FR2696903A1 - Germicidal composition and soap containing it. - Google Patents

Abstract

The invention relates to a germicidal composition and a soap containing it. The germicidal composition comprises diiodomethyl-p-tolylsulfone, as well as 5-amino-1,3-bis (2-ethylhexyl) -5-methylhexahydropyrimidine and / or a compound selected from chlorhexidine diacetate, chlorhexidine digluconate and chlorhexidine dihydrochloride, in a suitable solvent such as an alcohol, preferably ethanol. The composition is effective against a broad spectrum of microorganisms and can be used in particular to disinfect the skin. Field of application: antiseptics.

Description

The present invention generally relates to a germicidal composition and a

  soap containing it, and more particularly a composition having a broad spectrum of sterilization and harmless to the human body, and a soap containing it which is capable of inhibiting the growth of parasitic microorganisms on the skin that cause various skin conditions, and to destroy the parasites. By definition, microorganisms are organisms too small to be seen distinctly with the naked eye They are able to grow and reproduce under appropriate conditions regarding the availability of nutrients, moisture, temperature, etc. Microorganisms extend over a wide range of taxonomic distribution; they include some metazoans, protozoa, a large number of algae and

  of fungi, bacteria and viruses.

  These microorganisms are found everywhere, for example on human skin and even in places where magma erupts. They play important roles for the circulation of materials in the ecosystem. Moreover, they are used in important industrial processes such as production. essential drugs, food, etc. However, some microorganisms infect humans, animals or plants by making them suffer from various diseases Other microorganisms can corrupt timber, paper, fabrics, foodstuffs , etc., thereby degrading the

  quality of the environment of living beings.

  On human skin, microorganisms remain in an amount of about 104 colony-forming units (hereinafter rufcil) per cm 2 of skin This group of microorganisms is called a normal flora, which is harmless to the human body On the contrary, this flora is advantageous because it prevents the infection of the skin by other harmful microorganisms The density of the normal flora is kept constant by the bacteriolytic effects conjugated hydrolytic enzymes (for example lysozymes) which are widespread in the tissues and secretions, transferrin, which is also a type of secretion, and metabolites of the microorganisms themselves. However, if a human being suffers from a weakening of his immune system or comes into contact with a contaminated substance , particular pathogenic microorganisms propagate abnormally, and thereby contract bacterial or fungal diseases. construction, tissues, paper, food, etc., which are encountered in everyday life, can provide ideal habitats for microorganisms and are therefore often contaminated by them. Moreover, under extreme conditions such as nutrient availability, high temperature, dry environment, etc., microorganisms can produce microscopically detectable quiescent corpuscles (endospores) that are highly resistant to heat and drought, so that they can survive until the environmental conditions have improved. Therefore, there is still a risk that a human being will be infected with microorganisms by coming into contact with

  fabrics, wallpaper, cloth or food.

  It is recognized that infectious skin diseases (accounting for 5 to 10% of the total number of patients hospitalized in the USA) are contracted for a large part in a public health facility such as a hospital (nosocomial infection). It is considered that diseases spread between patients through the health care staff and instruments that are still in contact with patients. In addition, a patient whose immune function is weakened by the administration of drugs or as a result of surgery, which is therefore poorly resistant to infection, develops a state of

pathological very serious.

  In an attempt to solve these problems, Korean Patent Publication No. 90-2935 has suggested a germicidal cleanser in the form of an ointment or soap. However, the sterilization capability of this cleaning product is questionable. So far, no germicidal product has been developed that can be used easily at any time and in any place. To this end, it is necessary to develop a germicidal composition that is capable of preventing contamination of everyday products and protecting humans against infection by infectious microorganisms, and which is further effective in sterilizing and treat an infected area, while being harmless to humans, animals and plants. Difficulties encountered in developing a germicidal substance are the diversity of microorganisms and

  the requirement of safety for the human body.

  It is recognized that a large fundamental dichotomy exists between the various groups of microorganisms with respect to the internal structure of the cell. Radically different types of cells exist in the contemporary living world. The more complex eukaryotic cell is the structural unit. metazoans, protozoa, fungi and all but one of the groups in which algae have been traditionally classified The less complex prokaryotic cell is the structural unit of two microbial groups: eubacteria and Archaebacteria Among prokaryotes, eubacteria can be subdivided into Gram-negative eubacteria and Gram-positive eubacteria according to the structure of the cell wall. In general, microorganisms react

  various germicidal substances A germicidal substance is often ineffective against Gram-

  negative, even if it kills Gram-positive bacteria In addition, it is common that a substance endowed with a powerful

  sterilizing ability against both Gram-

  positive than Gram-negative is ineffective against eukaryotic microorganisms such as yeasts and fungi. In seeking to solve the aforementioned problems, the Applicant has recognized that there is a need for an effective germicidal composition against a broad spectrum of microorganisms, which is capable of inhibiting the growth of or destroying microorganisms and which is harmless to humans, animals and plants, and a need for a product form containing the composition

  germicide that can be used anytime and anywhere.

  Thus, in one aspect of the present invention, there is provided a germicidal composition that is capable of inhibiting growth or destroying microorganisms.

various groups.

  In another aspect of the present invention, there is provided a germicidal composition which is safe for humans and other living things such as animals and plants. In yet another aspect of the present invention, there is provided a soap that has an effect

  excellent inhibitor and disinfectant power against microorganisms.

  The above-mentioned objects of the invention are achieved by a composition which comprises a compound represented by the following formula I ## STR2 ##

CH 3 CL

  and at least one, or both, of the compounds represented by the following formulas II and III:

  C 4 H 9 CH (C 2 H 5) CH 2 N N CH 2 CH (C 2 H 5) C 4 HB

H 2 N CH

NH NH

(C Ha) s, R lIIIl

NH C NH-C-NH CI

(CH 2) 6, R

NH C NH C-NH Ci Il II

NH NH

  R is selected from diacetate, digluconate and dihydrochloride; and a solvent. The compounds of formulas I, II and III above

  are known to be harmless to the human body.

  These objectives, as well as others not specifically mentioned above, will become clear to the man of

  the art upon consideration of the following detailed description of the present invention.

  Diiodomethyl-p-tolylsulfone represented by Formula I, used as an ingredient of the germicidal composition of the invention, has a strong germicidal power against Gram-positive bacteria, yeasts and fungi, but is poorly effective against Gram bacteria. Another potent ingredient represented by Formula II, 5-amino-1,3-bis (2-ethylhexyl) -5-methylhexahydropyrimidine, is capable of destroying Gram-negative bacteria. The other compound represented by Formula III, which is selected from chlorhexidine diacetate {1,1'-hexamethylene-bisl 5- (4-chlorophenyl) biguanidel}, chlorhexidine digluconate or chlorhexidine dihydrochloride, is effective against Gram-negative bacteria and is superior to the compound of formula II for the destruction of Gram-positive bacteria

and mushrooms.

  According to the present invention the germicidal composition is prepared by combining the diiodomethyl-p-tolylsulfone of

  Formula I with 5-amino-1,3-bis (2-ethylhexyl) -5-

  methylhexahydropyrimidine of formula II and / or the compound of formula III, whereby the composition can destroy Gram-positive and Gram-negative bacteria, as well as

  eukaryotes such as yeasts and fungi.

  For example, the composition according to the present invention is effective against bacteria such as Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Micococcus multicida, Mycobacterium tuberculosis, Proteus vulgaris, Shiegella dysenteria, Staphylococcus aureus, Staphylococcus epidermis, Streptococcus faecalis, etc. The germicidal composition of the invention inhibits the growth of yeasts or fungi such as Aspergillus sp, Aerobacidium pullulans, Candida sp, Epidermophyton sp, Fusarium sp, Microsporum sp, Malassezia furfur, Penicillium citrinum, Trichophyton sp, etc. The mixing ratio of the ingredients is preferably of the order of 1: 1 by weight in the case where the germicidal composition comprises the compounds of formulas I and II or the compounds of formulas I and III. On the other hand, the ratio of The mixture is preferably on the order of 1: 1: 1 by weight in the case where the germicidal composition comprises all the compounds of formulas I, II and III.30 The preferred solvents for use in the present invention are alcohols, and very preferably ethanol. According to the present invention, the germicidal composition can be formed into a useful form comprising various other materials. For example, the germicidal composition of the invention can be mixed with a base soap to make a soap as described below. the present invention may also be added to an organic solvent such as ethanol to prepare an effective sterilizing solution for surgery. The germicidal composition and the soap which contains it exert an excellent effect of inhibiting the growth of microorganisms, so they can be used to clean or sterilize hard parts of household objects such as walls, floors, tables, plastic articles, etc., or for

  laundering laundry to sterilize it.

  In particular, the germicidal composition and the germicidal soap according to the present invention have a remarkable disinfecting power against yeasts and anthropophilic fungi which have a high power of penetration into the human body, such as Candida albicans, Trichophyton mentagrophytes and Epidermophyton floccosum These microorganisms are responsible for mycotic skin diseases such as eczematosis, dermatomycosis, trichophytosis, etc.

EXAMPLE 1

  Preparation of a germicidal composition

  First, 20 g of diiodomethyl-p-

  tolylsulfone in 1980 ml of 99% pure ethanol To this solution is added 20 g of 5-amino-1,3-bis (2-ethylhexyl) -5-methylhexahydropyrimidine and 20 g of chlorhexidine digluconate, and all is stirred vigorously for 5 minutes to prepare a germicidal composition. The prepared germicidal composition contains each

  of the three active ingredients at a rate of 20,000 ppm.

  It is obvious that the concentration of the active ingredients and their ratio may vary depending on the intended application. EXAMPLE 2 Growth inhibitory effects of the composition prepared in Example 1 are measured against various microorganisms The growth inhibitory effect is considered here as the value of the minimum inhibitory concentration (hereinafter CMI) of the germicidal composition, which is determined by inoculating a defined number of microorganisms into suitable culture media containing various concentrations of the respective germicidal compositions, cultivating the microorganisms at a constant temperature for a period of time and selecting the medium in which the microorganisms do not

  are not able to grow and that contains the lowest concentration of the composition.

  The compositions of the culture media for the growth of microorganisms are as described in Tables 1 and 2 below. TABLE 1 Growth medium for bacteria

TABLE 2

  Growth medium for mushrooms Malt extract 40 g Peptone 10 g Chloramphenicol 10 mg Distilled water 1 e (p H 5,6) For the preparation of a culture plate, agar

  is added in an amount of 1.5 k.

  The constituents of the medium are sterilized at 12 ° C. Yeast extract 3 g Tryptone 5 g Glucose 1 g Distilled water 1 e (p H 5,6) for 15 minutes according to a technique conventionally used. A mother solution of the microorganisms is prepared as follows: culture plates are seeded by taking a very small amount of bacteria and yeast cells on a platinum needle, previously sterilized by passing through the flame, and passing the needle several The microorganisms are cultured at 300 ° C. for 2 to 3 days to grow in isolated colonies. The microbial cells of the isolated colonies are collected on a single plate. loop and are suspended in 0.9 W NaCl solution (hereinafter "physiological saline solution"). In the case of fungi, these are incubated on a culture plate at 300 ° C. for 5 minutes. at 7 days to form spores A volume of 10 ml of a physiological saline solution containing about 5 2 in

  The weight of Tween 80 is poured onto the culture plate, and a spore suspension is prepared by scraping the surface of the culture with the aid of the loop.

  The stock solution thus prepared is measured by a conventional method to determine the total number of microorganisms contained therein, and then inoculated into liquid culture media respectively containing various concentrations of the germicidal compositions. The size of the inoculum should be maintained at 104 cfu / ml After inoculation, the culture vessel is rotated at a speed of 150 rpm at 300 C After 48 hours for bacteria, or 72 hours for mushrooms, the growth state is examined to determine MICs. The results obtained with the germicidal composition of Example 1 for each group of microorganisms are

  given in Table 3 below.

EXAMPLE 3

  The sterilizing effects of the germicidal composition prepared in Example 1 are measured for various microorganisms. The sterilizing effect is considered here as the value of the minimum biocidal concentration (hereinafter "CMB") of the germicidal composition, which is determined by inoculating a defined number of microorganisms into suitable culture media respectively containing various concentrations of the germicidal compositions, incubating the microorganisms for a time and selecting the medium which contains the lowest concentration of the composition and wherein the number of microorganisms less than 0.1% of that of the inoculum In the conventional method of enumeration of total viable cells, the value is determined by carrying out the experiment of Example 2 and in

  measuring the number of residual microorganisms that survived in culture media where microorganisms were unable to grow.

  The results obtained with the germicidal composition of Example 1 for each group of microorganisms are

given in the following Table 3.

TABLE 3

  MIC and CMB of germicidal composition for microorganisms Microorganisms MIC (ppm) MBC (ppm) Bacteria Bacillus subtilis 50 50 Escherichia coli 100 200 Mycobacterium tuberculosis 250 500 Staphylococcus aureus 200 300 Streptococcus faecalis 200 300 Yeasts Candida albicans 100 200 Mushrooms Aspergillus sp 38 75 Epidermophyton sp 38 75 Trichophyton sp 38 75

EXAMPLE 4

  Making a germicidal soap It is important to know the degree of dilution of each of the constituents of a soap when the soap is used, since the concentrations of each constituent must be determined in order to make a soap. taught in European Patent No. 363,215 (A 2) which makes it possible to analyze the influence of the constituents on the properties of the soap. Thus, it is supposed that the constituents of the soap are diluted 100 times when the soap is used. The germicidal composition of Example 1 is added at a concentration of at least 25% in the manufacture of a soap having a powerful sterilizing power towards all

  microorganisms listed in Table 3 above.

  The composition of the soap is as follows: Basic soap or pure soap 97.5 g The germicidal composition 25.0 ml Other additives Perfume 1.5 ml Pigment 0.01 g The basic soap is subjected to the grinding treatment for 5 minutes The germicidal composition and the other additives are added while stirring the sprayed soap. The resulting mixture is dried to evaporate the ethanol completely and bring the water content to less than 5 k. The dried mixture is again subjected to stirring. grinding for 15 minutes to completely mix the added components By maintaining the temperature between 32 and 370 C, the mixture is spun in a Stephen Beck extruder, then ejected in the form of a ribbon Using a miniature multiple press, the ejected mixture is pressed in a form of suitable soap. In the manufacture of a germicidal soap, each active ingredient may be incorporated at a concentration of 0.5 A, based on the weight of the base soap, instead of

  use the ethanolic solution containing the active ingredients.

EXAMPLE 5

  The growth inhibitory effects of the germicidal soap made in Example 4 are measured against various microorganisms. The growth inhibitory effect is here represented by the degree of growth inhibition (% -)

  which is a relative size expressing the growth inhibition of the microorganisms exerted by the aqueous soap solution containing the germicidal composition compared to that exerted by the aqueous soap solution not containing the germicidal composition.

  The growth inhibitory effect is determined as follows: A volume of 0.5 ml of stock solution containing various microorganisms at a concentration of 1000 cfu / ml is mixed with a 2 W soap solution (a suspension containing 2 g of soap and 100 ml sterilized distilled water), then the resulting solution is poured onto a culture plate and incubated at 300 C for 48 hours for the bacteria or for 72 hours for the yeasts and

  mushrooms, so that they grow by forming colonies.

  The number of colonies present on the culture plate is determined in order to compare the treatment with soap

  containing the germicidal composition with the soap treatment not containing the germicidal composition. The results obtained are given in Table 4.

TABLE 4

  Inhibitory effect of growth of germicidal soap on microorganisms

  * Degree of growth inhibition.

  ** A not containing the germicidal ingredients

B prepared according to Example 4.

EXAMPLE 6

  The sterilizing effects of the soap made in Example 4 are measured against various microorganisms.

  The sterilizing effect is here represented by the degree of sterilization which is a relative magnitude expressing the inhibition of growth of the microorganisms exerted by the aqueous soap solution containing the composition Staphylococcus Candi da aureus albicans Soap Rate Survival Rate I * suvie I * survival D (IU (ufc) s (ufc) (2 e) (ufc) (W)

At 1200 760 1070 -

B O 100 4 99 O 100

  germicidal compared to that exerted by the solution

  aqueous soap which does not contain the germicidal composition.

  The sterilizing effects are determined as follows: A volume of 0.5 ml of stock solution containing various microorganisms at a concentration of 1000 cfu / ml is mixed with 0.5 ml of a soap solution at 2 (a suspension containing 2 g of soap and 100 ml of sterilized distilled water) in a microcentrifuge tube, and the mixture is left at 300 ° C. for 10 minutes After the microorganisms have been inoculated in the soap solution, they are centrifuged at a rate of 8000 ° C. / min for 5 minutes The supernatant is carefully decanted 1 ml of physiological saline is poured on residual sedimented microorganisms to wash the soap solution This last step is repeated 2 or 3 times, then 1 ml of saline is poured

  physiological effect on residual sedimented microorganisms.

  The resulting solution is poured onto a culture plate which is then incubated at 300 ° C. for 48 hours for the bacteria and for 72 hours for the yeasts and fungi. The number of colonies present on each

  Culture plate is determined to compare soap treatment containing the germicidal composition with soap treatment not containing the germicidal composition.

  The results obtained are given in Table 5

TABLE 5

  Sterilizing effect of germicidal soap on microorganisms

* Degree of sterilization.

  ** A: not containing germicidal ingredients

B: prepared according to Example 4.

  As can be seen from the preceding examples, it is foreseeable that the germicidal composition and the soap which contains it according to the present invention are capable of preventing an infection of the skin by harmful microorganisms and also of sanitizing already infected regions. Since the present invention has been described with reference to certain preferred embodiments and particular examples, it will be apparent to those skilled in the art that many variations and modifications can be made without departing from the scope and spirit. of

the invention.

Staphylococcus Candida

Trichophyton sp.

  aureus albicans Soap Rate Rate Rate

D.S * D S * D S *

  survival survival survival (ufc) (ufc) (ufc) ()

A 700 825 730 -

B 7 99 8 99 204 72

Claims (6)

CLAIMS CATIONS   Germicidal composition, characterized in that it comprises: a compound represented by the following formula I: ## STR2 ## at least one or both of the compounds represented by formulas II and III: C 4 HQCFH (C 2 HS) CH 2 NN CH 2 CH (C 2 H 5) C 4 He III H 2 N CH 3 1 O NH NH (CH 2) 6, R lIl NH-C-NH-C NH CI   NH NH or R is selected from diacetate, digluconate and   dihydrochloride; and a solvent capable of dissolving these compounds.   Germicidal composition according to claim 1, characterized in that said solvent is an alcohol.   Germicidal composition according to claim 1, characterized in that said compound of formula I and said   Compounds of formula II or III are included at a weight ratio of 1: 1, or said compounds of formulas I, II and III are included at a weight ratio of 1: 1: 1.   4 Germicidal soap, characterized in that it comprises a composition which consists of: a compound represented by the following formula I: o O C H 3 S CHI   and at least one or both of the compounds represented by the following Formulas II and III: ## STR2 ## wherein: ## STR2 ## 4 h CH 3 NH fi II NH C NH (CH 2) e I NH -C NH NII NH NH -I C -NH '(-III) C-NH CI   NH or R is selected from diacetate, digluconate and dihydrochloride.   Germicidal soap according to claim 4, characterized in that the composition is directly added to a basic soap.   6 germicidal soap according to claim 4, lIIIl characterized in that the composition is dissolved in a   alcohol to be added to a basic soap.   Germicidal soap according to claim 6,   characterized in that the alcohol is ethanol.