NO174085B - PROCEDURE FOR THE PREPARATION OF SUKRAL DRUM PREPARATIONS - Google Patents
PROCEDURE FOR THE PREPARATION OF SUKRAL DRUM PREPARATIONS Download PDFInfo
- Publication number
- NO174085B NO174085B NO87871759A NO871759A NO174085B NO 174085 B NO174085 B NO 174085B NO 87871759 A NO87871759 A NO 87871759A NO 871759 A NO871759 A NO 871759A NO 174085 B NO174085 B NO 174085B
- Authority
- NO
- Norway
- Prior art keywords
- sucralfate
- preparation
- preparations
- sukral
- drum
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 11
- 238000000034 method Methods 0.000 title claims description 6
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 claims description 23
- 229960004291 sucralfate Drugs 0.000 claims description 22
- 239000002202 Polyethylene glycol Substances 0.000 claims description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- -1 sucrose sulfate ester Chemical class 0.000 claims description 3
- 239000008187 granular material Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 7
- 239000012530 fluid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229920003114 HPC-L Polymers 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av et sukralfatpreparat og det særegne ved oppfinnel-sen er at et aluminiumsalt av en sukrosesulfatester blandes med fra 0,1 til 10 vekt%, basert på vekten av sukralfat, av polyetylenglykol, hvoretter blandingen granuleres. The present invention relates to a method for producing a sucralfate preparation and the peculiarity of the invention is that an aluminum salt of a sucrose sulfate ester is mixed with from 0.1 to 10% by weight, based on the weight of sucralfate, of polyethylene glycol, after which the mixture is granulated.
I henhold til fremgangsmåten for den foreliggende oppfinnelse oppnås et preparat med økt nedbrytnings- og dispergeringsevne og dette gjør sukralfat mer anvendelig som medisin. According to the method of the present invention, a preparation with increased decomposition and dispersing ability is obtained and this makes sucralfate more usable as a medicine.
Sukralfat anvendes hovedsakelig som et behandlingsmiddel for fordøyelses-ulcus og har evnen til å beskytte substratpro-teinet (evnen til å beskytte mageslimhinnen) og til å under-trykke pepsinaktiviteten i magesaft såvel som at det har anti-syreeffekter. Det er generelt forstått at sukralfat bindes sterkt til proteinkomponenten i belegget på undersiden av ulcus til å danne et lag som kjemisk beskytter det angrepne området fra den sterke magesyren og fremmer dermed helbre-delsesprosessen (Nakazawa, S. et al., Dig. Dis. Sei., 26, 297 Sucralfate is mainly used as a treatment for digestive ulcers and has the ability to protect the substrate protein (the ability to protect the gastric mucosa) and to suppress pepsin activity in gastric juice as well as having anti-acid effects. It is generally understood that sucralfate binds strongly to the protein component of the coating on the underside of the ulcer to form a layer that chemically protects the affected area from the strong stomach acid and thus promotes the healing process (Nakazawa, S. et al., Dig. Dis. Sei., 26, 297
(1981); og A. Ishimori et al., Igaku to Yakugaku, 9, 25 (1983)). (1981); and A. Ishimori et al., Igaku to Yakugaku, 9, 25 (1983)).
På den annen side er sukralfat uløselig i vann og preparater derav må nedbrytes og spres raskt for at de effektivt skal bindes til området som er angrepet av ulcus. On the other hand, sucralfate is insoluble in water and its preparations must be broken down and dispersed quickly in order for them to be effectively bound to the area affected by the ulcer.
Norsk utlegningsskrift NO 170126 (PCT/EP84/00294) omhandler en sukralfatsuspensjon som eventuelt kan inneholde polyetylenglykol og som tilsettes selve suspenderingsvæsken som visko-sitetsøkende middel. Norwegian explanatory document NO 170126 (PCT/EP84/00294) deals with a sucralfate suspension which may possibly contain polyethylene glycol and which is added to the suspension liquid itself as a viscosity-increasing agent.
I forbindelse med den foreliggende oppfinnelse har man utført forskjellige studier for å utvikle et sukralfatpreparat med forbedret nedbrytnings- og dispergeringsevne. Som et resul-tat, har man funnet at dette kan oppnås ved at sukralfat blandes med polyetylenglykol. In connection with the present invention, various studies have been carried out in order to develop a sucralfate preparation with improved breaking down and dispersing ability. As a result, it has been found that this can be achieved by mixing sucralfate with polyethylene glycol.
Figurene 1 og 2 viser kurver for nedbrytning og dispergering for sukralfatpreparater som fremstilles i henhold til fremgangsmåten for den foreliggende oppfinnelse, og for sammen-likningspreparater. Figures 1 and 2 show curves for breakdown and dispersion for sucralfate preparations which are prepared according to the method of the present invention, and for comparison preparations.
Ifølge fremgangsmåten for den foreliggende oppfinnelse blandes sukralfat med de ovennevnte mengder av polyetylenglykol. Molekylvekten til polyetylenglykol som blandes med sukralfat er ikke begrenset til noen spesiell verdi. Ved peroral tilførsel vil sukralfatpreparatet fremstilt i henhold til den foreliggende oppfinnelse tillate at sukralfatet bindes effektivt til det ulcus-berørte området. Sukralfatpreparatet kan fremstilles i forskjellige enhetsdoseformer som pulver, fine granuler, granuler, tabletter og kapsler. For dette formål kan man anvende forskjellige tilsetningsmidler som bindemidler, oppløsningsmidler, smøremidler, eksipienser og fargestoffer. According to the method of the present invention, sucralfate is mixed with the above-mentioned quantities of polyethylene glycol. The molecular weight of polyethylene glycol mixed with sucralfate is not limited to any particular value. When administered orally, the sucralfate preparation produced according to the present invention will allow the sucralfate to bind effectively to the ulcer-affected area. The sucralfate preparation can be produced in different unit dosage forms such as powder, fine granules, granules, tablets and capsules. For this purpose, different additives can be used such as binders, solvents, lubricants, excipients and dyes.
De etterfølgende eksempler vil ytterligere illustrere den foreliggende oppfinnelse. The following examples will further illustrate the present invention.
Eksempel 1 Example 1
Et aluminiumsalt av sukrosesulfatester (sukralfat: 3, 920 g) ble godt blandet med 2000 g av en vandig 4 % polyetylenglykol-løsning (molekylvekt 1500) i en blander. Blandingen ble granulert i en sylindrisk granulator som var utstyrt med et nett med en maskestørrelse på 0,7 mm. Granulatet ble tørket ved 60°C i 3 timer i en brett-tørker. Det tørkede granulat ble siktet gjennom en sikt med maskestørrelse 16 mesh for å oppnå granuler. Sammenliknbare granuler ble fremstilt ved hjelp av den samme metoden som beskrevet over, med unntak av at den vandige 4 %ige polyetylenglykolløsningen ble byttet ut med vann. An aluminum salt of sucrose sulfate ester (sucralfate: 3.920 g) was well mixed with 2000 g of an aqueous 4% polyethylene glycol solution (molecular weight 1500) in a mixer. The mixture was granulated in a cylindrical granulator equipped with a mesh with a mesh size of 0.7 mm. The granulate was dried at 60°C for 3 hours in a tray dryer. The dried granules were sieved through a 16 mesh screen to obtain granules. Comparable granules were prepared using the same method as described above, except that the aqueous 4% polyethylene glycol solution was replaced with water.
Nedbrytnings- og dispergeringsevnen til de to granulprøvene er vist i fig. 1, uttrykt som forandring i turbiditet, idet verdien av en kontrollsuspensjon ble satt til 1. Kontroll-suspensjonen ble fremstilt ved at 1 g av et sukralfat ble dispergert i 1000 ml vann ved hjelp av ultralydbølger og turbiditeten til denne kontrollsuspensjon ble målt ved 540 nm idet tykkelsen av sjiktet i detektorcellen var 1 cm. Måling av turbiditet er beskrevet mere nøyaktig i det etterfølgende: Suspensjoner som hver inneholdt 200 mg sukralfat ble tilført til fem hjelperør i et nedbrytnings-prøveapparat (prøvefluid: 1000 ml vann ved 37 +. 2°C) og turbiditetene til fluidandeler som ble tatt ut omkring 5 cm under overflaten til prøve-fluidene ble målt. Basert på de oppnådde data ble de spesifikke turbiditeter til de individuelle prøver beregnet. The breaking down and dispersing ability of the two granule samples is shown in fig. 1, expressed as a change in turbidity, the value of a control suspension being set to 1. The control suspension was prepared by dispersing 1 g of a sucralfate in 1000 ml of water using ultrasonic waves and the turbidity of this control suspension was measured at 540 nm the thickness of the layer in the detector cell being 1 cm. Measurement of turbidity is described more precisely in the following: Suspensions each containing 200 mg of sucralfate were fed to five auxiliary tubes in a degradation test apparatus (test fluid: 1000 ml of water at 37 +.2°C) and the turbidities of fluid portions taken out about 5 cm below the surface of the sample fluids were measured. Based on the data obtained, the specific turbidities of the individual samples were calculated.
De to granulprøvene ble underkastet en akselerasjonstest ved 40°C x 75 % r.f. i 6 mnd. og deres dispergeringstilstand ble evaluert, uttrykt ved spesifikk turbiditet som ble beregnet som beskrevet over. Resultatene er vist i tabell 1. The two granule samples were subjected to an acceleration test at 40°C x 75% r.h. for 6 months and their state of dispersion was evaluated, expressed by specific turbidity which was calculated as described above. The results are shown in table 1.
Eksempel 2 Example 2
Sukralfat (4000 g) ble inngående blandet med 2000 g av en vandig 10 % polyetylenglykolløsning (molekylvekt 6000) i en blander. Blandingen ble deretter siktet gjennom en sikt med maskestørrelse 16 mesh for å danne en granulering som ble tørket ved 60°C i 3 timer i en brett-tørker og klassifisert ved passering gjennom en sikt med maskestørrelse 10 mesh. Sucralfate (4000 g) was thoroughly mixed with 2000 g of an aqueous 10% polyethylene glycol solution (molecular weight 6000) in a mixer. The mixture was then sieved through a 16 mesh sieve to form a granulation which was dried at 60°C for 3 hours in a tray drier and classified by passing through a 10 mesh sieve.
De oppnådde granuler (4000 g) ble blandet med 1376 g krystallinsk cellulose og 24 g magnesiumstearat og blandet i 5 min. i en V-type blander. The obtained granules (4000 g) were mixed with 1376 g of crystalline cellulose and 24 g of magnesium stearate and mixed for 5 min. in a V-type mixer.
Det oppnådde pulver ble plassert i en roterende tablettfrem-stillingsmaskin som var utstyrt med tablettformer og press-stempler (12 mm) og sammenpresset ved et totalt trykk på omtrent 2,5 tonn for å danne tabletter som hver veide 700 mg. The obtained powder was placed in a rotary tablet-making machine equipped with tablet molds and press punches (12 mm) and compressed at a total pressure of about 2.5 tons to form tablets each weighing 700 mg.
Sammenlikningstabletter ble fremstilt på samme måte som beskrevet over, med unntak av at den vandige 10 %ige polyetylenglykol løsning ble byttet ut med en vandig 10 % hydroksy-propylcelluloseløsning (Nisso HPC-L fra Nippon Soda Co., Ltd.) Comparison tablets were prepared in the same way as described above, with the exception that the aqueous 10% polyethylene glycol solution was replaced with an aqueous 10% hydroxy-propyl cellulose solution (Nisso HPC-L from Nippon Soda Co., Ltd.)
Nedbrytnings- og dispergeringsevnen til de to tablettprøvene er vist i fig. 2, uttrykt som forandring i turbiditet idet verdien til en kontro11suspensjon ble satt til 1. Kontroll-suspensjonen ble fremstilt ved å oppløse 1000 mg sukralfat, 344 mg krystallinsk cellulose og 6 mg magnesiumstearat i 1000 ml vann ved hjelp av ultralydbølger og turbiditeten til denne kontroll-suspensjonen ble målt ved 540 nm i en detektor-celle med en sjikttykkelse på 1 cm. Turbiditetsmålinger er beskrevet mere detaljert i det etterfølgende: To tabletter fra hver prøve ble tilført til en nedbrytnings-prøveapparat (prøvefluid: 1000 ml vann ved 37 +. 2°C) og turbiditetene til fluidandeler som var tatt ut omtrent 5 cm under overflaten av prøvefluidene ble målt. Basert på de oppnådde data ble den spesifikke turbiditet til de individuelle prøvene beregnet. The disintegrating and dispersing ability of the two tablet samples is shown in fig. 2, expressed as change in turbidity with the value of a control suspension set to 1. The control suspension was prepared by dissolving 1000 mg of sucralfate, 344 mg of crystalline cellulose and 6 mg of magnesium stearate in 1000 ml of water using ultrasonic waves and the turbidity of this control - the suspension was measured at 540 nm in a detector cell with a layer thickness of 1 cm. Turbidity measurements are described in more detail below: Two tablets from each sample were added to a degradation test apparatus (sample fluid: 1000 ml water at 37 +.2°C) and the turbidities of fluid portions sampled approximately 5 cm below the surface of the sample fluids was measured. Based on the data obtained, the specific turbidity of the individual samples was calculated.
De to tablettprøvene ble underkastet en akselerasjonstest ved 40°C x 75 % r.f. i 6 mnd. og deres dispergeringstilstand ble evaluert uttrykt som spesifikk turbiditet som ble beregnet på samme måte som beskrevet over. Resultatene er vist i tabell 2. The two tablet samples were subjected to an acceleration test at 40°C x 75% r.h. for 6 months and their state of dispersion was evaluated expressed as specific turbidity which was calculated in the same way as described above. The results are shown in table 2.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9990186 | 1986-04-30 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO871759D0 NO871759D0 (en) | 1987-04-28 |
| NO871759L NO871759L (en) | 1987-11-02 |
| NO174085B true NO174085B (en) | 1993-12-06 |
| NO174085C NO174085C (en) | 1994-03-16 |
Family
ID=14259677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO871759A NO174085C (en) | 1986-04-30 | 1987-04-28 | Process for the preparation of sucralfate preparations |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JP2542210B2 (en) |
| DE (1) | DE3714159C2 (en) |
| DK (1) | DK167735B1 (en) |
| ES (1) | ES2017805A6 (en) |
| FI (1) | FI89457C (en) |
| FR (1) | FR2598084B1 (en) |
| IT (1) | IT1208416B (en) |
| NO (1) | NO174085C (en) |
| SE (1) | SE503233C2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2735559B2 (en) * | 1988-03-02 | 1998-04-02 | 中外製薬株式会社 | Suspension |
| BR9507533A (en) * | 1994-04-26 | 1997-09-02 | Chugai Pharmaceutical Co Ltd | Fused granulated sucralfate preparations and a process for their production |
| KR19980701891A (en) * | 1995-02-02 | 1998-06-25 | 나가야마 나오루 | Sucralate formulations |
| ES2112765B1 (en) * | 1995-08-02 | 1999-03-01 | Cantabria Ind Farmaceutica Sa | PROCEDURE FOR OBTAINING RADIOLOGICAL CONTRAST FORMULATIONS, FOR GASTROINTESTINAL EXPLORATIONS FOR EXTEMPORARY AND DIRECT USE. |
| TW201132646A (en) * | 2010-02-22 | 2011-10-01 | Daiichi Sankyo Co Ltd | Oral solid extended release dosage form |
| TW201141544A (en) | 2010-02-22 | 2011-12-01 | Daiichi Sankyo Co Ltd | Oral solid extended release dosage form |
| KR102127625B1 (en) | 2012-09-03 | 2020-06-29 | 다이이찌 산쿄 가부시키가이샤 | Hydromorphone hydrochloride-containing oral sustained-release pharmaceutical composition |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3430809A1 (en) * | 1984-08-22 | 1986-03-06 | Merck Patent Gmbh, 6100 Darmstadt | SUCRALFAT SUSPENSION |
-
1987
- 1987-04-28 NO NO871759A patent/NO174085C/en unknown
- 1987-04-28 DE DE3714159A patent/DE3714159C2/en not_active Expired - Lifetime
- 1987-04-28 FI FI871852A patent/FI89457C/en not_active IP Right Cessation
- 1987-04-29 IT IT8767365A patent/IT1208416B/en active
- 1987-04-29 ES ES8701280A patent/ES2017805A6/en not_active Expired - Lifetime
- 1987-04-29 SE SE8701787A patent/SE503233C2/en not_active IP Right Cessation
- 1987-04-29 DK DK218587A patent/DK167735B1/en not_active IP Right Cessation
- 1987-04-30 JP JP62104612A patent/JP2542210B2/en not_active Expired - Lifetime
- 1987-04-30 FR FR878706196A patent/FR2598084B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK218587D0 (en) | 1987-04-29 |
| FI871852A (en) | 1987-10-31 |
| FR2598084B1 (en) | 1991-04-26 |
| ES2017805A6 (en) | 1991-03-01 |
| FR2598084A1 (en) | 1987-11-06 |
| FI89457C (en) | 1993-10-11 |
| NO174085C (en) | 1994-03-16 |
| IT1208416B (en) | 1989-06-12 |
| SE8701787D0 (en) | 1987-04-29 |
| DK218587A (en) | 1987-10-31 |
| NO871759L (en) | 1987-11-02 |
| JPS63107933A (en) | 1988-05-12 |
| DE3714159A1 (en) | 1987-11-05 |
| SE8701787L (en) | 1987-10-31 |
| NO871759D0 (en) | 1987-04-28 |
| DE3714159C2 (en) | 1996-09-19 |
| FI89457B (en) | 1993-06-30 |
| DK167735B1 (en) | 1993-12-13 |
| JP2542210B2 (en) | 1996-10-09 |
| SE503233C2 (en) | 1996-04-22 |
| IT8767365A0 (en) | 1987-04-29 |
| FI871852A0 (en) | 1987-04-28 |
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