Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1995-09-05
1998-02-10
MacMillan, Keith
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514630, 514823, 514710, 514922, 424 10, A61K 3105, A61K 3195, A61K 3116, A61K 3135
Patent
active
057169918
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/00446, filed Mar. 8, 1994, which claims priority to UK 93050581, filed Mar. 12, 1993.
This invention relates to analgesics and in particular to novel formulations of p-hydroxyacetanilide.
p-Hydroxyacetanilide or paracetamol finds wide use as an analgesic and has the particular advantage of having a relatively pure analgesic action with few side effects when used in normal dosages. However, overdoses of the drug can be very toxic and the ready availability of the drug has led to its use on a quite significant scale as a means of attempting suicide. Even when the overdose is not fatal it can lead to severe liver injury and the methods at present available for the treatment of an overdose of the drug are often ineffective in preventing this.
This problem has been recognised for a considerable time and in 1973, UK Patent Application 54098/73 was filed (published as UK Patent 1,463,505) describing a means of overcoming the problem. Thus, the toxicity of p-hydroxyacetanilide is due to the hepatic necrosis induced by a toxic metabolite to which the drug is converted in vivo. However, the compound glutathione, which is a tripeptide containing a central L-cysteine unit, is in some way involved with the toxic action of the metabolite in the body so that only when the liver has been depleted of glutathione does significant hepatic necrosis occur. Formulation of p-hydroxyacetanilide together with L-cysteine or a compound which is converted thereto in vivo has the very great advantage that an overdose of the drug automatically results in an increase in the amount of glutathione synthesised by the body thus countering the toxic effect of the overdose. The glutathione precursor may also detoxify the p-hydroxyacetanilide by providing intracellular sulphate, the formation of its sulphate being an alternative safe metabolic pathway for the disposal of p-hydroxyacetanilide.
However, although a product (Pameton) has for some time been available in the United Kingdom which avoids the dangers of overdose through the inclusion together with p-hydroxyacetanilide of the L-cysteine precursor DL-methionine, the major part of the market for p-hydroxyacetanilide is still met by products which provide no protection against an overdose. This is in significant measure due to the characteristic sulphur type odour which is associated with the marketed product that provides protection against an overdose, as discussed in UK Patent 1,583,602. It has now been found that it is possible to solve the problem of the potential extreme toxicity of overdoses of p-hydroxyacetanilide through formulating this compound together with DL-methionine or like compound in a manner which does not produce a product with a marked sulphur type odour, thereby providing a much more acceptable product which is suitable for the general market.
According to the present invention a process for the production of a pharmaceutical composition comprising p-hydroxyacetanilide and L-cysteine or a compound which is converted thereto in vivo comprises mixing p-hydroxyacetanilide and L-cysteine or its precursor in the solid state and then converting the solid mixture to a shaped product.
The term "shaped" is used herein in its normal sense of having a defined form as, for example, in a tablet, and "shaping" is used to indicate the production of such a defined form.
The problems of producing a shaped or formed product comprising p-hydroxyacetanilide are discussed in UK Patent 1,390,032 where it is indicated that a granular material must be employed for this purpose. Further attention is paid in UK Patent 2,124,078 and its equivalent European Patent Application A-0 100 168 to the problem of producing a shaped composition of p-hydroxyacetanilide, including one containing methionine, and the use of a wet-granulation technique is proposed. The final composition obtained by such techniques may not necessarily contain a significant amount of water but the defect of these prior art processes is that their initial stages involve a wet process, the p
British Technology Group Limited
MacMillan Keith
LandOfFree
Pharmaceutical compositions comprising paracetamol and L-cystein does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical compositions comprising paracetamol and L-cystein, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical compositions comprising paracetamol and L-cystein will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2077770