BE536866A - - Google Patents

Description

       

   <Desc / Clms Page number 1>
 



   The present invention relates to a liquid pharmaceutical composition comprising reserpine or its salts. Reserpine is a compound described in recent publications as having hypotensive and relaxing or tranquilizing action. When reserpine is taken by mouth, its effect manifests itself slowly over a period of days or even weeks. In some cases, however, it is desirable to be able to obtain as rapid an effect as possible from this drug. For this purpose, a form of this product which allows rapid absorption, for example by parentemal administration, is particularly desirable.



   Reserpine and its salts, for example its hydrochloride and sulfate, are insoluble in water. Therefore these compounds do not lend themselves readily to the formation of aqueous solutions permitting parenteral administration. Although soluble in some acidic solutions, these compounds are relatively unstable in such solutions when the pH value is higher. is quite far from the neutral value. Reserpine is, it is true, soluble in a number of organic solvents such as chloroform, benzyl alcohol and ethyl acetate, or acetic acid and phosphoric acid, but these solvents cannot be used for parenteral administration.



   The present invention relates to a pharmaceutical composition comprising reserpine or its salts in a liquid pharmaceutical carrier in which the reserpine and its salts are stable and which allows parenteral administration; this composition can be prepared by dissolving the reserpine or its salts in a medium comprising a mixture of ethanol, benzyl alcohol, glycerin, plyethlene glycol and water.



  The components of this composition are generally employed in such proportions as to provide a parenterally administrable solution. These solutions are easily prepared by dissolving reserpine or its salts in benzyl alcohol, then adding to the solution formed, ethanol, polyethylene glycol, glycerin and water for injection.



  Sterilization can be carried out either by treatment in the autoclave or by bacteriological filtration. Preferably, a polyethylene glycol having a molecular weight of about 300, briefly referred to as polyethylene glycol 300, will be employed.



   Particularly suitable compositions are those in which the concentration limits are approximately as follows:
 EMI1.1
 
<tb> Reserpine <SEP> or <SEP> salts, <SEP> up to <SEP> 0.1 <SEP> for <SEP> cent
<tb>
<tb> Ethanol <SEP> 4-5 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Benzyl alcohol <SEP> <SEP> 3-5 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Glycerin <SEP> 34-44 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Polyethylene, glycol <SEP> 300 <SEP> 36-42 <SEP> for <SEP> cent
<tb>
 
Water for injection: amount sufficient to make 100 percent
Compositions comprising these substances are stable, do not hemoglobin when administered intravenously, are well tolerated by intramuscular injections and can be diluted with infusion fluids.



   The following examples serve to illustrate the present invention without, however, limiting it. The amounts in percent indicated in these examples are understood to be by weight.

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    Example .... 1.
 EMI2.1
 
<tb> Réserpine <SEP> 0.05 <SEP> for <SEP> cent
<tb>
<tb> Benzyl alcohol <SEP> <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Ethanol <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Glycerin <SEP> 34 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Polyethylene glycol <SEP> 300 <SEP> 39 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Water <SEP> for <SEP> injection
<tb>
<tb> quantity <SEP> sufficient <SEP> for <SEP> do <SEP> 100 <SEP> for <SEP> hundred.
<tb>
 



   The ingredients are mixed with each other as indicated above and, if necessary, the pH is brought to 6.2 with citric acid.



   Example 2.
 EMI2.2
 
<tb>



  Reserpine <SEP> hydrochloride <SEP> 0.05 <SEP> for <SEP> cent
<tb>
<tb> Benzyl alcohol <SEP> <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Ethanol <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Glycerin <SEP> 34 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Polyethylene glycol <SEP> 300 <SEP> 39 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Water <SEP> for <SEP> injection <SEP>: <SEP>
<tb>
<tb> quantity <SEP> sufficient <SEP> for <SEP> do <SEP> 100 <SEP> for <SEP> hundred
<tb>
 
The ingredients are mixed with each other as indicated above and, if necessary, the pH is brought to 6.2 with citric acid.



   Example 3.
 EMI2.3
 
<tb>



  Reserpine <SEP> <SEP> <SEP> <SEP> 0.05 <SEP> for <SEP> cent
<tb>
<tb> Benzyl alcohol <SEP> <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Ethanol <SEP> 4 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Glycerin <SEP> 34 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Polyethylene glycol <SEP> 300 <SEP> 39 <SEP> for <SEP> cent
<tb>
<tb>
<tb> Water <SEP> for <SEP> injection <SEP>: <SEP>
<tb>
<tb>
<tb> quantity <SEP> sufficient <SEP> for <SEP> do <SEP> 100 <SEP> for <SEP> hundred.
<tb>
 



   The ingredients are mixed with each other .; as indicated above and, if and is necessary, the pH is brought to 6.2 with citric acid.



  CLAIMS. la) 'A process for preparing an aqueous pharmaceutical solution for parenteral application, characterized in that reserpine or its salts are dissolved in a mixture of ethanol, benzyl alcohol, glycerin , polyethylene glycol and water.

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Claims (1)

20) A process for preparing a pharmaceutical aqueous solution for parenteral application, characterized in that about 0.1% reserpine is dissolved in about 4 - 5% ethanol, about 3 - 5% reserpine. benzyl alcohol, about 34 - 44% glycerin, about 36 - 42% polyethylene glycol and enough water to make 100%. <Desc / Clms Page number 3> 3.) A process for preparing an aqueous pharmaceutical solution for parenteral application, characterized in that about 0.05% reserpine is dissolved in about 4% ethanol, about 4% al - benzylic cool, approximately 34% of glycerin, approximately 39% of polyethylene glycol 300 and a quantity of water sufficient to make 100%. 4.) A process for preparing an aqueous pharmaceutical solution for parenteral application, characterized in that about 0.05% reserpine hydrochloride is dissolved in about 4% ethanol, about 4% dar. Benzyl alcohol, about 34% glycerin, 39% polyethylene glycol 300 and enough water to make 100%. 5.) A process for preparing an aqueous pharmaceutical solution for parenteral application, characterized in that about 0.05% reserpine sulfate is dissolved in about 4% ethanol, envirion 4 % benzyl alcohol, about 34% glycerin, about 39% polyethylenglycol 300 and enough water to make 100%. As a new industrial product: 6.) A pharmaceutical aqueous solution for parenteral application, characterized by the fact that it contains reserpine or one of its salts, dissolved in a mixture of ethanol, benzyl alcohol , polyethylene glycol glycerin and water. 7.) A pharmaceutical aqueous solution for parenteral application, characterized in that it contains up to 0.1% reser- pine, about 4 - 5% ethanol, about 3 - 5% d Benzyl alcohol, about 34-44% glycerin, about 36-4% polyethylene glycol and enough water to make 100%. 8.) A pharmaceutical aqueous solution for parenteral application, characterized in that it contains about 0.05% reserpine, about 4% ethanol, about 4% benzyl alcohol, about 34% resin. glycerin, about 39% polyethylene glycol 300 and enough water to make 100%. 9.) A pharmaceutical aqueous solution for parenteral application, characterized in that it contains approximately 0.05% reserpine hydrochloride, approximately 4% ethanol, approximately 4% benzyl alcohol, about 34% glycerin, about 39% polyethylene glycol 300 and enough water to make 100%. 10.) A pharmaceutical aqueous solution for parenteral application, characterized by containing about 0.5% reserpine sulfate, about 4% ethanol, about 4% benzyl alcohol, about 34 % glycerin, about 39% polyethylene glycol 300 and enough water to make 100%. 11.) A pharmaceutical aqueous solution for parenteral application, as described in each of the examples above.