DE1642070A1 - Disinfectant mixture - Google Patents

Description

Cologne, He 2.1966 Eg / Ax

Johnson & Johnson, 501 George Street, New Brunswick, N.J.

(V. St. A.)

Disinfectant mixture

The invention relates to bactericidal agents containing a cationic quaternary ammonium compound and more particularly are beneficial as skin antiaeptics to eliminate contact infection in hospitals and homes

Contact infection through the transmission of pathogenic bacteria is a problem both in the home and in the hospital. A large part of the hospital staff, e.g. Xrste, Nurses and technicians, constantly contaminates hands with bacteria while performing your duties in caring for patients. They stay bacteria for a long time on the skin surface and can multiply under certain conditions · These hospital staff can therefore these bacteria are transmitted to other patients · Furthermore, members of the staff who carry nasal carriers can soloher Microorganisms are doing this with their hands on patients transfer. Likewise, you can take care of a sick person Family member in the apartment other family members infect · To reduce the risk of such contact infection, it is therefore necessary before touching Remove the bacteria from the hands of other patients or persons or reduce their numbers to a minimum.

ö 17/1936

The most common way to remove this bacteria is to wash your hands with soap and water, whereby Usually brushing and then drying the volumes with a sterile towel · Have examinations however, this method shows that this method is not very effective in removing the bacteria · Furthermore, it is side-consuming ο This led to the use of τοη antiseptics for cleaning handsο While this is more effective than washing with soap and water, but this does not sufficiently eliminate the bacteria »

Preparations and methods for disinfecting surfaces, ζ · Β · the skin of the hands, which both against Gram-positive and Gram-negative bacteria act quickly, easily available, easy to apply and gentle on the skin are. Preparations that act on the skin would also be desirable pull up and don't wash off easily

The invention solves these problems by providing a unique means of disinfecting τοη Surfaces, e.g. the skin of the hands, which is effective against both gram-negative and gram-positive bacteria and is kind to the skin, adheres firmly to the skin and feels light and can easily be applied directly to the desired surface.

The preparation according to the invention consists of a water-soluble cationic quaternary ammonium compound, which is a noun against the skin, a non-toxic, non-volatile organic acid, which is able to form a water-soluble salt with the cationic ammonium compound, and an ^egg dissolving, non-ionic, surface-active agent dissolved in an aqueous solution containing at least about 30% by weight of ethanol or isopropanol "

Cationic quaternary ammonium compounds are known effective bactericides and are used for this purpose. However, they are not effective when in the presence of

Ι09817 / 193Λ

Soap scraps are used »If they are, for example When applied to the skin, they are usually deactivated and lose some or all of their bactericidal properties Properties! because mostly on the skin Am kickstand of a fatty acid soap as a result of normal washing. These fatty acid soaps are anionic and deactivate the cationic quaternary ammonium compound through complex formation or precipitation when they come into contact with it · In this form, the cationic quaternary ammonium compounds do not exert their bactericidal effect.

It has now been found that by admixing the cationic I see quaternary ammonium compound to a carrier, which consists of an aqueous solution that is at least about 3O ^ ethanol or isopropanol (absolute) contains the deactivation of the cationic quaternary ammonium compound is prevented by a real fatty acid soap believed that the anionic-cationic precipitate which is formed is solubilized by the alcohol, thereby the cationic quaternary compounds become available in the form in which they exert their bactericidal activity can, i.e. in the ionized form · The preparation also advantageously contains a non-volatile organic Acid that is skin-friendly and with the cationic j

quaternary ammonium compound is able to form a water-soluble salt, and a water-soluble, nonionic surface active substance. The connection can be in any suitably formulated, however, it is preferably made up as an aerosol so that it is easily can be applied as a quick break foam. Below is a preferred embodiment of the invention all examples are given.

17/193 /.

example 1

Sew, -

Dequalinium acetate 0.2727

Cetyl pyridinium acetate 0.2727

Citric acid (monohydrate) * 0.22

Polyethylene glycol 6000

(Carbowax 6000, Union Carbide) 3.27

Polyoxyethylene sorbitol monolaurate 2.18 (Tw «en 20, Atlas Chemical Co.)

Ethanol (1: 0001g) 52.8

Perfume »Synfleur ¹ »

(Synfleur Laboratories) J-296

Waeser to replenish to 100

* The amount of citric acid can be adjusted so that a buffers of about 5.8 is obtained.

To prepare the product of the above composition, the calculated amount of water is placed in a stainless steel vessel equipped with a mechanical stirrer. The polyethylene glycol is added and mixed in until it dissolves. While stirring, the following ingredients are added in the order listed: The alcohol, the dequalinium acetate, the cetylpyridinium acetate, the polyoxyethylene sorbitas monolaurate and the perfume, whereupon the mixture is stirred until a clear solution has formed. The citric acid is then stirred in an amount such that the _pH value is about 5.8 of the solution. Stirring is then continued until a clear solution has formed, which is filtered before filling.

To produce an aerosol, this is the preferred embodiment of the invention, about 17.6-18.4 parts by weight of the product described above with 0.86 to 1.33 parts by weight of a propellant mixture consisting of Diohlordifluoromethane and Diohlortetrafluoroethane in weight ratio of 80:20 exists, filled in an aerosol can. When sprayed from the container, the product forms a

109817/1934

16A207Q

fast breaking foam. The product can also be such used or with other common carriers be combined·

Example 2

Grew. -9

Be quäl iniumohlo r i d 0.2727 Cetyl pyridinium chloride 0.273 Tartaric acid * 0.22 Polyethylene Glycol 6000 3.27 (Carbowax 6000, Union Carbide) Polyoxyethylene sorbitol * amonoatearate 2.18 (Tween 60, Atlas Chemical βο) Isopropyl alcohol 52.8 "Synfleur" perfume (Synfleur laboratories) J-296 Water to top up 100.0

♦ The amount of tartaric acid can be adjusted so that the is about 5.8

Example 3

Dequalinium Acetate O, 2727

Maleic acid * 0.22

Polyethylene glycol 6000 3.27 (Carbowax 6000, Union Carbide)

Polyoxyethylene stearate 2.18 (UXBJ 52, Atlas Chemical Co.)

Ethanol (100 # Lg) 52.8

Water to make up to 100.0

♦ The amount of maleins can be adjusted so that the is about 5.8 «

109817/1934

Example 4

Weight -

2727 O, 2727 O, 22nd 2, 18th

Dequalinium acetate 0.2727

Getyl pyridinium acetate 0.2727

Citric acid (monohydrate) 0.22

Polyethylene glycol 6000 3.27

(Garbowax 6000, Union Garbide)

Polyoxyethylene sorbitan monolaurate 2.18

(Tween 20, Atlas Chemical Go.)

Ethanol (100? Sig) 30.0

Perfume ^ Synfleur "(Synfleur Ghemioal) J-296

Water to make up to 100.0

'"The amount of citric acid can be adjusted so that the pw value is around 5.8 »

Example 5 - #

Benzalkonium chloride, oetylpyridinium chloride Succinic acid * polyoxyethylene lauryl ether (BEIJ 30, Atlas Chemioal Go ·)

ethanol (100%) 52.8

Barfum "Synf 1 eur ^H

(Synfleur Laboratories) J-296

Water to make up to 100.0

* The amount of succinic acid can be adjusted so that the power is about 5.8.

The products described above can be used as such or in other formats, e.g. as an aerosol wi in Example 1, can be applied.

The amount of alcohol used in the aqueous solution is important to the bactericidal effectiveness of the kationisohen quaternary ammonium compound in the presence of soaps to get lined up. Ee it was found that the The amount of alcohol in the solution is at least about 30% by weight

109817/1934

... 7 -

must wear. The need for this amount of alcohol arose from a series of experiments carried out with different eleven products containing the cationic quaternary ammonium compounds were carried out, However, in which the alcohol content was changed. Attempts have also been made with soap-containing aqueous alcohol solutions performed · The soap content in each solution was 1

The tests were carried out as follows: aliquots of 1 ml of a suspension of Staphylococcus aureus, each containing about 60 × 10 viable cells, were added to aliquots of 9 ml each of the solutions in test tubes. After exposure times of 15 seconds, 30 seconds, 1 minute, 5 minutes and 10 minutes, 1 ml of each mixture; removed and 9 ml of a neutralizing agent for the cationic quaternary ammonium compound were added. The mixtures and the serial dilutions made from them were plated out in an agar nutrient medium. After 48 hours of cultivation at 32 ⁰ O, the colonies present on the flat colonies were counted in order to determine the number of cells that survived each treatment period. The results are given in the table below.

109817/193 4

label 1 bacteria 49x10 ⁶ 61 χ 10 ⁶ Number of to Vaccinated Recovered bacteria
aureus per ml
15 sec. 30 sec. 1 min. 49x10 ⁶ Staphylooo ccus
5 min. 10 min _e Test-
material 66x1O ⁴ 12x10 ⁶ 60x10 ⁵ example 1
(115 * alcohol)
+ 1 # g, S * 13x10 ⁶ 17x10 ⁶ 14x10 ⁶ 1OjS alcohol
+ 1 * g.S. 500 500 example 1
(2256AIkOhOl)
+ 1j6 geS » 21xiO ⁵ 44x10 ⁵ 27x10 ⁵ 2 OJ * alcohol
+ 1 ^ goS 250 0 example 1
(335 * alcohol)
+1> g * S « 68x10 ⁵ 46x10 ⁵ 20th 12x1O ³ 60 30? I alcohol
+ 1 # gS 0 Example t
(44Ji alcohol)
+ 1 ^ goS. 24x10 ⁴ 36x10 ² 0 4OJi alcohol
+ 1Ji gS 0
40 example 1
(55 # alcohol)
+ 1 # g.S
50 * alcohol
+ 1J <g.S 0 example 1
(77J6 alcohol)
+ 1Ji gS 0 70j (alcohol
+ 1 * g.S,

♦ goS. m green soap 109817/1934

From the table above it can be seen that in Cases in which the aqueous solution contains at least about 303S alcohol, immediate effective bactericidal activity is to be determined »The test results show also that alcohol alone in equivalent concentrations is less effective as a bactericide than the product according to the invention.

A similar experiment with Escheriohia ooli, that of the belongs to gram-negative bacteria, brought similar results with regard to the bactericidal effectiveness of the product according to the invention in the presence of soaps

Table 2 Number of bacteria used for inoculation 93 ζ 10

Test recovered · Bacteria Escheriohia ooli material per ml after

15 SeIc ₀ 30 sec. 1 min. 5 min. 10 min.

example 1
(1OJfAIkOhOl) 109 8 O + 1 * g.S · « 74x10 ⁵ 10 * alcohol + 1 * g.S. example 1
(20JfAIkOhOl) O + 1 * g.S 20 * alcohol O + 1 * g.S. example 1 O (30 * alcohol) + 1 * g.S. O 30 * alcohol
+ 1 * g.S. 1 11 193A example 1 (40 * alcohol) + 1 * g.S. 40 * alcohol + 1 * g.S. example 1 (50 * alcohol)
+ 1 * g.S. 50 * alcohol + 1 * g.s.

500

500

500

93xtO ⁶ 95x1O ⁶

500

500

500

76x10 ⁶ 33x10 ⁶ 12xi! 0 ⁶

40x10 ⁴ 1OxIO ³ 680

Table 1 (cont.) Test material 15 sec 30 sec _o 1 min »5 min 10 min.

example 1

(70Ji alcohol)

+1 f> gS 0

alcohol g.So 0

* g, p. «Green soap

Patch tests carried out on the skin of test subjects hacking with a product that the components mentioned in Example 1 without the water-soluble fatty acid ester etherified with ethylene oxide of anhydroorbites and without citric acid, showed that the product caused primary irritation. It it was then found that the irritation caused by the addition of a water-soluble, nonionic surface-active agent, E.g. the water-soluble fatty acid ester of anhydro sorbitol etherified with ethylene oxide to the product could be prevented

A series of tests were then carried out to determine the subacute dermalicity of the product. The product according to Example 1 without the citric acid was used applied to the back of guinea pigs and rabbits in various amounts. A weight loss, «in Signs of a certain system effect were noted. It was theorized that this phenomenon was due to the volatility of the aetation from the Dequaliniumaoetat and Cetylpyridlniumacetat could be, whereby qua te mär β hydroxides are formed »which could exert the frictional effect or to ternary amines would be degraded, which are well-known ice creams. This problem was solved by adding a non-toxic, non-volatile organic acid was absorbed by the a water-soluble salt with the cationic quaternary Able to form ammonium compound. With this product

109817/1934

Animal experiments carried out showed that the toxicity was decreased. The preferred compound for this purpose is citric acid, but others are suitable Acids, e.g. the hydroxy acids, malic acid, lactic acid, glycolic acid and tartaric acid, as well as acids such as benzoic acid and succinic acid

The preferred cationic quaternary ammonium compound is Dequaliniumaeetat because it is against both gram positive as well as gram-negative bacteria and against Oandida albicans is effective. It is also a noun against the skin and therefore has a long-lasting effect. Furthermore, preferably getylpyridinium acetate added to the product, " because it is also effective against gram-positive and gram-negative bacteria. Cejrylpyridinium acetate exerts its bactericidal properties Effect quickly and dequalinium acetate kai η exercise its effect in the presence of antagonistic substances, e.g. body fluids and EaWäate "

Essentially all water-soluble, cationic quaternary ammonium compounds and their salts which are substan tive to the skin and suitable for topical application can be used for the purposes of the invention. Examples of these are aliphatic quaternary ammonium compounds, for example benzalkonium chloride, quaternary ammonium compounds of pyridine, for example oetylpyridi- nium chloride, quaternary ammonium compounds of ohinoline, 3 _e B. dequalinium, quaternary ammonium compounds of isoquinolines, isoquiniamine amines, such as quaternary ammonium quinolinium compounds of alkyl it Alkyl pyrimidinium chloride

ÄLe amount of water-soluble niohtionogene used Surface-active substance depends on the type and amount of the selected cationic quaternary ammonium compound & »The amount of beef type of non-flammable used organic acid is chosen according to similar criteria "

1098 17/1934 _B AD

The water-soluble, non-ionic surfactant prevents, as already noted, the irritation that can occur when the product larger amounts of cationic quaternary ammonium compounds containing · Preference Polyoxyäthylensorbit * UBmonölaurat (jTween 2O ^W X but other poly / oxyäthylensorbitaafettsäureester are suitable, for example, palmitate, stearate, monoleate and trioleate, as well as sorbitol fatty acid esters, glycerin fatty acid esters, polyalkylene fatty acid ethers and polyoxyalkylene fatty acid esters (compounds of this type are supplied by Atlas Chemical Co.) The water-soluble solid polyethylene glycols of the general formula HOOH ₂ (CH ₂ OOH ₂ ) CH ₂ OH, which are available under the trade name "Cjarbowax" (Union Carbide) If the product is filled as an aerosol, the nonionogenic surface-active substance promotes foam formation.

Heagenzglasversuche have shown that the invention Products, as already noted, their bactericidal effectiveness in the presence of green soap, as well as in the presence of detergents that contain 3 # hexachlorophene in the presence of lotions that contain hexachlorophene, as well as commercially available hand lotions · you will retain results obtained with products containing hexachlorophene and the lotions obtained are shown below · The same experimental method as in the detection the effectiveness of the product according to the invention in the presence of soap was applied.

109817/1934

Table 3

compatibility with other products * L. Test mix. Viable cells
aureus per ml of Staphylococcus Vaccinated Found again
after T5 seconds
Impact $ 99 Example 1
+194 preparation A * 100 χ 10 ⁶ 0 9996 example 1
+ 1 # preparation B ^ 78 χ 10 ⁶ O 959S example 1
+ 59 & preparation B « 0 9Ο9έ Example 1
+ 109 * preparation B H 0 75 * Example 1
+ 25 # preparation B It 0 5096 example 1
+5096 preparation B It 16 χ 10 ⁶ $ 99 Example 1
+195 preparation O *** Il 0 9§ # Example 1
+ 9f> preparation 0 Il 0 9096 example t
+ IO96 preparation 0 Il 0 759 * Example 1
+ 259ε preparation 0 ti 0

5? Example 1 + 509ε preparation 0

1! 6 χ 1O ⁵

♦ Preparation A = * T detergent with 3 # hexachlorophene ♦♦ Preparation B = hand lotion with hexrophorophene content ♦♦♦ Preparation 0 «hand lotion

The speed at which bacteria were removed from the skin surface with a preparation according to the invention was determined by applying 1 ml of the preparation to the hands, drying it and then removing bacterial cultures from the skin of the hands after 3, 5 and 10 minutes . The results obtained showed that the spraying of the total bacteria number after 3 minutes of contact.

109817/1934

-H-

time 74? ί, after 5 minutes 77 # and after 10 minutes fraud"

Attempts have been made to determine the effectiveness of the preparation according to the invention for pathogenic bacteria to determine which were applied to the gang with a culture of Staphylococcus aureua or »Paeudomon & s aeroginoaa (artificial infection). Here was found that the number of bacteria had been reduced by 94 or 97 # after an exposure time of 3 minutes. In cases in which the hands of the test subjects had been washed for 1 minute with soap or a detergent preparation containing 3ji hexachlorophene, the germicidal one was Effect of the product according to the invention comparable to that which was found in tests in which hands had not been washed in this way. This again shows that the effectiveness of the product according to the invention by the presence of soap residues Typically found on hands after washing is not affected

The long-lasting bactericidal effectiveness of the product according to the invention was further confirmed by a series of tests which were carried out as follows: A fixed amount of the product according to Example 1 was applied to the hands and the inner parts of the era of the test subjects · low applied amount was 0.3 ml / 7 ² · om Hautfläoh ,, on-de at hand · applied was 1.0 ml and well incorporated · During Versuohsdauer went dl · ^v ersuchspersonen übliohen their activity after. At various times up to 30 hours after application, round adhesive plaster bags were applied to the skin on which the product had been applied.After 30 seconds, the adhesive plaster was stripped from the skin and placed with the adhesive side close down on the surface. of agar plates inoculated with Staphylococcus aureus · Naoh incubation over

10981 7/1934

Those who appeared in the adhesive plaster pieces were naked Inhibition zones measured «The results below show that the bactericidal effectiveness of the Prodikt according to example 1 on the skin of the inner arms for up to 30 hours « and lasted on the hands for up to 24 hours after application

table 4

Duration of bactericidal activity on human skin after application of the product according to Example 1

The number of people who have bacteriostatic

Such trials show efficacy

area people 2 days 4 hours bh. 24 ~ 5ΐά «30 hours, arms 55 55 55 55 55 53 hands 5 5 5 5 3

Similar experiments in which the adhesive plaster pieces are applied to the skin and peeled off after a long period of time showed that the product according to the invention penetrated the skin, evidence of the ability of the product to to exercise its bactericidal effectiveness against bacteria present there

! Table g

Penetration depth of the preparation according to Example 1 into the human skin _

Treated area arms

Time on the number of subjects with the bakteriosta-nimbly-Vertischer activity development suohs- hr · persons

After wiping the
Adhesive tape

After wiping the
Adhesive tape

24

24

30th 30th 30th 22nd 30th 21st 30th 5

After six times Stripping the Adhesive tape 6 20

109817/1934

The products according to the invention are particularly suitable for the nursing staff, doctors and surgeons before and after the treatment of patients. When hands eohiiutBig, they should be appropriately washed and then are dried »whereupon the product according to the invention is applied · If the hands are not dirty, the product can be applied after contact with the patient. You sea infection τοη hands and other parts of the body can be further improved by first brushing in the usual way and then the product for a sour of about 1 minute after this applies · This Method results in a further reduction in the number of bacteria

You can according to the invention products in aerosol cans be filled, for example attached to the side of the patient's beds, or they can be in a dispenser that the doctor or nurse carries with them. If the product is to be applied, a small amount can be used directly Put on the hands and then work in well for about 1 minute. Sles represents a quick, simple and easy method the function of the hands before treating or under-lifting a new patient.

109817/1934

Claims (1)

I54ZU7Ü claims 1.) Disinfectant mixture effective in the presence of fatty acid soaps, characterized by the content of water-soluble cationic substances with a noun effect on the skin quaternary ammonium compounds, a non-toxic, non-volatile organic acid that reacts with the quaternary ammonium compound forms a water-soluble salt, a water-soluble non-ionic surface active By means of and an aqueous solution of at least 50% by weight of ethanol or isopropanol as a carrier. 2.) disinfectant mixture according to claim 1, characterized denotes overall ä that a hydroxy acid is contained as the organic acid. 5.) Disinfectant mixture according to one of claims 1 and 2, characterized in that the water-soluble nonionic surface-active agent is a water-soluble Fatty acid ester of an anhydrosorbitol etherified with ethylene oxide is used. 4.) disinfectant mixture according to any one of claims 1 to 5, characterized by containing a water-soluble, cationic quaternary ammonium compound having a rapid bactericidal activity and a water-i serlöslichen cationic quaternary ammonium compound having a long-lasting bactericidal activity. 5.) Disinfectant mixture according to one of claims 1 to 4, characterized by the content of a dequalinium salt and a cetyl pyridinium salt. 6.) Disinfectant mixture according to one of claims 1 to 5 *, characterized in that the non-toxic, non-volatile organic acid citric acid 1st. 109817/1934 7 ·) Disinfectant mixture according to one of claims 1. to 6, characterized by the content of about 0.25 % dequalinium acetate, about 0.25 % cetylpyridinium acetate, about 0.22% citric acid, about 2.18 % of a water-soluble fatty acid ester of anhydrosorbitol etherified with ethylene oxide and an aqueous, at least 50 wt. -% ethanol containing solution as a carrier. 8.) Disinfectant mixture according to one of claims 1 to 7 » daduroh characterized in that it is present in an aerosol container together with a propellant. 9.) Disinfectant mixture according to claim 8, characterized in that that dichlorodifluoromethane and dichlorotetrafluoromethane are used as propellants. 10.) Disinfectant mixture according to one of claims S and 9, characterized in that about 0.8 to 1.3 parts by weight of the propellant are used for 17 to 18 parts by weight of the disinfectant mixture. 1 09817/1934