[go: up one dir, main page]

WO2025078388A1 - Agonistes du récepteur bêta-3 adrénergique destinés à être utilisés pour favoriser la maturation du tissu nerveux - Google Patents

Agonistes du récepteur bêta-3 adrénergique destinés à être utilisés pour favoriser la maturation du tissu nerveux Download PDF

Info

Publication number
WO2025078388A1
WO2025078388A1 PCT/EP2024/078317 EP2024078317W WO2025078388A1 WO 2025078388 A1 WO2025078388 A1 WO 2025078388A1 EP 2024078317 W EP2024078317 W EP 2024078317W WO 2025078388 A1 WO2025078388 A1 WO 2025078388A1
Authority
WO
WIPO (PCT)
Prior art keywords
beta
adrenergic receptor
agonist
activator
use according
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
Application number
PCT/EP2024/078317
Other languages
English (en)
Inventor
Luca FILIPPI
Maurizio CAMMALLERI
Alessandro Pini
Patrizia NARDINI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universita degli Studi di Firenze
Universita di Pisa
Original Assignee
Universita degli Studi di Firenze
Universita di Pisa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universita degli Studi di Firenze, Universita di Pisa filed Critical Universita degli Studi di Firenze
Publication of WO2025078388A1 publication Critical patent/WO2025078388A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • eye opening affects the development of the neuronal circuit in the ascending retino-talamocortical pathway at all levels: retina (Feller, 2003; Tian and Copenhagen, 2003), superior colliculus (Zhao et al., 2006), lateral geniculate nucleus (Hooks and Chen, 2006; Levitt et al., 2001) and visual cortex (Hoy and Niell, 2015; Ko et al., 2013; Pecka et al., 2014).
  • beta 3 adrenergic receptor In the course of the present invention the role of the beta 3 adrenergic receptor and in particular of agonists or activators of this receptor has been identified as being able to promote the development of nerve tissue and accelerate neuronal and glial maturation.
  • the present invention instead relates to beta 3 adrenergic receptor agonists or activators for use in promoting neuronal and/or glial development in premature infants and in all those diseases in which the nervous system is compromised and the physiological repair mechanisms are insufficient or temporarily unacceptable (infants with asphyxia at birth, adults with stroke, degenerative diseases of the central and peripheral nervous system). None of the prior art documents describe or suggest this inductive effect of nerve tissue maturation exerted by beta 3 adrenergic receptor agonism/activation.
  • a further object of the invention is a pharmaceutical composition
  • a pharmaceutical composition comprising a beta-3 adrenergic receptor agonist and/or an activator of beta-3 adrenergic receptor expression as defined above and at least one pharmaceutically acceptable excipient, for use in the treatment and prevention of diseases of the central and/or peripheral nervous system and/or for use in promoting and/or accelerating neuronal and/or glial maturation.
  • Figure 3 Analysis of the density of both glial cells (S100-beta+) and neurons (PGP9.5+) in the mienteric plexus of the ascending colon.
  • salt as used herein is to be understood as any form of an active compound used according to this invention wherein said compound is in ionic form or is charged and coupled to a counterion (a cation or anion) or is in solution.
  • This definition also includes quaternary ammonium salts and active molecular complexes with other molecules and ions, in particular complexes formed by ionic interactions.
  • Physiologically acceptable salts are particularly encompassed by the definition. This term shall be understood to be equivalent to “pharmacologically acceptable salts” or “pharmacologically acceptable salts”.
  • physiologically tolerated acid salts are: hydrochloric acid, bromic acid, sulphuric acid, hydrobromide, monohydrobromide, monohydrochloride or hydrochloride, methanesulphonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, hippuric acid, picric acid and/or salts of aspartic acid.
  • physiologically tolerated base salts are the alkali and alkaline earth metal salts and the ammonium salts.
  • solvate is to be understood as any form of the active compound according to the invention wherein this compound is bound to another molecule (usually a polar solvent) by means of a non-covalent bonding, in particular including hydrates and alcoholates, such as methanolate, for example.
  • Newborn rats were treated every 12 hours with the beta 3 adrenergic receptor agonist, BRL37344, at a daily dose of 3 mg/kg starting on the day of birth through the fourteenth postnatal day by subcutaneous injections.
  • BRL37344 beta 3 adrenergic receptor agonist
  • Animals were observed every 4 hours, in order to be able to identify with certainty the moment of eye opening.
  • the animals were sacrificed by injection of lethal dose anesthetic, the colon was excised, which was subsequently washed in PBS, cut to 1 cm from the ileum and fixed in 4% buffered paraformaldehyde. Colon samples were then processed, embedded in paraffin and cut transversely into 5 pm sections.
  • Immunofluorescence analyses were performed on colon sections (at least 3 per sample). In particular, after rehydration the sections were boiled in citrate buffer at pH 6 for 10 minutes for the unmasking of specific binding sites, incubated with 3% bovine serum albumin (BSA) to saturate non-specific binding sites and then incubated for 12 hours at 4°C with the primary anti-PGP9.5 antibody (GTX634797, Genetex Irvine, California, USA), pan-neuronal marker (10.3390/cellsl0010047, 10.1007/s00418-023-02208-2), in 1 :300 dilution in phosphate buffer and 1% BSA, or with the primary anti-SlOO-beta antibody (GTX129573, Genetex Irvine, California, USA), glial cell marker (10.3390/cellsl0010047, 10.3389/fncel.2022.858347), in 1 :500 dilution in phosphate buffer and 1% BSA.
  • BSA bovine serum albumin
  • Immunofluorescence reactions were revealed using the appropriate secondary antibodies conjugated to the fluorochrome Alexa 488 or Alexa 594 (Jackson ImmunoResearch, Baltimore Pike, West Grove, PA 19390, USA) in 1 : 175 dilution in phosphate buffer and 1% BSA. The sections (at least 2 per sample) were then observed and digitized using the Leica Stellaris 5 confocal microscope, equipped with the Leica Plan Apo 63X/1.43NA immersion objective.
  • SH-SY5Y cells (ATCC, CRL-2266, human neuroblastoma cell line) were cultured in DMEM/F12 (Sigma- Aldrich, Milan, Italy) supplemented with 10% (v/v) fetal bovine serum (FBS) (Sigma-Aldrich), 250 U mL-1 penicillin G, and 250 pg mL-1 streptomycin (Sigma-Aldrich). Cells were maintained at 37 °C in a 5% CO2 humidified incubator, and the culture medium was changed twice a week.
  • FBS fetal bovine serum
  • the cells were fixed with buffered 4% paraformaldehyde for 10 minutes at room temperature (RT). Subsequently, membrane permeabilization was carried out using a 0.2% triton X-PBS solution for 1 hour at RT, followed by DAPI (Merck, Darmstadt, Germany) nuclear staining. The observations were made using a Leica Stellaris 5 confocal microscope (Leica Microsystem, Wetzlar, Germany), equipped with a Leica Plan Apo 63X/1.43NA oil immersion objective.
  • the images of DAPI-stained cells were digitized using the navigator tool to obtain three merged tiles for each sample.
  • the number of D API-positive cells was determined using the threshold tool of ImageJ bundled with Zulu OpenJDK 13.0.6 software (NIH, Bethesda, MD, USA).
  • the data were normalized to normoxia and expressed as fold change over normoxia ⁇ S.D.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un agoniste ou activateur du récepteur bêta-3 adrénergique destiné à être utilisé pour accélérer la maturation neuronale et dans le traitement et/ou la prévention de maladies du système nerveux central et périphérique, ainsi qu'une composition pharmaceutique à base de celui-ci.
PCT/EP2024/078317 2023-10-13 2024-10-09 Agonistes du récepteur bêta-3 adrénergique destinés à être utilisés pour favoriser la maturation du tissu nerveux Pending WO2025078388A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT102023000021417A IT202300021417A1 (it) 2023-10-13 2023-10-13 Agonisti o attivatori del recettore adrenergico beta-3
IT102023000021417 2023-10-13

Publications (1)

Publication Number Publication Date
WO2025078388A1 true WO2025078388A1 (fr) 2025-04-17

Family

ID=89474299

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/078317 Pending WO2025078388A1 (fr) 2023-10-13 2024-10-09 Agonistes du récepteur bêta-3 adrénergique destinés à être utilisés pour favoriser la maturation du tissu nerveux

Country Status (2)

Country Link
IT (1) IT202300021417A1 (fr)
WO (1) WO2025078388A1 (fr)

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0662324A1 (fr) 1987-09-15 1995-07-12 The Rowett Research Institute Utilisation d'agonistes bêta-adrénergiques pour le traitement des pertes de fonction des muscles striés
WO2011075777A1 (fr) * 2009-12-21 2011-06-30 The University Of Queensland Stimulation neuronale
CN102764438A (zh) 2012-01-30 2012-11-07 林曙光 β3肾上腺素受体激动剂的新用途
EP2891490A1 (fr) 2012-08-29 2015-07-08 Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III - CNIC Utilisation d'agonistes sélectifs de récepteurs bêta-3 adrénergiques pour le traitement de l'hypertension pulmonaire
WO2016097670A1 (fr) 2014-12-19 2016-06-23 Imperial Innovations Limited Procédés de mobilisation de populations de cellules souches
WO2017106584A1 (fr) * 2015-12-16 2017-06-22 The Board Of Trustees Of The Leland Stanford Junior University Traitement du système nerveux central et de troubles mentaux avec des agonistes des récepteurs bêta-3 adrénergiques
EP3377061A1 (fr) 2015-11-17 2018-09-26 Sorbonne Université Mirabégron pour le traitement de maladies rétiniennes
WO2019224788A1 (fr) 2018-05-23 2019-11-28 Urovant Sciences Gmbh Utilisation de vibegron pour traiter la douleur associée au syndrome du côlon irritable
WO2020204624A1 (fr) 2019-04-02 2020-10-08 제이투에이치바이오텍 주식회사 Composé de promédicament de mirabegron, et utilisation pharmaceutique de celui-ci pour traiter ou soulager la maladie de la vessie hyperactive
CN112336862B (zh) * 2020-11-04 2022-02-22 天津医科大学总医院 β3-肾上腺素能受体激动剂在制备治疗神经系统疾病的药物中的应用

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0662324A1 (fr) 1987-09-15 1995-07-12 The Rowett Research Institute Utilisation d'agonistes bêta-adrénergiques pour le traitement des pertes de fonction des muscles striés
WO2011075777A1 (fr) * 2009-12-21 2011-06-30 The University Of Queensland Stimulation neuronale
CN102764438A (zh) 2012-01-30 2012-11-07 林曙光 β3肾上腺素受体激动剂的新用途
EP2891490A1 (fr) 2012-08-29 2015-07-08 Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III - CNIC Utilisation d'agonistes sélectifs de récepteurs bêta-3 adrénergiques pour le traitement de l'hypertension pulmonaire
WO2016097670A1 (fr) 2014-12-19 2016-06-23 Imperial Innovations Limited Procédés de mobilisation de populations de cellules souches
EP3377061A1 (fr) 2015-11-17 2018-09-26 Sorbonne Université Mirabégron pour le traitement de maladies rétiniennes
US20180353482A1 (en) * 2015-11-17 2018-12-13 Sorbonne Universite Mirabegron for the treatment of retinal diseases
WO2017106584A1 (fr) * 2015-12-16 2017-06-22 The Board Of Trustees Of The Leland Stanford Junior University Traitement du système nerveux central et de troubles mentaux avec des agonistes des récepteurs bêta-3 adrénergiques
WO2019224788A1 (fr) 2018-05-23 2019-11-28 Urovant Sciences Gmbh Utilisation de vibegron pour traiter la douleur associée au syndrome du côlon irritable
WO2020204624A1 (fr) 2019-04-02 2020-10-08 제이투에이치바이오텍 주식회사 Composé de promédicament de mirabegron, et utilisation pharmaceutique de celui-ci pour traiter ou soulager la maladie de la vessie hyperactive
CN112336862B (zh) * 2020-11-04 2022-02-22 天津医科大学总医院 β3-肾上腺素能受体激动剂在制备治疗神经系统疾病的药物中的应用

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
CELLEK, S.THANGIAH, R.BASSIL, A. K.CAMPBELL, C. A.GRAY, K. M.STRETTON, J. L.LALUDE, O.VIVEKANANDAN, S.WHEELDON, A.WINCHESTER, W. J: "Demonstration of functional neuronal beta3-adrenoceptors within the enteric nervous system", GASTROENTEROLOGY, vol. 133, no. 1, 2007, pages 175 - 183, XP022135965, DOI: 10.1053/j.gastro.2007.05.009
DHANISHA J JHAVERI ET AL: "Norepinephrine Directly Activates Adult Hippocampal Precursors via B3-Adrenergic Receptors", THE JOURNAL OF NEUROSCIENCE, SOCIETY FOR NEUROSCIENCE, US, vol. 30, no. 7, 17 February 2010 (2010-02-17), pages 2795 - 2806, XP008163574, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.3780-09.2010 *
ELI LILLY: "Assay Guidance Manual Version 5.0", 2008, NIH CHEMICAL GENOMICS CENTER
GRUDELL, A. B.CAMILLERI, M.JENSEN, K. L.FOXX-ORENSTEIN, A. E.BURTON, D. D.RYKS, M. D.BAXTER, K. L.COX, D. S.DUKES, G. E.KELLEHER, : "Dose-response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health", AMERICAN JOURNAL OF PHYSIOLOGY. GASTROINTESTINAL AND LIVER PHYSIOLOGY, vol. 294, no. 5, 2008, pages G 1114 - G 1119, XP055443798, DOI: 10.1152/ajpgi.00051.2008
J CARDIOVASC PHARMACOL, vol. 69, 2017, pages 71 - 78
KROGSGAARD-LARSEN ET AL.: "Medicinal Chemistry and Drug Discovery", April 2002, HARWOOD ACADEMIC PUBLISHERS
MASOOD N. KHANJOHN W. FINDLAY: "Ligand-Binding Assays: Development, Validation, and Implementation in the Drug Development Arena", 2010, JOHN WILEY & SONS
SCHEMANN, M.HAFSI, N.MICHEL, KKOBER, O. I.WOLLMANN, J.LI, Q.ZELLER, F.LANGER, R.LEE, K.CELLEK, S.: "The beta3-adrenoceptor agonist GW427353 (Solabegron) decreases excitability of human enteric neurons via release of somatostatin", GASTROENTEROLOGY, vol. 138, no. 1, 2010, pages 266 - 274, XP027471274, DOI: 10.1053/j.gastro.2009.09.046
TAKUSAGAWA, S.USHIGOME, F.NEMOTO, H.TAKAHASHI, YLI, Q.KERBUSCH, V.MIYASHITA, A.IWATSUBO, T.USUI, T.: "Intestinal absorption mechanism of mirabegron, a potent and selective β -adrenoceptor agonist: involvement of human efflux and/or influx transport systems", MOLECULAR PHARMACEUTICS, vol. 10, no. 5, 2013, pages 1783 - 1794

Also Published As

Publication number Publication date
IT202300021417A1 (it) 2025-04-13

Similar Documents

Publication Publication Date Title
JP6608309B2 (ja) Ｃｍｔ及び関連疾患の処置のための新規な治療的アプローチ
US20100178277A1 (en) Methods and compositions for stimulating cells
WO2009135091A1 (fr) Utilisation d’asénapine et composés associés pour le traitement de maladies ou de conditions neurales ou non
JP6893917B2 (ja) 神経変性疾患の処置
KR102527378B1 (ko) 2'-fl을 함유하는 도파민 감소로 말미암아 발생하는 질환의 개선, 예방 또는 치료용 조성물
JP2003535062A (ja) Ｊｎｋ阻害剤としての（二置換フェニル）ピリミジニルイミダゾール誘導体の使用
JPWO2021066144A1 (ja) ヘテロシクリデンアセトアミド誘導体含有医薬
US20230100102A1 (en) Cxcr7 inhibitors for the treatment of cancer
WO2025078388A1 (fr) Agonistes du récepteur bêta-3 adrénergique destinés à être utilisés pour favoriser la maturation du tissu nerveux
AU2019247871A1 (en) Compositions and methods for increasing remyelination
WO2016145219A1 (fr) Traitement de neuropathies périphériques
JP6709493B2 (ja) 進行性骨化性線維異形成症治療剤
CA2540151A1 (fr) Chelerythrine, analogues de celle-ci et leur utilisation pour traiter un trouble et d'autres troubles cognitifs
TWI721274B (zh) 組合物用於製備治療發育性視網膜血管疾病的藥物之用途
CN115487183B (zh) 萘脲类化合物在制备治疗翼状胬肉的药物中的应用
US20230201168A1 (en) New therapy for the treatment of tumors
KR101367896B1 (ko) Ｍｓｍ을 유효성분으로 포함하는 뼈 성장 활성용 조성물
WO2002024191A1 (fr) Medicament permettant de traiter et de prevenir la myopie
JP6791977B2 (ja) 骨格筋の肥大剤としてのフロスタン−３オール誘導体
US20250319078A1 (en) Method for synergistic enhancement of remyelination via modulation of rxr and a heterodimeric partner
JP2017145215A (ja) 神経新生促進剤及びその使用
US20200063098A1 (en) Use of n-butylidenephthalide in dopaminergic progenitor cell transplantation
US20250195547A1 (en) Compositions and methods of treatment for congenital diarrheal disorder
WO2025021911A1 (fr) Agonistes du récepteur bêta-3 adrénergique pour la prévention et le traitement de la fibrose pulmonaire
WO2011103563A1 (fr) Procédés et compositions pour inhiber et prévenir la croissance de mastocytes malins

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24786808

Country of ref document: EP

Kind code of ref document: A1