CS260795B1 - Disinfectant tincture with dimethylbenzyl laurylammonium bromide - Google Patents

Abstract

The solution concerns a liquid dosage form for application as a surface antiseptic and disinfectant. It solves the composition of a disinfectant tincture containing 0.9 to 1.1% by weight of dimethylbenzyllauryl ammonium bromide, the essence of which consists in the use of ethanol in an amount of 5 to 7% by weight and alkylaryl polyglycol ether in an amount of up to 3% by weight. The composition ensures non-flammability during operations using an electric knife, eliminates significant injuries caused by burns and has a higher economic effect in reducing material costs, while the preparation complies with the prescribed tests from a pharmaceutical point of view.

Description

The invention relates to the composition of a disinfectant tincture with dimethylbenzyllauryl ammonium bromide, which is used as an external antiseptic and disinfectant.

Known compositions of tinctures with a wide variety of active ingredients use a high ethanol content of at least 50% by weight (ČsL 3, USP XXI j. It can be generally stated that the presence of ethanol in tinctures has a disinfectant effect, which is most advantageously manifested in concentrations of 50 to 70% ethanol (Ticháček B.: Theoretical and methodological foundations of disinfection, State Medical Publishing House, pp. 60 to 61, Prague 1968 j. It is also cited here that alcohol has a bacteriostatic effect even in concentrations representing fractions of a percent.

Domagk proposed the use of aqueous solutions of alkyldimethylbenzylammonium chlorides as disinfectants, and thanks to him, dimethylbenzyllaurylammonium bromide (Zephirol) was introduced into practice as the first substance of this type (Domagk G.: Deut. med. Voehschr. 61, 829/ /1935). Then its analogues were introduced into practice, which are listed in world pharmacopoeias under the name Benzalkonium bromide.

A disadvantage of the methods of preparing dimethylbenzyllauryl ammonium bromide (Czech Patent No. 87,359, Polish Patent No. 62,185) was that aqueous solutions prepared from the product were unstable, which was manifested by turbidity, color, precipitation of the product or unreacted starting materials.

This disadvantage in disinfection practice was eliminated in the Czechoslovak Socialist Republic by the use of a disinfectant tincture (Ajatin tincture), which contains up to 52% by weight of ethanol, distilled water, the dye tartrazine (citronella C 201) and the emulsifier polyoxyethylene(2)-sorbitan monooleate (Twen 80).

The disadvantage of this composition is that in various medical facilities there have been serious burns during operations using an electric knife after preparing the operating pole with a disinfectant tincture with a high ethanol content. The high ethanol content and the use of an economically less advantageous emulsifier significantly burden the production from an economic point of view.

The stated disadvantageous properties of the disinfectant tincture containing 0.9 to 1.1% by weight of dimethylbenzyllauryl ammonium bromide, about 52% by weight of ethanol, water, dye and emulsifier are eliminated by the disinfectant tincture according to the invention containing 0.9 to 1.1% by weight of dimethylbenzyllauryl ammonium bromide, ethanol, water and dye, the essence of which is that it contains 5 to 7% by weight of ethanol and optionally up to 3% by weight of alkylaryl polyglycol ether as an emulsifier.

This composition of the disinfectant solution increases work safety during production, transportation and applications in the healthcare field, because it is non-flammable. It has been found that a disinfectant solution containing 10% by weight and 20% by weight ethanol is classified in the II. hazard class according to ČSN 65 0201, while concentrations of 30 to 50% by weight ethanol classify the tincture up to the I. hazard class. By reducing the ethanol (its content), the disinfectant effect does not change. The use of an emulsifier, which is chemically alkylaryl polyglycol ether (Slovafol X) in an amount of up to 3% by weight, has the advantage of maintaining the stability of the disinfectant tincture.

The active ingredient dimethylbenzyllauryl ammonium bromide is prepared in a concentration of 80% by weight in the presence of 20% water (art. AO number 175 712). A crystalline product (art. AO number 127 909) can be prepared from this product, or it can be diluted with distilled water after preparation to a concentration of 9 to 11% by weight of dimethylbenzyllauryl ammonium bromide (Ajatin sol.).

'A disinfectant tincture with the composition according to the invention is prepared from the above products. Tests have shown that the new composition of the disinfectant tincture with dimethylbenzyllauryl ammonium bromide also has the advantage that the material costs for its production are significantly reduced with comparable antimicrobial efficacy, dermal irritation, physicochemical stability and lower toxicity.

It has further been found that the emulsifier can be omitted from the formulation if the product dimethylbenzyllauryl ammonium bromide, which is used to prepare the disinfectant solution, does not contain accompanying substances (lauryl bromide, benzyldimethylamine). Stability is maintained. The invention is illustrated, but not limited, by the following examples.

Example 1 wt. %

Distilled water 79.95 Ethanol 96% by weight 7.00 Aqueous solution of dimethylbenzyl lauryl ammonium bromide with a content of 9.5% by weight 10.00 Tartrazine (lemon rye C 201) 0.05 Alkylaryl polyglycol ether (Slovafol X) 3.00

The dye tartrazine (lemon rye C 201) in an amount of 0.05 g is dissolved in 14.95 g of distilled water. To the solution prepared in this way, 10 g of an aqueous solution of dimethylbenzyllauryl ammonium bromide with a content of 9.5% by weight, 65 g of distilled water and finally a solution of 3 g of alkylaryl polyglycol ether (Slovafol X) in 7 g of ethanol 96% by weight are gradually added while stirring. After thorough mixing for 10 minutes, the solution is left to stand for 60 min., filtered and is ready for filling into vials. The disinfectant tincture contains 0.95% by weight of the active substance.

Example 2 wt. % wt. %

Distilled water 82.95 Ethanol 96% by weight Aqueous solution of dimethylbenzyllauryl ammonium bromide 5.50 with a content of 11% by weight 10.00 Tartrazine (lemon rye C 201] 0.05 Slovafol X 1.50 The modification is carried out according to example 1. A disinfectant tincture is created by percentage of the active ingredient. content 1.1 Example 3 wt. % Distilled water 93.25 Ethanol 96% by weight 5.60

Disinfectant tincture

Crystalline product with % mass content. dimethylbenzyllaurylammonium bromide 1.10

Lemon rye C 201 0.05

The procedure is as in Example 1. A disinfectant tincture containing 1.03% by weight of active substance is obtained.

We requested testing of the products prepared according to the above examples from authorized organizations. Tests were performed for flammability, acute toxicity, dermal irritation, microbiological efficacy and stability.

During flammability tests, it was found that the disinfectant solution according to the invention is not a flammable liquid within the meaning of ČSN 65 0201 — — unlike the disinfectant tincture currently produced, as shown in the table:

Produced at the present time Produced according to the invention

Flash point (PM) 21 °C 52 °C

Flash point (C) 32 °C 90 °C

The combustion temperature is 32 °C.

Hazard class I. class is not flammable

In the assessment of acute toxicity, it was found that the disinfectant tincture produced in the same way is more toxic in both application routes, as shown in the table:

Acute toxicity in ml/10 g body weight:

Disinfectant tincture

Currently manufactured Manufactured according to the invention

Application path — p. c. 0.05 to

Application path — i. Mr. 0.02 to

The table shows the ranges of sample volumes per 10 g of mouse weight, in which the median lethal dose LD50 is found. Since the tested application products will be used dermally, their s. c. and i. p. toxicity does not pose a danger if the principles of good practice are observed during use.

The skin irritation assessment was carried out in accordance with ČSN 66 4055. On the skin of experimental animals at the application site, the disinfectant tincture currently produced was 1.2 ml, with 0.05 to 0.3 ml.

1.03 ml 0.02 to 0.04 ml also according to the invention on the 5th day after application caused grade I irritation in each experimental group in one animal (testing always on 3 animals).

Based on this evaluation, the products were deemed satisfactory by the authorized organization.

Evaluation of antimicrobial efficacy by minimum inhibitory concentration and minimum bactericidal concentration was done by dilution method with results as shown in the table:

Minimum inhibitory concentration

Minimum bactericidal concentration disinfectant tincture

Microbial strains currently produced according to the invention currently produced according to the invention S. aureus E. coli A. niger C, Albisans 2 mg/ml 60 mg/ml 7 mg/ml 10 mg/ml 4 mg/ml 70 mg/ml 7 mg/ml 5 mg/ml 2 mg/ml 60 mg/ml 0 20 mg/ml 4 mg/ml 70 mg/ml 0 10 mg/ml

The table shows that changing the composition of the disinfectant tincture did not result in significant changes in its antimicrobial activity.

The results of stability tests of the disinfectant tincture according to the invention are comparable to the results of the disinfectant tincture currently produced. On this basis, the preparation is considered satisfactory.

Claims (3)

260795 7 8 Minimum inhibitory concentration Minimum bactericidal concentration disinfectant tincture Microbial strain presently produced according to the invention according to the invention S. aureus E. coli A. niger C albisans 2 mg / ml 60 mg / ml 7 mg / ml 10 mg / ml 4 mg / ml 70 mg / ml 7 mg / ml 5 mg / ml 2 mg / ml 60 mg / ml 0 20 mg / ml 4 mg / ml 70 mg / ml 0 10 mg / ml \ t there was no substantial change in its antimicrobial activity. The results of the stability tests of the disinfectant tincture according to the invention are comparable with the result! disinfectant tincture currently produced. Accordingly, the formulation is considered satisfactory. OBJECT Disinfectant tincture containing 0.9 to 1.1%. wt. dimethylbenzyl laurylammonium bromide, ethanol, water and a dye, characterized in that it contains 5 to 7 wt. ethanol. 2, A disinfectant tincture according to claim 1, characterized in that it contains an emulsifier. 3. Disinfectant tincture according to claim 2, characterized in that it contains up to 3 wt. alkylaryl polyglycol ether. Severografia, n. P. Plant 7, Most Cen · 2.40 KČS