DE2220500A1 - MEDICINAL MIXTURE - Google Patents

Description

Drug mixture

The present invention relates to a drug mixture.

It has been since the synthesis of H. Stenzel in 194-6 "known that phenylbutazone (1 ^ -diphenyl-J ^ -dioxo- ^ l-n-butyl-pyrazolidine) analgetis and anti-rheumatic effectiveness owns. Since then, phenylbutazone has been considered the most effective anti-inflammatory drug alongside steroids. -The application of phenylbutazone in effective doses is «however, with significant side effects due to its inhibitory effects linked to certain enzymatic reactions in the body.

It is also known that these lifting effects are caused by a reducing dose of phenylbutazone in combination with an analgesic can be avoided.

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British patent specification 1 081 105 discloses a drug with anti-inflammatory and analgesic effects, consisting of a mixture of butazone (1-phenyl-3,5-dioxo-4 - n-butyl-butazolidine) and d-propoxyphene (1,2-diphenyl-2-propionoxy-3-methyl-4-dimethylaminobutazone hydrochloride) known, whereby the analgesic effect of d-propoxyphene is potentiated by the combination with butazone. It is from this patent also known that this potentiation in combinations of phenylbutazone with propoxyphene does not occur, so these combinations as medicinal products are unsuitable. On the other hand, however, there has long been a general need, precisely because of it, phenylbutazone Compared to butazone, very strong anti-rheumatic effect with analgesics while achieving a potentiating effect Combine effects.

However, a potentiating effect of the phenylbutazone could so far have only been achieved in combination with e.g. morphine, codeine or methadone. However, these combinations show have the disadvantage that they are addictive to the patient and are therefore less desirable.

It is therefore an object of the present invention to provide a phenylbutazone-based medicament with preservation the well-known anti-rheumatic effect of phenylbutazone,

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but with a high analgesic effect at the same time Reducing doses to eliminate or at least reduce the known side effects.

Contrary to the well-known view that combinations of phenylbutazone with propoxyphene are unsuitable as drugs this task has now become surprising solved that the drug mixture consists of phenylbutazone and dextropropoxyphene.

A simultaneous application of phenylbutazone and dextropropoxyphene turned out to be extraordinary high potentiation of the analgesic effect and an additional retardation of this analgesia is achieved. It is thus become possible to keep therapeutic doses of the individual components in the mixture so low that the known side effects are largely avoided.

! In the following the invention is based on 'examples explained in more detail.

Series tests have shown that particularly good results are obtained when the drug mixture consists of dextropropants and phenylbutazone in a molar ratio of 1: 2. The following are to clarify this! Result some

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the values obtained are compiled in a table as an example. They show the effectiveness of the individual mixtures, based on the molar ratio 1: 2, as a percentage.

Table 1:

1 : 16 1 : 8th 1
1 : 4
: 2 1 : 1

Mo 1 ν received ni s

d-propoxyphene / 45 '90'

Phenylbutazone

57 % 75

81 % 85

94 % 97

100% 100

74% 98

This optimal mixture with a molar ratio phenylbutazone / Dextropropoxyphene = 2: 1 showed in those listed below Try new interesting pharmacological effects :;

In the inalgesia test (writhing on mice), dextropropoxyphene mixed with phenylbutazone under optimal conditions compared to dextropropoxyphene alone shows up to 4.2-fold increased analgesia, as a comparison of the corresponding values of the ED ₁ -Q shows. The relation to different time \ score is given in Table II again.

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Table II:

Substances: 15? 0 60 120 180 240

A- dextropropoxyphene 24-23 31, 71 135 150 B - dextropropoxyphene

calculated in accordance with C 13 11 16 27 32 37

C- mixture of dextropropoxyphene / phenylbutazon,
Molverh. 1: 2 33 30 53 72 85 97

D - phenylbutazone 350 360 390 650 650 900

in. mg / kg body weight

Duration of action (min)

The following diagram I illustrates the exponentiation factors resulting from the table:

Diagram I:

In addition, diagram I shows another interesting effect for the therapy:

Y? mg of dextropropoxyphene hydrochloride as the pure substance are sufficient for approx. 70 minutes of analgesia. In contrast, the same dose of pextropropoxyphene in the mixture discussed here ensures an equally strong analgesia even after 4 hours (see diagram II).

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tu: ei

The results of extensive clinical and field tests 413 patients are in the following overall statistics (Table TIT).

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- 8 Table III:

Degenerative spinal syndromes with or without radiculitis such as
Spondylarthrosis ankylosing spondylitis osteochondrosis cervical spine, occipital syndrome, thoracic syndrome lumbar spine, lumbosacral syndrome
Disc prolapse

Osteoarthritis

Arthritis

Neuralgia, neuritis

Soft tissue nexma

Periarthritis

Posttratimatic states

number
of the falls s ^ tn? p; ut put moderate ineffective
sam 9 2 197 49 19th 14th 1 1 !Rome 44 9 24 S. 3 35 2 31 - 2 2 ? 46 14th 24 1 - 22nd 8th 12th 37 24 14th 5 55 24 30th 41? 111 241

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In 85.2 % of these cases, the examining doctors rated the success of the treatment as very good and good. The excellent analgesic effect becomes particularly clear when looking at the post-traumatic cases. On the other hand, the treatment successes in typical rheumatic diseases show that the anti-rheumatic properties of phenylbutazone in this combination, despite the significantly reduced dose, correspond to the effects observed so far in treatment with the known high doses of phenylbutazone.

This succeeded, despite a reduction in the phenylbutazone dose to 1/3 of the usual to ensure a successful anti-rheumatic therapy. ■

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Claims (2)

File number: P 22 20 500.1 a22 ~ ZÜ5ÖO received on. £ ".! ± 5. ^ 4 «* - PATENT CLAIMS 1. Mixture of drugs,
characterized in that it consists of phenylbutazone and dextropropoxyphene. 2. drug mixture according to claim 1, ι characterized, that phenylbutazone and dextropropoxyphene in the molar ratio 2: 1 can be used. 309845/1125 /