DE1942102A1 - Process for the preparation of the solution of a tetracycline or a tetracycline salt and such a solution - Google Patents

Description

Applicant: Stuttgart, August 18, 1969

Company KeIa P 2026 S / O

Kempisch Laboratory '
Vrijheld 220
Hoogstraten (Belgium)

Process for the preparation of the solution of a tetracycline or a tetracycline salt and such a solution

The invention relates to a method of manufacture the solution of a tetracycline or a ^ etracycline salt. In known processes of this kind organic solvents are used to produce such solutions. However, it has been found that aqueous solutions have better properties »However, tetracyclines are not soluble in water.

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The invention is based on the object of a method to create, with the help of which an aqueous and injectable Solution of a tetracycline or a tetracycline salt can be produced.

This object is achieved according to the invention by that on the one hand urea dissolved in water and added to this solution the selected tetracycline or tetracycline salt and on the other hand a mixture of benzyl alcohol and propylene glycol made and then this Mixture is combined with the urea solution containing a tetracycline or a tetracycline salt.

This method is advantageously carried out with the exclusion of light, i.e. in the dark.

The urea solution is preferably added before the addition a tetracycline or tetracycline salt brought to ambient temperature.

In an advantageous embodiment of the invention the actual tetracycline is added to the solution of urea in water. In another embodiment of the invention becomes the solution of urea added chlortetracycline in water. It is also possible to add oxytetracycline to the solution of urea in water to add. In yet another embodiment of the invention, urea becomes the solution in water the chlorohydrate of one of the tetracyclines is added.

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In a further embodiment of the invention, the A lot of chloramphenicol can be added before the mixture of benzyl alcohol and propylene glycol Mixture is combined with the urea solution containing a tetracycline or a tetracycline salt.

The invention also includes -the solutions of tetracyclines or their salts, which according to the processes according to the invention have been produced.

Further details, refinements and advantages of the invention can be found in the following description of embodiments of the invention.

In the case of the method according to the invention, initially in Water dissolved an amount of powdered urea, which is between 4 and 40% by weight of the final product Solution moves. The solution of the urea is endothermic, so that the temperature of the urea solution sinks. The temperature of this urea solution is then allowed to return to ambient temperature increase, after which an amount of powdered tetracycline is added to this solution, the maximum 10 wt # of the final solution to be prepared. ■ The powdered tetracycline is preferably tetracycline itself, chlortetracycline or oxytetracycline or a salt such a tetracycline.

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On the other hand, an amount of about 1 to 5% by weight of the final solution benzyl alcohol with an amount of 30 "to 60% by weight of the final solution of propylene glycol mixed. The mixture thus obtained is added to the above-mentioned urine solution which contains a tetracycline or a tetracyclineζ.

The preparation obtained is then diluted to the desired final volume with the aid of water.

This procedure is carried out in the dark.

The final aqueous solution produced in this way Solution is injectable and loses approximately annually 5% of its activity.

A variant of the method described above consists of adding an amount of powdery chloramphenicol to the mixture of benzyl alcohol and propylene glycol, which is a maximum of about 10% by weight the desired final solution. is before this mixture is combined with the urea solution containing a tetracycline or a tetracycline salt. The chloramphenicol slowly dissolves in the mixture of Benzyl alcohol and propylene glycol.

Some examples for the application of the method according to the invention are given below:

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Example 1:

For the preparation of a 5% solution of tetracycline chlorohydrate first 5 g of powdered urea dissolved in 25 g of water. This urea solution is left come back to ambient temperature and then add 5 g of powdered tetracycline chlorohydrate * to this solution

On the other hand, there are 4 g of benzyl alcohol and 60 g of propylene glycol mixed and this mixture is added to the urea solution containing the tetracycline chlorohydrate contains. The whole is then diluted to 100 ml with water.

Example 2:

For the preparation of a 5% solution of the chlorohydrate of chlortetracycline becomes 30g powdered urea dissolved in 25g of water. When this solution returns to ambient temperature 5g chlorine hydrate of chlortetracycline are added to it.

On the other hand, there are 5 g of benzyl alcohol and 40 g of propylene glycol mixed and it becomes this mixture to the urea added solution containing the chlorohydrate of chlortetracycline. Then with water on 100 ml diluted.

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Example 5;

For the preparation of a 5% solution of the chlorohydrate Oxytetracycline is 30 g of powdered urea dissolved in 25 g of water. The solution is left at ambient temperature come back and then add 5 g of powdered oxytetracycline chlorohydrate.

On the other hand, 5 g of benzyl alcohol and 40 g of propylene glycol are mixed. This mixture is added to the urea solution, which contains the chlorohydrate of oxytetracycline. It is then diluted to 100 ml with water.

In the examples given above, worked under exclusion of light.

The invention is in no way restricted to the details given, since they are indeed variants possible without departing from the scope of the invention. So are only a few '^ etrecycline in the examples in Has been considered »It is understood, however, that the Invention generally applies to all tetracyclines and to their Salts is applicable. .

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Claims (16)

Claims · / Process for the preparation of the solution of a Tetracycline or a Tetracyclinealζes, characterized in that on the one hand urea is dissolved in water and a tetracycline or a ¹ ^ e tr acyc lins al ζ is added to this solution and on the other hand a mixture of benzyl alcohol and propylene glycol is produced and then this mixture is combined with the urea solution containing a tetracycline or a tetracycline salt. 2. The method according to claim 1, characterized in that it is carried out with exclusion of light. 3. The method according to claim 1 or 2, characterized in that that the urea solution before adding a tetracycline or tetracycline salt is brought to ambient temperature. 4 ·. Method according to one of the preceding claims, characterized in that actual tetracycline is added to the solution of urea in water. 5 · Method according to one of Claims 1 to 3 »thereby characterized in that to the solution of urea in water Chlortetracycline is added. 00 9 827/2 G.r. 6. The method according to any one of claims 1 to 3 »characterized _i that oxytetracycline is added to the solution of urea in water. 7 »Method according to one of claims 1 to 3, characterized characterized in that to the solution of urea in The hydrochloride of a tetracycline is added to water will. 8 * Method according to claim 7, characterized in that the chlorohydrate of the actual, 'tetracycline added will. ■ 9. The method according to claim 7, characterized in that the chlorohydrate iron chlortetracycline or oxytetracycline will be added. 10. The method according to any one of the preceding "claims, characterized in that to the mixture of benzyl alcohol and propylene glycol an amount of chlorainphenicol is added "before using the a tetracycline: or a tetracycline oil containing urea solution is combined * 11. The method according to any one of the preceding claims, gekennzöichnet that a lot of Tetracyciiä or ■ '■' etracycline salz is used, the highest \ 10% by weight of the final solution is * - 0 0 9 8Γ2 7 / 2Q / C 4 12. The method according to any one of the preceding claims, characterized in that an amount of urea is used, which is between 4 and 30% by weight of the final solution is. 13. Method according to one of the preceding claims, characterized in that an amount of benzyl alcohol is used which is between 1 and 5% by weight of the final Solution is. 14. The method according to any one of the preceding claims, characterized in that an amount of propylene glycol is used, which is between 30 and 60 wt% of final solution is. 15 · Method according to one of the preceding claims, characterized in that the tetracycline or tetracycline salt is used in the form of a powder which is added to the solution of urea in water. 16. Solution of a tetracycline or a tetracycline salt, characterized in that it is formed from a solution of urea in water to which the tetracycline or a tetracycline salt added and made with a mixture of benzyl alcohol and propylene glycol has been combined. 009827/2054