DE2137045A1 - Drug preparation - Google Patents

Description

Dr. Ing. A. Yin Her Werth "■ Dr. h-uiii Lcueref · Z 3rd JUH PATENT LAWYERS

RAN W5A

F. Hoflmann-La Rochc & Co. Aktiengesellschaft, Basel / Switzerland

Drug preparation

The present invention relates to a new pharmaceutical preparation with antimalarial effect, with an influence on the amine metabolism, or with antihypertensive properties, which by a content of l, l-Piethyl-3- (2-thiazolyl} -2-thioureaj l-methyl-3 - (2-thiazolyl) -2-thiourea, l l _{J-dimethyl-3-} (4-methyl-2-thiazolyl) -2-thiourea and / or an acid addition salt of such a compound is characterized, with possible tautomeric forms of these three compounds are included.

In addition to the active ingredient, the pharmaceutical preparation contains non-toxic, inert solid and / or liquid carriers customary in pharmacy which are suitable for therapeutic administration and / or excipients.

The medicament according to the invention is particularly geelg-Zü / 3.5.71 109885/1879

net to fight malaria. This can be shown, for example, in mice with the following experimental set-up:

6 mice each are parasitized at 10 'by Plasmodium berghei Mouse erythrocytes infected intraperitoneally. The active ingredient is used for the first time approx. 4 hours before the infection, then administered orally 24, 48 and 72 hours after infection. 24 hours after the end of the treatment A blood smear was made for all animals and stained according to Giernsa. Microscopically the degree of infection is compared to untreated infected control animals. As DE .__

po, the dose is assumed that in the treated animals the Able to reduce the number of parasitized erythrocytes by half.

Some exemplary results are in the following Table I summarized:

Table I.

link ^DE 50
mg / kg po 1,1-diethyl-3- (2-thiazolyl) -2-thiourea
1-methyl-3- (2-thiazolyl) -2-thiourea 7th
approx 10

The acute toxicity of compounds of the formula I im Mouse test is generally between 500 and 5000 mg / kg p.o.

Purely the pharmaceutical form according to the invention comes in the Oral, rectal and parenteral administration in question. Oral administration is for prophylaxis and Therapy is planned while the parenteral application is

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is predominantly of importance for the therapy of severe cases.

In the case of daily administration, the dose applied at one time for an adult can be between 100 and 1000 mg; it is preferably between 300 and mg. When injecting for therapeutic purposes, the dosage is expediently higher, namely preferably between 500 and 1000 mg.

The inventively proposed thiazole derivatives have the advantage that they are by no known antimalarials * Show ne cross-resistance and thus the disease can also be used in countries for the treatment, in which known antimalarials fail.

The three thiazole derivatives mentioned also influence the amine metabolism. For example, they have an extraordinary effect strong inhibition of the enzyme dopamIn-P> -hydroxylase. It was also found that compounds with this inhibitory effect can lower blood pressure.

The inhibitory effect of these compounds on the enzyme dopamine beta-hydroxylase can be in vivo with the following experimental λ test arrangement:

The substance is administered orally five times over a period of 2.5 days to groups of 6 male rats weighing 150-180 g each. 3 hours after the last application, the following changes in the brain, given in Table II, are found in percent (control = 100 %) :

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Table II

substance dose Noradre Dopamine μΜοΐ / kg nalin l, l-diethyl -> (2- thiazolyl) -2-thiourea 300 19th 95 l-methyl-5- (2-thiazolyl) - 2-thiourea 100 18th 106

The pharmaceutical preparation according to the invention can said thiazole derivatives in a mixture with suitable pharmaceutical, contain organic and inorganic carrier materials. Especially for oral and parenteral administration for example starch, lactose, magnesium stearate, Talc, vegetable oils, organic solubilizers such as polyalkylene glycol or glycerin formal, water, as well as organic and inorganic bases in embossing. The drug preparation can be in solid form, e.g. * as tablets, coated tablets, suppositories, Capsules, or in liquid form, e.g. as solutions, suspensions or emulsions. If necessary, it is sterilized and / or contains auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers, salts for modification osmotic pressure or buffer. It can also contain other therapeutically valuable substances.

The following examples serve to illustrate the invention:

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example 1

Tablets of the following composition are made:

1) l, l-diethyl-3- (2-thiazoLyl) -2-

thiourea / 250 mg

Corn starch 278 mg

Milk sugar 70 mg

Magnesium stearate 2 mg

600 mg. ^

2) l-methyl -> (2-thiazolyl) -2-

thiourea 250 mg

Corn starch 278 mg

Milk sugar 70 mg

Magnesium stearate 2 mg

000 mg

The active ingredient and some of the excipients are with granulated with corn starch paste «After drying, a powder of corn starch and magnesium stearate is added and on a tablet machine to form tablets 13 mm thick, mg weight and a hardness of 6-8 SCE pressed.

Example 2
An injection solution can have the following composition

point:

1,1-diethyl -> (2-thiazolyl) -2-

thiourea 500 mg

Glycerin formal 0.5 ml diethanolamine 0.076 ml

Water 0.5 ml

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The solution is prepared according to the usual methods, filtered and either a preservative is added and filled into ampoules in an inert atmosphere or filled into ampoules without preservatives under inert gas and sterilized.

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Claims (1)

Claims 1. Process for the production of a pharmaceutical preparation with anti-malarial activity, influence on amine metabolism, or with antihypertensive properties, characterized in that l, l ~ diethyl-3- (2-thiazolyl) -2 ~ thiourea, l-methyl-3- {2-thiazolyl) -2-thiourea, l, l-dimethyl-3- (4-methyl-2-thiazolyl) -2-thiourea and / or an acid addition » salt of such a compound for therapeutic administration suitable, non-toxic, inert * solid or liquid carriers normally used in such preparations " and / or excipients and mixed together to form a medicinal preparation, such as tablets, coated tablets, capsules, suppositories as they are used in pharmacy, compounded » 2. The method according to claim 1, characterized in that that one l, l-diethyl-3- (2-thiazolyl) -2-thiourea, 1-methyl-3- (2-thiazolyl) -2-thiourea and / or an acid addition salt of such a compound is used » 109885/1879 3 drug preparation effective against malaria, Influence on the amine metabolism, or with antihypertensive Properties, characterized in that they contain 1,1-diethyl-3- (2-thiazolyl) -2-thiourea, l-methyl-3- (2-thiazolyl) -2-thiourea, 1,1-Dimethyl-3- (4-methyl-2-thiazolyl ^ -thiourea and / or an acid addition salt of such a compound mixed with customary solid or liquid carrier materials contains. k. Preparation according to claim 3j, characterized in that it contains l, l-diethyl-3- (2-thiazolyl) -2-thiourea, 1-methyl-3- (2-thiazolyl) -2-thiourea and / or an acid addition salt of such a compound contains. 5. Preparation according to claim 3 or k, characterized in that it contains 100 mg to 1000 mg of such a compound. 6. Preparation according to claim 5 * characterized in that that it contains 300 mg to 6θΟ mg of such a compound. 10 9885/18 79 ORHaINAL INSPECTED