SK151997A3 - Disinfectant with 2-amino tridecane hydrogeneadipate - Google Patents

Abstract

The composition of disinfectant with 2- -aminotridecan hydrogenadipate in aqueous or water-ethanolic solution containing 1 to 15% weight. % of the active ingredient, 85 to 99 wt. distilled % water, 0 to 7 wt. % ethanol and 0 to 0.5 wt. dye, which is used as an antiseptic and disinfectant.

Description

Technical field

The invention relates to a liquid dosage form for administration as a topical antiseptic and disinfectant.

BACKGROUND OF THE INVENTION

To date, it is known to formulate aqueous-ethanolic and aqueous solutions with a wide variety of active ingredients, with different ethanol contents, most often around 50% by weight. (CSL 4. USP XXI.) In general, the presence of ethanol increases the disinfectant effect, which is most preferably present in a concentration of 50 to 70% by weight. Ethanol / Ticháček B .: Theoretical and Methodological Basis of Disinfection, SZN, pp. 60-61, Prague 1968 /. It is also cited herein that the bacteriostatic effect of ethanol is also at concentrations representing fractions of a percentage. There is a known case containing 5-7% ethanol with a satisfactory disinfectant effect (CS AO No. 260 795).

Research Institute for Pharmacy and Biochemistry introduced in. 1972 into practice the disinfectant substance 2-aminotridecane hydrogenadipate (Regulation for the preparation of tridecain / 2aminotridecane) and its salts: acid adipate, undecylate and 2-chloro-4-nitrophenolate., VÚFB Prague, 1972). After this, the disinfectant Decidin (List of Pharmaceuticals, 1980-1984, Spofa, pp. 160-161, Prague 1980) was introduced into practice. According to ČSN 65 0201, solutions containing 10% by weight are used. and 20% by weight. of ethanol in the hazard class II. A concentration of 30 to 50% by weight of ethanol classifies the solution into hazard class I. Concentration of 5-7% by weight. it is not a flammable liquid in the sense of ČSN 65 0201, which makes it possible to use such a solution also in operations with an electric knife when there is a possibility of ignition. The high ethanol content of the disinfectants also makes production economically difficult.

SUMMARY OF THE INVENTION

The present invention is based on an aqueous ethanolic or aqueous solution of 2-aminotridecane hydrogen adipate having a content of 1 to 15% by weight, with an ethanol content of 0 to 7% by weight, a coloring content of 0 to 0.5% by weight. and the distilled water content is 85 to 99% by weight.

The advantage is greater solubility of the active substance and thus better absorption of the active substance into the skin. Another advantage is the non-flammability of the disinfectant and the improvement of the antimicrobial effectiveness of the composition, while reducing the material cost of production and expanding the possibilities of use in the medical field, particularly in electric knife operations.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

2-aminotridecane hydrogen adipate Ethanol 96% by weight.

Water distilled (purified) Dye

1.50 wt.% 5.00 wt.% 93.45 wt.% 0.01 wt.%

Dye in the prescribed amount is dissolved in 100 g of distilled water. The active substance is dissolved in other quantities of distilled water. To this solution is gradually added a dye solution, a previously prepared and prescribed amount of ethanol 96% by weight. After thorough mixing for 10 min. the solution is allowed to settle, filtered and ready to be filled into vials. The disinfectant solution contains 1.5% by weight. of the active substance.

Example 2

2-aminotridecane hydrogen adipate 1.50 wt.%

Ethanol 96% by weight. 5.00 wt.%

Distilled / purified water / 93.50% by weight

The procedure is as in Example 1 except that dye handling is not required.

Example 3

2-aminotridecan hydrogen adipate 10.00%

Distilled / purified water / 90,00%

The operating procedure is the same as in Example 1, except that the dissolution of the dye and the addition of alcohol are not carried out. The disinfectant solution contains 10% by weight of the active ingredient.

Evaluation of antimicrobial activity

Antimicrobial activity was tested by the dilution method. For bacteria and yeast, the micromethod was used, in the case of filamentous fungi the classical dilution method was more suitable for these microorganisms. Since the samples contain different amounts of the active ingredient and other ingredients, the inhibitory activity is expressed by the highest dilution of the original solution in which growth was still suppressed.

Composition of test solutions: Tab.1

Sample no. 2-ATD hydrogen adipate (%) ethanol 96% no. destil.voda dye (orange 241) ethanol 96% team. First 0.5 5 94.45 0.05 Second 0.85 5 94.10 0.05 - Third 1.0 5 93.95 0.05 - 4th 1.5 5 93.45 0.05 - 5th 0.85 50 49.10 0.05 - 6th 0.5 - 94.45 0.05 5 7th 0.85 - 94.10 0.05 5 8th 1.0 - 93.95 0.05 5 9th 1.5 - 93.45 0.05 5 10th 0.85 - 49.10 0.05 50

Microbial strains:

Staphylococcus auresus Mau 29/58

Escherichia coli Ec 377/79

Candida albicans 45/53

Trichophyton terrestre 61/62

Microsporum gypseum 109/56

Cultivation media:

Nutrient broth

Nutrient agar # 2

Sabouraud's liquid and solid soil

Thioglycolate soil

All cultivation media originated from Imuna Šarišské Michaľany.

methods:

The micromethod used for S. aureus, E.coli and C albicans was transferred in microtiter plates which were sterilized in persteril vapors. Test solutions were diluted in appropriate culture broth by two-fold dilution with a multichannel pipette from 1: 1 to 1: 4096. After addition of the standard inoculum, the plates were incubated at 37 ° C for 24 hours. The highest inhibition dilution was read after inoculation on the respective culture broth and after incubation.

The dilution standard method was carried out in two stages. As a precursor, the sample in question was diluted by decimal dilution from 1:10 to 1: 1 000 000. After addition of the standard inoculum and incubation at 20 ° C for 72 hours, approximate efficacy was determined. Depending on the result of the precaution, the effective dilution was determined more accurately in the main experiment.

inoculum

From the purified strain of the strain (bacteria 24 h culture, yeast and microscopic filamentous fungi 72 h culture), 4 isolated colonies were inoculated into the respective culture broth. After 2 hours For incubation, the culture was diluted so that 1 drop inoculated at a micrometer with an inoculum apparatus, in a dilution standard method, with a 1 ml syringe over a # 8 needle, contained 5.10 ⁶ to 5.10 ⁷ cells in yeast and 3.10 ⁵ cells.

The results:

Highest inhibitory effective dilution of solutions Tab.2

Sample no. S. aureus E.coli C.alb. M.gypseum T.terrestre First 1: 128 1: 256 1:32 1: 2000 1: 1000 Second 1: 256 1: 512 1: 128 1: 1000 1: 1000 Third 1: 512 1: 1024 1: 128 1: 1000 1: 1000 4th 1: 1024 1: 1024 1: 256 1 1100 1: 1000 5th 1: 512 1: 512 1: 128 1: 1000 1: 1000 6th 1: 256 1: 256 1:64 1: 500 1: 1000 7th 1: 256 1: 512 1: 128 1: 700 1: 1000 8th 1: 512 1: 512 1: 128 1: 1000 1: 1000 9th 1: 512 1: 1024 1: 256 1: 1000 1: 1000 10th 1: 256 1: 256 1: 128 1: 1000 1 1100

All solutions showed excellent inhibitory activity against filamentous fungi, surprisingly the relatively low activity against yeast. The most effective of the solutions tested is # 4, which contains 1.5% 2-aminotridecane hydrogen adipate, 5% ethanol 96%, and 93.45% distilled water.

Other tests of the disinfectant solution according to the invention:

The methods used were published in the following works:

1. Kneiflová, J. (1985): Standard Methods for Evaluation of Disinfection Effectiveness of Chemical Substances. Annex AHEM, 1, p. 1-25.

Actions: Place Hold Add to Cart 2. Bydžovská, O. and Kneiflova J. (1983): Assayment of Viral Disinfection by Means of Bacteriophage ΦΧ.174, J.Hyg.Epid.Microbiol.Imun. 37, 60-66.

3. Van der Voorde et al. (1984): The Choice of Fungi as Test Organisms in Disinfectant Testing, Zbl.Bakt.Hyg.I.Abt.Orig. B 179,125-129.

Bactericidal effect:

The bactericidal effect was determined by a qualitative suspension test. The effect of the substance in the protein environment was determined by a qualitative suspension test, and the efficacy of a certain concentration of the substance was evaluated in the presence of 5% (not 20%) of horse serum (1).

Sporicidal effect:

It was determined by a qualitative suspension test.

Fungistatic effect:

The concentration of 500 µg of the substance in ml of culture medium, at which growth of the test strain must be inhibited, is given as a criterion of theungistatic value.

Fungicidal effect:

Test strains: Candida albicans CNCTC 49/64 Geotrichum candidum Aspcrgillus flavus Trichophyton mentagrophytes

The fungicidal effect in Candida albicans was determined by the qualitative suspension test reported by Kneifl. The other micromycetes strains mentioned above were also used in the evaluation of efficacy. To evaluate the effects of disinfectants on microscopic filamentous fungi, the method of Van der Voord et al. (3).

Viralinactivating effect:

Bacteriophage ΦΧ 174, host strain: Escherichia coli CNCTC 427/82, ATCC 13706

The virininactivating effect was determined in a bacteriophage ΦΧ 174 model (host strain Escherichia coli). Bacteriophage ΦΧ 174 has inactivation resistance comparable to small animal viruses of the family Picornaviridae and Parvoviridae. The determination procedure is according to the work of Bydžovská and Kneiflová (2).

The results:

The preparation contains 1.5 ml of 2-aminotridecane hydrogen adipate, 5 ml of 96% ethanol and 93.45 ml of distilled water and 0.05 g of dye (thymol blue).

Bactericidal effect: Tab.3.

tribe % Concentration Exposure in min Pseudomonas aeruginosa CNCTC 168/79, ATCC 15442 1 1 + 5% serum 1 1 Proteus vulgaris OCNCTC 11/70, NCTC 4635 1 1 + 5% serum 1 1 Staphylococcus aureus Mau CNCTC 43/60, SG 511 1 3 Escherichia coli CNCTC 324/70 1 1 Salmonella typhimurium CNCTC 4/49 1 1 Serratia marcescens hospital strain 1 1

The concentrations and exposures given in Table 3 are the lowest values at which all germs of the test microbes in the experiment are killed. The approximate density in 0.1 ml of the bacterial suspension in the experiment is 10 ⁶ - ⁸ individuals. The results show that a 1% solution of the preparation is already bactericidal.

Sporicidal effect:

Table 4

tribe concentration Exposure in min. Bacillus subtilis CNCTC 4/42 100% *> 15

* concentrate ineffective at 15 min. exposure, longer exposure not made.

Fungistatic effect:

Test strains: Aspergillus flavus, Aspergillus igigatus, Aspergillus niger,

Paecilomyces variotii, Bysochlamys nivea, Scopulariopsis brevicaulis, Geotrichum candidum, Candida albicans are not inhibited in growth at a concentration of 500 µg of the substance in 1 ml of Sabouraud soil (this is the concentration of the preparation and not the concentration of the active substance in the preparation).

Fungicidal effect:

Tab.5

tribe % Concentration Exposure in min Candida albicans 1 30 CNCTC 49/64 1 + 5% serum 100 30 1 Trichophyton mentagrophytes 100 1-5 Geot.ri c & um ~ c.PJidid um 100 ..1-.3 Aspergillus flavus 100 1-5

The table shows the shortest exposures and the lowest concentrations at which all germs tested in the experiment are killed.

Viralinactivating effect:

tribe % Concentration Exposure in min Bacteriophage ΦΧ 174 host: E. coli ATCC 13 706, CNCTC 427/82 1OO ·> 15

* The reduction in the number of PFUs does not occur under the conditions given in the table.

Summary of results:

A disinfectant composition of the invention comprising 1.5% 2-aminotridecane hydrogen adipate,% concentrated ethanol in distilled water, respectively. also containing a dye in an amount of 0.01% or 0.05% is bactericidal, with already 1% solution at short exposures all the tested bacteria are killed, even in the case of protein contamination (5% horse serum was used in the experiment). The sample is also fungicidal in dilute solutions, however, only 100% fungicidal effect at short exposure times has only the undiluted product, and therefore it is recommended to use the undiluted product prior to surgical procedures for disinfection and surgical field designation, intramuscular and intravenous injections and the like. The composition is also suitable for disinfection of instrumentation or instruments, where it is not possible to use alcohol - flammable. Colorless solution can be recommended even in 1% dilution for surface disinfection.

The composition is not sporicidal and also has no virininactivation effect. The advantage of the formulation is that it is not flammable and at a lower antimicrobial content (which is both ecological and economic) has the same effect as 70% ethanol.

The disinfectant solution containing 10% 2-aminotridecane hydrogen adipate according to Example 3 is bactericidal even at a 1% concentration during a minute treatment. A 1 to 5% solution of the formulation is fungicidal in 5 to 30 min. action. Relative loss of pathogenic micromycetes (by approximately three logarithms) occurs already after several minutes of treatment with 1 to 5% of the preparation solution. The solutions of the formulation are bactericidal and fungicidal even in the presence of organic substances in the environment. Also, the concentrated formulation is not sporicidal.

Industrial usability

The present invention is useful in the manufacture of disinfectants and in disinfection practice, particularly in the medical field.

Claims (2)

PATENT CLAIMS Disinfectant with 2-aminotridecane hydrogen adipate, characterized in that it contains 1 to 15% by weight. 2-aminotridecane hydrogen adipate, 85 to 99% by weight. distilled water, 0 to 7 wt%. ethanol and 0 to 0.5 wt.%. dye.