DE1182656B - Process for the preparation of N-benzenesulfonyl-N'-cyclohexyl-ureas - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Boarding school Class: C 07 c

German KL: 12 ο - 25

Number: 1182 656

File number: F 21005IV b / 12 ο

Filing date: October 14, 1955

Opening day: December 3, 1964

The subject of the German patent 965 400 is a process for the production of new benzenesulfonylureas the general formula

Process for the production of Ϋοη N-benzenesulfonyl-N'-cyclohexylureas

Addendum to the patent: 965 400

X = -

-SO.— NH-CO - NH- ( H

wherein R stands for hydrogen or a low molecular weight alkyl radical or alkoxy radical, which is characterized is that one

a) optionally alkylated or alkoxylated benzenesulfonyl isocyanates with cyclohexylamine or N-cyclohexyl isocyanate or such compounds, which convert into cyclohexyl isocyanate in the course of the reaction, with those of the above formula converts corresponding sulfonic acid amides; or

b) optionally alkylated or alkoxylated benzenesulfonyl urethanes with cyclohexylamine or N-cyclohexyl urethanes with optionally alkylated ones or brings alkoxylated benzenesulfamides to reaction; or

c) Cyclohexylcarbamic acid halides with optionally alkylated or alkoxylated benzenesulfonic acid amides or the corresponding benzenesulfonylcarbamic acid halides with cyclohexylamine implements; or

d) optionally alkylated or alkoxylated benzenesulfonylureas which _{are unsubstituted in the NH 2} group are converted into the corresponding cyclohexyl compounds by reaction with cyclohexylamine; or

e) N-Cyclohexylurea with optionally alkylated ones or brings alkoxylated benzenesulfonic acid amides to reaction; or

f) Isourea ethers, expediently in the form of their salts, with optionally alkylated or alkoxylated Brings benzenesulfonic acid halides to the reaction and the products thus obtained then hydrolyzed under acidic conditions; or

g) produces and desulfurizes the corresponding thioureas; or

h) optionally alkylated or alkoxylated N-benzenesulfonyl-N'-cyclohexylguanidines and hydrolyzes them.

The present invention relates to a modification of the process for the preparation of N-benzenesulfonyl-N'-cyclohexylureas the general formula

? - SO "- NH - CO - NH -

where R is hydrogen or a low molecular weight alkyl radical or alkoxy radical, according to the patent Applicant:

Farbwerke Hoechst Aktiengesellschaft formerly
ίο Master Lucius & Brüning, Frankfurt / M.

Named as inventor:,

Dr. Heinrich Ruschig, Bad Soden (Taunus),

Dr. Hans Wagner,

Frankfurt / M.-Unterliederbäch,

Dr. Gerhard Korger, Frankfurt / M.-Höchst,

Dr. Walter Aumüller, Kelkheim (Taunus),

Dr. Josef Scholz, Frankfurt / M.-Höchst,
Dr. Alfred Bänder, Hofheim (Taunus)

965 400, which is characterized in that instead of the cyclohexyl derivatives, the corresponding Cycloalkyl or cycloalkylalkyl derivatives of other ring size with a maximum of 8 carbon atoms according to the implements known methods listed in the main patent. Draw the process products are characterized by a very strong and long-lasting lowering of the blood sugar value.

The processes specified in the main patent can vary widely in terms of their reaction conditions and adapted to the respective conditions. For example, the implementations can be made using of solvents at room temperature or at elevated temperature. As by simple procedure and by high yields particularly suitable methods are It should be emphasized that on the conversion of benzenesulfonyl isocyanates or of benzenesulfonyl carbamic acid esters with corresponding amines or vice versa on the implementation of benzenesulfonic acid amides based with appropriate isocyanates. The starting materials come after the process according to the invention the following benzenesulfonyl compounds into consideration: benzenesulfonyl isocyanates, the in the benzene nucleus in any position by alkyl groups or alkoxy groups can be substituted, in particular compounds are suitable which in the p-position a methyl group or a methoxy

409 730/38 *

3 4

group wear; appropriately substituted benzene and 21.3 g (0.25 mol) of cyclopentylamine with stirring

sulfonic acid amides; appropriately substituted benzene at 2O ⁰ C slowly added dropwise. The mixture is then stirred until

sulfonyl urethanes, e.g. B. in the urethane compo- the smell of isocyanate has disappeared, cools

nente a low molecular weight alkyl radical, for example, and sucks the precipitated in good yield

wise contain a methyl or ethyl radical; ent- 5 N - (4 - methyl - benzenesulfonyl) - N '- cyclopentyl-

Speaking substituted benzenesulfonylureas; de-urea. For cleaning, dissolve in diluted

Speaking substituted benzenesulfonic acid halides. Ammonia, clarifies with charcoal and drops the compound

For the reaction with the above with dilute acid again off. The melting point

According to the invention, compounds can, for example, be present after recrystallization from acetonitrile

as cycloalkylamines, cyclopentylamine and cyclo- io 169 to 170 ° C.

heptylamine and, as cycloalkylalkylamines, cyclo- B e i s d i e 1 2 hexylmethylamine and cyclohexylethylamine are used

will. N- ^ methyl-benzenesulfonyQ-N'-cyclohexylmethyl-

Instead of the amines mentioned, urea

The method of the invention also includes the corresponding 15 In a solution of 28.3 g (0.25 mol) of cyclohexyl and isocyanates which can be prepared from these amines, methylamine in 200 ecm of absolute benzene Urethanes, carbamic acid halides, ureas and, with cooling and vigorous stirring, 49.3 g of 4-methyl isourea ether slowly added dropwise to react with the corresponding benzenesulfonyl isocyanate. Unsubstituted Benzenesulphonic acid amides or halides are then countered under reflux for a further 1 hour be used. 20 cooks. Then cool down, dilute with ether and

Particularly suitable thioureas are N- (4-methyl- sucks off the precipitate. The in

or methoxybenzenesulfonyty-N'-cycloalkyl- or cy- good yield obtained N- (4-methyl-benzenesulfonyl) -

cloalkylalkylureas suitable, which differ from the pre-N'-cyclohexylmethyl urea is in dilute

Derive listed amines. The excess ammonia dissolved. The solution is made with charcoal

leading these thioureas into the desired 25 clarified and with dilute hydrochloric acid under vigorous

Compounds can be acidified again with the help of heavy metal stirring. The failed connection

Oxides or salts, for example of lead or copper manure, are sucked off and washed well with water

or silver, in aqueous or alcoholic solution and recrystallized from acetonitrile. Melting point

be made. 178 to 179 ° C.

The desired connections 30

also example 3 constructed accordingly by hydrolysis

Guanidines with diluted acids or alkalis “. ,. ., _it _,,. _{ir Ιλ XT,,} . ,

can be obtained. N- ^ methyl-benzenesulfonyO-N'-cyclopentyl-

The urea by the method according to the invention

Available compounds are characterized by large 35 17.7 g of 4-methylbenzenesulfonamide are in 120 ml Stability. Compared to the chemotherapy acetone with 22 g of ground potassium carbonate 1 hour Aminobenzenesulfonamides came to the importance heated to boiling with stirring. Then drips is mainly their resistance to oxidizing 10 g of cyclopentyl isocyanate and boiling under remarkable influences. You keep stirring at reflux until the smell refluxes full remedies that have disappeared in particular due to their 4 ° isocyanate. The solvent will distinguish blood sugar-lowering effectiveness. then largely distilled off, the residue in

Compared to that taken from the German Medical Water, clarified with some charcoal and Wochenschrift, 80 (1955), p. 1449, known blood- the filtrate acidified with dilute hydrochloric acid. Of the sugar-lowering substance BZ 55, the precipitated N- (4-methylbenzenesulfonyl) -N'-cyclo process products are distinguished by the fact that they do not suck off any pentyl urea, wash them off and show chemotherapeutic effects. Accordingly, it is recrystallized from acetonitrile. The melting point makes it possible to take the process products over longer periods of 169 to 170 ^° C. without the risk of a

Damage to vital bacteria to be observed. B e i s ρ 1 e 1 4

fear is. 5 ° _XT ,, _{τ ,,, 1r n XI} ,,. ,

The process products are said to be used for the production of N- (4-isopropyl-benzenesulfonyl) -N -cyclopentyl-

Orally administrable preparations with blood sugar ^arns °

lowering effect for the treatment of sugars- 10 g of 4-isopropyl-benzenesulfonamide are used with 20 g of urinary dysentery. ground potassium carbonate in 50 ml of acetone under The compounds mentioned can be heated to boiling as such 55 stirring. 7 g of cyclopentylcarbamic acid chloride are added dropwise to this mixture or in the form of their salts or in the presence of 7 g of cyclopentylcarbamic acid chloride (substances which lead to salt formation are shown, conversion from cyclopentyl isocyanate by passing in dry use. For salt formation, for example, hydrogen chloride) is slowly added and stirred still wisely used: ammonia, alkaline 8 hours at boiling temperature after. The solvent, such as alkali metal or alkaline earth metal hydroxides, alkali metal medium is then possible carbonates or bicarbonates, furthermore physiologically lent, completely distilled off under reduced pressure, the residue with compatible organic bases. Treated water, filtered off undissolved material and the. -I ₁ clear solution extracted once with ether. Man example! Acidify the aqueous phase with dilute hydrochloric acid N- (4-methyl-benzolsuh ^c onyl) _{-N'-cyclopentyl-65 at> sucks} the deposited substance from, it dissolves in about l ° urea / pc alcohol ammonia, filtered and precipitated again 49, 3 g (0.25 mol) of 4-methyl-benzenesulfonyl-iso- with dilute hydrochloric acid. The sucked off N- (4-isocyanate are dissolved in 250 ecm of absolute benzene propyl-benzenesulfonyty-N'-cyclopentyl-urea

5 6

Recrystallized from ethanol-water and melts benzenesulfonyty-N'-cyclopentylurea from the melt at 144-146 ° C. point 139 to 14O ⁰ C.

Example 5 Example 9

N- (4-methyl-benzenesulfonyl) -N'-cyclopropyl- N- (4-methyl-benzenesulfonyl) -N '- ^ - cyclohexylethyl-

urea urea

12 g of 4-methyl-benzenesulfonyl-carbamic acid chloride, 22.9 g of p-toluenesulfonylmethyl urethane and 12.7 g

are mixed with cooling in excess cyclopropyl-ß-cyclohexyl-ethylamine and enter 40 miamin. After completion of the reaction io grooves heated to 130 to 14O ⁰ C. The melt is dissolved, the mixture is poured into water, filtered and acidified in approx. 11% dilute ammonia (1:25), suctioned off with dilute hydrochloric acid until a Congo acidic reac- tion of a little undissolved matter and the filtrate is clarified with ion. The precipitated reaction product becomes coal. The precipitate obtained after acidification with dilute after cooling and obtained from ethanol-water hydrochloric acid is recrystallized from about. The N- (4-methyl-benzenesulfonyl) - 15,200 cc of methanol with the addition of charcoal to-N'-cyclopropyl-urea melting at 165-168 ⁰ C. crystallized. The N- (4-methyl-benzene-

sulf onyl) -N'-jS-cyclohexylethyl urea from melting example 6 point 122 to 124 ⁰ C.

N- (4-methyl-benzenesulfonyl) -N'-cyclobutyl urea ²⁰ B bis ρ ie 1 10

20 g of 4-methyl-benzenesulfonamide sodium are triturated well N- (4-methoxy-ben olsulfonyl _Z) -N'-cyclopentyl-harnmit 28 g of milled potassium carbonate

and with 13 g of cyclobutylcarbamic acid methyl ester To a solution of 83 g of 4-methoxy-benzenesulfo-

^{Heated to 130 °} C. in the bath for 3 hours. After the 25 nyl-methyl urethane in ethyl acetate, 28.6 g of cyclo-cooling are dissolved, the reaction mixture is dissolved in water, pentylamine is added, salt-filtered while warming and the filtrate is added until Congo-acidic formation occurs. The ethyl acetate is then reacted with hydrochloric acid. The crude precipitate is distilled off under reduced pressure and the viscous, oily one is suctioned off, treated with about 1% ammonia, the residue is ^{heated to 130 °} C. for 1 hour in a heating bath, any undissolved sulfonamide is suctioned off and this is finally dissolved to a solid mass Filtrate, the reaction product in turn precipitated with the solidified reaction product after cooling in thin hydrochloric acid. The N- (4-methyl- dilute ammonia obtained, filtered and acidified the benzenesulfonyl) -N'-cyclobutylurea melts after the filtrate until the Congo acidic reaction with hydrochloric acid, drying and recrystallization from ethyl acetate. The precipitated N- (4-methoxy-benzenesulfonyl) -at 163 to 165 ° C. 35 N'-cyclopentyl urea is filtered off with suction, with water

washed and recrystallized from ethanol. Example 7 melting point is 182 to 184 ° C.

_{xT,. T,,,,} "", _T , _{/ o} ,,, In an analogous manner one obtains using

N- (4-Isopropyl-benzenesulfonyl) -N - (^ - cyclohexyl- _yon ^ Cyclohexylethylamine den N- (4-methoxy-benzene-

atnyi) -narnstori ₄₀ suifonylj-N'-iS-cyclohexylethyl urea, which according to the

25.7 g of N- (4-isopropyl-benzenesulfonyl) -carbamine- recrystallize from methanol at 149 to 151 ⁰ C and 12.7 g /? - Cyclohexylethylamine melts.

are mixed well together and 45 minutes Example 11

heated to 120 to 13O ⁰ C. The resulting melt

is taken up in dilute ammonia, the 45 N- (4-methyl-benzenesulfonyl) -N'-cyclohexylmethyl solution separated from undissolved matter, the filtrate with urea

Clarified and acidified coal. The precipitating 20 g of 4-methylbenzenesulfonamide sodium and 16 g

semi-solid precipitate is after separation hexahydrobenzyl urea are recrystallized twice from methanol in the mortar. Is obtained, and the mixture for 6 hours at 160 ⁰ C to N in the bath - (4 - isopropyl - benzenesulfonyl) - N '- (. Heated j3-cyclo- 50 The solid after cooling Reaktionshexyläthyl) urea as white crystals from the mixture is taken up with slight warming in water, melting point 109 to 111 ^° C., the solution filtered and the filtrate

with hydrochloric acid until the Congo acid reaction

Example 8 is sour. The precipitate which has separated out is sucked off

55 and treats it with about 10% ammonia.

N- (4-ethylbenzenesulfonyl) -N'-cyclopentylurea. Undissolved sulfonamide is filtered off and the solution again acidified with hydrochloric acid.

36.5 g of N- (4-ethylbenzenesulfonyl) -carbamic acid- precipitated N- (4-methylbenzenesulfonyl) -N'-cyclomethyl ester and 12.7 g of cyclopentylamine become hexylmethylurea after suction and 35 minutes at 130 ° C merged. The melt is recrystallized 60 washing from ethanol-water and treated with dilute ammonia (1:50), then melts at 178 to 179 ° C.
with only the sulfonylurea formed as ammonium Example 12

salt goes into solution. One separates from the insoluble

Material, clarifies the filtrate with charcoal and acidifies N- (4-isopropyl-benzenesulfonyl) -N '- (^ - cyclohexyl-

slowly with dilute hydrochloric acid. The aus- (ethyl) urea

falling crystallized precipitate is filtered off with suction, 24 g of 4-isopropyl-benzenesulfonyl-urea become

washed with water, dried and combined twice with 12.7 g of iS-cyclohexylethylamine, with Recrystallized ethyl acetate. The N- (4-ethyl heating is obtained. The heating is carried out for about 1½ hours

to 130 to 135 ^° C., the reaction product treats this with 4-methylbenzenesulfonyl chloride in the presence, after cooling, with dilute ammonia and alkali in the N- (4-methylbenzenesulfonyl) -filtrated from insoluble constituents. The filtrate N '- (| ö-cyclohexylethyl) -guanidine transferred, clarified with charcoal and acidified with dilute hydrochloric acid 3 g of the resulting N- (4-methylbenzenesulfonyl). The precipitated N- (4-isopropyl-benzene-5 N'-G8-cyclohexylethyl) -guanidins are with 3 g nasulfonyl) -N '- (/? - cyclohexylethyl) urea can be obtained from trium hydroxide and 12 ml of water for 3 hours Recrystallize from ethanol-water. The melting point of the reflux condenser is heated to the boil. After the temperature is 109 to 110 ^° C., water is added, some dissolved un-example 13 is filtered off, the filtrate is acidified and the mixture is treated

ίο precipitated and sucked substance with about 1% ^em

N - ^ - methyl-benzenesulfonyO-N'-cyclohexylmethyl ammonia. Insoluble parts are separated off

urea _and the filtrate again with dilute hydrochloric acid

31 g of hexahydrobenzyl urea are acidified with 19 ml. The precipitated N- (4-methylbenzenesulfo-

Dimethyl sulfate is heated on the steam bath until nyl) -N '- (j9-cyclohexyläthyi) -urea is converted from metha-

the mixture begins to liquefy and the temperature 15 recrystallizes and melts at 122 to 123 ° C.

temperature increased by the reaction to about 12O ⁰ C Beisoiel 16

is. Allow to cool, take up in 100 ml of water,,, _

gives a solution of 38 g of p-toluenesulfonyl chloride in N- (3-methylbenzenesulfonyl) -N-cyclopentylurea

50 ml of acetone to, some of the sulfochlo- 34.5 g (3-methyl-benzenesulfonyl) -carbamic acid precipitates out again in finely divided form and 20 methyl esters are added dropwise with 13 g of cyclopentylamine in the solution with ice-cooling and stirring in an oil bath for 1 hour heated to 13O ⁰ C. It increases in 100 ml of water of 18 g of sodium hydroxide, the product, after cooling, diluted in Ammoderart that the temperature not exceeding 40 ⁰ C rises niak, filtered and precipitated by addition of SaIz- and the solution kept slightly alkaline acid. The obtained N- (3-methyl-benzenesulfonyl) -will. After the end of the dropping, the mixture is stirred for about 1 hour under the N'-cyclopentylurea melts after cooling around with ice; separated crude isourea ether and after a short example 17 rinsing with water with about double. , ,, _ Amount of concentrated hydrochloric acid on the steam bath N- (4-methyl-benzenesulfonyl) -N-cycloheptyl-urea

heated. With evolution of methyl chloride, the isourea ether formed is cleaved with a mixture of 35.0 g (0.14MoI) of 4-methyl and converted into the good benzenesulfonyl urethane and 15.8 g (0.14MoI) of cyclocrystallized N- (4-methylbenzenesulfonyl) -N '-cy- heptylamine is converted to clohexylmethyl urea in an oil bath for 2 hours. Treating 125 to 130 ⁰ C and then heated, filters the crude product stirred with about l% strength ammonia ^e m so long as it is until it became sufficiently fluid. The triert and precipitates from the clear solution with acid. The ethanol formed in the reaction is distilled off, urea precipitates, which after recrystallization by first melting ^{a vacuum of 100 torr for ethanol-water at 178 to 179 ° C.} 1 hour and then a vacuum of 15 to

Example 14 ^ O ^ orr ^ ^for ^ hours. The return

stand is after cooling with a solution of

N- (4-methyl-benzenesulfonyl) -N'-cyclohexylmethyl ₄₀ ammonium hydroxide in a ratio of 1:25 was added urea _{un (j,} the reaction mixture stirred until the

32.6 g of N- (4-methyl-benzenesulfonyl) -N'-cyclohexyl precipitation has separated out clearly. After filtration methyl-thiourea a melting point of 153-155 ⁰ C is added a hydrochloric acid solution, once again (prepared by reacting 4-methyl-benzene-filtered and the residue was stirred again with said sulfonamide with cyclohexylmethyl-mustard oil-in counter 45 ammonium hydroxide This reaction of potassium carbonate and acetone) is filtered into the mixture, and the combined acetone is dissolved. This solution is mixed with ammoniacal solutions and acidified with acetic acid, stirring with a solution of 8 g of sodium nitrite. The white precipitate obtained is collected in 50 ecm of water. It is now cooled to about 5 ° C., washed with water and recrystallized from ethanol, regardless of a slight crystal deposit. 23.0 g of N- (4-methylbenzenesolene) are obtained with stirring and, in the course of one hour, sulfonyty-N'-cycloheptylurea in the form of drops of 60 ecm of 5N acetic acid ⁰ C. then stirs for a further 3 hours at room

temperature after, diluted with water and sucks off 4-methoxy-benzenesulfonyl urethane with cycloheptyl the deposited precipitate. This is treated with ammonia 55 amine N- (4-methoxy-benzoIsulfonyl) -N'-cycloheptyll%, the resulting urea of melting point 161 to 163 ⁰ C obtained. Sulphonylurea goes into solution. It is filtered from Beisoiell8

the sulfur formed in the reaction, ^ ₁ . ,. .,,,,,,. ,. _XT,,,,, ~

clarifies the filtrate with charcoal and acidifies with dilute N- (3-methylbenzenesulfonyl) -N -cycloheptylurea

Hydrochloric acid. The deposited precipitate is 60 46 g of N-ß-methyl-benzenesulfonylJ-carbamic acid

suctioned off, washed with water and from acetomethyl ester and 22.6 g of cycloheptylamine are added

recrystallized nitrile. Melting point 178 to 179 ⁰ C. melted together. The melt is 90 minutes

Example 15 heated to 130 to 140 ⁰ C and then with warmer

l% ig ^he treated ammonia solution. One receives a

N- (4-methylbenzenesulfonyl) -N '- (/? - cyclohexyI- ₆₅ Crystals of the ammonium salt of N- (3-methyl-

ethyl) urea benzenesulfonyl) -N'-cycloheptyl urea, moderately soluble

/ 5-Cyclohexylethylamine hydrochloride is borrowed with cyano in ammonia, which with the help of hydrochloric acid

amide is converted to / J-Cyclohexyläthylguanidin and cleaved. After recrystallization from methanol

one obtains the desired urea in a yield of 45 g of melting point 137 to 139 ⁰ C. In an analogous manner, 46 g of N- (3-methylbenzenesulfonyl) -carbamic acid methyl ester and 25.4 g of cyclooctylamine 42 g N- (3-methyl -benzenesulfonyl) -N'-cyclooctylurea from melting point 130 to 132 ⁰ C.

Example 19
N- (4-methyl-benzenesulfonyl) -N'-cyclooctyl urea

A mixture of 24.33 g (0.1 mol) of 4-methyl-benzolsulfonylurethan and 12.72 g (0.1 mole) of cyclooctylamine was heated with stirring for 2 hours at 13O ⁰ C. The alcohol formed and excess amine are removed by applying a vacuum of 100 torr for 1 hour and then of 20 torr for 2 hours. After cooling, 4000 ml of an ammonium hydroxide solution are added in a ratio of 1:25. The mixture obtained is stirred until most of the solid constituents are dissolved. The liquid part of the reaction mixture is decanted and acidified with glacial acetic acid. The crude precipitate is recrystallized from alcohol to give 19.15 g of the above compound obtained in the form of yellow colored prisms, which melt from 144.5 to 146.5 ⁰ C. A second recrystallization from alcohol gives analytically pure N - (4 - methylbenzenesulfonyl) -N'-cyclooctylurea with a melting point between 145 and 146 ° C.

In an analogous manner, N - (4 - methoxy - benzenesulfonyl) - N '- cyclooctylurea with a melting point of 160 to 163 ^° C. is obtained from 4-methoxybenzenesulfonyl urea and cyclooctylamine.

Example 20

N-ß-methoxy-benzenesulfonyty-N'-cyclooctyl urea 25 g cyclooctylamine and 49 g N- (3-methoxy-ben-

zolsulfonyl) carbamic acid methyl ester are combined. Salt formation occurs with a positive warming effect. The salt is heated to 130 to 140 ° C. in an oil bath for 90 minutes, then brought to cool and dissolved in ethyl acetate. This solution is extracted three times with 200 ecm of a 10% aqueous ammonia solution. After clarification with charcoal, N- (3-methoxy-benzenesulfonyl) -N'-cyclooctylurea is obtained in the form of a crystalline precipitate by acidifying the ammoniacal solution with dilute hydrochloric acid. The precipitate is filtered off with suction, washed with water and recrystallized from ethanol. This gives 38 g of the desired product of melting point 117 to 119 ⁰ C. Jj

Claims (1)

Claim: Modification of the process for the preparation of N-benzenesulfonyl-N'-cyclohexylureas der formula R ' SO ₈ -NH-CO-NH wherein R is hydrogen or a low molecular weight alkyl radical or alkoxy radical, according to Patent 965400, characterized in that instead of the cyclohexyl derivatives, the corresponding cycloalkyl or cycloalkylalkyl derivatives other ring size with a maximum of 8 carbon atoms according to the methods known per se listed in the main patent. Considered publications: German Patent Nos. 741 533, 910 779;
French Patent No. 877 129;
Swiss Patent No. 231 025.