A.W. Merrill, M.I. Carstens, et al. Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential role in itch J Neurosci, 29, pp. 6691-6699; , Kienzler Michael A, Lyman K, Olsen Anne Sofie B, Wong Justin F, Stucky Cheryl L, et al. (2015).
Les fibres C sont également impliquées dans la génération de la toux. On pense que les fibres C sont importantes pour la toux de type sèche, qui est utilisé pour se débarrasser d'une sensation de démangeaison dans la gorge. Ce sentiment est plus typique de la toux chronique.C fibers are also involved in the generation of cough. C fiber is believed to be important for dry type cough, which is used to get rid of an itchy feeling in the throat. This feeling is more typical of chronic cough.
La sérotonine et ses récepteurs peuvent également jouer un rôle similaire dans les poumons (Pecova T, Kocan I, Vysehradsky R, Pecova R. Itch and Cough - Similar Role of Sensory Nerves in Their Pathogenesis. Physiol Res. 2020 Mar 27;69(Suppl 1):S43-S54.).Serotonin and its receptors may also play a similar role in the lungs (Pecova T, Kocan I, Vysehradsky R, Pecova R. Itch and Cough - Similar Role of Sensory Nerves in Their Pathogenesis. Physiol Res. 2020 Mar 27;69(Suppl 1):S43-S54.).
En effet, la sérotonine exerce un effet stimulant intense sur les terminaisons de la fibre C pulmonaire par l'intermédiaire d'une activation du récepteur de la sérotonine 5-HT3, ce qui peut contribuer à l'hypersensibilité des voies respiratoires sous inflammation pulmonaire (Potenzieri C, Meeker S, Undem BJ. Activation of mouse bronchopulmonary C-fibres by serotonin and allergen-ovalbumin challenge. J Physiol. 2012 Nov 1;590(21):5449-59. ; Hsu CC, Ruan T, Lee LY, Lin YS. Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors. Front Physiol. 2019 May 28;10:642.).Indeed, serotonin exerts an intense stimulating effect on the terminals of the pulmonary C fiber through activation of the serotonin 5-HT3 receptor, which may contribute to the hypersensitivity of the airways under pulmonary inflammation ( Potenzieri C, Meeker S, Undem BJ. Activation of mouse bronchopulmonary C-fibers by serotonin and allergen-ovalbumin challenge. Lin YS. Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors.
Lors d’infections et d’inflammation des tissus, le nombre des cellules d’origine myéloïde à caractère suppressif augmentent très significativement (Ost, M., Singh, A., Peschel, A., Mehling, R., Rieber, N., and Hartl, D. (2016). Myeloid Derived Suppressor Cells in Bacterial Infections. Front. Cell. Infect. Microbiol. 6).During infections and tissue inflammation, the number of cells of myeloid origin with a suppressive nature increases very significantly (Ost, M., Singh, A., Peschel, A., Mehling, R., Rieber, N. , and Hartl, D. (2016).
En réponse à un signal inflammatoire, les cellules myéloïdes produites par la moelle osseuse, migrent dans le sang et deviennent fonctionnellement actives, dans le but de restaurer ou de remplacer les populations périphériques endommagées (Panopoulos, A.D., and Watowich, S.S. (2008). Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and emergency hematopoiesis. Cytokine 42, 277–288.).In response to an inflammatory signal, myeloid cells produced by the bone marrow migrate into the blood and become functionally active, with the aim of restoring or replacing damaged peripheral populations (Panopoulos, A.D., and Watowich, S.S. (2008). Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and emergency hematopoiesis. Cytokine 42, 277–288.).
En plus de ces cellules immunitaires effectrices conventionnelles, il a été démontré que les cellules souches hématopoïétiques participent directement au processus inflammatoire dans des maladies respiratoires, telle que l’asthmes, l’allergies, etc… (Massberg S, Schaerli P, Knezevic-Maramica I, Köllnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, von Andrian UH. (2007) “Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues.” Cell. 131(5):994-1008 ; Allakhverdi, Z., Comeau, M. R., Smith, D. E., Toy, D., Mfuna Endam, L., Desrosiers, M., Liu, Y-. J., Howie, K. J., Denburg, J. A., Gauvreau, G. M., Delespesse, G. (2009): “CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation”. Journal of Allergy and Clinical Immunology, Volume 123, Issue 2, Pages 472-478.e1; Blanchet, M. R., McNagny, K. M. (2009) : “Stem cells, inflammation and allergy”. Allergy Asthma Clin Immunol. 5(1):13; Fischer, K. D., & Agrawal, D. K. (2013): “Hematopoietic stem and progenitor cells in inflammation and allergy”. Frontiers in immunology, 4, 428.).In addition to these conventional immune effector cells, it has been demonstrated that hematopoietic stem cells participate directly in the inflammatory process in respiratory diseases, such as asthma, allergies, etc. (Massberg S, Schaerli P, Knezevic-Maramica I, Köllnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, von Andrian UH (2007) “Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues.” (5):994-1008; Allakhverdi, Z., Comeau, M. R., Smith, D. E., Toy, D., Mfuna Endam, L., Desrosiers, M., Liu, J., Howie, K. J., Denburg. , J. A., Gauvreau, G. M., Delespesse, G. (2009): “CD34+ hemopoietic progenitor cells are potent effectors of allergic inflammation”. M. R., McNagny, K. M. (2009): “Stem cells, inflammation and allergy”. Allergy Asthma Clin Immunol. 5(1):13; Fischer, K. D., & Agrawal, D. K. (2013): “Hematopoietic stem and progenitor cells in inflammation.” and allergy”. Frontiers in immunology, 4, 428.).
Ces résultats sont confirmés par les travaux de l’inventeur : une grande quantité de cellules souches hématopoïétiques sont visible sur les biopsies issues des patients souffrant des maladies inflammatoires. De plus, la sérotonine a été détecté dans ces cellules souches hématopoïétiques.These results are confirmed by the inventor's work: a large quantity of hematopoietic stem cells are visible on biopsies taken from patients suffering from inflammatory diseases. Additionally, serotonin was detected in these hematopoietic stem cells.
Tel que mentionné précédemment, lors d’une inflammation, les cellules hématopoïétiques s’agrègent et produisent de la sérotonine, responsable en partie des démangeaisons, stimulus de la toux sèche.As mentioned previously, during inflammation, hematopoietic cells aggregate and produce serotonin, partly responsible for itching, the stimulus for dry cough.
Le demandeur a découvert que le polysulfate de pentosane modifiait la morphologie des cellules hématopoïétiques. La modification de morphologie de ces cellules, limite voire empêche leurs agrégations lors d’un processus d’inflammation, limitant la libération de sérotonine.The applicant discovered that pentosan polysulfate changed the morphology of hematopoietic cells. The modification of the morphology of these cells limits or even prevents their aggregations during an inflammation process, limiting the release of serotonin.
Le polysulfate de pentosane, également nommé, pentosane polysulfate ou polyester sulfurique de pentosane, a été utilisé dans différentes applications thérapeutiques.Pentosan polysulfate, also named, pentosan polysulfate or pentosan sulfuric polyester, has been used in different therapeutic applications.
Le polysulfate de pentosane est un analogue des glucosaminoglycanes, dérivé de l’héparine, aux propriétés anticoagulante, fibrinolytique et anti-inflammatoire.Pentosan polysulfate is a glucosaminoglycan analogue, derived from heparin, with anticoagulant, fibrinolytic and anti-inflammatory properties.
Le document WO 93/23059 décrit l’utilisation de composition comprenant du polysulfate de pentosane dans le traitement des thrombopénies.Document WO 93/23059 describes the use of composition comprising pentosan polysulfate in the treatment of thrombocytopenia.
Le document WO 2019/023761 divulgue l’utilisation de polysulfate de pentosane dans le traitement de maladies ou de troubles associés à des pathologies de la moelle osseuse.Document WO 2019/023761 discloses the use of pentosan polysulfate in the treatment of diseases or disorders associated with bone marrow pathologies.
Le document EP 1 038 528 décrit l’utilisation de polysulfate de pentosane dans le traitement de la fibrose.Document EP 1 038 528 describes the use of pentosan polysulfate in the treatment of fibrosis.
Le document EP 1 488 788 décrit l’utilisation de composition comprenant du polysulfate de pentosane dans le traitement des troubles gastro-intestinaux.Document EP 1 488 788 describes the use of composition comprising pentosan polysulfate in the treatment of gastrointestinal disorders.
Le document EP 2 164 501 divulgue l’utilisation de polysulfate de pentosane dans le traitement de maladies telles que l'asthme, la rhinite allergique et la bronchopneumopathie chronique obstructive.EP 2 164 501 discloses the use of pentosan polysulfate in the treatment of diseases such as asthma, allergic rhinitis and chronic obstructive pulmonary disease.
Le polysulfate de pentosane est également employé en tant que principe actif dans des crèmes visant à lutter contre l'inflammation. Elles sont utilisées dans le traitement local des contusions et des hématomes, voire des douleurs musculaires et articulaires.Pentosan polysulfate is also used as an active ingredient in creams aimed at combating inflammation. They are used in the local treatment of bruises and hematomas, even muscle and joint pain.
Le polysulfate de pentosane est également indiqué dans le traitement du syndrome de la vessie douloureuse caractérisé par des glomérulations ou bien des ulcères de Hunner chez les adultes souffrant de douleurs modérées à importantes, d'impériosité urinaire et de pollakiurie. Son mécanisme d'action dans le traitement du syndrome de la vessie douloureuse est mal connu ; le polysulfate de pentosane semble agir par un effet local dans la vessie par liaison des glycosaminoglycanes à la muqueuse vésicale et par un effet anti-inflammatoire.Pentosan polysulfate is also indicated for the treatment of painful bladder syndrome characterized by glomerulations or Hunner's ulcers in adults with moderate to severe pain, urinary urgency and urinary frequency. Its mechanism of action in the treatment of painful bladder syndrome is poorly understood; pentosan polysulfate seems to act through a local effect in the bladder by binding of glycosaminoglycans to the bladder mucosa and by an anti-inflammatory effect.
Une toux excessive ou chronique est un problème majeur qui est mal gérée par les thérapies actuellement disponibles.Excessive or chronic cough is a major problem that is poorly managed by currently available therapies.
Ainsi, un besoin de développement de nouveau médicament se fait ressentir.Thus, a need for the development of new drugs arises.
La présente invention propose de traiter les toux sèches excessives ou chroniques par l’utilisation de compositions comprenant du polysulfate de pentosane.The present invention proposes to treat excessive or chronic dry coughs by the use of compositions comprising pentosan polysulfate.
La présente invention concerne donc une composition comprenant une quantité efficace de polysulfate de pentosane (PPS) pour une utilisation comme médicament dans le traitement de la toux sèche.The present invention therefore relates to a composition comprising an effective amount of pentosan polysulfate (PPS) for use as a medicament in the treatment of dry cough.
La mise en œuvre de l’invention sera mieux comprise à l’aide de la description détaillée qui est exposée ci-après en regard des figures annexées dans lesquels :The implementation of the invention will be better understood with the help of the detailed description which is set out below with reference to the appended figures in which:
Les figures 1 à 3 illustrent des images de poumons, de morceau de parenchyme pulmonaire et de morceaux d’anneaux bronchiques.Figures 1 to 3 illustrate images of lungs, pieces of lung parenchyma and pieces of bronchial rings.
Les figures 5 et 6 illustrent des images obtenues par microscope optique de cellules de congestions sanguines d'un donneur allergique, avec un agrandissement x20.Figures 5 and 6 illustrate images obtained by optical microscope of blood congestion cells from an allergic donor, with a x20 magnification.
Les figures 7 et 8 illustrent des images obtenues par microscope optique de cellules de congestions sanguines colorées positives pour le récepteur de la sérotonine 5HT2C par un anticorps monoclonal spécifique, avec un agrandissement x20.Figures 7 and 8 illustrate images obtained by optical microscope of blood congestion cells stained positive for the serotonin 5HT2C receptor by a specific monoclonal antibody, with a magnification x20.
Les figures 9 à 11 illustrent des images obtenues par microscope optique de cellules de congestions sanguines.Figures 9 to 11 illustrate images obtained by optical microscope of blood congestion cells.
Ainsi l’invention concerne le traitement de la toux sèche comprenant l'administration d’une composition comprenant une quantité efficace de polysulfate de pentosane, pendant une durée et dans des conditions suffisantes pour le traitement de la toux sèche.Thus the invention relates to the treatment of dry cough comprising the administration of a composition comprising an effective quantity of pentosan polysulfate, for a duration and under conditions sufficient for the treatment of dry cough.
Plus précisément, l’invention concerne l'utilisation de polysulfate de pentosane dans la fabrication d'un médicament pour le traitement de la toux sèche.More specifically, the invention relates to the use of pentosan polysulfate in the manufacture of a medicine for the treatment of dry cough.
Le terme "quantité efficace" de polysulfate de pentosane tel qu'utilisé, signifie une quantité suffisante de polysulfate de pentosane pour fournir l'effet thérapeutique ou physiologique souhaité.The term "effective amount" of pentosan polysulfate as used means a sufficient amount of pentosan polysulfate to provide the desired therapeutic or physiological effect.
La quantité exacte requise varie d'un sujet à l'autre, de l'âge et de l'état général du sujet, du mode d'administration, etc.The exact amount required varies from subject to subject, age and general condition of the subject, method of administration, etc.
Une "quantité efficace" appropriée peut être déterminée en utilisant une expérimentation de routine. La quantité efficace dans ce contexte comprend une quantité requise pour traiter la toux sèche.An appropriate "effective amount" can be determined using routine experimentation. The effective amount in this context includes an amount required to treat dry cough.
Ces compositions sont proposées pour une utilisation en tant que compositions ou formulations pharmaceutiques.These compositions are proposed for use as pharmaceutical compositions or formulations.
Les compositions comprennent des solutions avantageusement aqueuses et stériles.The compositions include preferably aqueous and sterile solutions.
Les solutions stériles sont préparées en incorporant une quantité requise de polysulfate de pentosane dans un solvant approprié, avec éventuellement d'autres ingrédients actifs, suivis d'une stérilisation ou au moins d'un processus pour réduire les virus, bactéries ou autres entités biologiques contaminants à des niveaux acceptables.Sterile solutions are prepared by incorporating a required amount of pentosan polysulfate in a suitable solvent, optionally with other active ingredients, followed by sterilization or at least a process to reduce contaminating viruses, bacteria or other biological entities at acceptable levels.
Le polysulfate de pentosan (PPS) est de préférence choisi dans le groupe constitué par : le sel de sodium de polysulfate de pentosane (NaPPS), le sel de magnésium de polysulfate de pentosane (MgPPS), le sel de calcium de polysulfate de pentosane (CaPPS), et le sel de zinc de polysulfate de pentosane (ZnPPS).Pentosan polysulfate (PPS) is preferably chosen from the group consisting of: the sodium salt of pentosan polysulfate (NaPPS), the magnesium salt of pentosan polysulfate (MgPPS), the calcium salt of pentosan polysulfate ( CaPPS), and zinc salt of pentosan polysulfate (ZnPPS).
De préférence, le polysulfate de pentosane (PPS) est le polysulfate de pentosane sodique (NaPPS).Preferably, the pentosan polysulfate (PPS) is pentosan polysulfate sodium (NaPPS).
Selon des modes de réalisation, le médicament est administré par inhalation ou sous forme de pulvérisation nasale, délivré par un inhalateur.According to embodiments, the medication is administered by inhalation or in the form of a nasal spray, delivered by an inhaler.
Selon une caractéristique, la concentration massique de polysulfate de pentosane, exprimée en pourcentage, est comprise entre 0,5 et 3 %.According to one characteristic, the mass concentration of pentosan polysulfate, expressed as a percentage, is between 0.5 and 3%.
Selon un mode d’exécution, la concentration massique de polysulfate de pentosane, exprimée en pourcentage, est égale à 1 %.According to one embodiment, the mass concentration of pentosan polysulfate, expressed as a percentage, is equal to 1%.
Le solvant est de préférence une solution aqueuse saline, par exemple comprenant une concentration massique, exprimée en pourcentage, de chlorure de sodium de 0,9 %, tamponnée avec 10mM HEPES (ou acide 4-(2-hydroxyéthyl)-1-pipérazine éthane sulfonique).The solvent is preferably an aqueous saline solution, for example comprising a mass concentration, expressed as a percentage, of sodium chloride of 0.9%, buffered with 10mM HEPES (or 4-(2-hydroxyethyl)-1-piperazine ethane acid). sulfonic).
Il est entendu par autres ingrédients actifs, une molécule antibiotique ou antivirale.It is understood by other active ingredients, an antibiotic or antiviral molecule.
Des poumons sains sont plus ou moins uniformes en couleur et en forme, tels qu’illustrés à la
Les parenchymes pulmonaires ainsi que les bronches de patients atteints de maladies respiratoires chroniques, telles que la fibrose kystique, la fibrose pulmonaire idiopathique, la sarcoïdose, présentent des zones d’agrégation de cellules hématopoïétiques de couleurs rouges en couleurs réelles et illustrées par des zones sombres, telles qu’illustrées aux figures 2 à 4.The lung parenchymas as well as the bronchi of patients with chronic respiratory diseases, such as cystic fibrosis, idiopathic pulmonary fibrosis, sarcoidosis, present areas of aggregation of hematopoietic cells in red colors in real colors and illustrated by dark areas , as illustrated in Figures 2 to 4.
Ces zones d’agrégation cellulaires sont communément appelées congestion sanguine des poumons.These areas of cell aggregation are commonly called blood congestion in the lungs.
Ces congestions sanguines participent ainsi directement aux réponses inflammatoires et à la réparation des tissus.These blood congestions thus participate directly in inflammatory responses and tissue repair.
Par immuno-cytochimie, le demandeur a découvert que l’agrégation de cellules hématopoïétiques dans les poumons expriment une grande quantité de sérotonine, telles qu’illustrées à la
Ces observations de la présence de la sérotonine ont été confirmées par deux anticorps différents dans plusieurs expériences indépendantes, avec les mêmes résultats, un exemple d’une telle confirmation est illustré à la
Ainsi, non seulement l’agrégation de cellules hématopoïétiques dans les poumons expriment la sérotonine, mais également un récepteur de la sérotonine, 5-HT2C (
Sur la base de ces données, le demandeur propose le schéma suivant de la toux chronique : lors d'infections virales ou bactériennes, ou de lésions tissulaires, les médiateurs pro-inflammatoires, dont la sérotonine, sont libérés dans la zone touchée.Based on these data, the applicant proposes the following scheme of chronic cough: during viral or bacterial infections, or tissue damage, pro-inflammatory mediators, including serotonin, are released in the affected area.
Ces médiateurs recruteront les cellules hématopoïétiques à partir des tissus pulmonaires environnants ainsi que de la circulation sanguine.These mediators will recruit hematopoietic cells from surrounding lung tissues as well as the bloodstream.
La sérotonine agirait sur les cellules hématopoïétiques principalement via les récepteurs 5HT2C de manière paracrine et autocrine, amplifiant la réponse inflammatoire.Serotonin appears to act on hematopoietic cells mainly via 5HT2C receptors in a paracrine and autocrine manner, amplifying the inflammatory response.
Un grand nombre de cellules hématopoïétiques s'accumuleront rapidement dans la zone affectée, ce qui rendra la zone affectée de couleur rouge.A large number of blood-forming cells will quickly accumulate in the affected area, making the affected area red in color.
Les cellules hématopoïétiques libèrent une quantité croissante de sérotonine qui active les fibres C provoquant une sensation de démangeaison via le récepteur 5HT3 ou 5HT7, activant le réflexe de la toux.Hematopoietic cells release an increasing amount of serotonin which activates C fibers causing an itching sensation via the 5HT3 or 5HT7 receptor, activating the cough reflex.
Tant que des zones d’agrégation importantes de cellules hématopoïétiques sont présentes, par exemple telles qu’illustrées aux figures 2 et 3, la toux sèche ne devrait pas s'arrêter, en raison de la libération continue de sérotonine par les agrégats de cellules hématopoïétiques.As long as significant areas of hematopoietic cell aggregation are present, for example as shown in Figures 2 and 3, the dry cough should not stop, due to the continued release of serotonin from the hematopoietic cell aggregates .
De plus, la toux sèche peut encore augmenter la sécrétion de sérotonine, créant une boucle de rétroaction positive.Additionally, dry cough can further increase serotonin secretion, creating a positive feedback loop.
Le demandeur a découvert que le polysulfate de pentosane, a un effet direct sur les cellules hématopoïétiques localisées dans les agrégats de cellules : en tant qu'anticoagulant.The applicant has discovered that pentosan polysulfate has a direct effect on hematopoietic cells located in cell aggregates: as an anticoagulant.
En effet, le polysulfate de pentosane modifie considérablement la morphologie des cellules hématopoïétiques in vitro, telle qu’illustrée à la
Lors du traitement avec le polysulfate de pentosane, les cellules hématopoïétiques extraites des agrégats, ont changées de morphologie, vers une forme d’aiguille, ou de clou, tels qu’illustrés aux figures 10 et 11.During treatment with pentosan polysulfate, the hematopoietic cells extracted from the aggregates changed in morphology, towards a needle or nail shape, as illustrated in Figures 10 and 11.
Pour s'agréger, les cellules doivent avoir la forme d'un disque, telles qu’illustrées à la
Ce changement morphologique induit par le polysulfate de pentosane empêcherait les cellules hématopoïétiques de former des agrégats cellulaires.This morphological change induced by pentosan polysulfate would prevent hematopoietic cells from forming cellular aggregates.
Cette hypothèse fournit non seulement une explication sur le fonctionnement du polysulfate de pentosane, mais également une justification de son utilisation comme médicament pour briser le cercle vicieux de l'inflammation chronique dans diverses maladies inflammatoires, en particulier les maladies respiratoires, fréquemment associées à la toux chronique.This hypothesis provides not only an explanation for how pentosan polysulfate works, but also a rationale for its use as a drug to break the vicious cycle of chronic inflammation in various inflammatory diseases, especially respiratory diseases, frequently associated with cough chronic.
Une application locale et directe de polysulfate de pentosane par inhalation ou sous forme de pulvérisation nasale, sur les voies respiratoires, aura un double bénéfice, à savoir une efficacité médicamenteuse accrue et une réduction de la toxicité du médicament.Local and direct application of pentosan polysulfate by inhalation or in the form of a nasal spray, to the respiratory tract, will have a dual benefit, namely increased drug effectiveness and reduced drug toxicity.
De plus, en agissant directement sur les agrégats de cellules hématopoïétiques, le polysulfate de pentosane n'altère pas le réflexe de la toux, préservant ainsi les effets protecteurs de la toux contre les agents nocifs des voies respiratoires.In addition, by acting directly on hematopoietic cell aggregates, pentosan polysulfate does not alter the cough reflex, thus preserving the protective effects of cough against harmful agents of the respiratory tract.
Matériels et méthodes :Materials and methods :
Les poumons et les biopsies pulmonaires :Lungs and lung biopsies:
Les morceaux d’organes illustrés aux figures 2 à 4 ont été obtenus à partir de patients ayant subi une transplantation pulmonaire ou une polypectomie. Toutes les procédures expérimentales ont été expliquées dans leur intégralité, et tous les sujets ont reçu consentement éclairé. L'étude a été menée conformément à la déclaration de Helsinki sur la recherche biomédicale (amendement de Hong Kong, 1989), et a reçu l'approbation de la commission d'éthique locale.The organ pieces shown in Figures 2 to 4 were obtained from patients who underwent lung transplantation or polypectomy. All experimental procedures were explained in full, and all subjects received informed consent. The study was conducted in accordance with the Declaration of Helsinki on Biomedical Research (Hong Kong Amendment, 1989), and received approval from the local ethics committee.
Isolation des cellules souches hématopoïétiques du parenchyme pulmonaire :Isolation of hematopoietic stem cells from lung parenchyma:
Les échantillons de tissu pulmonaire ont été disséqués en morceaux d'environ 5 mm3. Environ 10 g de tissus hachés ont été placés dans des tubes coniques de 50 ml, remplis de tampon de lavage (Dulbecco’s Phosphate Buffered Saline (DPBS) contenant chacun 100U/mL de pénicilline et streptomycine). Les tubes ont été retournés pour laver le tissu et le surnageant retiré, en répétant ces opérations trois fois. Le plus possible de liquide a été retiré, les tissus hachés et lavés ont été filtrés à travers une couche de gaze stérile. Les tissus sur la gaze ont été répartis dans des tubes Falcon de 15 ml, comprenant environ 1,5 g de tissus par tube. Les filtrats ont été passés à travers un tamis cellulaire de 10 μm. Les cellules ont été recueillies par centrifugation.The lung tissue samples were dissected into pieces of approximately 5 mm 3 . Approximately 10 g of minced tissue was placed in 50 ml conical tubes, filled with washing buffer (Dulbecco's Phosphate Buffered Saline (DPBS) each containing 100 U/mL of penicillin and streptomycin). The tubes were inverted to wash the tissue and the supernatant removed, repeating these operations three times. As much liquid as possible was removed, chopped and washed tissues were filtered through a layer of sterile gauze. The tissues on the gauze were distributed into 15 ml Falcon tubes, comprising approximately 1.5 g of tissue per tube. The filtrates were passed through a 10 μm cell strainer. Cells were collected by centrifugation.
Immuno-coloration, figures 5, 6 et 8 :Immunostaining, figures 5, 6 and 8:
Les cellules sont cultivées sur une lamelle, puis fixées avec une solution de formaldéhyde titrée à 2%, et de glutaraldéhyde titrée à 2,5% dans du tampon de 0,1 M phosphate de sodium, pendant 30 minutes à température ambiante. Les cellules fixées sont ensuite rincées plusieurs fois (3 X) avec du PBS (tampon phosphate salin). Pour faciliter l’accès d’anticorps, les cellules fixées sont ensuite perméabilisées avec 0,25% Triton-X-100. Les cellules fixées sont rincées plusieurs fois (3 X) avec du PBS. Une solution de 100 µl de PBS supplémentée de 10% de sérum (bovin, Chèvre, ou humain, en fonction de l’anticorps primaire utilisé), a été appliquée pendant 60 minutes à température ambiante. 100 µl, ou un volume suffisant pour couvrir les cellules, d'anticorps primaire ont été appliqué et incubé pendant 30-60 minutes. Les cellules ont été rincées avec du PBS 3 fois pendant 2 minutes. 100 µl, ou un volume suffisant pour couvrir les cellules a été appliqué, d'une solution d’anticorps secondaire conjugué avec un fluorophore (Alexa 488, Alexa 560 ). La lamelle est ensuite montée sur une lame de verre pour l’observation sous un microscope à fluorescence.The cells are cultured on a coverslip, then fixed with a solution of formaldehyde titrated to 2%, and glutaraldehyde titrated to 2.5% in 0.1 M sodium phosphate buffer, for 30 minutes at room temperature. The fixed cells are then rinsed several times (3X) with PBS (phosphate-buffered saline). To facilitate antibody access, the fixed cells are then permeabilized with 0.25% Triton-X-100. The fixed cells are rinsed several times (3X) with PBS. A solution of 100 µl of PBS supplemented with 10% serum (bovine, goat, or human, depending on the primary antibody used), was applied for 60 minutes at room temperature. 100 µl, or a volume sufficient to cover the cells, of primary antibody was applied and incubated for 30-60 minutes. Cells were rinsed with PBS 3 times for 2 min. 100 µl, or a volume sufficient to cover the cells was applied, of a solution of secondary antibody conjugated with a fluorophore (Alexa 488, Alexa 560). There Coverslip is then mounted on a glass slide for observation under a fluorescence microscope.
Pour l’échantillon illustré à la
Pour l’échantillon illustré à la
For the sample shown in
Claims (4)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR2300233A FR3144752A1 (en) | 2023-01-10 | 2023-01-10 | USE OF PENTOSAN POLYSULFATE FOR THE TREATMENT OF DRY COUGH |
| PCT/EP2024/050326 WO2024149719A1 (en) | 2023-01-10 | 2024-01-09 | Use of pentosan polysulfate for the treatment of dry cough |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR2300233 | 2023-01-10 | ||
| FR2300233A FR3144752A1 (en) | 2023-01-10 | 2023-01-10 | USE OF PENTOSAN POLYSULFATE FOR THE TREATMENT OF DRY COUGH |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| FR3144752A1 true FR3144752A1 (en) | 2024-07-12 |
Family
ID=85792695
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR2300233A Pending FR3144752A1 (en) | 2023-01-10 | 2023-01-10 | USE OF PENTOSAN POLYSULFATE FOR THE TREATMENT OF DRY COUGH |
Country Status (2)
| Country | Link |
|---|---|
| FR (1) | FR3144752A1 (en) |
| WO (1) | WO2024149719A1 (en) |
Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0274845A1 (en) | 1986-12-10 | 1988-07-20 | The Boots Company PLC | Stable solid pharmaceutical composition containing ibuprofen and codeine |
| WO1993023059A1 (en) | 1992-05-15 | 1993-11-25 | Institut Des Vaisseaux Et Du Sang | Use of exogeneous glycosaminoglycanes or derivatives in the treatment of thrombopenias |
| US5288704A (en) * | 1991-01-31 | 1994-02-22 | Farmitalia Carlo Erba S.R.L. | Synergistic composition comprising a fibroblast growth factor and a sulfated polysaccharide, for use as antiviral agent |
| EP1038528A1 (en) | 1991-05-31 | 2000-09-27 | Gliatech, Inc. | Pentosan polysulfate containing medicament and implant for treating fibrosis |
| EP1488788A1 (en) | 1999-12-10 | 2004-12-22 | Novartis AG | Pharmaceutical combinations and their use in treating gastrointestinal disorders |
| US20090111771A1 (en) * | 2006-09-27 | 2009-04-30 | Sylvan Pharmaceuticals Pty. Ltd. Can 102 641 332 | Inhibition of cathepsin k activity and the treatment and prevention of disease |
| EP2106258A2 (en) | 2006-10-20 | 2009-10-07 | Bayer Consumer Care AG | Non-steroid antiphlogistics against coughing |
| EP2164501A1 (en) | 2007-05-31 | 2010-03-24 | Glycan Biosciences | Sulphated xylans for treatment or prophylaxis of respiratory diseases |
| US20130203695A1 (en) * | 2010-10-29 | 2013-08-08 | Opko Health, Inc. | Hypersulfated disaccharides to treat elastase related disorders |
| AU2014200346A1 (en) * | 2007-05-31 | 2014-02-06 | Paradigm Biopharmaceuticals Ltd | Sulphated xylans for treatment or prophylaxis of respiratory diseases |
| WO2014161811A1 (en) | 2013-04-02 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Lozenge for treating a sore throat, hoarseness, and associated dry cough and for treating inflammatory diseases of the oral cavity and of the pharynx |
| EP3086799A1 (en) | 2013-12-23 | 2016-11-02 | Aboca S.p.A. Società Agricola | Composition for use in the treatment of persistent cough |
| WO2019023761A1 (en) | 2017-08-04 | 2019-02-07 | Paradigm Biopharmaceuticals Ltd | Treatment of bone marrow pathologies with polysulfated polysaccharides |
| WO2021179047A1 (en) * | 2020-03-12 | 2021-09-16 | Cullis Hill Sydney David | Treatment for coronavirus infection and associated cytokine toxicity |
| US20220347093A1 (en) * | 2019-09-20 | 2022-11-03 | University Of Fukui | Pharmaceutical composition |
-
2023
- 2023-01-10 FR FR2300233A patent/FR3144752A1/en active Pending
-
2024
- 2024-01-09 WO PCT/EP2024/050326 patent/WO2024149719A1/en unknown
Patent Citations (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0274845A1 (en) | 1986-12-10 | 1988-07-20 | The Boots Company PLC | Stable solid pharmaceutical composition containing ibuprofen and codeine |
| US5288704A (en) * | 1991-01-31 | 1994-02-22 | Farmitalia Carlo Erba S.R.L. | Synergistic composition comprising a fibroblast growth factor and a sulfated polysaccharide, for use as antiviral agent |
| EP1038528A1 (en) | 1991-05-31 | 2000-09-27 | Gliatech, Inc. | Pentosan polysulfate containing medicament and implant for treating fibrosis |
| WO1993023059A1 (en) | 1992-05-15 | 1993-11-25 | Institut Des Vaisseaux Et Du Sang | Use of exogeneous glycosaminoglycanes or derivatives in the treatment of thrombopenias |
| EP1488788A1 (en) | 1999-12-10 | 2004-12-22 | Novartis AG | Pharmaceutical combinations and their use in treating gastrointestinal disorders |
| US20090111771A1 (en) * | 2006-09-27 | 2009-04-30 | Sylvan Pharmaceuticals Pty. Ltd. Can 102 641 332 | Inhibition of cathepsin k activity and the treatment and prevention of disease |
| EP2106258A2 (en) | 2006-10-20 | 2009-10-07 | Bayer Consumer Care AG | Non-steroid antiphlogistics against coughing |
| US20200054668A1 (en) * | 2007-05-31 | 2020-02-20 | Pardigm Biopharmaceuticals Limied | Sulphated xylans for treatment or prophylaxis of respiratory diseases |
| EP2164501A1 (en) | 2007-05-31 | 2010-03-24 | Glycan Biosciences | Sulphated xylans for treatment or prophylaxis of respiratory diseases |
| AU2014200346A1 (en) * | 2007-05-31 | 2014-02-06 | Paradigm Biopharmaceuticals Ltd | Sulphated xylans for treatment or prophylaxis of respiratory diseases |
| US20130203695A1 (en) * | 2010-10-29 | 2013-08-08 | Opko Health, Inc. | Hypersulfated disaccharides to treat elastase related disorders |
| WO2014161811A1 (en) | 2013-04-02 | 2014-10-09 | Boehringer Ingelheim International Gmbh | Lozenge for treating a sore throat, hoarseness, and associated dry cough and for treating inflammatory diseases of the oral cavity and of the pharynx |
| EP3086799A1 (en) | 2013-12-23 | 2016-11-02 | Aboca S.p.A. Società Agricola | Composition for use in the treatment of persistent cough |
| WO2019023761A1 (en) | 2017-08-04 | 2019-02-07 | Paradigm Biopharmaceuticals Ltd | Treatment of bone marrow pathologies with polysulfated polysaccharides |
| US20220347093A1 (en) * | 2019-09-20 | 2022-11-03 | University Of Fukui | Pharmaceutical composition |
| WO2021179047A1 (en) * | 2020-03-12 | 2021-09-16 | Cullis Hill Sydney David | Treatment for coronavirus infection and associated cytokine toxicity |
Non-Patent Citations (21)
| Title |
|---|
| AGOSTONI, E.CHINNOCK, J. E.DE DALY, M. B.MURRAY, J. G.: "Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat", J. PHYSIOL., vol. 135, 1957, pages 182 - 205 |
| ALLAKHVERDI, Z.COMEAU, M. R.SMITH, D. E.TOY, D.MFUNA ENDAM, L.DESROSIERS, M.LIU, Y-. J.HOWIE, K. J.DENBURG, J. A.GAUVREAU, G. M.: "CD34+ hemopoietic progenitor cells arc potent effectors of allergie inflammation", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 123, 2009, pages 472 - 478 |
| BLANCHET, M. R.MCNAGNY, K. M: "Stem cells, inflammation and allergy", ALLERGY ASTHMA CLIN IMMUNOL, vol. 5, no. 1, 2009, pages 13, XP021068842 |
| CANNING BJMORI NMAZZONE SB: "Vagal afferent nerves regulating the cough reflex", RESPIR PHYSIOL NEUROBIOL, vol. 152, no. 3, 2006, pages 223 - 242, XP025120836, DOI: 10.1016/j.resp.2006.03.001 |
| CARR, M. J.UNDEM, B. J.: "Bronchopulmonary afferent nerves", RESPIROLOGY, vol. 8, 2003, pages 291 - 301 |
| FISCHER, K. D.AGRAWAL, D. K.: "Hematopoietic stem and progenitor cells in inflammation and allergy", FRONTIERS IN IMMUNOLOGY, vol. 4, 2013, pages 428 |
| HSU CCRUAN TLEE LYLIN YS: "Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT3 Receptors", FRONT PHYSIOL, vol. 10, 28 May 2019 (2019-05-28), pages 642 |
| HSU, C. C.LIN, R. L.LEE, L. Y.LIN, Y. S.: "Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: rôle of TRPA1 receptors", AM. J. PHYSIOL. REGUL. INTEGR. COMP. PHYSIOL, vol. 305, 2013, pages R769 - R779 |
| KRISHNAN RAVI ET AL: "Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation", FRONTIERS IN IMMUNOLOGY, vol. 14, 9 February 2023 (2023-02-09), XP093059906, DOI: 10.3389/fimmu.2023.1030879 * |
| LIEU TUNDEM BJ: "Neuro-plasticity in vagal afferent neurons involved in cough", PULM PHARMACOL THER, vol. 24, no. 3, 2011, pages 276 - 279 |
| LINAN-RICO, A. ET AL., FRONT. NEUROSCI., vol. 10, 2016, pages 564 |
| MASSBERG SSCHAERLI PKNEZEVIC-MARAMICA IKΔLLNBERGER MTUBO NMOSEMAN EAHUFF IVJUNT TWAGERS AJMAZO IB: "Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues", CELL, vol. 131, no. 5, 2007, pages 994 - 1008, XP002672553, DOI: 10.1016/j.cell.2007.09.047 |
| MORITA T, MCCLAIN SHANNAN P, BATIA LYN M, PELLEGRINO M, WILSON SARAH R, KIENZLER, MICHAEL A, LYMAN K, OLSEN ANNE SOFIE B, WONG JUS: "HTR7 Mediates Serotonergic Acute and Chronic Itch", NEURON, vol. 87, 2015, pages 124 - 138 |
| MORITA TMCCLAIN SPBATIA LM ET AL.: "HTR7 Médiates Serotonergic Acute and Chronic Itch", NEURON, vol. 87, 2015, pages 124 - 38 |
| OST, M.SINGH, A.PESCHEL, A.MEHLING, R.RIEBER, N.HARTL, D.: "Myeloid Derived Suppressor Cells in Bacterial Infections", FRONT. CELL. INFECT. MICROBIOL., 2016, pages 6 |
| PANOPOULOS, A.D.WATOWICH, S.S.: "Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and emergency hematopoiesis", CYTOKINE, vol. 42, 2008, pages 277 - 288, XP022696622, DOI: 10.1016/j.cyto.2008.03.002 |
| PECOVA TKOCAN IVYSEHRADSKY RPECOVA R: "Itch and Cough - Similar Role of Sensory Nerves in Their Pathogenesis", PHYSIOL RES, vol. 69, 27 March 2020 (2020-03-27), pages S43 - S54 |
| POTENZIERI CMEEKER SUNDEM BJ: "Activation of mouse bronchopulmonary C-fibres by serotonin and allergen-ovalbumin challenge", J PHYSIOL., vol. 590, no. 21, 1 November 2012 (2012-11-01), pages 5449 - 59 |
| T. AKIYAMAA.W. MERRILLM.I. CARSTENS ET AL.: "Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential rôle in itch", J NEUROSCI, vol. 29, 2009, pages 6691 - 6699 |
| TAYLOR-CLARK TE: "Peripheral neural circuitry in cough", CURR OPIN PHARMACOL, vol. 22, June 2015 (2015-06-01), pages 9 - 17 |
| X. DONG: "Peripheral and central mechanisms of itch", NEURON, vol. 98, 2018, pages 482 - 494 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024149719A1 (en) | 2024-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6316501B2 (en) | Composition for treatment or prevention of metabolic diseases comprising extracellular vesicles derived from Ackermansia mucinifira as an active ingredient | |
| Wang et al. | Depletion of microglia attenuates dendritic spine loss and neuronal apoptosis in the acute stage of moderate traumatic brain injury in mice | |
| Liu et al. | Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway | |
| Goebel et al. | Argon reduces microglial activation and inflammatory cytokine expression in retinal ischemia/reperfusion injury | |
| JP2022095884A (en) | Pharmaceutical composition for preventing or treating rheumatoid arthritis comprising isolated mitochondria | |
| Mi et al. | Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier | |
| Norte-Muñoz et al. | Neuroprotection and axonal regeneration induced by bone marrow mesenchymal stromal cells depend on the type of transplant | |
| Yin et al. | Zinc oxide nanoparticles ameliorate collagen lattice contraction in human tenon fibroblasts | |
| Han et al. | Antiangiogenic effects of catalpol on rat corneal neovascularization | |
| Fafure et al. | Fermented maize slurry (Ogi) and its supernatant (Omidun) mitigate elevated intraocular pressure by modulating BDNF expression and glial plasticity in the retina-gut axis of glaucomatous rats | |
| KR101662720B1 (en) | Composition for the treatment of corneal diseases or conjunctival diseases | |
| Chen et al. | Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions | |
| Yan et al. | Functionalized curcumin/ginsenoside Rb1 dual-loaded liposomes: Targeting the blood-brain barrier and improving pathological features associated in APP/PS-1 mice | |
| Huang et al. | Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway | |
| Zhao et al. | COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury | |
| Li et al. | Trehalose protects motorneuron after brachial plexus root avulsion by activating autophagy and inhibiting apoptosis mediated by the AMPK signaling pathway | |
| WO2024149719A1 (en) | Use of pentosan polysulfate for the treatment of dry cough | |
| CH720425A2 (en) | Use of pentosan polysulfate for the treatment of dry cough | |
| Feng et al. | Anemoside B4 ameliorates dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome and modulating gut microbiota | |
| JP2024532157A (en) | Composition for treating muscle loss-related diseases comprising exosomes derived from tonsillar mesenchymal stem cells | |
| Tang et al. | Hypoxic preconditioned mesenchymal stem cells ameliorate rat brain injury after cardiopulmonary resuscitation by suppressing neuronal pyroptosis | |
| Jiang et al. | LXA4 attenuates perioperative neurocognitive disorders by suppressing neuroinflammation and oxidative stress | |
| TW201932130A (en) | Lipocalin-type prostaglandin D2 synthase production promoter | |
| TWI488633B (en) | Use of black soybean for treating ophthalmic diseases | |
| Luan et al. | Exosomes derived from umbilical cord-mesenchymal stem cells inhibit the NF-κB/MAPK signaling pathway and reduce the inflammatory response to promote recovery from spinal cord injury |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PLFP | Fee payment |
Year of fee payment: 2 |
|
| PLSC | Publication of the preliminary search report |
Effective date: 20240712 |