IL89056A - Pharmaceuticals to increase mental function in humans consisting of a release factor of a growth hormone or somatostatin - Google Patents
Pharmaceuticals to increase mental function in humans consisting of a release factor of a growth hormone or somatostatinInfo
- Publication number
- IL89056A IL89056A IL8905689A IL8905689A IL89056A IL 89056 A IL89056 A IL 89056A IL 8905689 A IL8905689 A IL 8905689A IL 8905689 A IL8905689 A IL 8905689A IL 89056 A IL89056 A IL 89056A
- Authority
- IL
- Israel
- Prior art keywords
- grf
- somatostatin
- pharmaceutical composition
- growth hormone
- releasing factor
- Prior art date
Links
- 230000003340 mental effect Effects 0.000 title claims abstract description 13
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 title claims description 128
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 title claims description 128
- 101710142969 Somatoliberin Proteins 0.000 title claims description 122
- 102000005157 Somatostatin Human genes 0.000 title claims description 55
- 108010056088 Somatostatin Proteins 0.000 title claims description 55
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 title claims description 55
- 229960000553 somatostatin Drugs 0.000 title claims description 55
- 230000002708 enhancing effect Effects 0.000 title claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 title claims 9
- 239000012634 fragment Substances 0.000 claims description 10
- 238000007920 subcutaneous administration Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 8
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims 6
- 230000006870 function Effects 0.000 abstract description 14
- 229940088597 hormone Drugs 0.000 abstract description 13
- 239000005556 hormone Substances 0.000 abstract description 13
- 230000002267 hypothalamic effect Effects 0.000 abstract description 5
- 238000012360 testing method Methods 0.000 description 72
- 230000000694 effects Effects 0.000 description 53
- 102000018997 Growth Hormone Human genes 0.000 description 41
- 108010051696 Growth Hormone Proteins 0.000 description 41
- 239000000122 growth hormone Substances 0.000 description 41
- 208000024827 Alzheimer disease Diseases 0.000 description 29
- 206010039966 Senile dementia Diseases 0.000 description 26
- 241000700159 Rattus Species 0.000 description 22
- 238000002347 injection Methods 0.000 description 22
- 239000007924 injection Substances 0.000 description 22
- 230000006742 locomotor activity Effects 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 230000004044 response Effects 0.000 description 18
- 230000035939 shock Effects 0.000 description 18
- 230000003542 behavioural effect Effects 0.000 description 16
- 230000007935 neutral effect Effects 0.000 description 16
- 206010012289 Dementia Diseases 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 210000003169 central nervous system Anatomy 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000006872 improvement Effects 0.000 description 10
- 230000033001 locomotion Effects 0.000 description 10
- 208000012902 Nervous system disease Diseases 0.000 description 8
- 108090000189 Neuropeptides Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000006399 behavior Effects 0.000 description 8
- 230000015654 memory Effects 0.000 description 8
- 238000012544 monitoring process Methods 0.000 description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 6
- 241000557626 Corvus corax Species 0.000 description 6
- 101800000736 Growth hormone-releasing factor Proteins 0.000 description 6
- 239000000474 Pituitary Hormone-Releasing Hormone Substances 0.000 description 6
- 102000005726 Pituitary Hormone-Releasing Hormones Human genes 0.000 description 6
- 108010031037 Pituitary Hormone-Releasing Hormones Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 230000000763 evoking effect Effects 0.000 description 6
- 238000000185 intracerebroventricular administration Methods 0.000 description 6
- 230000036997 mental performance Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 230000002263 peptidergic effect Effects 0.000 description 6
- 239000000902 placebo Substances 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 208000020016 psychiatric disease Diseases 0.000 description 6
- 230000006403 short-term memory Effects 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 4
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 4
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- KFGRVLINLVVMJA-MITYVQBRSA-N chembl440262 Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=C(O)C=C1 KFGRVLINLVVMJA-MITYVQBRSA-N 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000006735 deficit Effects 0.000 description 4
- 230000003412 degenerative effect Effects 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 238000002592 echocardiography Methods 0.000 description 4
- 210000001652 frontal lobe Anatomy 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 230000001730 monoaminergic effect Effects 0.000 description 4
- 230000001722 neurochemical effect Effects 0.000 description 4
- 230000000955 neuroendocrine Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000003997 social interaction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 108010056001 somatotropin releasing hormone (1-29) Proteins 0.000 description 4
- 230000007480 spreading Effects 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- IVDRCZNHVGQBHZ-UHFFFAOYSA-N 2-butoxyethyl 2-(3,5,6-trichloropyridin-2-yl)oxyacetate Chemical compound CCCCOCCOC(=O)COC1=NC(Cl)=C(Cl)C=C1Cl IVDRCZNHVGQBHZ-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 241000947912 Cardiobacteriales Species 0.000 description 2
- 208000017701 Endocrine disease Diseases 0.000 description 2
- 238000001135 Friedman test Methods 0.000 description 2
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 241000947853 Vibrionales Species 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000007177 brain activity Effects 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000006998 cognitive state Effects 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000003748 differential diagnosis Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 208000030172 endocrine system disease Diseases 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 230000003370 grooming effect Effects 0.000 description 2
- 210000003100 hypothalamo-hypophyseal system Anatomy 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000009191 jumping Effects 0.000 description 2
- 230000003137 locomotive effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 210000000869 occipital lobe Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 229940001470 psychoactive drug Drugs 0.000 description 2
- 239000004089 psychotropic agent Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 230000026267 regulation of growth Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000002099 somatostatinotropic effect Effects 0.000 description 2
- 210000005070 sphincter Anatomy 0.000 description 2
- 238000010972 statistical evaluation Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/31—Somatostatins
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Surgery (AREA)
- Neurology (AREA)
- Medical Informatics (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/148,667 US4939124A (en) | 1988-01-26 | 1988-01-26 | Treatment and diagnosis of dementia |
| US07/206,100 US5089472A (en) | 1988-01-26 | 1988-06-13 | Use of growth hormone releasing factor for improving mental function |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL89056A0 IL89056A0 (en) | 1989-08-15 |
| IL89056A true IL89056A (en) | 1994-07-31 |
Family
ID=26846051
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL8905689A IL89056A (en) | 1988-01-26 | 1989-01-24 | Pharmaceuticals to increase mental function in humans consisting of a release factor of a growth hormone or somatostatin |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5089472A (fi) |
| EP (1) | EP0326381B1 (fi) |
| JP (2) | JP2847098B2 (fi) |
| KR (1) | KR970002484B1 (fi) |
| CN (1) | CN1055641C (fi) |
| AT (1) | ATE106745T1 (fi) |
| AU (1) | AU615714B2 (fi) |
| CA (1) | CA1341017C (fi) |
| DE (1) | DE68915793T2 (fi) |
| DK (1) | DK174866B1 (fi) |
| FI (1) | FI890389A (fi) |
| IL (1) | IL89056A (fi) |
| NO (1) | NO890336L (fi) |
| RU (1) | RU2024261C1 (fi) |
| UA (1) | UA19804A (fi) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6449594A (en) * | 1993-04-02 | 1994-10-24 | Ohio University | Enhancement of learning and/or memory by a human somatotropin |
| JP2010539063A (ja) * | 2007-09-11 | 2010-12-16 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | Ｇｒｆ−１（１−２９）および副腎皮質刺激ホルモン放出因子の、治療剤としての使用 |
| US9265458B2 (en) | 2012-12-04 | 2016-02-23 | Sync-Think, Inc. | Application of smooth pursuit cognitive testing paradigms to clinical drug development |
| US9380976B2 (en) | 2013-03-11 | 2016-07-05 | Sync-Think, Inc. | Optical neuroinformatics |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8318552D0 (en) * | 1983-07-08 | 1983-08-10 | Sandoz Ltd | Organic compounds |
| US4747825A (en) * | 1984-06-29 | 1988-05-31 | Ferring Laboratories, Inc. | Apparatus and methodology for pulsed administration of growth promoting agents |
| JPH085913B2 (ja) * | 1985-09-12 | 1996-01-24 | ザ・アドミニストレ−タ−ズ・オブ・ザ・ツ−レイン・エデユケイシヨナル・フアンド | 治療用ソマトスタチン同族体 |
| US4939124A (en) * | 1988-01-26 | 1990-07-03 | Laboratorios Serono S.A. | Treatment and diagnosis of dementia |
-
1988
- 1988-06-13 US US07/206,100 patent/US5089472A/en not_active Expired - Lifetime
-
1989
- 1989-01-23 AU AU28700/89A patent/AU615714B2/en not_active Expired
- 1989-01-24 IL IL8905689A patent/IL89056A/en unknown
- 1989-01-25 KR KR89000761A patent/KR970002484B1/ko not_active IP Right Cessation
- 1989-01-25 UA UA4613597A patent/UA19804A/uk unknown
- 1989-01-25 RU SU894613597A patent/RU2024261C1/ru active
- 1989-01-25 JP JP1017386A patent/JP2847098B2/ja not_active Expired - Lifetime
- 1989-01-25 DK DK198900314A patent/DK174866B1/da not_active IP Right Cessation
- 1989-01-26 FI FI890389A patent/FI890389A/fi not_active Application Discontinuation
- 1989-01-26 AT AT89300751T patent/ATE106745T1/de not_active IP Right Cessation
- 1989-01-26 CN CN89101534A patent/CN1055641C/zh not_active Expired - Lifetime
- 1989-01-26 CA CA000589280A patent/CA1341017C/en not_active Expired - Fee Related
- 1989-01-26 EP EP89300751A patent/EP0326381B1/en not_active Expired - Lifetime
- 1989-01-26 DE DE68915793T patent/DE68915793T2/de not_active Expired - Lifetime
- 1989-01-26 NO NO89890336A patent/NO890336L/no unknown
-
1998
- 1998-02-16 JP JP10032715A patent/JP2965949B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2847098B2 (ja) | 1999-01-13 |
| KR970002484B1 (en) | 1997-03-05 |
| UA19804A (uk) | 1997-12-25 |
| JPH10251167A (ja) | 1998-09-22 |
| JPH0242025A (ja) | 1990-02-13 |
| DE68915793T2 (de) | 1995-03-09 |
| EP0326381A3 (en) | 1991-08-14 |
| RU2024261C1 (ru) | 1994-12-15 |
| EP0326381B1 (en) | 1994-06-08 |
| ATE106745T1 (de) | 1994-06-15 |
| US5089472A (en) | 1992-02-18 |
| AU615714B2 (en) | 1991-10-10 |
| CN1036509A (zh) | 1989-10-25 |
| AU2870089A (en) | 1989-07-27 |
| EP0326381A2 (en) | 1989-08-02 |
| DK31489D0 (da) | 1989-01-25 |
| CN1055641C (zh) | 2000-08-23 |
| DK174866B1 (da) | 2004-01-05 |
| FI890389A0 (fi) | 1989-01-26 |
| FI890389A (fi) | 1989-07-27 |
| JP2965949B2 (ja) | 1999-10-18 |
| KR890011572A (ko) | 1989-08-21 |
| NO890336D0 (no) | 1989-01-26 |
| DE68915793D1 (de) | 1994-07-14 |
| DK31489A (da) | 1989-07-27 |
| NO890336L (no) | 1989-07-27 |
| CA1341017C (en) | 2000-06-06 |
| IL89056A0 (en) | 1989-08-15 |
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