DD293488A5 - PROCESS FOR PREPARING MEDICAMENT FOR RECTAL APPLICATION - Google Patents

Abstract

The invention relates to a method for producing Wirkgesteigerter drugs for rectal administration, which is characterized in that as resorption-enhancing component, an amino acid fatty acid condensation product is used. It finds particular application for the active ingredient chloramphenicol. Fig. 1 and 2 {biologically active substances; absorption; An amino acid, fatty acid condensation product; suppositories; Method; Increase in activity; Medicinal, native, synthetic; Hydrolysis; chloramphenicol}

Description

Field of application of the invention

The invention relates to the increase in activity of biologically active substances, which are represented by poor or slow absorption in rectal administration and have no peptide structure.

Characteristic of the known state of the art

It is known that pharmaceutical active substances, in particular analgesics, anti-inflammatory drugs, anti-inflammatory drugs such as propiophenazone, indomethacin, but also chemotherapeutic agents in the form of suppositories are used because the oral administration leads to adverse side effects for the patient. Disadvantage of this procedure for some of the substances, however, is their insufficient or delayed resorbability from the rectum. This is countered by the fact that the active ingredient in the suppository is dosed considerably higher, in comparison to the per-os application to achieve approximately analogous results. The use of resorption-promoting substances has hitherto been described in the rectal use of peptide active ingredients, since these active ingredients are mostly unstable in the intestine and therefore must reach the bloodstream very quickly.

Z'el of the invention

The aim of the invention is to reduce the use of active ingredient by improving the absorption of biologically active substances from the rectum, to allow the rectal absorption at all or to accelerate the absorption with the aim of faster onset of action.

Explanation of the nature of the invention

The object of the invention is to find a way to reduce this overdose of the active ingredient. As active ingredients, chloramphenicol and propyphena / in are preferably mentioned here. The absorption improvement is achieved in that the absorption-enhancing component is an amino acid-fatty acid condensation product, wherein the amino acid may also be a low molecular weight native hydrolytically or synthetically derived polypeptide. The fatty acid component usually has a chain length of Ci ₀ to C _w , wherein the range C _{) 2} to C _{18 is} preferred, the resorption-increasing component is used in concentrations of 0.1 to 20%, based on the total mass. As biologically active substances, for example chloramphenicol or propyphenazine can be used.

It was surprising that, apart from a positive influence on the absorbable amount of the active biological substance, the absorption rate could also be influenced as a function of the concentration of the absorption-enhancing component.

embodiments example 1 Male rabbits with a weight of 3,8kg, kept under standardized,

conventional environmental conditions, a Chloramphenicol suppository was introduced 16 hours after food withdrawal and the anus was closed with a rubber band for 90 minutes.

The chloramphenicol was determined quantitatively in the blood serum according to the method of BESSMANN and STEPHENS (1950). (Lit .: BESSMANN and STEPHENS, S., A Colorimetric Method for the Determination of Chloromycetin in Serum or Plasma, J. Lab. elin. Med.

35, S.129,1950) (Fig.2).

Example 2

Clinically healthy rabbits weighing 2.5 to 3.5 kg, maintained under standardized environmental conditions, were given Pyrecol (purified lipopolysaccharide) i.v. injected, which led to fever. The decrease in temperature by propyphenazine doses (150 mg) with and without absorption influence was compared (FIG. 1).

Claims (4)

claims: 1. A process for the preparation of medicaments for rectal administration with increased activity of biologically active substances which are not peptides, characterized in that the biologically active substance having a resorption-enhancing component of 0.1 to 20% of an amino acid-fatty acid condensation product, which is composed of simple or peptidically condensed amino acids and fatty acids of chain length C ₁₀ to C ₂₀ is used. 2. The method according to claim 1, characterized in that the amino acid-fatty acid condensation product consists of simple or peptide-fused amino acids and fatty acids of chain length C ₁₂ to C ₁ B. 3. Process according to Claims 1 and 2, characterized in that the peptidically condensed starting amino acid products are both native and of synthetic origin or are obtained by hydrolysis from native material. 4. Process according to Claims 1 to 3, characterized in that chloramphenicol is used as the biologically active substance.