GB2293765A - Disinfectant composition - Google Patents

Abstract

A disinfectant composition contains an antimicrobial agent combined with an activity-enhancing phenolic compound, the composition comprising the following constituents in proportions by weight: 2,4,4'-trichloro-2'-hydroxy diphenyl ether ("Triclosan") 0.1 - 5 % at least one substituted phenolic compound 0.1 - 5 % citric acid 0.1 - 5 % viscosity builder/emulsifier 0.1 - 5 % stabiliser 0.01 - 1 % surfactant 1 - 30 % suspending agent 1 - 20 % emollient/humectant 0 - 5 % Balance, water to 100 % It can be used as a skin scrub or for wound dressing.

Description

SYNERGISTIC SKIN SCRUB COMPOSITION The present invention relates to disinfectant compositions and, in particular, to a disinfectant composition suitable for use as a skin scrub, wound dressing or the like.

Although there is currently no internationally accepted generic designation for such compositions, it is generally understood that hygienic hand or skin disinfectants are surfactant and/or alcohol-containing products, mostly in liquid form, containing antimicrobial ingredients. Used in circumstances requiring a high standard of hygiene, they prevent the propagation of undesirable microorganisms by eliminating them from the skin, most especially from the hands.

Typical outlets for such products include hospitals, general nursing centres, doctors' consulting rooms, animal breeding and care centres, the foodstuffs, cosmetic and pharmaceutical industries, the food distribution trade, and hotels and restaurants.

In the medical profession, including veterinary medicine, hand disinfection forms an important part of routine hygiene and helps to reduce the risk of hospital-acquired infections (first demonstrated by Semmelweiss in 1847). Pathogenic organisms can survive for long periods on the skin, the hands being a prominent vector for their transmission.

Likewise, in the foodstuffs industry it is generally accepted that most outbreaks of food poisoning could have been avoided by careful adherence to the principle of hand disinfection. Nowadays, hand washing is a major factor in controlling the spread of harmful bacteria.

In the cosmetics and pharmaceutical industries, preventing contamination with bacteria from human sources is an integral part of good manufacturing practice in the production and processing of cosmetics, toiletries and pharmaceuticals.

So-called "surgical scrubs" are well known in the art.

They are used to clean the hands of staff and to prepare patients' skin prior to surgical or operative procedures. In surgery, the scrub is used to cleanse mechanically the area of skin to be cut by the surgeon's scalpel in order to degrease the skin and remove perspiration and dead skin cells.

It also serves to kill bacteria found on the skin. Such antibacterial activity is necessary so that the act of making an incision does not transport bacteria into the incision, thereby promoting wound infection.

Typical of the skin-surface microorganisms which are killed by surgical scrubs are staphylococcus aureus, including methicillen-resistant strains thereof, escherichia coli, pseudomonas aeruginosa and candida albicans. An ideal skin scrub composition has detergents for cleaning, detergent emulsifiers for degreasing the skin, and antimicrobial agents that kill bacteria instantly (rapidly) on contact.

One widely-used pre-operative skin care product or scrub contains the active antimicrobial ingredient povidone iodine.

Another uses chlorhexidine gluconate as its active ingredient.

A number of generic products also use the same active constituents, but both of the aforementioned examples suffer from various drawbacks: Povidone iodine can stain the skin, bed linens, and the user's hands. Neither povidone iodine nor chlorhexidine gluconate is suitable for use on an open wound such as a laceration or abrasion.

Another widely used germicide is benzalkonium chloride, a quaternary ammonium disinfectant consisting of a mixture of alkyldimethylbenzyl ammonium chlorides. It is principally used as a germicide for instruments, etc., but is poorly suited for human skin. It is also used as an antiseptic for skin pre-operatively in veterinary cases, but is unsuitable for use as a surgical scrub because it is incompatible with anionic detergents, such as soap, which are necessary for effective cleansing of the pre-operative area.

United States Patent No 3,063,895, entitled "Disinfectant Compositions", discloses a composition comprising a phenol, an alcohol, ammonium salts and a chlorophenol embodied in an aqueous solution, serving as a disinfectant for the destruction of bacteria, fungi, and fungal and bacterial spores.

United States Patent No 4,125,628 relates to a disinfectant composition made up of quaternary ammonia, a phenol or derivatives thereof, and formaldehyde. It is used principally to fight bacteria, and has its most effective usage in animal husbandry, most particularly in the treatment of poultry. It is an antimicrobial composition, incorporating quaternary ammonia compounds, antifungal agents, phenols, and a variety of antiseptics, antibiotics and the like. It may be used both as a surgical scrub solution and as a topical wound dressing. More specifically, the patent describes that it is an antimicrobial composition incorporating a cyclohexyl phenol.

None of the foregoing compositions combines an antimicrobial agent with degreasants, emulsifiers and surfactants, together with skin conditioners and humectants.

It is an object of the present invention to provide a disinfectant composition which achieves enhanced broad spectrum antimicrobial activity at lower chemical concentrations than hitherto with known disinfectants. It is also an object of the present invention to provide a skin disinfectant which can be used as both a surgical scrub and as a disinfectant for open wounds such as lacerations or abrasions. It is a further object of the invention to provide a disinfectant composition which is effective to clean and degrease the skin and which eliminates over 99% of targeted bacteria within 30 seconds of application. It is yet another object of the invention to provide a disinfectant composition that is pleasant to use through being gentle on the skin, nonstaining and which eliminates dermal irritation.Still another object of the invention is to provide a surgical scrub that is practically non-toxic and which conforms to various national constraints relating to hazardous substances, for example the Federal Hazardous Substances Act in the United States of America. It is yet another object of the invention to provide a cost effective, convenient infection control product that is pleasant to use and easy to package and store.

The invention is a disinfectant composition containing an antimicrobial agent combined with an activity-enhancing phenolic compound, the composition comprising the following constituents in proportions by weight: 2,4,4' -trichloro-2 '-hydroxy diphenyl ether ("Triclosan") 0.1 - 5 % at least one substituted phenolic compound 0.1 - 5 % citric acid 0.1 - 5 % viscosity builder/emulsifier 0.1 - 5 % stabiliser 0.01 - 1 % surfactant 1 - 30 % suspending agent 1 -20 % emollient/humectant 0 - 5 % Balance, water to 100 % In addition to the above, the composition may also contain permitted fragrances and/or colouring agents within proportions customary in the art. It is also feasible that some of the chosen constituents will fulfil more than one of the functions listed above.

For example, cocamidopropyl betaine may be used as both a viscosity builder and an emulsifier. Similarly, propylene glycol performs both as a suspending agent and as a humectant.

The function of each of the essential constituents of the inventive composition will now be explained: 2,4,4' -trichloro-2 , -hydroxydiphenyl ether ("Triclosan") is the principal disinfectant constituent of the composition and is required in proportions of at least 0.1 % by weight in order to exert its antimicrobial effect. If present in proportions higher than 5 % by weight, the limit of solubility is likely to be exceeded and the triclosan may also cause skin irritation in some users.

The substituted phenolic compound has a stated range of 0.1 to 5 % by weight. At lower proportions than this there is no enhancement in antimicrobial activity. On the other hand, at concentrations higher than 5 % by weight, there is a problem with dissolution of the phenol and the room temperature cloud point is exceeded. Also, higher concentrations of phenol could lead to skin sensitivity in some users.

Citric acid is added to adjust the pH to around 5.2 - 5.6 in order to match the acid mantle of the skin. This is also the most effective pH range for triclosan activity.

The viscosity builder/emulsifier is added to thicken the product for improved consumer acceptance and to prevent runoff when administered from a dispenser, for example of the hydraulic plunger type.

A stabiliser is added in the proportions 0.01 to 1 % by weight to improve the effectiveness of the composition in hard water areas. This also reduces any formulation interaction with any added essential oil fragrance.

Surfactant is used to reduce surface tension and thereby aid soil removal from the surface of the skin.

The suspending agent, present in the proportions 1 to 20 % by weight, serves to hold the triclosan and substituted phenol in solution.

As indicated above, the emollient/humectant constituents are added to improve skin feel. At proportions below the stated range, the effect is inadequate to be detectable and the composition is less pleasant in use. At proportions higher than the stated range, product foaming is adversely affected and the after-use feel on the skin is not acceptable.

An especially preferred formulation for the composition is given below, in proportions by weight: 2,4,4'-trichloro-2'-hydroxy 0.1 - 5 % diphenyl ether ("Triclosan") at least one substituted phenolic 0.1 - 5 % compound citric acid 0.1 - 5 % cocamidopropyl betaine 0.1 - 5 % (viscosity builder/emulsifier) EDTA 0.01 - 1 % (stabiliser) sodium lauryl sulphate 1 - 30 % (surfactant) cocamide DEA 1 - 30 % (viscosity builder) propylene glycol 1 -20 % (suspending agent/humectant) aloe vera 0 - 5 % (emollient) Balance, demineralised water to 100 % It is preferred to use demineralised water because this increases the effectiveness of many of the constituents, for example the surfactant component(s), particularly in hard water areas.

As before, the composition may also contain permitted fragrances and colouring agents in customary proportions. For example, the composition may contain an essential oil fragrance in proportions of around 0.1 to 5 % by weight.

Also, it may contain an approved water soluble colour in the proportions 0.0001 to 0.1 % by weight.

Examples of the substituted phenolic compounds which may be used in the present invention include p-chloro-m-xylenol, phenoxy-2-propanol, or related chlorophenols.

A convenient method of preparation of a disinfectant composition according to the above formulations may be carried out as follows: (1) Heat about two thirds of the water to roughly 70"C and, whilst maintaining the water at this temperature, add the following constituents in order: (a) citric acid (b) viscosity builder/emulsifier (c) stabiliser (d) surfactant (e) viscosity builder (if different from (b) above; (2) Pre-mix the following constituents in order: (f) suspending agent (g) triclosan (h) phenolic compound(s); (3) When the constituents from step (1) above are fully dissolved in the water, add the mixture from step (2); (4) Stir the mixture obtained from step (3) until a uniform mixture is obtained, cool to approximately 300C and then add the remaining ingredients; (5) Add the remaining third of the water.

The product thus obtained is an aqueous solution of the aforementioned materials having a pH of between 5.0 and 8.0, and a specific gravity of 0.5 to 1.5.

The invention demonstrates the following antimicrobial activity:

PERCENTAGE BACTERIAL REDUCTION Organism used Contact time % Reduction Staphylococcus aureus 30 seconds 99.99% Methicillen-resistant 30 seconds 99.99% Staphylococcus aureus Escherichia coli 30 seconds 99.99 % Pseudomonas aeruginosa 30 seconds 99.99% Candida albicans 30 seconds 99.99% Further test results showing the efficacy of the skin scrub composition against various microbial cultures are presented below:: Chlorine Equivalency Subculture Results on Surgical Scrub Sample Organism Subculture Series NaOCl - 200 ppm S.aureus - - - - + + + + + NaOCI - 100 ppm S.aureus - - - + + + + + + + NaOC1 - 50 ppm S.aureus - - - + + + + + + + Surgical Scrub S.aureus Phenol Resistance of Staphylococcus aureus ATCC #6538: Hour Broth Culture Phenol Dilute on Spin. 10 Min. 15 Min.

1: 60 - 1: 70 + + + Sample Organism Subculture Series NaOCl - 200 ppm S.typhi - - - - + + + + + + NaOCl - 100 ppm S.typhi - - + + + + + + + NaOC1 - 50 ppm S.typhi - - + + + + + + + + Surgical Scrub S.typhi Phenol Resistance of Salmonella typhi ATCC # 6539: 24 Hour Broth Culture Phenol Dilution 5 Min. 10 Min. 15 Min.

1: 90 + 1:100 + + % Reduction of Time Kill Organisms with Surgical Scrub Reduction of Test Organism After Exposure Starting Count to Handsoap Sample Organism (CFU/ml) for 30 seconds Surgical S.aureus 2.5 x 106 > 99.99 Scrub P.aeruginosa 2.6 x 106 > 99.99 S.typhi 1.9 x 106 > 99.99 Mode of Action Tests with Escherichia coli show that the disclosed formula prevents the intake of various essential substances by the microorganism. The antimicrobial action causes bursting of the cytoplasmic membrane, the function of which is to transmit essential substances. This unspecific mode of action is not conducive to the possible emergence of true resistant strains.

In order to ensure rapid destruction of bacteria as specified in all countries, for example in the well-known suspension test with 15 to 30 seconds' exposure, the composition uses selected surfactants and its bactericidal action is assisted and reinforced by the specified additions.

Further comparative results showing the efficacy of the disinfectant composition of the present invention are described below with reference to the drawings, in which: Figure 1 is a graph showing bactericidal efficacy in the suspension test; Figure 2 shows bactericidal efficacy against Staphylo coccus aureus (ATCC 6538) in the chlorine equivalent test, and Figure 3 is a graph similar to Figure 2, showing bactericidal efficacy against Salmonella typhi (ATCC 6539) in the chlorine equivalent test.

Bactericidal Efficacy in the Suspension Test Referring now to Figure 1, the bactericidal efficacy of the disinfectant composition of the present invention was compared in the suspension test after 30 seconds of contact against formulations having 4 % chlorhexidine digluconate (CHDG) or 7.5 PVP-iodine complex as active constituent.

In this test, a suspension containing about 10 million bacteria per millilitre was added to the undiluted disinfectant composition. After 30 seconds of contact, the disinfectant was inactivated and the number of surviving bacteria was determined.

The results are presented in graphical form in Figure 1.

This shows that the composition of the present invention is more effective than hand disinfectants having 4 % chlorhexidine digluconate as the active constituent against Gram-positive staphylococci and streptococci, and more effective than those with the PVP-iodine complex against streptococci, Escherichia coli and Serratia marcesens.

Bactericidal Efficacy in the Chlorine Equivalent Test Bactericidal activity was tested against Staphylococcus aureus (ATCC 6538) after 60 seconds' contact using the chlorine equivalent test. In a corresponding test, bactericidal efficacy was also tested against Salmonella typhi (ATCC 6539) after 60 seconds' contact time. The disinfectant composition of the present invention was compared against a placebo formulation and formulations with 4 % chlorhexidine digluconate (CHDG) and 7.5 % PVP-iodine complex.

The object of the chlorine equivalent test is to find out how often a product can be exposed to bacteria until its bactericidal activity is exhausted.

The bactericidal effect of the undiluted disinfectant composition of the present invention was compared with that of solutions containing 50, 100 and 200 mg/l (ppm) of available chlorine. As depicted in Figures 2 and 3, an activity of 100 % indicates that the product of the present invention still had a bactericidal effect after contamination 10 times with bacteria.

By contrast, it can be seen that formulations containing 100 ppm available chlorine lost their efficacy after a third or fourth exposure. The composition according to the present invention was remarkably more effective against the bacteria than the products containing 4 % chlorhexidine digluconate or 7.5 % PVP-iodine complex. The placebo formulation was ineffective.

The invention is practically non-toxic according to the toxicity ratings defined in "Clinical Toxicology of Commercial Products", by Martin H Gleason, et al., 1963, and non-toxic by definition in the Federal Hazardous Substances Act (FHSA).

Moreover, skin scrub formulations in accordance with the present invention exhibit minimal dermal irritation with a 0.8 % Draize equivalent in the Draize Dermal Irritation Test.

Claims (8)

1. A disinfectant composition containing an antimicrobial agent combined with an activity-enhancing phenolic compound, the composition comprising the following constituents in proportions by weight: 2,4,4' -trichloro-

2 '-hydroxy diphenyl ether ("Triclosan") 0.1 - 5 % at least one substituted phenolic compound 0.1 - 5 % citric acid 0.1 - 5 % viscosity builder/emulsifier 0.1 - 5 % stabiliser 0.01 - 1 % surfactant 1 - 30 % suspending agent 1 -20 % emollient/humectant 0 - 5 % Balance, water to 100 % 2. A disinfectant composition as claimed in claim 1, further comprising permitted fragrances and/or colouring agents within proportions customary in the art.

3. A disinfectant composition as claimed in claim 1 or claim 2 wherein said substituted phenolic compounds are selected from the group consisting of p-chloro-m-xylenol, phenoxy-2-propanol, or related chlorophenols.

4. A disinfectant composition as claimed in any preceding claim wherein the viscosity builder is a water soluble gum or polymer.

5. A disinfectant composition as claimed in any preceding claim wherein the surfactant is of any ionic configuration.

6. A disinfectant composition as claimed in any preceding claim comprising the following constituents in proportions by weight: 2,4,4'-trichloro-2'-hydroxy 0.1 - 5 % diphenyl ether ("Triclosan") at least one substituted phenolic 0.1 - 5 % compound citric acid 0.1 - 5 % cocamidopropyl betaine 0.1 - 5 % (viscosity builder/emulsifier) EDTA 0.01 - 1 (stabiliser) sodium lauryl sulphate 1 - 30 % (surfactant) cocamide DEA 1 - 30 % (viscosity builder) propylene glycol 1 -20 % (suspending agent/humectant) aloe vera 0 - 5 % (emollient) Balance, demineralised water to 100 %

7. A disinfectant composition as claimed in any preceding claim formulated for use as a skin scrub preparation.

8. A disinfectant composition substantially as herein described.