DE3634671A1 - Antirheumatic agents with reduced toxicity - Google Patents

Abstract

Antirheumatic agents with reduced toxicity brought about by adding L-tryptophan and L-methionine are reported.

Description

It is well known that the anti-inflammatory drugs are often long-lasting Periods must be taken. They unfold accordingly also undesirable side effects that become dangerous over time chronic chronic disease. So are Known side effects from the much used aspirin, the are life threatening. There are also dangerous side effects after continuous intake of indomethacin, penicillamine and gold preparations such as the Auranofin u. a. on.

Numerous efforts have been made through change the constitution of chemical substances undesirable To take side effects. So far, however, all attempts have been few successful.

Now the surprising observation has been made that the amino acids L-methionine and L-tryptophan, along with anti-inflammatory drugs administered, a very favorable influence on the elimination have undesirable side effects. Although at different Liver disorders often have a protective effect of certain amino acids acids have been reported, for example in OS-PS 20 13 026 of leucine, isoleucine, Lysine, phenylalanine and / or tryptophan; amino acid infu Solutions are for the treatment of severe liver insufficiency have been proposed (OS-PS 29 44 341).

Table 1 shows the influence of various anti-inflammatory drugs the liver is shown using various enzyme activities. It is generally accepted that the serum enzymes glutamate oxylate Transaminases (GOT) and glutamate pyroxal transaminase (GPT) Liver damage increase. From our working group observed that the activity of tyrosine aminotransferase (TAT) can be increased by a number of substances. Here it is the first enzyme to break down tyrosine.

The activity of the enzyme is also in the course of liver damage Adenosine diphosphatribose transferase (ADPR transferase) increased. This enzyme transfers ADPR to the Pro by cleaving NAD complexion. The result is a change in the conformation of the protein. This enables regulation.  

A significant increase in the activities of GOT, GPT and TAT can be observed when aspirin, auranofin, Indomethacin and diclofenac. This also happens in part to an increase in ADPR transferase activity. Simultaneously Administration of methionine and tryptophan prevents this increase considerably.

Our experimental setup shows:
L-methionine and L-tryptophan were mixed in equal parts and triturated. Rats received 600 mg / kg intraperitoneally from this mixture called Metryphan. The antirheumatic substances were administered intraperitoneally together with the metryphan in the doses indicated in Table 1. The animals were sacrificed after three hours. The GOT and GPT were according to HU Bergmeyer (methods of enzymatic analysis vol. I, S 492, Verlag Chemie, 1974), tyrosine amino transferase (TAT) according to H. Kröger and Mitarb. (Biochem. Z. 341, 190, 1965) and ADPR transferase according to RR Kidwell and Mitarb. (Biochem. Biophys. Res. Commun. 61, 766, 1974). Dimethyl sulfoxide was diluted 1: 2 with 0.1 M NaCl; 0.15 M NaCl served as a control. Table 1 shows the results.

What more precise mechanism is this unique Effect acts, and that with the multitude of different of chemical constitutions should still be an open question stay.

Metryphan can be in the form of tablets, capsules, coated tablets, drops, Syrups and the like directly with the anti-rheumatic bodies be administered or separately.

Examples shown in Table 2 are intended to implement the Show invention.  

Table 1

Acetylsalicylic acid 400 mg L-methionine 200 mg L-tryptophan 200 mg tablet excipients, ad.1000 mg

Tablet production in a conventional manner at 1 g.

Example 3 Capsules

Diclofenac sodium 25 mg L-methionine 200 mg L-tryptophan 200 mg

The ingredients are mixed and in a conventional manner filled in capsules.

Example 4

Auranofin 3 mg L-methionine 100 mg L-tryptophan 100 mg

Ingredients are mixed, granulated in the conventional way and in Capsules brought.

Example 5

Sodium gentiate 90 mg L-methionine 150 mg L-tryptophan 150 mg

are processed in a conventional manner to 500 mg coated tablets

Example 6

Indomethacin 50 mg L-methionine 100 mg L-tryptophan 100 mg

Capsules the conventional way.

Example 7

Ibuprofen 400 mg L-methionine 200 mg L-tryptophan 200 mg

Capsules the conventional way.

Claims (2)

1. Anti- rheumatic drugs with reduced toxicity, characterized in that they additionally contain the amino acids L-methionine and L-tryptophan. 2. Antirheumatics according to claim 1, characterized in that that it ent the amino acids in equal parts by weight holds. This claim is based above all on the examples.