EP1865943A1 - Utilisation de l'acetyl-leucine pour la preparation d'un medicament destine au traitement de troubles de l'equilibre - Google Patents
Utilisation de l'acetyl-leucine pour la preparation d'un medicament destine au traitement de troubles de l'equilibreInfo
- Publication number
- EP1865943A1 EP1865943A1 EP06725137A EP06725137A EP1865943A1 EP 1865943 A1 EP1865943 A1 EP 1865943A1 EP 06725137 A EP06725137 A EP 06725137A EP 06725137 A EP06725137 A EP 06725137A EP 1865943 A1 EP1865943 A1 EP 1865943A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- leucine
- acetyl
- unilateral
- syndromes
- 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.)
- Withdrawn
Links
- 229960000669 acetylleucine Drugs 0.000 title claims abstract description 30
- WXNXCEHXYPACJF-ZETCQYMHSA-N N-acetyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-N 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 title claims abstract description 7
- 229940079593 drug Drugs 0.000 title abstract 2
- 208000012639 Balance disease Diseases 0.000 title description 3
- 230000001720 vestibular Effects 0.000 claims abstract description 34
- 230000006735 deficit Effects 0.000 claims abstract description 20
- 230000001154 acute effect Effects 0.000 claims abstract description 15
- 238000012360 testing method Methods 0.000 claims abstract description 11
- 208000011580 syndromic disease Diseases 0.000 claims description 17
- 210000000860 cochlear nerve Anatomy 0.000 claims description 7
- 210000005036 nerve Anatomy 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000002173 dizziness Diseases 0.000 claims description 3
- 206010030113 Oedema Diseases 0.000 claims description 2
- 230000006835 compression Effects 0.000 claims description 2
- 238000007906 compression Methods 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims 1
- WXNXCEHXYPACJF-UHFFFAOYSA-N N-acetyl-leucine Chemical compound CC(C)CC(C(O)=O)NC(C)=O WXNXCEHXYPACJF-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 14
- 238000011282 treatment Methods 0.000 description 12
- 210000002569 neuron Anatomy 0.000 description 10
- 239000012528 membrane Substances 0.000 description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
- 239000000902 placebo Substances 0.000 description 8
- 229940068196 placebo Drugs 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 208000012886 Vertigo Diseases 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 231100000889 vertigo Toxicity 0.000 description 7
- 230000010355 oscillation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 3
- 230000001144 postural effect Effects 0.000 description 3
- 238000002611 posturography Methods 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 210000000613 ear canal Anatomy 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000002310 reflectometry Methods 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 208000000187 Abnormal Reflex Diseases 0.000 description 1
- 208000001111 Bilateral Vestibulopathy Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010021089 Hyporeflexia Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003060 endolymph Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000000256 facial nerve Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- -1 lyocs Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 230000003565 oculomotor Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000272 proprioceptive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000002480 semicircular canal Anatomy 0.000 description 1
- 210000003949 semicircular duct Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 210000003273 vestibular nerve Anatomy 0.000 description 1
- 201000000200 vestibular neuronitis Diseases 0.000 description 1
- 210000004440 vestibular nuclei Anatomy 0.000 description 1
- 210000001213 vestibule labyrinth Anatomy 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
- A61K31/185—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
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- acetyl-leucine which has no effect in a population of patients exhibiting a vestibular function abolished before the neurotomy, makes it possible to accelerate the compensation observed in a population. of patients with residual vestibular function.
- the syndromes are acute intermittent deafferentiation syndromes resulting from an imbalance in the circulation of the predominantly unilateral nerve impulses in the auditory nerve.
- the syndromes are acute intermittent deafferentiation syndromes following any event leading to the unilateral disruption of the circulation of the nerve impulse in the auditory nerve accompanied by dizziness.
- Acute deafferentiation syndromes may be consecutive to unilateral surgical neurotomy and acute intermittent deafferentiation syndromes may be consecutive, especially to unilateral neurotomy selected from the group comprising traumatic unilateral neurotomies, unilateral neurotomies associated with acute auditory nerve ischemia , unilateral neurotomies due to extrinsic compressions, unilateral neurotomies due to structural edemas and unilateral neurotomies following endogenous viral attacks.
- the vestibular deficit is assessed by the caloric test which provides information on vestibular reflectivity, i.e. the ability of the vestibule to respond to stimulation (caused by irrigation of the external auditory canal with hot water and then cold).
- f acetyl-leucine may be administered orally at doses between 500 mg and 10 g per day, advantageously between 1 and 2 g per day. It can also be administered intravenously at a rate of 500 mg to 1 g per day continuously.
- the deficit is measured according to the methods described by Les vertiges and the practitioner of P. Tran Ba Huy and C. De Waele (Coll. Pathologie Sciences Formation, Ed. John Libbey Eurotext, Paris, 1996) and by Les Vertiges by G. Rancurel, 0. Sterkers, E. Vitte, Preface by G. Freyss (Ed. Méd. Spécia., 1989 ).
- the tonic postural activity results in an overall attitude of the human body, fixing the different joints in determined positions, interdependent with each other, mainly in response to the forces of gravity.
- Vestibular afferents, extrinsic ocular musculature, proprioceptive afferents and finally visual afferents play a major role in maintaining the standing position. Standing, at rest, the subject is never perfectly still, he oscillates constantly.
- statokinesigram The movements of the subject's center of gravity during a given time are called the statokinesigram. This plot allows a study of the amplitudes of the oscillations, of the surface described by them. The "antero-posterior" oscillations can be separated from the “right-left” oscillations. 3.2. Results.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0502696A FR2883180B1 (fr) | 2005-03-18 | 2005-03-18 | Utilisation de l'acetyl-leucine pour la preparation d'un medicament destine au traitement de troubles de l'equilibre |
| PCT/EP2006/060841 WO2006097527A1 (fr) | 2005-03-18 | 2006-03-17 | Utilisation de l'acétyl-leucine pour la préparation d'un médicament destiné au traitement de troubles de l'équilibre |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1865943A1 true EP1865943A1 (fr) | 2007-12-19 |
Family
ID=35134794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP06725137A Withdrawn EP1865943A1 (fr) | 2005-03-18 | 2006-03-17 | Utilisation de l'acetyl-leucine pour la preparation d'un medicament destine au traitement de troubles de l'equilibre |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20080108702A1 (https=) |
| EP (1) | EP1865943A1 (https=) |
| JP (2) | JP2008533102A (https=) |
| CA (1) | CA2601101A1 (https=) |
| FR (1) | FR2883180B1 (https=) |
| WO (1) | WO2006097527A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TN2010000251A1 (fr) * | 2010-06-03 | 2011-11-11 | Rekik Raouf | N-acetyl-dl-leucine medicament neuro et retino protecteur |
| ES2994242T3 (en) * | 2016-04-19 | 2025-02-05 | Intrabio Ltd | Acetyl-leucine or a pharmaceutically acceptable salt thereof for improved mobility |
| DK3359146T3 (en) * | 2016-08-11 | 2019-04-08 | Intrabio Ltd | PHARMACEUTICAL COMPOSITIONS AND USES AGAINST LYSOSOMAL STORAGE DISEASES |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3455638B2 (ja) * | 1996-02-23 | 2003-10-14 | 株式会社モリタ製作所 | 平衡機能検査装置 |
| FR2749512B1 (fr) * | 1996-06-10 | 1999-08-13 | Pf Medicament | Utilisation de l'acetyl dl leucine pour le traitement des tremblements |
| ID29095A (id) * | 1998-10-02 | 2001-07-26 | Novartis Ag Cs | Antagonis mglur5 untuk pengobatan rasa sakit dan kegelisahan |
| WO2004096256A1 (en) * | 2001-01-23 | 2004-11-11 | The United States Of America, As Represented By The Secretary Of The Navy | Methods for preventing and treating loss of balance function due to oxidative stress |
-
2005
- 2005-03-18 FR FR0502696A patent/FR2883180B1/fr not_active Expired - Lifetime
-
2006
- 2006-03-17 CA CA002601101A patent/CA2601101A1/fr not_active Abandoned
- 2006-03-17 WO PCT/EP2006/060841 patent/WO2006097527A1/fr not_active Ceased
- 2006-03-17 US US11/886,419 patent/US20080108702A1/en not_active Abandoned
- 2006-03-17 JP JP2008501329A patent/JP2008533102A/ja active Pending
- 2006-03-17 EP EP06725137A patent/EP1865943A1/fr not_active Withdrawn
-
2013
- 2013-04-09 JP JP2013081360A patent/JP2013173759A/ja active Pending
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2006097527A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008533102A (ja) | 2008-08-21 |
| FR2883180B1 (fr) | 2007-05-25 |
| WO2006097527A1 (fr) | 2006-09-21 |
| CA2601101A1 (fr) | 2006-09-21 |
| FR2883180A1 (fr) | 2006-09-22 |
| JP2013173759A (ja) | 2013-09-05 |
| US20080108702A1 (en) | 2008-05-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20070924 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR |
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| AX | Request for extension of the european patent |
Extension state: AL BA HR MK YU |
|
| 17Q | First examination report despatched |
Effective date: 20090622 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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| 18D | Application deemed to be withdrawn |
Effective date: 20141001 |