CZ291349B6 - Léčivo pro prevenci nebo léčbu závislosti na benzodiazepinech - Google Patents

Léčivo pro prevenci nebo léčbu závislosti na benzodiazepinech Download PDF

Info

Publication number: CZ291349B6
Authority: CZ; Czechia
Prior art keywords: melatonin; medicament; benzodiazepine; treatment; preparation
Prior art date: 1995-02-01

Application number

CZ19972405A

Other languages

Czech (cs)

English (en)

Other versions

CZ240597A3 (cs

Inventor

Nava Zisapel

Original Assignee

Neurim Pharmaceuticals Ltd.

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.)

1995-02-01

Filing date

1996-01-29

Publication date

2003-02-12

1995-02-01 Priority claimed from US08/381,535 external-priority patent/US6469044B1/en

1996-01-29 Application filed by Neurim Pharmaceuticals Ltd. filed Critical Neurim Pharmaceuticals Ltd.

1998-01-14 Publication of CZ240597A3 publication Critical patent/CZ240597A3/cs

2003-02-12 Publication of CZ291349B6 publication Critical patent/CZ291349B6/cs

Links

229940049706 benzodiazepine Drugs 0.000 title claims abstract description 100
239000003814 drug Substances 0.000 title claims abstract description 95
238000011282 treatment Methods 0.000 title claims abstract description 56
206010012335 Dependence Diseases 0.000 title claims description 9
150000001557 benzodiazepines Chemical class 0.000 title description 20
238000011321 prophylaxis Methods 0.000 title 1
DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims abstract description 133
YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims abstract description 130
229960003987 melatonin Drugs 0.000 claims abstract description 130
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims abstract description 80
230000002265 prevention Effects 0.000 claims abstract description 12
238000004519 manufacturing process Methods 0.000 claims abstract description 8
229940079593 drug Drugs 0.000 claims description 43
238000002360 preparation method Methods 0.000 claims description 17
208000024891 symptom Diseases 0.000 claims description 17
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 15
229960003529 diazepam Drugs 0.000 claims description 15
239000003607 modifier Substances 0.000 claims description 13
102000001419 Melatonin receptor Human genes 0.000 claims description 10
108050009605 Melatonin receptor Proteins 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 10
238000013270 controlled release Methods 0.000 claims description 9
ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 claims description 8
229960004535 oxazepam Drugs 0.000 claims description 8
DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 claims description 6
229960004391 lorazepam Drugs 0.000 claims description 6
SDWAACKJISOIGZ-UHFFFAOYSA-N 7-chloro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one;2,2,2-trichloroethane-1,1-diol Chemical compound OC(O)C(Cl)(Cl)Cl.N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SDWAACKJISOIGZ-UHFFFAOYSA-N 0.000 claims description 5
WYCLKVQLVUQKNZ-UHFFFAOYSA-N Halazepam Chemical compound N=1CC(=O)N(CC(F)(F)F)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 WYCLKVQLVUQKNZ-UHFFFAOYSA-N 0.000 claims description 5
MWQCHHACWWAQLJ-UHFFFAOYSA-N Prazepam Chemical compound O=C1CN=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2N1CC1CC1 MWQCHHACWWAQLJ-UHFFFAOYSA-N 0.000 claims description 5
SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 claims description 5
229960002200 flunitrazepam Drugs 0.000 claims description 5
229960003528 flurazepam Drugs 0.000 claims description 5
SAADBVWGJQAEFS-UHFFFAOYSA-N flurazepam Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F SAADBVWGJQAEFS-UHFFFAOYSA-N 0.000 claims description 5
229960002158 halazepam Drugs 0.000 claims description 5
230000003340 mental effect Effects 0.000 claims description 5
229960004856 prazepam Drugs 0.000 claims description 5
229960003188 temazepam Drugs 0.000 claims description 5
PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 claims description 4
239000002671 adjuvant Substances 0.000 claims description 4
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 claims description 4
229960004538 alprazolam Drugs 0.000 claims description 4
229960004782 chlordiazepoxide Drugs 0.000 claims description 4
ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 claims description 4
JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 claims description 4
229960003386 triazolam Drugs 0.000 claims description 4
230000007423 decrease Effects 0.000 claims description 3
-1 chlorideazepoxide Chemical compound 0.000 claims description 2
239000002904 solvent Substances 0.000 claims 2
102000013138 Drug Receptors Human genes 0.000 claims 1
108010065556 Drug Receptors Proteins 0.000 claims 1
230000027455 binding Effects 0.000 description 24
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241001465754 Metazoa Species 0.000 description 13
230000000694 effects Effects 0.000 description 13
239000000203 mixture Substances 0.000 description 12
239000003826 tablet Substances 0.000 description 12
QQEILXDLZRLTME-UHFFFAOYSA-N 6-sulfatoxymelatonin Chemical compound C1=C(OS(O)(=O)=O)C(OC)=CC2=C1NC=C2CCNC(C)=O QQEILXDLZRLTME-UHFFFAOYSA-N 0.000 description 9
238000009472 formulation Methods 0.000 description 8
206010022437 insomnia Diseases 0.000 description 8
210000002700 urine Anatomy 0.000 description 8
241000700159 Rattus Species 0.000 description 7
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 7
210000004556 brain Anatomy 0.000 description 6
230000002035 prolonged effect Effects 0.000 description 6
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230000001684 chronic effect Effects 0.000 description 5
239000003326 hypnotic agent Substances 0.000 description 5
230000000147 hypnotic effect Effects 0.000 description 5
230000003860 sleep quality Effects 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
230000003247 decreasing effect Effects 0.000 description 4
239000003651 drinking water Substances 0.000 description 4
235000020188 drinking water Nutrition 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
238000000034 method Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
230000033764 rhythmic process Effects 0.000 description 4
230000004622 sleep time Effects 0.000 description 4
RSTKLPZEZYGQPY-UHFFFAOYSA-N 3-(indol-3-yl)pyruvic acid Chemical compound C1=CC=C2C(CC(=O)C(=O)O)=CNC2=C1 RSTKLPZEZYGQPY-UHFFFAOYSA-N 0.000 description 3
229920003134 Eudragit® polymer Polymers 0.000 description 3
241000282412 Homo Species 0.000 description 3
241000282414 Homo sapiens Species 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
210000002745 epiphysis Anatomy 0.000 description 3
230000029142 excretion Effects 0.000 description 3
230000006872 improvement Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
230000000422 nocturnal effect Effects 0.000 description 3
239000000902 placebo Substances 0.000 description 3
229940068196 placebo Drugs 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
238000009256 replacement therapy Methods 0.000 description 3
230000028327 secretion Effects 0.000 description 3
230000004620 sleep latency Effects 0.000 description 3
229920003159 Eudragit® RS 100 Polymers 0.000 description 2
102000004300 GABA-A Receptors Human genes 0.000 description 2
108090000839 GABA-A Receptors Proteins 0.000 description 2
206010019233 Headaches Diseases 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
241000473945 Theria <moth genus> Species 0.000 description 2
230000002411 adverse Effects 0.000 description 2
230000000949 anxiolytic effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000003350 crude synaptosomal preparation Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
231100000869 headache Toxicity 0.000 description 2
230000036541 health Effects 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
206010027599 migraine Diseases 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
239000004925 Acrylic resin Substances 0.000 description 1
229920000178 Acrylic resin Polymers 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
206010052804 Drug tolerance Diseases 0.000 description 1
206010019133 Hangover Diseases 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
FJDDSMSDZHURBJ-UHFFFAOYSA-N N-[2-(2-iodo-5-methoxy-1H-indol-3-yl)ethyl]acetamide Chemical compound COC1=CC=C2NC(I)=C(CCNC(C)=O)C2=C1 FJDDSMSDZHURBJ-UHFFFAOYSA-N 0.000 description 1
102000001490 Opioid Peptides Human genes 0.000 description 1
108010093625 Opioid Peptides Proteins 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
208000034972 Sudden Infant Death Diseases 0.000 description 1
206010042440 Sudden infant death syndrome Diseases 0.000 description 1
229940123445 Tricyclic antidepressant Drugs 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000036528 appetite Effects 0.000 description 1
235000019789 appetite Nutrition 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000037396 body weight Effects 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
238000007580 dry-mixing Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
238000005286 illumination Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
210000001767 medulla oblongata Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
230000003533 narcotic effect Effects 0.000 description 1
238000010984 neurological examination Methods 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
210000004560 pineal gland Anatomy 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000009101 premedication Methods 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000008521 reorganization Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
230000004799 sedative–hypnotic effect Effects 0.000 description 1
239000003772 serotonin uptake inhibitor Substances 0.000 description 1
238000001629 sign test Methods 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
230000004617 sleep duration Effects 0.000 description 1
230000008454 sleep-wake cycle Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
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230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
238000012360 testing method Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
239000003029 tricyclic antidepressant agent Substances 0.000 description 1
230000007306 turnover Effects 0.000 description 1
238000005353 urine analysis Methods 0.000 description 1
230000002618 waking effect Effects 0.000 description 1
230000003313 weakening effect Effects 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
- 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

Landscapes

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

CZ19972405A 1995-02-01 1996-01-29 Léčivo pro prevenci nebo léčbu závislosti na benzodiazepinech CZ291349B6 (cs)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/381,535 US6469044B1 (en)	1995-02-01	1995-02-01	Method for treating patients suffering from drug dependencies which lead to plasma melationin deficiencies
EP95303853A EP0724878B1 (en)	1995-02-01	1995-06-06	Use of melatonin for treating patients suffering from drug dependencies

Publications (2)

Publication Number	Publication Date
CZ240597A3 CZ240597A3 (cs)	1998-01-14
CZ291349B6 true CZ291349B6 (cs)	2003-02-12

Family

ID=26140195

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CZ19972405A CZ291349B6 (cs)	1995-02-01	1996-01-29	Léčivo pro prevenci nebo léčbu závislosti na benzodiazepinech

Country Status (22)

Country	Link
JP (1)	JP4516159B2 (2)
CN (1)	CN1083263C (2)
AT (1)	AT408188B (2)
AU (1)	AU695366B2 (2)
BG (1)	BG62876B1 (2)
BR (1)	BR9607169A (2)
CZ (1)	CZ291349B6 (2)
DK (1)	DK176081B1 (2)
EE (1)	EE03384B1 (2)
FI (1)	FI119586B (2)
IS (1)	IS1980B (2)
LU (1)	LU90118B1 (2)
LV (1)	LV11940B (2)
MD (1)	MD1716C2 (2)
NO (1)	NO312814B1 (2)
NZ (1)	NZ298878A (2)
PL (1)	PL183148B1 (2)
SI (1)	SI9620022A (2)
SK (1)	SK284521B6 (2)
TR (1)	TR199700723T1 (2)
TW (1)	TW483757B (2)
WO (1)	WO1996023496A1 (2)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HK1052655A1 (zh)	2000-01-05	2003-09-26	纽里姆药品(1991)有限公司	用於治療對抗高血壓藥的抗藥性和相關病症的方法和製劑
IL149377A (en) *	2002-04-28	2012-10-31	Neurim Pharma 1991	Pharmaceutical formulation comprising melatonin for the potentiation of the effect of hypnotic compounds
US9119846B2 (en)	2003-04-29	2015-09-01	Neurim Pharmaceuticals (1991) Ltd.	Method and composition for enhancing cognition in alzheimer's patients
IL155666A (en)	2003-04-29	2013-12-31	Neurim Pharma 1991	Insomnia treatment
CA3085116C (en)	2012-01-26	2022-07-19	Vanda Pharmaceuticals Inc.	Treatment of circadian rhythm disorders
US11918557B2 (en)	2012-01-26	2024-03-05	Vanda Pharmaceuticals Inc.	Treatment of circadian rhythm disorders
KR102148990B1 (ko)	2012-12-18	2020-08-27	반다 파마슈티칼즈, 인코퍼레이티드.	일주기 리듬 장애의 치료
US10376487B2 (en)	2013-11-12	2019-08-13	Vanda Pharmaceuticals Inc.	Method of treatment
US11090285B2 (en)	2013-11-12	2021-08-17	Vanda Pharmaceuticals Inc	Treatment of circadian rhythm disorders
MX386987B (es) *	2016-10-31	2025-03-19	Neurim Pharma 1991	Mini-tabletas de melatonina y métodos de fabricación de las mismas.

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0518468B1 (en) *	1991-05-09	1999-06-30	Neurim Pharmaceuticals (1991) Limited	Melatonin containing compositions
IT1251544B (it) *	1991-05-13	1995-05-17	Gabriele Biella	Composizioni farmaceutiche attive nella terapia dei disturbi del sonno comprendenti melatonina o un suo derivato in associazione con un derivato benzodiazepinico

1996
- 1996-01-29 WO PCT/IB1996/000082 patent/WO1996023496A1/en not_active Ceased
- 1996-01-29 AT AT0901396A patent/AT408188B/de not_active IP Right Cessation
- 1996-01-29 BR BR9607169A patent/BR9607169A/pt not_active Application Discontinuation
- 1996-01-29 SK SK1030-97A patent/SK284521B6/sk unknown
- 1996-01-29 MD MD97-0254A patent/MD1716C2/ro not_active IP Right Cessation
- 1996-01-29 PL PL96321630A patent/PL183148B1/pl unknown
- 1996-01-29 EE EE9700166A patent/EE03384B1/xx not_active IP Right Cessation
- 1996-01-29 NZ NZ298878A patent/NZ298878A/xx not_active IP Right Cessation
- 1996-01-29 TR TR97/00723T patent/TR199700723T1/xx unknown
- 1996-01-29 CN CN96191750A patent/CN1083263C/zh not_active Expired - Lifetime
- 1996-01-29 SI SI9620022A patent/SI9620022A/sl not_active IP Right Cessation
- 1996-01-29 AU AU44574/96A patent/AU695366B2/en not_active Expired
- 1996-01-29 JP JP52338596A patent/JP4516159B2/ja not_active Expired - Lifetime
- 1996-01-29 CZ CZ19972405A patent/CZ291349B6/cs not_active IP Right Cessation
- 1996-04-12 TW TW085104319A patent/TW483757B/zh not_active IP Right Cessation
1997
- 1997-07-24 LV LVP-97-144A patent/LV11940B/en unknown
- 1997-07-25 IS IS4532A patent/IS1980B/is unknown
- 1997-07-30 BG BG101803A patent/BG62876B1/bg unknown
- 1997-07-30 DK DK199700896A patent/DK176081B1/da not_active IP Right Cessation
- 1997-07-31 FI FI973185A patent/FI119586B/fi not_active IP Right Cessation
- 1997-07-31 NO NO19973531A patent/NO312814B1/no not_active IP Right Cessation
- 1997-08-01 LU LU90118A patent/LU90118B1/fr active

Also Published As

Publication number	Publication date
FI973185A0 (fi)	1997-07-31
SK284521B6 (sk)	2005-05-05
AT408188B (de)	2001-09-25
AU695366B2 (en)	1998-08-13
PL183148B1 (pl)	2002-05-31
NO973531L (no)	1997-09-30
SI9620022A (sl)	1998-10-31
PL321630A1 (en)	1997-12-08
CN1172431A (zh)	1998-02-04
FI119586B (fi)	2009-01-15
BR9607169A (pt)	1997-11-11
MX9705856A (es)	1998-07-31
NZ298878A (en)	1999-05-28
TW483757B (en)	2002-04-21
BG62876B1 (bg)	2000-10-31
WO1996023496A1 (en)	1996-08-08
LV11940B (en)	1998-05-20
MD970254A (en)	1999-05-31
DK176081B1 (da)	2006-04-18
BG101803A (en)	1998-04-30
EE03384B1 (et)	2001-04-16
DK89697A (da)	1997-07-30
CZ240597A3 (cs)	1998-01-14
EE9700166A (et)	1998-02-16
JPH10513177A (ja)	1998-12-15
JP4516159B2 (ja)	2010-08-04
NO973531D0 (no)	1997-07-31
AU4457496A (en)	1996-08-21
LU90118B1 (fr)	1997-11-13
MD1716B2 (en)	2001-08-31
IS1980B (is)	2005-01-14
ATA901396A (de)	2001-02-15
CN1083263C (zh)	2002-04-24
SK103097A3 (en)	1998-01-14
IS4532A (is)	1997-07-25
NO312814B1 (no)	2002-07-08
TR199700723T1 (xx)	1998-02-21
FI973185L (fi)	1997-09-30
MD1716C2 (ro)	2002-02-28
LV11940A (lv)	1998-01-20

Legal Events

Date	Code	Title	Description
2000-06-30	PD00	Pending as of 2000-06-30 in czech republic
2016-02-10	MK4A	Patent expired	Effective date: 20160129

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