DE1941583C3 - Analgesic - Google Patents

Description

The subject matter of the invention is the use of the analgesic agents specified in more detail in the claim Combinations of morphine (component a) and one that potentiates the effect of this analgesic 2- (3- or 4-phenoxyphenyl) propionic acid (component b) which can be administered orally or parenterally Anaigeticum. The individual active ingredients used in each case represent known compounds which are optionally also used in the form of their customary pharmaceutically acceptable salts can. Such salts of component b) include, for example, the sodium, potassium, calcium, Ammonium and benzylamine salts. It was found that the use of the appropriate Salts of the respective free compounds give a comparable synergistic effect.

The mentioned phenoxyphenylpropionic acids are anti-inflammatory agents and quite the opposite to the strong analgesic effect that is achieved with morphine, in itself only weakly aspirin-like analgesic effect, similar to acetylsalicylic acid. The reinforcement of the anaigetic effectiveness of the narcotically active morphine, which is combined with the administration of phenoxyphenylpropionic acids is achieved with this active ingredient is therefore very surprising and completely unexpected.

When the morphine is used according to the invention with a potentiating agent of the type indicated then the same analgesic effect can be achieved in smaller doses than with this one otherwise usual therapeutic dosage amounts. The narcotic effects of morphine can be reduced therefore reduce when used according to the invention.

In practice, the phenoxyphenylpropionic acids are used in mammals in doses of 0.25 to 50 mg / kg Body weight in combination with half the known therapeutic doses of morphine or less administered and need given with only 10% of the known therapeutic doses of morphine will. For the treatment of extremely severe pain that no longer responds even to morphine, full therapeutic doses are preferred. The phenoxyphenylpropionic acids are at effective for oral or parenteral administration.

Regarding the usual dosage values and routes of administration for morphine and other analgesics is referred to Physicians' Desk Reference to Pharmaceutical Specialties and Biological (22nd Edition, 1967, issued by Medical Economics, Inc., a subsidiary of Chapman-Reinhold, Inc., Oradell, N.J.).

Use in analgesic treatment can be in customary therapeutic preparation forms take place.

Solid preparations for oral administration are, for example, tablets, pills, powders and filled capsules and granules. In such solid preparations, the active ingredients are to be mixed with at least one inert diluent, such as sucrose, lactose or starch. The preparations can also correspond to in accordance with normal practice, in addition to inert diluents, other substances, for example lubricants, such as magnesium stearate. Liquid

ίο are preparation forms for oral administration for example pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs, the Inert diluents customary for this purpose, for example water, contain. Except inert diluents Such preparation forms can also use auxiliaries such as wetting agents and emulsifiers or suspending agents, and sweeteners, flavorings or fragrances.

Preparations that can be administered parenterally include sterile aqueous or non-aqueous solutions, Suspensions or emulsions. Examples of non-aqueous solvents or carriers are propylene glycol, Polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Such preparations can also contain auxiliaries, for example preservatives, Wetting agents, emulsifiers and dispersants. The preparations can, for example, by filtration through a bacteria-retaining filter, through the addition of sterilizing agents to the preparations, sterilized by irradiation or by heating. Dosage forms for parenteral Administration can also be prepared in the form of sterile solid preparations immediately be dissolved in sterile water or other sterile injectable medium before use can.

Filled capsules are preferred because of their ease of administration and their stability therapeutic dosage form. Such filled capsules can be mixed with conventional carriers and excipients can be easily manufactured.

Morphine or corresponding pharmaceutically acceptable salts thereof occasionally have a have poor oral effects and are therefore usually administered parenterally. Would you like this According to the invention, therefore, reinforce analgesic, then the respective potentiating agent is used Phenoxyphenylpropionic acid usually separately

so in any of the conventional oral therapeutic dosage forms or administered parenterally, for example by intramuscular or by subcutaneous injection. The analgesic activity is potentiated when one uses phenoxyphenylpropionic acid either in the same dosage form or in a different dosage form is convenient at the same time or 1 hour before to 1 hour after the administration of the morphine.

The invention is further illustrated below with the aid of examples.

example 1

Morphine and 2- (4-phenoxyphenyl) propionic acid are separated and shared on rats after a b5 Test method checked, in which the reaction time of treated and untreated rats on the action of a heat stimulus on the rat tail serves as a measure of the analgesic effect. These

Test method is described in Journal of the Armican Pharmaceutical Association Vol. 44, p. 497 (1955). The compounds are administered subcutaneously. The reaction to the heat stimulus will be 30 minutes and determined 1 hour after injection. The reaction time is determined as the time it takes to act heat stimulus elapses until the tail is moved away from the heat source. The average The reaction time of untreated control groups is about 4 seconds. The test results are listed in Table I below. The reaction time given in Table I is the average Response time of groups of 4 rats.

link

Table I.

dose
mg / kg (sc)

Response time (seconds)

(Control)

Morphine 2

2- (4-phenoxyphenyl) -

propionic acid 100

Morphine + 2

2- (4-phenoxyphenyl) -

propionic acid 10

Morphine + 2

2- (4-phenoxyphenyl) -

propionic acid 20

4.50 8.08

3.80 8.40

9.58

Morphine +
2- (4-phenoxyphenyl) propionic acid

13.30

Example 2

Morphine and 2- (3-phenoxyphenyl) propionic acid are separated and shared on rats after Test method described in Example 1 tested. The response to the heat stimulus will follow 30 minutes of the injection. The test results are shown in Table II below.

Table II

link dose reaction time mg / kg (s.c.) (Seconds) (Control) _ 4.2 Morphine 2 8.8 2- (3-phenoxyphenyl) - propionic acid 100 3.8 Morphine + 2 9.6 2- (3-phenoxyphenyl) - propionic acid 10 Morphine + 2 10.9 2- (3-phenoxyphenyl) - propionic acid 20th Morphine + 2 15.0 2- (3-phenoxyphenyl) - propionic acid 40

Claims (1)

Claim: use of a) morphine and b) 2- (3-phenoxyphenyl) propionic acid or 2- (4-phenoxyphenyl) propionic acid in the ratio of 20 to 40 parts by weight a) to 2 parts by weight b) for the oral or parenteral analgesic treatment.