BE861521A - PROCESS FOR PREPARING 2-SUBSTITUTED BENZIMIDAZOLE COMPOUNDS AND THE ACID ADDITION SALTS THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS AS AN ACTIVE COMPONENT - Google Patents

PROCESS FOR PREPARING 2-SUBSTITUTED BENZIMIDAZOLE COMPOUNDS AND THE ACID ADDITION SALTS THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS AS AN ACTIVE COMPONENT

Info

Publication number
BE861521A
BE861521A BE2056490A BE2056490A BE861521A BE 861521 A BE861521 A BE 861521A BE 2056490 A BE2056490 A BE 2056490A BE 2056490 A BE2056490 A BE 2056490A BE 861521 A BE861521 A BE 861521A
Authority
BE
Belgium
Prior art keywords
emi
compounds
preparing
acid addition
addition salts
Prior art date
Application number
BE2056490A
Other languages
Dutch (nl)
Original Assignee
Kanebo 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.)
Filing date
Publication date
Application filed by Kanebo Ltd filed Critical Kanebo Ltd
Publication of BE861521A publication Critical patent/BE861521A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Description

       

  Werkwijze ter bereiding van 2-gesubstitueerde benzimidazoolver-

  
bindingen en de zuuradditiezouten daarvan alsmede farmaceutische

  
preparaten die deze verbindingen als actieve componenten bevatten. 

  
 <EMI ID=1.1> 

  
 <EMI ID=2.1> 

  
nen.

  
De uitdrukkingen "lager alkyl" en "lager alkoxy" betekenen

  
 <EMI ID=3.1>  <EMI ID=4.1>  getica.

  
Deze verbindingen volgens formule 1 kunnen op geschikte wijze

  
 <EMI ID=5.1> 

  
 <EMI ID=6.1> 

  
 <EMI ID=7.1> 

  
 <EMI ID=8.1> 

  
voorkeur onder een stroom stikstofgas. Voorbeelden van condensatiemid-

  
 <EMI ID=9.1> 

  
ters, waterstofchloride, waterstofbromide en boorzuur. De reactie kan desgewenst worden uitgevoerd in een inert oplosmiddel, zoals 0-dichloorbenzeen, nitrobenzeen of diglyme. Polyfosforzuur en esters daarvan hebben voor deze reactie de meeste voorkeur omdat zij een verhoogde  <EMI ID=10.1> 

  
 <EMI ID=11.1> 

  
 <EMI ID=12.1> 

  
ten.

  
De bcnzimidazoolverbindingen volgens formule 1-a, waarin R, en

  
 <EMI ID=13.1> 

  
 <EMI ID=14.1> 

  
 <EMI ID=15.1> 

  
 <EMI ID=16.1> 

  
 <EMI ID=17.1> 

  
derivaten daarvan als zodanig kunnen worden toegepast. De reactie kan j &#65533;__   <EMI ID=18.1> 

  
 <EMI ID=19.1> 

  
 <EMI ID=20.1> 

  
 <EMI ID=21.1> 

  
 <EMI ID=22.1> 

  
 <EMI ID=23.1> 

  
in aanwezigheid van een base bij een temperatuur van kamertemperatuur tot het kookpunt van het oplosmiddel, een zuur aan het reactiemengsel

  
 <EMI ID=24.1>  oplosmiddel. 

  
 <EMI ID=25.1> 

  
 <EMI ID=26.1> 

  
 <EMI ID=27.1> 

  
 <EMI ID=28.1> 

  
 <EMI ID=29.1>   <EMI ID=30.1> 

  
T..::.1Jel A

  

 <EMI ID=31.1> 


  
Zoals uit de tabel blijkt varen de verbindingen volgens de uitvinding significant beter dan het bekende anti-ontstekingsmiddel fenylbutazon. 

  
De verbindingen volgens de uitvinding kunnen voor warmbloedige dieren worden toegepast, in het bijzonder zoogdieren, als medicamenten in de vorm van farmaceutische preparaten die de verbindingen bevatten gemengd of in samenhang met een farmaceutische .organische of anorgani-

  
 <EMI ID=32.1> 

  
diening. 

  
 <EMI ID=33.1> 

  
 <EMI ID=34.1> 

  
 <EMI ID=35.1> 

  
 <EMI ID=36.1> 

  
teneinde verschillende hoeveelheden van de actieve stoffen aan te duiden. 

  
Harde gelatinecapsules kunnen b.v. korrels van de samenstelling

  
 <EMI ID=37.1> 

  
se, saccharose, sorbitol, mannitol en verder zetmeelprodukten zoals 

  
 <EMI ID=38.1>  . gelatine alsmede magnesiumstearaat of stearinezuur. 

  
 <EMI ID=39.1> 

  
 <EMI ID=40.1> 

  
 <EMI ID=41.1> 

  
caoboter en de zetpillen worden op gebruikelijke vijze gevormd. 

  
De verbindingen volgens de uitvinding en de bereiding daarvan worden in de volgende voorbeelden geïllustreerd. Deze voorbeelden zijn  niet beperkend bedoeld. 

  
Voorbeeld I

  
 <EMI ID=42.1> 

  
 <EMI ID=43.1> 

  
 <EMI ID=44.1> 

  
 <EMI ID=45.1> 

  
 <EMI ID=46.1> 

  
 <EMI ID=47.1> 

  
 <EMI ID=48.1>  .Voorbeeld II

  
 <EMI ID=49.1> 

  
zwavelpoeder werden gedurende 8 ur en op 160 - 170[deg.]C verhit. Aan het reactiemengsel werd 200 cm methanol toegevoegd.

  
Het mengsel werd fegiltreerd ter verwijdering van zwavelpoeder en in vacuum ingedampt , teneinde het  <EMI ID=50.1> 

  
door verdamping onder vacuum verwijderd. Het residu werd onderworpen aan silicagelkolomchromatografie en uit ethylacetaat gerekristalliseerd. Het produkt toonde geen sneltpuntverlaging na mengen met het produkt

  
 <EMI ID=51.1> 

  
sche waarde). 

  
 <EMI ID=52.1> 

  
 <EMI ID=53.1> 

  
 <EMI ID=54.1> 

  
Analyse: <EMI ID=55.1> 

  
 <EMI ID=56.1> 

  
Voorbeeld IX

  
 <EMI ID=57.1> 

  
lyfosforzuur werden onder een stikstotgasstroori onder roeren gedurende

  
 <EMI ID=58.1> 

  
 <EMI ID=59.1> 

  
 <EMI ID=60.1> 

  
 <EMI ID=61.1> 

  
 <EMI ID=62.1> 

  
Voorbeeld X 

  
 <EMI ID=63.1> 

  
polyfosforzuur werden onder een stikstofgasstroom onder roeren geduren- <EMI ID=64.1> 

  
 <EMI ID=65.1> 

  
Analyse&#65533; 

  
 <EMI ID=66.1> 

  
 <EMI ID=67.1> 

  
_Voorbee;.d '_=

  
 <EMI ID=68.1> 

  
 <EMI ID=69.1> 

  
onderworpen via een silicagelkolom en uit cyclohexaan gerekristalli-

  
 <EMI ID=70.1> 

  
 <EMI ID=71.1> 

  
Voorbeeld XIII

  
Bereiding van 2-(2-pyridyl)-5(6)-methoxybenzimidazool:'

  
 <EMI ID=72.1> 

  
zuur en 40 g polyfosforzuur verden onder een stikstofgasstroom onder

  
 <EMI ID=73.1> 

  
 <EMI ID=74.1>   <EMI ID=75.1> 

  
 <EMI ID=76.1> 

  
 <EMI ID=77.1> 

  
Voorbeeld XVI

  
 <EMI ID=78.1> 

  
 <EMI ID=79.1> 

  
 <EMI ID=80.1> 

  
grafeerd via een silicagelkolom (ontvikkeld met 8 : 2 mengsel benzeen-

  
 <EMI ID=81.1> 

  
 <EMI ID=82.1> 

  
 <EMI ID=83.1>  

  
 <EMI ID=84.1> 

  
 <EMI ID=85.1> 

  
 <EMI ID=86.1> 

  
Z?&#65533;,5[deg.]C. 

  
 <EMI ID=87.1> 

  
 <EMI ID=88.1> 

  
 <EMI ID=89.1> 

  
 <EMI ID=90.1>  

  
 <EMI ID=91.1> 

  
 <EMI ID=92.1> 

  
 <EMI ID=93.1> 

  
Voorbeeld XXII

  
 <EMI ID=94.1> 

  
 <EMI ID=95.1> 

  
 <EMI ID=96.1> 

  
 <EMI ID=97.1> 

  
 <EMI ID=98.1> 

  
 <EMI ID=99.1> 

  
 <EMI ID=100.1> 

  
 <EMI ID=101.1> 

  
 <EMI ID=102.1> 

  
 <EMI ID=103.1> 

  
beeld V.

  
Voorbeeld XXIII

  
 <EMI ID=104.1> 

  
fosforzuur werden onder een stikstofgasstrooa onder roeren gedurehde 4  <EMI ID=105.1> 

  
 <EMI ID=106.1> 

  
kregen kristallen werden uit acetonitrile gerekristalliseerd. Er werd

  
 <EMI ID=107.1> 

  
 <EMI ID=108.1> 

  
 <EMI ID=109.1> 

  
 <EMI ID=110.1> 

  
 <EMI ID=111.1> 

  
 <EMI ID=112.1> 

  
Voorbeeld XXV.

  
Bereiding van 2-(m-ethylfenyl)-benzimidazool: 

  
 <EMI ID=113.1> 

  
 <EMI ID=114.1> 

  
 <EMI ID=115.1>  

  
 <EMI ID=116.1> 

  
 <EMI ID=117.1> 

  
 <EMI ID=118.1> 

  
Voorbeeld XXVII

  
 <EMI ID=119.1> 

  
 <EMI ID=120.1> 

  
 <EMI ID=121.1> 

  
 <EMI ID=122.1> 

  
 <EMI ID=123.1> 

  
 <EMI ID=124.1> 

  
 <EMI ID=125.1> 

  
 <EMI ID=126.1> 

  
 <EMI ID=127.1>   <EMI ID=128.1> 



  Process for the preparation of 2-substituted benzimidazole derivatives

  
bonds and their acid addition salts as well as pharmaceuticals

  
preparations containing these compounds as active components.

  
 <EMI ID = 1.1>

  
 <EMI ID = 2.1>

  
nen.

  
The terms "lower alkyl" and "lower alkoxy" mean

  
 <EMI ID = 3.1> <EMI ID = 4.1> getica.

  
These compounds of formula 1 can suitably be used

  
 <EMI ID = 5.1>

  
 <EMI ID = 6.1>

  
 <EMI ID = 7.1>

  
 <EMI ID = 8.1>

  
preferably under a stream of nitrogen gas. Examples of condensation agent

  
 <EMI ID = 9.1>

  
ters, hydrogen chloride, hydrogen bromide and boric acid. The reaction can, if desired, be carried out in an inert solvent, such as 0-dichlorobenzene, nitrobenzene or diglyme. Polyphosphoric acid and its esters are most preferred for this reaction because they have an increased <EMI ID = 10.1>

  
 <EMI ID = 11.1>

  
 <EMI ID = 12.1>

  
ten.

  
The benzimidazole compounds of formula 1-a, wherein R 1 and

  
 <EMI ID = 13.1>

  
 <EMI ID = 14.1>

  
 <EMI ID = 15.1>

  
 <EMI ID = 16.1>

  
 <EMI ID = 17.1>

  
derivatives thereof can be used as such. The response may j &#65533; __ <EMI ID = 18.1>

  
 <EMI ID = 19.1>

  
 <EMI ID = 20.1>

  
 <EMI ID = 21.1>

  
 <EMI ID = 22.1>

  
 <EMI ID = 23.1>

  
in the presence of a base at a temperature from room temperature to the boiling point of the solvent, an acid to the reaction mixture

  
 <EMI ID = 24.1> solvent.

  
 <EMI ID = 25.1>

  
 <EMI ID = 26.1>

  
 <EMI ID = 27.1>

  
 <EMI ID = 28.1>

  
 <EMI ID = 29.1> <EMI ID = 30.1>

  
T .. ::. 1 Jel A

  

 <EMI ID = 31.1>


  
As shown in the table, the compounds of the invention fare significantly better than the known anti-inflammatory agent phenylbutazone.

  
The compounds of the invention can be used for warm-blooded animals, in particular mammals, as medicaments in the form of pharmaceutical preparations containing the compounds mixed or in combination with a pharmaceutical organic or inorganic

  
 <EMI ID = 32.1>

  
ministry.

  
 <EMI ID = 33.1>

  
 <EMI ID = 34.1>

  
 <EMI ID = 35.1>

  
 <EMI ID = 36.1>

  
to indicate different amounts of the active substances.

  
Hard gelatin capsules can e.g. granules of the composition

  
 <EMI ID = 37.1>

  
se, sucrose, sorbitol, mannitol and further starch products such as

  
 <EMI ID = 38.1>. gelatin as well as magnesium stearate or stearic acid.

  
 <EMI ID = 39.1>

  
 <EMI ID = 40.1>

  
 <EMI ID = 41.1>

  
caobutter and the suppositories are formed in usual manner.

  
The compounds of the invention and their preparation are illustrated in the following examples. These examples are not intended to be limiting.

  
Example I

  
 <EMI ID = 42.1>

  
 <EMI ID = 43.1>

  
 <EMI ID = 44.1>

  
 <EMI ID = 45.1>

  
 <EMI ID = 46.1>

  
 <EMI ID = 47.1>

  
 <EMI ID = 48.1>. Example II

  
 <EMI ID = 49.1>

  
sulfur powder was heated at 160-170 [deg.] C for 8 hours. 200 ml of methanol were added to the reaction mixture.

  
The mixture was filtered to remove sulfur powder and evaporated in vacuo to give the <EMI ID = 50.1>

  
removed by evaporation under vacuum. The residue was subjected to silica gel column chromatography and recrystallized from ethyl acetate. The product showed no drop point decrease after mixing with the product

  
 <EMI ID = 51.1>

  
value).

  
 <EMI ID = 52.1>

  
 <EMI ID = 53.1>

  
 <EMI ID = 54.1>

  
Analysis: <EMI ID = 55.1>

  
 <EMI ID = 56.1>

  
Example IX

  
 <EMI ID = 57.1>

  
lyphosphoric acid were stirred under a nitrogen gas stream while stirring

  
 <EMI ID = 58.1>

  
 <EMI ID = 59.1>

  
 <EMI ID = 60.1>

  
 <EMI ID = 61.1>

  
 <EMI ID = 62.1>

  
Example X.

  
 <EMI ID = 63.1>

  
polyphosphoric acid were stirred under a nitrogen gas stream with stirring <EMI ID = 64.1>

  
 <EMI ID = 65.1>

  
Analysis &#65533;

  
 <EMI ID = 66.1>

  
 <EMI ID = 67.1>

  
_Example; .d '_ =

  
 <EMI ID = 68.1>

  
 <EMI ID = 69.1>

  
subjected through a silica gel column and recrystallized from cyclohexane

  
 <EMI ID = 70.1>

  
 <EMI ID = 71.1>

  
Example XIII

  
Preparation of 2- (2-pyridyl) -5 (6) -methoxybenzimidazole:

  
 <EMI ID = 72.1>

  
acid and 40 g of polyphosphoric acid continued under a nitrogen gas stream

  
 <EMI ID = 73.1>

  
 <EMI ID = 74.1> <EMI ID = 75.1>

  
 <EMI ID = 76.1>

  
 <EMI ID = 77.1>

  
Example XVI

  
 <EMI ID = 78.1>

  
 <EMI ID = 79.1>

  
 <EMI ID = 80.1>

  
graphed via a silica gel column (de-plated with 8: 2 mixture of benzene

  
 <EMI ID = 81.1>

  
 <EMI ID = 82.1>

  
 <EMI ID = 83.1>

  
 <EMI ID = 84.1>

  
 <EMI ID = 85.1>

  
 <EMI ID = 86.1>

  
Z? &#65533;, 5 [deg.] C.

  
 <EMI ID = 87.1>

  
 <EMI ID = 88.1>

  
 <EMI ID = 89.1>

  
 <EMI ID = 90.1>

  
 <EMI ID = 91.1>

  
 <EMI ID = 92.1>

  
 <EMI ID = 93.1>

  
Example XXII

  
 <EMI ID = 94.1>

  
 <EMI ID = 95.1>

  
 <EMI ID = 96.1>

  
 <EMI ID = 97.1>

  
 <EMI ID = 98.1>

  
 <EMI ID = 99.1>

  
 <EMI ID = 100.1>

  
 <EMI ID = 101.1>

  
 <EMI ID = 102.1>

  
 <EMI ID = 103.1>

  
picture V.

  
Example XXIII

  
 <EMI ID = 104.1>

  
phosphoric acid were stirred under a nitrogen gas stream while stirring 4 <EMI ID = 105.1>

  
 <EMI ID = 106.1>

  
crystals obtained were recrystallized from acetonitrile. There was

  
 <EMI ID = 107.1>

  
 <EMI ID = 108.1>

  
 <EMI ID = 109.1>

  
 <EMI ID = 110.1>

  
 <EMI ID = 111.1>

  
 <EMI ID = 112.1>

  
Example XXV.

  
Preparation of 2- (m-ethylphenyl) -benzimidazole:

  
 <EMI ID = 113.1>

  
 <EMI ID = 114.1>

  
 <EMI ID = 115.1>

  
 <EMI ID = 116.1>

  
 <EMI ID = 117.1>

  
 <EMI ID = 118.1>

  
Example XXVII

  
 <EMI ID = 119.1>

  
 <EMI ID = 120.1>

  
 <EMI ID = 121.1>

  
 <EMI ID = 122.1>

  
 <EMI ID = 123.1>

  
 <EMI ID = 124.1>

  
 <EMI ID = 125.1>

  
 <EMI ID = 126.1>

  
 <EMI ID = 127.1> <EMI ID = 128.1>

Claims (1)

i <EMI ID=129.1> i <EMI ID = 129.1> <EMI ID=130.1> <EMI ID = 130.1> <EMI ID=131.1> <EMI ID = 131.1> <EMI ID=132.1> <EMI ID = 132.1> <EMI ID=133.1> <EMI ID = 133.1> benzimidazool. benzimidazole. <EMI ID=134.1> <EMI ID = 134.1> benzimidazool. benzimidazole. <EMI ID=135.1> <EMI ID = 135.1> benzimidazool. benzimidazole. 11. Verbinding volgens conclusie 1, 2-(m-ethylfenyl)-benzimidazool. A compound according to claim 1, 2- (m-ethylphenyl) -benzimidazole. 12. Werkwijze ter bereiding van een verbinding volgens conclusie 1, . A method of preparing a compound according to claim 1. <EMI ID=136.1> <EMI ID = 136.1> genoemde betekenissen heeft, of een zuuradditiezout daarvan in has said meanings, or an acid addition salt thereof <EMI ID=137.1> <EMI ID = 137.1> <EMI ID=138.1> <EMI ID = 138.1> <EMI ID=139.1> <EMI ID = 139.1> <EMI ID=140.1> <EMI ID = 140.1> <EMI ID=141.1> <EMI ID = 141.1> <EMI ID=142.1> <EMI ID=143.1> <EMI ID = 142.1> <EMI ID = 143.1> <EMI ID=144.1> <EMI ID = 144.1> <EMI ID=145.1> <EMI ID = 145.1> <EMI ID=146.1> <EMI ID = 146.1> <EMI ID=147.1> <EMI ID = 147.1> stofbromide of boorzuur is. dust bromide or boric acid. <EMI ID=148.1> <EMI ID = 148.1> 15. Werkwijze ter 'bereiding van een verbinding volgens formule 1-a, 15. Process for preparing a compound of formula 1-a, <EMI ID=149.1> <EMI ID = 149.1> <EMI ID=150.1> <EMI ID = 150.1> <EMI ID=151.1> <EMI ID = 151.1> noemde betekenissen heeft, in reactie wordt gebracht, mat de verbinding has said meanings, being reacted measured the connection <EMI ID=152.1> <EMI ID = 152.1> aanwezigheid van zwavel. presence of sulfur. 16. Werkwijze ter bereiding van de verbinding volgens formule 2, 16. Process for preparing the compound of formula 2, <EMI ID=153.1> <EMI ID = 153.1> <EMI ID=154.1> <EMI ID = 154.1> daarna het verkregen produkt wordt behandeld met een alkali onder verhitting. then the product obtained is treated with an alkali under heating. <EMI ID=155.1> <EMI ID = 155.1> generingsmiddel een hypochloriet of tert.-butylhypochloriet is. generating agent is a hypochlorite or tert-butyl hypochlorite. 18. Werkwijze volgens conclusie 16, met het kenmerk, dat de verbinding Method according to claim 16, characterized in that the connection <EMI ID=156.1> <EMI ID = 156.1> waarin R.. de voornoemde betekenissen heeft, in reactie te brengen met in which R .. has the aforementioned meanings, to be reacted with <EMI ID=157.1> <EMI ID = 157.1> <EMI ID=158.1> <EMI ID = 158.1> <EMI ID=159.1> <EMI ID = 159.1> <EMI ID=160.1> <EMI ID = 160.1> <EMI ID=161.1> <EMI ID = 161.1> in reactie te brengen met anhydrische methanol of ethanol onder zure i react with anhydrous methanol or ethanol under acid i <EMI ID=162.1> <EMI ID=163.1> <EMI ID = 162.1> <EMI ID = 163.1> <EMI ID=164.1> <EMI ID = 164.1> <EMI ID=165.1> <EMI ID = 165.1>
BE2056490A 1976-12-07 1977-12-06 PROCESS FOR PREPARING 2-SUBSTITUTED BENZIMIDAZOLE COMPOUNDS AND THE ACID ADDITION SALTS THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS AS AN ACTIVE COMPONENT BE861521A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP51148495A JPS5850997B2 (en) 1976-12-07 1976-12-07 New benzimidazole compound

Publications (1)

Publication Number Publication Date
BE861521A true BE861521A (en) 1978-03-31

Family

ID=15454019

Family Applications (1)

Application Number Title Priority Date Filing Date
BE2056490A BE861521A (en) 1976-12-07 1977-12-06 PROCESS FOR PREPARING 2-SUBSTITUTED BENZIMIDAZOLE COMPOUNDS AND THE ACID ADDITION SALTS THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS AS AN ACTIVE COMPONENT

Country Status (3)

Country Link
JP (1) JPS5850997B2 (en)
BE (1) BE861521A (en)
ZA (1) ZA777168B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4769106B2 (en) * 2006-03-28 2011-09-07 忠行 丹下 Multipurpose hot water bottle

Also Published As

Publication number Publication date
JPS5850997B2 (en) 1983-11-14
ZA777168B (en) 1978-09-27
JPS5371080A (en) 1978-06-24

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