BG62876B1 - Използване на мелатонин за лечение на пациенти,страдащи от лекарствена зависимост - Google Patents

Използване на мелатонин за лечение на пациенти,страдащи от лекарствена зависимост Download PDF

Info

Publication number: BG62876B1
Authority: BG; Bulgaria
Prior art keywords: melatonin; benzodiazepine; treatment; daily; use according
Prior art date: 1995-02-01

Application number

BG101803A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG101803A (en

Inventor

Nava Zisapel

Original Assignee

Neurim Pharmaceuticals (1991) 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

1997-07-30

Publication date

2000-10-31

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

1997-07-30 Application filed by Neurim Pharmaceuticals (1991) Ltd. filed Critical Neurim Pharmaceuticals (1991) Ltd.

1998-04-30 Publication of BG101803A publication Critical patent/BG101803A/xx

2000-10-31 Publication of BG62876B1 publication Critical patent/BG62876B1/bg

Links

DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 title claims abstract description 117
YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 title claims abstract description 114
229960003987 melatonin Drugs 0.000 title claims abstract description 114
239000003814 drug Substances 0.000 title claims abstract description 56
206010012335 Dependence Diseases 0.000 title abstract description 10
229940049706 benzodiazepine Drugs 0.000 claims abstract description 79
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims abstract description 63
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
230000002265 prevention Effects 0.000 claims abstract description 6
229940079593 drug Drugs 0.000 claims description 50
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
239000000203 mixture Substances 0.000 claims description 13
238000013270 controlled release Methods 0.000 claims description 11
102000001419 Melatonin receptor Human genes 0.000 claims description 10
108050009605 Melatonin receptor Proteins 0.000 claims description 10
239000003607 modifier Substances 0.000 claims description 9
238000009472 formulation Methods 0.000 claims description 7
239000002552 dosage form Substances 0.000 claims description 6
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 6
229960004535 oxazepam Drugs 0.000 claims description 6
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 5
229960002200 flunitrazepam Drugs 0.000 claims description 5
229960004391 lorazepam Drugs 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 4
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 4
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
239000000654 additive Substances 0.000 claims description 4
230000000996 additive effect Effects 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
229960004362 clorazepate Drugs 0.000 claims description 4
XDDJGVMJFWAHJX-UHFFFAOYSA-N clorazepic acid Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)O)N=C1C1=CC=CC=C1 XDDJGVMJFWAHJX-UHFFFAOYSA-N 0.000 claims description 4
230000007423 decrease Effects 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
229960002158 halazepam Drugs 0.000 claims description 4
229960004856 prazepam Drugs 0.000 claims description 4
229960003528 flurazepam Drugs 0.000 claims description 3
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 3
230000002688 persistence Effects 0.000 claims description 3
206010052804 Drug tolerance Diseases 0.000 claims description 2
230000026781 habituation Effects 0.000 claims description 2
230000027455 binding Effects 0.000 description 23
150000001557 benzodiazepines Chemical class 0.000 description 15
230000000694 effects Effects 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 10
241001465754 Metazoa Species 0.000 description 10
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210000002700 urine Anatomy 0.000 description 9
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208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 7
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210000004556 brain Anatomy 0.000 description 6
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239000003651 drinking water Substances 0.000 description 5
235000020188 drinking water Nutrition 0.000 description 5
239000006187 pill Substances 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
229920003134 Eudragit® polymer Polymers 0.000 description 4
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
230000002618 waking effect 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
241000282412 Homo 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
230000029142 excretion Effects 0.000 description 3
230000006872 improvement Effects 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
238000000034 method Methods 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
230000033764 rhythmic process Effects 0.000 description 3
230000028327 secretion Effects 0.000 description 3
230000004620 sleep latency Effects 0.000 description 3
230000004622 sleep time Effects 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
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
241000282414 Homo sapiens Species 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
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 description 2
230000000949 anxiolytic effect Effects 0.000 description 2
210000003710 cerebral cortex Anatomy 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
238000003350 crude synaptosomal preparation Methods 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
206010013663 drug dependence Diseases 0.000 description 2
-1 flunitarazepam Chemical compound 0.000 description 2
231100000869 headache Toxicity 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
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 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
238000012423 maintenance Methods 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
210000004560 pineal gland Anatomy 0.000 description 2
239000000902 placebo Substances 0.000 description 2
229940068196 placebo Drugs 0.000 description 2
230000003449 preventive effect Effects 0.000 description 2
230000007425 progressive decline Effects 0.000 description 2
238000003127 radioimmunoassay Methods 0.000 description 2
238000009256 replacement therapy Methods 0.000 description 2
230000003860 sleep quality Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
208000011117 substance-related disease Diseases 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
229960003188 temazepam Drugs 0.000 description 2
238000012360 testing method Methods 0.000 description 2
210000000707 wrist Anatomy 0.000 description 2
239000004925 Acrylic resin Substances 0.000 description 1
229920000178 Acrylic resin Polymers 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
206010013654 Drug abuse Diseases 0.000 description 1
229920003159 Eudragit® RS 100 Polymers 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
108010093625 Opioid Peptides Proteins 0.000 description 1
102000001490 Opioid Peptides Human genes 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
206010048010 Withdrawal syndrome Diseases 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000003444 anaesthetic effect 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
230000010455 autoregulation Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process Effects 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
230000008859 change Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000003759 clinical diagnosis Methods 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000007580 dry-mixing Methods 0.000 description 1
230000000517 effect on sleep Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
230000006870 function Effects 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
230000001771 impaired effect Effects 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000007774 longterm Effects 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002483 medication Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
238000010984 neurological examination Methods 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
230000000422 nocturnal effect Effects 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 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
238000000554 physical therapy Methods 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
230000001817 pituitary effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000004321 preservation Methods 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011084 recovery Methods 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
238000012552 review Methods 0.000 description 1
230000004799 sedative–hypnotic effect Effects 0.000 description 1
230000035807 sensation Effects 0.000 description 1
239000003772 serotonin uptake inhibitor Substances 0.000 description 1
208000019116 sleep disease Diseases 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
238000006467 substitution reaction Methods 0.000 description 1
230000001629 suppression Effects 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
229960003386 triazolam Drugs 0.000 description 1
JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 1
239000003029 tricyclic antidepressant agent Substances 0.000 description 1
230000007306 turnover Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Addiction (AREA)
Psychiatry (AREA)
Toxicology (AREA)
Anesthesiology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

BG101803A 1995-02-01 1997-07-30 Използване на мелатонин за лечение на пациенти,страдащи от лекарствена зависимост BG62876B1 (bg)

Applications Claiming Priority (3)

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 (de)	1995-02-01	1995-06-06	Verwendung von Melatonin zur Behandlung von Patienten die an Drogenabhängigkeit leiden
PCT/IB1996/000082 WO1996023496A1 (en)	1995-02-01	1996-01-29	Use of melatonin for treating patients suffering from drug addiction

Publications (2)

Publication Number	Publication Date
BG101803A BG101803A (en)	1998-04-30
BG62876B1 true BG62876B1 (bg)	2000-10-31

Family

ID=26140195

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG101803A BG62876B1 (bg)	1995-02-01	1997-07-30	Използване на мелатонин за лечение на пациенти,страдащи от лекарствена зависимост

Country Status (22)

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

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL150190A0 (en)	2000-01-05	2002-12-01	Neurim Pharma 1991	Method and formulation for treating resistance to antihypertensives and related conditions
IL149377A (en) *	2002-04-28	2012-10-31	Neurim Pharma 1991	Pharmaceutical formulation comprising melatonin for the potentiation of the effect of hypnotic compounds
IL155666A (en)	2003-04-29	2013-12-31	Neurim Pharma 1991	Insomnia treatment
US9119846B2 (en)	2003-04-29	2015-09-01	Neurim Pharmaceuticals (1991) Ltd.	Method and composition for enhancing cognition in alzheimer's patients
IL330095A (en)	2012-01-26	2026-08-01	Vanda Pharmaceuticals Inc	Tesimalta for use in the treatment of asynchronous circadian rhythm of cortisol
US11918557B2 (en)	2012-01-26	2024-03-05	Vanda Pharmaceuticals Inc.	Treatment of circadian rhythm disorders
IL266159B2 (en)	2012-12-18	2024-07-01	Vanda Pharmaceuticals Inc	Treatment of circadian rhythm disorders
US11090285B2 (en)	2013-11-12	2021-08-17	Vanda Pharmaceuticals Inc	Treatment of circadian rhythm disorders
US10376487B2 (en)	2013-11-12	2019-08-13	Vanda Pharmaceuticals Inc.	Method of treatment
DK3337462T3 (da) *	2016-10-31	2020-10-12	Neurim Pharma 1991	Melatonin-minitabletter og fremgangsmåde til fremstilling heraf

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69229490T2 (de) *	1991-05-09	2000-02-17	Neurim Pharmaceuticals (1991) Ltd., Tel Aviv	Melatonin enthaltende Arzneimittel
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 MD MD97-0254A patent/MD1716C2/ro not_active IP Right Cessation
- 1996-01-29 TR TR97/00723T patent/TR199700723T1/xx unknown
- 1996-01-29 BR BR9607169A patent/BR9607169A/pt not_active Application Discontinuation
- 1996-01-29 CN CN96191750A patent/CN1083263C/zh not_active Expired - Lifetime
- 1996-01-29 CZ CZ19972405A patent/CZ291349B6/cs not_active IP Right Cessation
- 1996-01-29 NZ NZ298878A patent/NZ298878A/xx not_active IP Right Cessation
- 1996-01-29 EE EE9700166A patent/EE03384B1/xx not_active IP Right Cessation
- 1996-01-29 WO PCT/IB1996/000082 patent/WO1996023496A1/en not_active Ceased
- 1996-01-29 PL PL96321630A patent/PL183148B1/pl unknown
- 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 SI SI9620022A patent/SI9620022A/sl not_active IP Right Cessation
- 1996-01-29 SK SK1030-97A patent/SK284521B6/sk unknown
- 1996-01-29 AT AT0901396A patent/AT408188B/de 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 DK DK199700896A patent/DK176081B1/da not_active IP Right Cessation
- 1997-07-30 BG BG101803A patent/BG62876B1/bg unknown
- 1997-07-31 NO NO19973531A patent/NO312814B1/no not_active IP Right Cessation
- 1997-07-31 FI FI973185A patent/FI119586B/fi not_active IP Right Cessation
- 1997-08-01 LU LU90118A patent/LU90118B1/fr active

Also Published As

Publication number	Publication date
PL183148B1 (pl)	2002-05-31
CZ240597A3 (cs)	1998-01-14
BR9607169A (pt)	1997-11-11
MD1716C2 (ro)	2002-02-28
PL321630A1 (en)	1997-12-08
EE9700166A (et)	1998-02-16
ATA901396A (de)	2001-02-15
JP4516159B2 (ja)	2010-08-04
SK284521B6 (sk)	2005-05-05
FI973185A0 (fi)	1997-07-31
MD970254A (en)	1999-05-31
SI9620022A (sl)	1998-10-31
TW483757B (en)	2002-04-21
TR199700723T1 (xx)	1998-02-21
EE03384B1 (et)	2001-04-16
NZ298878A (en)	1999-05-28
IS1980B (is)	2005-01-14
DK89697A (da)	1997-07-30
MX9705856A (es)	1998-07-31
AU4457496A (en)	1996-08-21
FI119586B (fi)	2009-01-15
SK103097A3 (en)	1998-01-14
JPH10513177A (ja)	1998-12-15
CN1083263C (zh)	2002-04-24
BG101803A (en)	1998-04-30
NO973531L (no)	1997-09-30
WO1996023496A1 (en)	1996-08-08
CZ291349B6 (cs)	2003-02-12
CN1172431A (zh)	1998-02-04
LV11940A (lv)	1998-01-20
AT408188B (de)	2001-09-25
MD1716B2 (en)	2001-08-31
LV11940B (en)	1998-05-20
FI973185L (fi)	1997-09-30
DK176081B1 (da)	2006-04-18
AU695366B2 (en)	1998-08-13
IS4532A (is)	1997-07-25
NO973531D0 (no)	1997-07-31
NO312814B1 (no)	2002-07-08
LU90118B1 (fr)	1997-11-13

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