BE878168A

BE878168A - BENZAMIDO-ALKYL-MERCAPTANS MUCOLYTIC MEDICINAL PRODUCTS

Info

Publication number: BE878168A
Application number: BE0/196670A
Authority: BE
Inventors: R Alphin
Original assignee: Robins Co Inc A H
Priority date: 1978-08-10
Filing date: 1979-08-09
Publication date: 1979-12-03
Also published as: ZA794170B; JPS5536487A; PH15608A

Description

       

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peuvent être identiques ou différents ; et peuvent se; trouver dans des  positions mutuelles variées:  <EMI ID=12.1> 
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On écrase cette nasse et on la triture avec soin avec de l'essence de 

  
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de pyridine sèche. On cote 'un léger dégagement de chaleur. Après agi-

  
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de réaction au reflux pendant 4 h, on refroidit et on coule sur 400 g de glace. On extrait le mélange de réaction à quatre reprises avec

  
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deux reprises avec 200 ni d'eau glacée. Après séchage sur sulfate de magnésium, on concentre l'extrait par évaporation; on obtient une huile de couleur crème qui se solidifie au'repos. On agite cette

  
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EXEMPLE 2 

  
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une petite quantité d'insoluble et on la rejette. On extrait le fil-

  
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Analyse élémentaire : 

  

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EXEMPLE 7 

  
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A. une solution de 5,6 g (0,10 mole) d'hydroxyde de potas-

  
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 <EMI ID=46.1>  extrait à'nouveau. On combine les extraits, on sèche, on concentre puis on dilue à l'essence de pétrole légère. On recristallise la substance solide dans un mélange benzène/essence de pétrole légère. On

  
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, EXEMPLE 8

  
Lorsque, dans l'opération de l'exemple 7, on remplace le

  
 <EMI ID=50.1>  chlorhydrate de l'ester 2-aminoêthylique de l'acide

  
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EXEMPLE 9 

  
Lorsque, dans l'opération de l'exemple 7, oa remplace le <EMI ID=52.1>  

  
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suffisante pour manifester une action réelle sur la congestion des poumons de patients mammifères en application topique par inhalation avec un véhicule acceptable. 

  
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suffisante pour déclencher la liquéfaction du mucus dans la voie res-

  
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techniques variées d'inflation ou d'instillation sous forme de gouttes nasales, de pulvérisations, d'aérosols et sous des formes analogues. Parmi les véhicules liquides acceptables pour- l'usage pharmaceutique,  on citera l'eau et le polyéthylèneglycol 300. On peut également admi-

  
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ultrafines en exploitant uniquement .l'effet d'inspiration ou en faisant appel à des propulseurs d'aérosols. En général, la quantité de composé actif, dans la composition pour inhalation varie d'environ 0, 5

  
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l'aide d'ua atomiseur, d'un nébuliseur, d'un aérosol ou d'un dispositif analogue. On peut également utiliser des poussières contenant'

  
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la substance active. 

  
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observer avec un patient particulier est fonction de la sévérité de

  
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du poids et de l'état physique général du patient. Des doses individuel-les allant d'environ 5 à 100 mg par inhalation, chez l'homme,  conviennent et peuvent être exigées pour que l'effet mucolytique se manifeste. 

  
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tions et suspensions dans des liquides administrés correctement en inhalation. 

  
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rompre la paroi de la capsule avant l'administration.

  
Il est clair que l'invention n'est nullement limitée aux  =des de réalisation décrits ci-dessus à titre d'exemples et que l'homme de l'art peut y apporter des modifications sans pour autant  sortir désencadre. 

  
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dans laquelle : 

  
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des positions mutuelles différentes sur le cycle.

  
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can be the same or different; and can be; find in various mutual positions: <EMI ID = 12.1>
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We crush this trap and carefully triturate it with the essence of

  
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of dry pyridine. There is a slight release of heat. After agi-

  
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reaction at reflux for 4 h, cooled and poured onto 400 g of ice. The reaction mixture is extracted four times with

  
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twice with 200 ni of ice water. After drying over magnesium sulfate, the extract is concentrated by evaporation; a cream-colored oil is obtained which solidifies on reposition. We shake this

  
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EXAMPLE 2

  
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a small amount of insoluble and discarded. We extract the wire-

  
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Elemental analysis:

  

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EXAMPLE 7

  
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A. a solution of 5.6 g (0.10 mole) of potassium hydroxide

  
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 <EMI ID = 46.1> retrieved again. The extracts are combined, dried, concentrated and then diluted with light petroleum spirit. The solid is recrystallized from a benzene / light petroleum mixture. We

  
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, EXAMPLE 8

  
When, in the operation of Example 7, the

  
 <EMI ID = 50.1> 2-aminoethyl acid ester hydrochloride

  
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EXAMPLE 9

  
When, in the operation of Example 7, oa replaces the <EMI ID = 52.1>

  
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sufficient to manifest an effective action on the congestion of the lungs of mammalian patients when applied topically by inhalation with an acceptable vehicle.

  
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sufficient to trigger the liquefaction of mucus in the respiratory tract.

  
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various techniques of inflation or instillation in the form of nasal drops, sprays, aerosols and the like. Among the liquid carriers acceptable for pharmaceutical use are water and polyethylene glycol 300. It is also possible to administer.

  
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ultrafine by using only the inspiration effect or by using aerosol propellants. In general, the amount of active compound in the inhalation composition varies from about 0.5

  
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using an atomizer, nebulizer, aerosol or the like. Dust containing '

  
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the active substance.

  
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observed with a particular patient depends on the severity of

  
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the weight and general physical condition of the patient. Individual doses ranging from about 5 to 100 mg by inhalation, in humans, are suitable and may be required for the mucolytic effect to manifest.

  
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tions and suspensions in fluids administered correctly by inhalation.

  
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rupture the wall of the capsule before administration.

  
It is clear that the invention is in no way limited to the embodiments described above by way of examples and that a person skilled in the art can make modifications thereto without, however, going outside the box.

  
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in which :

  
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different mutual positions on the cycle.

  
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Claims

6. Therapeutic compositions in liquid form, usable

acceptable for pharmaceutical use.

pharmaceutical composition containing them,

that it declares to have been the subject of a patent application

cause. <EMI ID = 80.1>

tick containing them .. '<EMI ID = 81.1>

useful for dissolving and diluting mucus in warm-blooded animals with congested lungs.

The ^ compounds described below and represented by

before: to place it in 1 .; ' drug solution. Discard the stomachs present ;, odor -of feces or -containing

stomachs. The mean differences between the values found in the treated animals and the control animals are expressed as a percentage.

metric. Place in the refrigerator and use only for a week.

Solution 2: Sucrose 0.25 M (1 liter)

85.6 g of sucrose are added to a volumetric flask.

use only for 1 week.

1 liter volumetric flask. The volume is completed with deionized water.

The subject of the invention is therefore certain new salts

The invention also relates to the use of

lungs..

pharmaceuticals containing compounds useful for limiting <EMI ID = 110.1>

tront to those skilled in the art on reading the following description of the best mode of implementation of the invention.

In the definition of symbols and in formula 1 above, and in the remainder of the present description, the terms used have the following meanings.

phenyl radical which is substituted by 1 to 3 radicals chosen from

the group defined above in the definition of 8, these substituents possibly being in the various positions available in the ring

can be identical- or different and in the various combinations of position relative to each other. Substituents

straight or branched chain carbon. Mention may be made, as examples of preferred substituents, of the methyl, ethyl, propyl, butyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy,

for the preparation of benzene derivatives, represented by the following equation:

Generally, the reactants are mixed and heated with a steam jet until a crystalline mass is formed. The mass of crystals is then ground, triturated with ligrdine and recrystallized from anhydrous ethanol.

The following examples illustrate the invention without, however, limiting its scope. <EMI ID = 118.1>

Anhydrous ethanol gives a colorless solid which melts at

red (IR) all confirm the structure of the research compound.

EXAMPLE 2 '

moisture, a mixture of 60 ml (0.47 mole) of chloride

EXAMPLE

When replaced, in the operating mode of

respectively...

steam, for 6 h, mixture of 15.8 g (0.108 mole) of chloride

<EMI ID = 151.1> ONLY

or ultrafine powder using only the energy for the inspiratory action. or by the use of aerosol propellants.

correct, of the compound used for a particular subject is determined

as the age, sex, weight and general condition of the subject. Doses

Pharmaceutical compositions; may appear

solutions and suspensions in liquids suitably delivered for inhalation, as illustrated below.

A. Powder for administration by means of an inhaler device.

We. dissolves ingredients 1 and 2 by heating and

C. Aqueous solution.

dosage and administered by means of a. inhaler or aerosol device,.

embodiments. preferred described above by way of illustration and that those skilled in the art will be able to add codifications to them without departing from the scope of the invention. <EMI ID = 169.1>