WO2015055234A1

WO2015055234A1 - Use of an active solid for cleaning and inactivating unconventional infectious agents on surfaces

Info

Publication number: WO2015055234A1
Application number: PCT/EP2013/071536
Authority: WO
Inventors: Carola Stingl; Laurence Geret; Bernhard Meyer
Original assignee: Ecolab Inc.
Priority date: 2013-10-15
Filing date: 2013-10-15
Publication date: 2015-04-23

Abstract

The invention relates to the use of a solid alkaline composition for cleaning of and/or destruction of prions on surfaces contaminated with unconventional infectious agents, comprising at least one alkaline source, at least one polyethylene glycol and optional at least one corrosion inhibitor, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1.

Description

Use of an active solid for cleaning and inactivating unconventional infectious agents on surfaces

Field of the Invention

The invention relates to the use of a concentrated solid alkaline composition for inactivating and/or reducing unconventional infectious agents, such as prions, on surfaces. The invention relates further to the use of a concentrated solid alkaline composition for automated cleaning and disinfection processing of surfaces that can be contaminated with unconventional infectious agents. In particular, the invention relates to the use of solid alkaline concentrated compositions useful in the cleaning and/or disinfecting of articles or surfaces that are potentially contaminated with unconventional infectious agents, including plastic articles, plastic surfaces, metal articles, metal surfaces, such as surgical, medical, and dental instruments.

Background of the Invention

The term "destruction of prions" as used herein means an irreversible destruction of infectivity and/or reduction of unconventional infectious agents, such as prions, on a surface to which the disinfectant composition in form of a solution is applied. Particularly, the term "destruction of prions" as used herein means the irreversible destruction of infectivity and/or reduction of unconventional infectious agents, such as prions, on a surface to which the disinfectant composition in form of a solution is applied according to a standard protocol published by the French medical device authority Agence National de Securite du Medicaments et de produits de sante (ANSM).

The term "unconventional infectious agents" are agents that are effective to cause degeneration of the central nervous system. Unconventional infectious agents are for example prions.

The term prion is derived from the phrase "proteinaceous infectious particle" and is used to describe relatively similar brain diseases in a number of mammals and in man, which are invariably fatal. These diseases are generally referred to as transmissible spongiform encephalopathies (TSEs). Transmissible spongiform encephalopathies include Creutzfeldt-Jakob disease (CJD) in humans, Bovine Spongiform Encephalopathy (BSE) in cattle, Scrapie in sheep, and Wasting Disease in elk. These diseases attack the neurological organs, the brain and nervous system.

Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, prion diseases can be transmitted through contact with infected tissue, body fluids, for example brain tissue, cerebral spinal fluids, and eye tissue and fluids or contaminated medical instruments.

Surgical, medical, and dental instruments after use are typically contaminated with blood and other body matter and potentially with infectious agents. Before being reused in a future procedure surgical instrument, particularly neurosurgical and ophthalmological instruments are washed and disinfected as indicated.

However, prions are resistant to routine physical and chemical disinfection and sterilization measures and normal sterilization procedures such as liquid sterilization systems, boiling or irradiating materials fail to render prions non-infective. Unlike microorganisms, prions appear not to have any recognizable nucleic acid component, and therefore may be resistant to conventional inactivation techniques for infectious agents.

For prion deactivation instruments are treated with 1 N sodium hydroxide or high

concentration of hypochlorite according to the advice of the World Health Organization. Aggressive chemical treatments, such as strong alkali however often are damaging or destructive to medical devices, particularly devices with plastic, brass, or aluminum parts.

Sodium hydroxide concentrated compositions and high concentration of hypochlorite causes chemical "burns" if splashed onto the skin and causes corrosion of sensitive metal surfaces that come into contact therewith.

Further, alkali cleaners know in prior art comprising tensides show when used, for example in automated cleaning processing, increased foam formation.

The formation of foam lowers the cleaning properties, due to the reduced contact area as well as due to the loss of mechanical agitation. Further, pumping of foam dramatically reduces the liquid flow rates, thus causes dosing and transport problems in the sump, liquid conduits, as well as in the dispensing drawer. Thus, foam in general is not acceptable for cleaning and disinfection processing, including automated processing, of surfaces that can be contaminated with unconventional infectious agents.

Many articles having a surface that are potentially contaminated with unconventional infectious agents require cleaning and disinfection. Using alkali cleaners has disadvantages when used on alkaline sensitive metals, such as, aluminum. A problem with using aqueous alkali systems to clean aluminum surfaces is the potential to corrode and/or discolor.

It is still a need in prior art to provide a solid concentrated alkaline composition for automated cleaning processing of hard and/or soft surfaces that is effective against prions. In particular, it is a need to provide alkaline composition for automated cleaning processing of metal surface layers that avoid the disadvantages of transport and storage of liquids, provides a rapid dissolution in water, and develops after dissolution a good cleaning effect and is effective against prions. Further, it shows practical no foam formation during the automated processing and prevents corrosion of metal surfaces that are exposed to aqueous alkaline solutions.

Therefore, the object underlying the present invention is to provide a composition that can be used effective against unconventional infectious agents, such as prions and has a good cleaning performance, low foaming, and are fewer surface destructive, especially for metal surfaces. Summary of the Invention

Therefore, the object underlying the present invention is to provide a use of a composition that is effective to irreversible destroy and/or to reduce unconventional infectious agents, such as prions and has a good cleaning performance, low foaming, and are fewer surface destructive, especially for metal and/or plastic surfaces.

Another aspect is the use of a solid alkaline composition for cleaning processing of surfaces, such as hard and/or soft surfaces, effective to inactivate and/or to reduce unconventional infectious agents, such as prions and has a good cleaning performance, low foaming, and are fewer surface destructive, especially for metal surfaces.

Another aspect is the use of a solid alkaline composition for automated cleaning processing of surfaces, such as hard surfaces and/or soft surfaces, for example metal and/or plastic surfaces, effective to inactivate and/or to reduce unconventional infectious agents, such as prions and has a good cleaning performance, low foaming, and are fewer surface destructive, especially for metal surfaces.

This objective is achieved by the use of a solid alkaline composition comprising at least one alkaline source, at least one polyethylene glycol and at least one corrosion inhibitor, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1.

According to one embodiment of the invention a solid alkaline composition may be used comprising at least one alkaline source, at least one polyethylene glycol and at least one corrosion inhibitor, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1.

According to the invention the solid alkaline composition can be used for cleaning and/or destruction of prions of surfaces contaminated with unconventional infectious agents, comprising at least one alkaline source and at least one polyethylene glycol, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1, wherein the composition comprises at least one corrosion inhibitor. The composition may comprises at least one corrosion inhibitor in an amount of > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, wherein the weight-% of the corrosion inhibitor are based on the total weight of the solid composition and more preferred the corrosion inhibitor is free of a silicate.

According to one aspect, the unconventional infectious agents comprising agents that are effective to cause degeneration of the central nervous system, preferably the unconventional infectious agents are prions.

It was surprisingly found that the use of a solid alkaline composition comprising at least one alkaline source, at least one polyethylene glycol and at least one corrosion inhibitor, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1 is effective to irreversibly destroy and/or to reduce unconventional infectious agents, such as prions on surfaces, contaminated therewith. Moreover, it is surprisingly found that a low alkaline ready-to-use solution is effective to irreversibly destroy and/or to reduce unconventional infectious agents, such as prions on surfaces, contaminated therewith.

The solid concentrated alkaline composition can be used for automated cleaning processing of metal surface layers to remove blood or other matter are allowed to dry and irreversibly destroys and/or reduces unconventional infectious agents, such as prions.

For use the solid concentrated alkaline composition shows a rapid dissolution in water, and develops after dissolution based on a low active concentration a good cleaning effect and irreversibly destroys and/or reduces unconventional infectious agents, such as prions.

The solid alkaline composition can be used according to the invention for automated cleaning processing of surfaces, such as hard and/or soft surfaces, for example metal and/or plastic surfaces to effectively irreversibly destroy and/or to reduce unconventional infectious agents, such as prions contaminated therewith. Further, using the alkaline composition shows practical no foam formation during the automated processing and prevents corrosion of metal surfaces that are exposed to aqueous alkaline solutions. Thus, using the alkaline cleaning composition is remarkable sensitive to metal articles, metal surfaces, plastic articles and/or plastic surfaces.

According to the invention the alkaline composition can be used to inactivate and/or to reduce unconventional infectious agents on surfaces in hospitals, industrial facilities and research

laboratories, particularly selected from surfaces of instruments employed in medical, dental, and pharmaceutical procedures, surfaces of equipment, processing facilities or containers used in the food service, food processing, butchery, dairy, beverage, brewery, and pharmaceutical industries, work surfaces, walls, floors, ceilings, fermentation tanks, and fluid supply lines.

The term "alkaline sensitive metal" identifies those metals that exhibit corrosion and/or discoloration when exposed to an aqueous alkaline solution. An aqueous alkaline solution is an aqueous solution having a pH that is greater than about 8. Exemplary alkaline sensitive metals include soft metals such as aluminum, nickel, tin, zinc,/copper, brass, bronze, and mixtures thereof. Aluminum and aluminum alloys are common alkaline sensitive metals that can be cleaned by the cleaning compositions of the invention.

References herein to a "solid" composition are to those, which are solid at about 15° C and up to about 60° C. Preferably, the shape of the solid composition of the present invention is preferably stable and/or the solid composition is rigid.

For use a solvent, preferably water, can be added add. 100 wt.-% to the composition of the invention. The solvent content, such as the water content, of the composition for use according to the invention is simply determined by subtracting the amounts of all the usual ingredients from 100 wt. %.

The weight-% (wt.-%) of the components are calculated based on the total weight amount of the composition, if not otherwise stated.

The ratio of components is parts by weight, if not otherwise stated. The total amount of all components of the composition does not exceed 100 wt.-%.

It should be understood that the addition of other surfactants to the solid as well as to the liquid alkaline composition for automated cleaning processing of hard and/or soft surfaces is optional and can be omitted. Preferably, the compositions for use according to the invention are free of other surfactants, except polyethylene glycol.

It should be understood that the compositions for use according to the invention can be free of a hydrotrope component.

It should be understood that the compositions for use according to the invention can be free of a zeolite.

It should be understood that the compositions for use according to the invention can be free of at least one additive, preferably all additives, selected from the group of antimicrobials, fungicides, fragrances, dyes, antistatic agents, UV absorbers, reducing agents and/or buffering compounds.

The combination of an alkaline source in combination with a polyethylene glycol leads to an increased foam formation, thus not suitable for use in an automated cleaning processing. However, it has been surprisingly found, that at a specific ratio of the alkaline source to the polyethylene glycol provides a low foaming composition suitable for automated cleaning processing of hard and/or soft surfaces, such as metal articles, metal surfaces, plastic articles and/or plastic surfaces.

The specific ratio of the alkaline source to polyethylene glycol according to the present invention provides a good cleaning effect in combination with low foaming as required for an automated processing of metal articles, metal surfaces, plastic articles and/or plastic surfaces.

At the time of dissolution with the solvent, such as water, a spontaneous and intensive foam formation in the dispensing draw of an apparatus for cleaning processing as well as in the cleaning chamber is observed, if the ratio or concentration of polyethylene glycol in the solid alkaline composition for use according to the invention is selected to high. However, if the ratio or concentration of polyethylene glycol is selected to low, the cleaning action is insufficient.

For use according to the present invention the ratio of alkaline source to polyethylene glycol can be in the range from about 30 : 1 to about 2 : 1, preferably about 25 : 1 to about 5 : 1, further preferred about 22 : 1 to about 8 : 1, also preferred about 20 : 1 to about 10 : 1 and in addition preferred about 18.5 : 1 to about 16 : 1.

No or practical no foam formation is observed using the compositions, especially in the dispensing draw of an apparatus for cleaning processing as well as in the cleaning chamber.

Due to none or marginal foam formation the automated pumping flow rate of water-dissolved composition is not affected at use.

Further, the cleaning and destruction of prions action of a solid alkaline composition for use according to the invention used in an automated washing process is surprisingly good, although the concentration of the polyethylene glycol in the solid alkaline composition for use according to the invention is relatively low. Especially, body fluids, such as blood, lipids and synovial fluids from joints adhere to the items metal surface used during a procedure. As these fluids dry, the adhesion gets stronger and the fluids get harder to dissolve using ordinary cleaning methods. Blood in particular becomes much more difficult to remove once it has dried. Eventually, the adhesion of the soils becomes too strong for normal detergents to break and the instruments remain soiled after cleaning. Moreover, using normal detergents are not effective to inactivate and/or reduce unconventional infectious agents as required by national guidelines, as for instance from the Robert Koch Institute (RKI) or the Agence National de Securite du Medicaments et de produits de sante (ANSM).

A problem with using aqueous alkali systems to clean metal surfaces, such as aluminum surfaces is the potential to corrode and/or discolor. Therefore, a corrosion inhibitor is used to prevent corrosion of metal surfaces that are exposed to aqueous alkaline solutions.

It should be understood that a silicate(s) corrosion inhibitor is optional and can be omitted. Silicates, comprising sodium silicate, have a tendency to begin precipitating from aqueous solution at a pH below 11 , thus reducing its effectiveness to prevent corrosion of the contacted surfaces when used in aqueous cleaning solutions having a lower pH. Additionally, when silicates are allowed to dry on the surface to be cleaned, films or spots are often formed, which are visible and they are very difficult to remove. The presence of these silicon-containing deposits can affect the texture of the cleaned surface, the appearance of the surface, and on cooking or storage surfaces, can affect the taste of the materials that come into contact with the cleaned surfaces. Further, the alkaline composition for use according to the invention it is found to be a sensitive metal and/or plastic cleaning composition. Thus, the sensitive metal and/or plastic cleaning composition for use according to the invention in use minors or avoids corrosion in such an extent that the addition of silicate(s) corrosion inhibitor is not required.

However, a solid composition comprising a silicate(s) corrosion inhibitor can be used according to the present invention. The silicate(s) corrosion inhibitor can be an alkali silicate, particularly preferably crystalline or amorphous alkali disilicates in quantities of about > 0.05 to about < 10, preferably about > 0.1 to about < 5 and more preferred of about > 0.5 to about < 2; wherein the weight- % of the components are based on the total weight of the composition.

An aqueous alkaline composition having a high pH are often more corrosive than an aqueous composition having a light acidic pH. In order to minimize the potential to corrode and/or discolor the metal surface, the pH of the aqueous alkaline solutions of the solid alkaline composition can be adjusted to a lower pH in the range of about > 11 pH to about < 13.5 pH.

The soil removal or cleaning action as well as the activity to destroy prions and/or to reduce unconventional infectious agents as required by national guidelines, as for instance from the Robert Koch Institute (RKI) or the Agence National de Securite du Medicaments et de produits de sante (ANSM), using according to the present invention an aqueous solution of the solid alkaline composition can be improved by adding at least one sequestering agent to the solid alkaline composition, preferably at least one sequestering agent that exhibits soil removal properties.

Alkaline Source

The source of alkalinity can be any source of alkalinity that is compatible with the other components of the concentrated solid alkaline composition and that will provide the use of a solution, i.e. concentrated liquid composition as well as the ready-to-use solution with the desired pH and is effective to inactivate and/or to reduce unconventional infectious agents, such as prions, on surfaces that are potentially contaminated therewith. Exemplary sources of alkalinity include alkali metal hydroxides, alkali metal salts, phosphates, amines, and mixtures thereof.

Exemplary alkali metal hydroxides include sodium hydroxide, potassium hydroxide, and lithium hydroxide.

Exemplary alkali metal salts include sodium carbonate, trisodium phosphate, potassium carbonate, and mixtures thereof.

Exemplary phosphates include sodium pyrophosphate, potassium pyrophosphate, and mixtures thereof.

Exemplary amines include alkanolamine selected from the group comprising triethanolamine, monoethanolamine, diethanolamine, and mixtures thereof.

The source of alkalinity, preferably an alkali metal hydroxide, may be added to the composition in a variety of forms, including for example in the form of solid beads, dissolved in an aqueous solution or a combination thereof. Alkali metal hydroxides are commercially available as pellets or beads having a mix of particle sizes ranging from 12-100 U. S. mesh, or as an aqueous solution, as for example, as about 45 wt. %, about 50 wt. % and about 73 wt. % solution.

The source of alkalinity, preferably an alkali metal hydroxide, and more preferred sodium hydroxide, can be used in quantities of about > 10 wt.-% to about < 50 wt.-%, preferably about > 15 wt- % to about < 45 wt.-%, further preferred about > 20 wt- % to about < 40 wt- %, also preferred about > 30 wt-% to about < 38 wt.-%and more preferred about > 35 wt-% to about < 37 wt-%;

wherein the weight- % of the components are based on the total weight of the composition.

Polyethylene Glycol

A suitable polyethylene glycol for use in the present invention can have a molecular weight (MW) in the range of about > 4000 to about < 12000, preferably about > 6000 to about < 10000 and more preferred of about > 7000 to about < 8000. Polyethylene glycol that can be used are marketed for example by BASF under the tradename PLURIOL^®.

The source of polyethylene glycol, preferably a polyethylene glycol with a MW in the range of 4.000 to 12.000, can be used in quantities of about > 0.1 wt-% to about < 15 wt-%, preferably about > 0.5 wt.-%> to about < 10 wt.-%>, further preferred about > 1 wt.-%> to about < 5 wt.-%>, and more preferred about > 2 wt.-% to about < 3 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

Corrosion Inhibitor

The corrosion inhibitor can be selected from the group comprising silicate, calcium acetate, calcium chloride, calcium gluconate, calcium phosphate, calcium borate, calcium carbonate, calcium citrate, calcium lactate, calcium sulfate, calcium tartrate, benzotriazole, 1,2,3-benzotriazole and mixtures thereof.

More preferred, the corrosion inhibitor is a heterocyclic compound, a triazole derivate, such as a benzotriazole or 1,2,3-benzotriazole and mixtures thereof.

Exemplary silicates include sodium metasilicates, sesquisilicates, orthosilicates, potassium silicates, and mixtures thereof. However, most preferred can be sodium silicate.

The silicates may comprise at least one crystalline layer-forming silicate of the general formula NaMSix02x+l .yH20, wherein M represents sodium or hydrogen, x is a number from about 1.9 to about 22, preferably about 1.9 to about 4 and y stands for a number from about 0 to about 33.

The crystalline layer-forming silicates of the formula NaMSix022x+l .yH20 are marketed for example by Clariant GmbH (Germany) under the trade names Na-SKS, eg.

Na-SKS-1 (Na2Si22045.xH20, Kenyait), Na-SKS-2 (Na2Sil4029.xH20, Magadiit), Na-SKS-3 (Na2Si8017.xH20) or Na-SKS-4 (Na2Si409.xH20, Makatit).

Crystalline, layered silicates of the above formula, in which x stands for 2, are particularly suitable for the purposes for use according to the invention.

Na-SKS-5 (alpha -Na2Si205), Na-SKS-7 (beta -Na2Si205, Natrosilit), Na-SKS-9

(NaHSi205.H20), Na-SKS-10 (NaHSi205.3H20, Kanemit), Na-SKS-11 (t-Na2Si205) and Na-SKS- 13 (NaHSi205) are most notably suitable, particularly Na-SKS-6 (delta -Na2Si205).

In the context of the present application, silicates can comprise a content by weight of crystalline layered silicates of formula NaMSix02x+l.yH20 of 0.1 to 20 wt. %, preferably about 0.2 to about 15 wt. % and particularly about 0.4 to about 10 wt. %, each based on the total weight of the corrosion inhibitor agent.

Particularly preferred are especially those that have a total silicate content about > 0 and below about 7 wt.- %, advantageously below about 6 wt.- %, preferably below about 5 wt.- %, particularly preferably below about 4 wt.- %, quite particularly preferably below about 3 wt. -% and especially below about 2.5 wt.- %, wherein this silicate, based on the total weight of the comprised silicate, is advantageously at least about 70 wt.- %, preferably at least about 80 wt.- % and especially at least about 90 wt.- % of a silicate of the general formula NaMSix02x+l .yH20.

As already mentioned before, it should be understood that a silicate(s) corrosion inhibitor is optional and can be omitted. However, other corrosion inhibitors can be suitable added to the solid alkaline composition of this invention include magnesium and/or zinc ions and Ca (N0₂) 2· Preferably, the metal ions are provided in water-soluble form.

Examples of useful water-soluble forms of magnesium and zinc ions are the water-soluble salts thereof including the chlorides, nitrates and sulfates of the respective metals. If any of the alkalinity providing agents are the alkali metal carbonates, bicarbonates or mixtures of such agents, magnesium oxide can be used to provide the Mg ion. The magnesium oxide is water soluble and is a preferred source of Mg ions.

In order to maintain the dispersibility of the magnesium and/or zinc corrosion inhibitors in aqueous solution, and in the presence of agents which would otherwise cause precipitation of the zinc or magnesium ions, e. g. , carbonates, phosphates, etc. , it might be advantageous to include a carboxylated polymer to the solution.

The useful carboxylated polymer corrosion inhibitors may be generically categorized as water- soluble carboxylic acid polymers such as polyacrylic and polymethacrylic acids or vinyl addition polymers, in addition to the acid-substituted polymers used in the present invention.

Of the vinyl addition polymer corrosion inhibitors contemplated, maleic anhydride copolymers as with vinyl acetate, styrene, ethylene, isobutylene, acrylic acid and vinyl ethers are examples.

The polymers tend to be water-soluble or at least colloidally dispersible in water. The molecular weight of these polymers may vary over a broad range although it is preferred to use polymers having average molecular weights ranging between about 1,000 up to about 1,000, 000. These polymers have a molecular weight of about 100,000 or less and between about 1,000 and about 10,000.

The polymers or copolymers (either the acid-substituted polymers or other added polymers) may be prepared by either addition or hydrolytic techniques. Thus, maleic anhydride copolymers are prepared by the addition polymerization of maleic anhydride and another comonomer such as styrene.

The low molecular weight acrylic acid polymer corrosion inhibitors may be prepared by addition polymerization of acrylic acid or its salts either with itself or other vinyl comonomers.

Alternatively, such polymers may be prepared by the alkaline hydrolysis of low molecular weight acrylonitrile homopolymers or copolymers.

The corrosion inhibitor can be used in quantities of about > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%; wherein the weight- % of the components are based on the total weight of the composition.

Threshold Inhibitor/Crystal Modifier The solid alkaline composition that can be used according to the present invention can comprise at least one threshold inhibitor/crystal modifier. The amount of threshold inhibitor/crystal modifier can be about > 1 wt.-% to about < 15 wt.-%, preferably about > 3 wt.-% to about < 12 wt.-%, further preferred about > 5 wt.-% to about < 16 wt.-%, and more preferred about > 6 wt.-% to about < 8 wt.-%, wherein the weight-% of the components are based on the total weight of the composition.

The threshold inhibitor/crystal modifier can be selected from the group comprising salts of phosphonocarboxylic acids, phosphonates, salts of 1 -hydroxy ethylidene -1,1,-diphosphonic acid (HEDP), salts of acid substituted polymers, and mixtures thereof, preferably salts of acid substituted polymers of monomers of acrylate, methacrylate, salts of polyitaconic acid, salts of polymaleic acid, and mixtures thereof. In particular preferred are salts of polyacrylic acid.

Sequestering Agent

The solid alkaline composition that can be used according to the present invention can comprise at least one sequestering agent. The amount of sequestering agent can be about > 5 wt.-% to about < 40 wt.-%, preferably about > 10 wt.-% to about < 35 wt.-%, further preferred about > 20 wt- % to about < 30 wt.-%, and more preferred about > 25 wt.-% to about < 28 wt.-%, wherein the weight- % of the components are based on the total weight of the composition.

The sequestering agent can be selected from the group of sodium gluconate, pentasodium salt of diethylenetriamine pentaacetic acid, sodium glucoheptonate, salts of ethylene diamine tetraacetic acid, salts of ethylene diamine tetraacetic acid, salts of hydroxyethyl ethylene diamine triacetic acid, salts of hydroxyethyl ethylene diamine triacetic acid, salts of nitrilotriacetic acid, salts of

nitrilotriacetic acid, diethanolglycine sodium salt, ethanoldiglycine disodium salt, salts of

hydroxymonocarboxylic acid compounds, salts of hydroxydicarboxylic acid compounds, salts of amine containing carboxylic acids, terasodium N,N-bis(carboxylatomethyl)-L-glutamate (GDLA) and mixtures thereof.

In particular preferred is at least one sequestering agent that exhibits soil removal properties when used at a pH of at least about 10.0. The sequestering agent is provided for tying up metals in the soil to assist in cleaning and detergency. The sequestering agent can be provided as part of the solid alkaline composition. Exemplary sequestering agents that exhibit soil removal properties at a pH of greater than about 10.0 that can be used according to the invention include sodium gluconate, pentasodium salt of diethylenetriamine pentaacetic acid (available under the name Versenex 80), sodium glucoheptonate, ethylene diamine tetraacetic acid (EDTA), salts of ethylene diamine tetraacetic acid, hydroxyethyl ethylene diamine triacetic acid (HEDTA), salts of hydroxyethyl ethylene diamine triacetic acid, nitrilotriacetic acid (NTA), salts of nitrilotriacetic acid, diethanolglycine sodium salt (DEG), ethanoldiglycine disodium salt (EDG), tetrasodium N,N-bis(carboxylatomethyl)-L- glutamate (GLDA), methyl glycine diacetic acid (MGDA)and mixtures thereof. Exemplary salts of ethylene diamine tetraacetic acid include disodium salts, tetrasodium salts, diammonium salts, and trisodium salts. An exemplary salt of hydroxy ethyl ethylene diamine triacetic acid is the trisodium salt.

It should be understood that the sequestering agent can include mixtures of different sequestering agents.

Solvents

Suitable solvents include, but are not limited to, water, alcohols, glycols, glycol ethers, esters, and the like, or combinations thereof. Suitable alcohols include, but are not limited to, ethanol, isopropanol (propan-2-ol), 2-butoxy ethanol (butyl glycol), 1-decanol, benzyl alcohol, glycerin, monoethanolamine (MEA), and the like, or combinations thereof.

Suitable glycols include, but are not limited to, ethylene glycol (monoethylene glycol or MEG), diethylene glycol (propylene glycol or butoxy diglycol or DEG), triethylene glycol (TEG), tetraethylene glycol (TETRA EG), glycerin, propylene glycol, dipropylene glycol, hexylene glycol, and the like, or combinations thereof. Preferably the composition that can be used comprises at least two solvents and more preferred the composition comprises water and hexylene glycol.

A Solid Alkaline Composition for use

A solid alkaline composition that can be used according to the invention and is effective to inactivate and/or to reduce unconventional infectious agents, such as prions, on surfaces that are potentially contaminated therewith comprises:

- about > 10 wt.-% to about < 50 wt.-%, preferably about > 15 wt.-% to about < 45 wt.-%, further preferred about > 20 wt.-% to about < 40 wt.-%, also preferred about > 30 wt.-% to about < 38 wt.-%, and more preferred about > 35 wt.-% to about < 37 wt.-%, of at least one alkaline source;

- about > 0.1 wt.-% to about < 15 wt.-%, preferably about > 0.5 wt.-% to about < 10 wt.-%, further preferred about > 1 wt.-% to about < 5 wt.-%, and more preferred about > 2 wt.-% to about < 3 wt- %, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of 4.000 to 12.000; and

- > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is free of a silicate; and a solvent, preferably water, is added add. 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

According to another embodiment of the invention, a solid alkaline composition can be used comprising: - about > 10 wt.-% to about < 50 wt.-%, preferably about > 15 wt.-% to about < 45 wt.-%, further preferred about > 20 wt.-% to about < 40 wt.-%, also preferred about > 30 wt.-% to about < 38 wt.-%, and more preferred about > 35 wt.-% to about < 37 wt.-%, of at least one alkaline metal hydroxide, preferably sodium hydroxide;

- about > 0.1 wt.-% to about < 15 wt.-%, preferably about > 0.5 wt.-% to about < 10 wt.-%, further preferred about > 1 wt.-% to about < 5 wt.-%, and more preferred about > 2 wt.-% to about < 3 wt- %, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of 4.000 to 12.000;

- about > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is a heterocyclic compound and more preferred a benzotriazol;

- about > 1 wt.-% to about < 15 wt.-%, preferably about > 5 wt.-% to about < 10 wt.-%, and more preferred about > 6 wt.-% to about < 8 wt.-% of at least one threshold inhibitor/crystal modifier, preferably the threshold inhibitor/crystal modifier is a salt of a polyacrylic acid; and

- about > 5 wt.-% to about < 40 wt.-%, preferably about > 15 wt.-% to about < 30 wt.-%, and more preferred about > 25 wt.-% to about < 28 wt.-% of at least one sequestering agent, preferably the sequestering agent is a salt of an amine containing carboxylic acid; a solvent, preferably water, is added add. 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

Liquid Alkaline Composition

Another Aspect is directed to the use of a liquid alkaline composition obtained from the solid alkaline composition for use according to the invention to irreversibly detroy infectivity and/or to reduce unconventional infectious agents as required by national authorities, as for instance the Robert Koch Institute (RKI) or the Agence National de Securite du Medicaments et de produits de sante (ANSM),

Using the cleaning compositions according to the invention can take the form of a single concentrate or multiple concentrates that can be diluted and combined to provide a ready-to-use solution, and as a ready-to-use liquid composition that can be used to clean articles having a metal or plastic surface, such as surgical, medical, and dental instruments, including endoscopes and to irreversibly destroy and/or to reduce unconventional infectious agents as required National guidelines, as for instance from the Robert Koch Institute (RKI) or the Agence National de Securite du

Medicaments et de produits de sante (ANSM),The solution can be in the form of a concentrate that can be diluted with a solvent, such as water, to provide a ready-to-use solution that can be used for cleaning and to irreversibly destroy infectivity and/or to reduce unconventional infectious agents applied to articles having a metal or plastic surface, such as surgical, medical, and dental instruments.

In addition, the solutions can be provided as a relatively dilute solution that can be, without the addition of water, to provide an organic ready-to use solution, for example an alcohol based ready-to use solution, that can be for cleaning and for inactivating and/or reducing unconventional infectious agents applied to articles having a metal surface, such as surgical, medical, and dental instruments.

It is advantageous to provide the solution as a concentrate and then to dilute the concentrate at the place of use in order to decrease transportation costs associated with transporting large amounts of solvent, such as water.

The concentrate liquid composition and/or the ready-to-use solution can be used to irreversibly detroy infectivity and/or to reduce unconventional infectious agents according to the invention in an automated washing process for cleaning and disinfection metal surfaces, in particular metal or plastic surfaces of surgical, medical, and dental instruments including endoscopes, from body fluids, such as blood, lipids, contrast agent and synovial fluids from joints adhere to the metal surface used during a procedure.

Concentrated Alkaline Liquid Composition

The source of alkalinity and addition of the solvent, preferably water, are provided so that the concentrated, preferably aqueous, liquid composition of the solid alkaline composition for the use of inactivating and/or reducing unconventional infectious agents according to the present invention may have a pH in the range of about 12 pH to about 14 pH, preferably a pH in the range of about 12.5 pH to about 13.5 pH and more preferred a pH of about 13 pH.

The ratio of the solvent, preferably water, to solid, to provide a concentrated liquid composition for the use of inactivating and/or reducing unconventional infectious agents according to the present invention, preferably an aqueous solution, of the solid alkaline composition can be in the range of from about 200 : 1 to about 10 : 1, preferably about 100 : 1 to about 12 : 1, further preferred about 50 : 1 to about 15 : 1, also preferred about 40 : 1 to about 17 : 1 and in particular preferred about 30 : 1 to 20 : 1.

According to one embodiment of the invention, the alkaline concentrated liquid composition can comprise for the use of irreversibly destroying infectivity and/or reducing unconventional infectious agents:

- about > 0.05 wt.-% to about < 5 wt.-%, preferably about > 0.3 wt.-% to about < 3.75 wt.-%, further preferred about > 0.8 wt.-% to about < 2.6 wt.-%, and more preferred about > 1 wt.-% to about < 2 wt.-%, of at least one alkaline source;

- about > 0.0025 wt.-% to about < 2 wt.-%, preferably about > 0.01 wt.-% to about < 1.5 wt.-%, further preferred about >0.04 wt.-% to about < 0.5 wt.-%, and more preferred about > 0.08 wt.-% to about < 0.2 wt.-%, of at least one polyethylene glycol; - about > 0.01 wt.-% to about < 1 wt.-%, preferably about > 0.03 wt.-% to about < 0.75 wt.-%, further preferred about > 0.08 wt.-% to about < 0.5 wt.-%, and more preferred about > 0.16 wt.-% to about < 0.3 wt.-%, of at least one corrosion inhibitor; and

- a solvent, preferably water, is added add 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

According to another embodiment of the invention, the solid alkaline composition can comprise for the use of irreversibly destroying infectivity and/or reducing unconventional infectious agents:

- about > 0.05 wt.-% to about < 5 wt.-%, preferably about > 0.3 wt.-% to about < 3.75 wt.-%, further preferred about > 0.8 wt.-% to about < 2.6 wt.-%, and more preferred about > 1 wt.-% to about < 2 wt.-%, of at least one alkaline source, preferably sodium hydroxide;

- about > 0.0025 wt.-% to about < 2 wt.-%, preferably about > 0.01 wt.-% to about < 1.5 wt.-%, further preferred about >0.04 wt.-% to about < 0.5 wt.-%, and more preferred about > 0.08 wt.-% to about < 0.2 wt.-%, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of about 4000 to about 12000;

- about > 0.01 wt.-% to about < 1 wt.-%, preferably about > 0.03 wt.-% to about < 0.75 wt.-%, further preferred about > 0.08 wt.-% to about < 0.5 wt.-%, and more preferred about > 0.16 wt.-% to about < 0.3 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is a heterocyclic compound and more preferred a benzotriazol;

- about > 0.005 wt.-% to about < 1.5 wt.-%, preferably about > 0.05 wt.-% to about < 0.8 wt.-%, further preferred about >0.08 wt.-% to about < 0.5 wt.-% and more preferred about > 0.1 wt.-% to about < 0.35 wt.-% of at least one threshold inhibitor/crystal modifier, preferably the threshold inhibitor/crystal modifier is a salt of a polyacrylic acid;

- about > 0.025 wt.-% to about < 4 wt.-%, preferably about > 0.15 wt.-% to about < 2.5 wt.-%, further preferred about > 0.4 wt.-% to about < 2 wt.-% and more preferred about > 0.8 wt.-% to about < 1.5 wt.-% of at least one sequestering agent, preferably the sequestering agent is a salt of an amine containing carboxylic acid; and

Ready-To-Use Solution

The source of alkalinity and addition of solvent, preferably water, are provided so that the aqueous ready-to-use solution of the solid alkaline composition for use according to the present invention may have a pH in the range of about > 10 pH to about < 11.5 pH and preferably a pH in the range of about > 10.0 pH to about < 11.0 pH.

The ratio of the solvent, preferably water, to solid, to provide a ready-to-use solution, preferably an aqueous solution, of the solid alkaline composition for use according to the invention can be in the range of from about 10,000 : 1 to about 100 : 1, preferably about 5,000 : 1 to about 300 : 1, further preferred about 3,000 : 1 to about 500 : 1, also preferred about 2,500 : 1 to about 750 : 1 and in particular preferred about 2,000 : 1 to about 1,000 : 1.

According to one embodiment for the use of irreversibly destroying infectivity and/or reducing unconventional infectious agents the ready-to-use solution can comprise:

- about > 0.001 wt.-% to about < 0.1 wt.-%, preferably about > 0.002 wt.-% to about < 0.08 wt.-%, further preferred about > 0.003 wt.-% to about < 0.05 wt.-%, and more preferred about > 0.004 wt.-% to about < 0.03 wt.-%, of at least one alkaline source;

- about > 0.00008 wt.-% to about < 0.01 wt.-%, preferably about > 0.0001 wt.-% to about < 0.003 wt.-%, further preferred about > 0.00015 wt.-% to about < 0.002 wt.-%, and more preferred about > 0.0002 wt.-% to about < 0.001 wt.-%, of at least one polyethylene glycol;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0003 wt.-% to about < 0.005 wt.-%, further preferred about > 0.0004 wt.-% to about < 0.004 wt.-%, and more preferred about > 0.0005 wt.-% to about < 0.003 wt.-%, of at least one corrosion inhibitor; and

a solvent, preferably water, is added add 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

According to another embodiment for the use of irreversibly destroying infectivity and/or reducing unconventional infectious agents the ready-to-use solution can comprise:

- about > 0.001 wt.-% to about < 0.1 wt.-%, preferably about > 0.002 wt.-% to about < 0.08 wt.-%, further preferred about > 0.003 wt.-% to about < 0.05 wt.-%, and more preferred about > 0.004 wt.- % to about < 0.03 wt.-%, of at least one alkaline source, preferably sodium hydroxide;

- about > 0.00008 wt.-% to about < 0.01 wt.-%, preferably about > 0.0001 wt.-% to about < 0.004 wt.-%, further preferred about > 0.00015 wt.-% to about < 0.002 wt.-%, and more preferred about > 0.0002 wt.-% to about < 0.001 wt.-%, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of about 4000 to about 12000;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0003 wt.-% to about < 0.005 wt- %, further preferred about > 0.0004 wt.-% to about < 0.004 wt.-%, and more preferred about > 0.0005 wt.-% to about < 0.003 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is a heterocyclic compound and more preferred a benzotriazol;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0002 wt.-% to about < 0.01 wt- %, further preferred about > 0.0003 wt.-% to about < 0.005 wt.-% and more preferred about > 0.0004 wt.-% to about < 0.0035 wt.-% of at least one threshold inhibitor/crystal modifier, preferably the threshold inhibitor/crystal modifier is a salt of a polyacrylic acid;

- about > 0.001 wt.-% to about < 0.01 wt.-%, preferably about > 0.002 wt.-% to about < 0.05 wt.-%, further preferred about > 0.003 wt.-% to about < 0.02 wt.-%, and more preferred about > 0.004 wt.- % to about < 0.014 wt.-% of at least one sequestering agent, preferably the sequestering agent is a salt of an amine containing carboxylic acid; and - a solvent, preferably water, is added add 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

Manufacture of Solid Alkaline Composition

There are a number of processes known in prior art to provide a solidified product. For example, all components of the solid alkaline composition can be mixed together or added portionwise or one after the other. A cast process then solidifies the heated slurry, e.g. the solidification can erupt after cooling down a NaOH melt by crystallization.

Cleaning Apparatus

Another object is directed to a cleaning apparatus that can be used. The cleaning apparatus can be used to provide the concentrated solution or ready-to-use solution which can be used to irreversibly destroy infectivity and/or to reduce unconventional infectious agents, such as prions, on surfaces, such as surgical, medical, and dental instruments that are potentially contaminated therewith.

The cleaning apparatus includes at least a first tank to receive the solid alkaline composition of the invention; at least a second component tank to receive water diluted concentrated composition or a ready-to-use solution of said solid alkaline composition of the invention, a water feed, and a use solution line; and optional a third component tank to receive a day portion of the concentrated composition or a ready-to-use solution of the invention.

The first component tank is provided for containing the solid alkaline composition of the invention. The first component tank can be provided for mixing water to the solid alkaline

composition to provide a concentrated liquid composition. The solid alkaline composition can be mixed with water in a circulation method to obtain a defined alkaline aqueous concentrated liquid composition.

The second component tank is provided for receiving the aqueous concentrated liquid composition or for mixing water to the alkaline aqueous concentrated liquid composition to provide an alkaline ready-to-use solution.

The optional third component tank is provided for receiving a day portion of the aqueous concentrated liquid composition or for mixing water to the alkaline aqueous concentrated liquid composition to provide a day portion of an alkaline ready-to-use solution.

The water feed is provided for conveying water to the first tank, second tank (makeup tank) and/or third tank (day tank) for dissolving the solid alkaline composition (first tank) and/or for providing an aqueous concentrated alkaline liquid composition or alkaline ready-to-use solution (second tank) and/or for providing an aqueous alkaline ready-to-use solution (third tank). It can be preferred that the aqueous concentrated alkaline liquid composition is transferred to the day tank, by the time the defined concentration, pH, volume and/or temperature is reached. However, the makeup tank (second tank) and more preferred the third tank (day tank) can be used to receive and stock the alkaline aqueous concentrated liquid composition or the ready-to-use solution. Most preferred is to provide the ready-to-use solution at the place of use, for example in an applicator, by adding sufficient water. The aqueous concentrated alkaline liquid composition can be conveyed from the second tank or a day tank (optional third tank) to a dispenser and the dispenser sprays out the ready-to-use solution at the place of operation in a defined concentration.

The solution line is provided for conveying solution from the second container to a use solution applicator.

In more detail, the solid alkaline composition can be used in combination with a healthcare solid dispenser. This dispenser sprays out the solid alkaline composition having the form of a capsule in a circulation method to a defined concentration. This alkaline aqueous concentrated liquid composition is collected in a makeup tank and transferred to a day tank as soon as the concentration and referring conductivity has reached the defined level. From there the pumps of the washer disinfectors dose the cleaning alkaline aqueous concentrated liquid composition in the cleaning cycle of the reprocessing step. The solid can be diluted to a 5% alkaline aqueous concentrated liquid composition in the dispenser.

The ready-to-use solution or the concentrated liquid composition for use according to the invention can be in any form including liquid, gel, paste and slurry.

The cleaning solutions, i.e. ready-to-use solution and/or the concentrated liquid composition, are suitable to treat any metal or plastic surface contaminated with unconventional infectious agents, such as prions.

Exemplary contaminants include body fluids, such as blood, lipids and synovial fluids and chemical residues.

The aqueous cleaning solutions that can be used according to the invention, i.e. the aqueous alkaline ready-to-use solution and/or the concentrated aqueous alkaline liquid composition, may be used at any temperature, including an elevated temperature of from about 30° C to about 70° C, preferably about 45° C to about 60° C and more preferred about 55° C. After contact with the cleaning solution, the solution is removed from the metal or plastic surface.

The contact time of the aqueous cleaning solution in an automated process, i.e. ready-to-use solution and/or the concentrated liquid composition, with the metal substrates will vary depending upon the degree of contamination but broadly will range of about > 5 minute to about < 60 minutes, with about > 10 minutes to about < 30 minutes being more typical and also preferred is about > 10 minutes to about < 20 minutes.

According to a preferred embodiment the contact time of the aqueous cleaning solution at about > 55° C to about < 70° C in an automated process, i.e. ready-to-use solution and/or the concentrated liquid composition, with the metal substrates may range of about > 5 minute to about < 60 minutes, with about > 10 minutes to about < 30 minutes being more typical and also preferred is about > 10 minutes to about < 20 minutes.

A cleaning apparatus that can be used according to the invention may comprise:

(a) a first container comprising an alkaline solid composition according to claims 1 to 10;

(b) a second container comprising a concentrated liquid composition of the solid composition according to claim 12 or 14 having a pH of about > 12.5 to about < 13.5, preferably a pH of about 13;

(c) optional a third container comprising a day solution of the concentrated liquid composition or a ready to use solution having a pH of about > 10.0 to about < 11,5;

(c) a water feed for conveying water to the first container for forming said solution from water;

(d) a solution line for conveying solution from the first container to the second container;

(e) optional a third container that is connected with the second container with a solution line for conveying solution from the second container to the third container; and

(f) a use solution line for conveying the use solution from the second container and/or third container to a use solution applicator and/or to the place of use.

The following examples are presented to help illustrate the invention and should not be construed as limiting the invention.

When processing solids in the cast process there are different ways to ensure a solidification of the product. The solidification can erupt after cooling down a NaOH melt by crystallization, e.g. with silicates and polyethylene glycol. Foaming of this formula was observed to an extent that was not acceptable in the field of automated reprocessing. If the cleaner generates too much foam in the washer, the cleaning efficiency goes down due to lack of mechanical agitation in the washer.

It was observed that polyethylene glycol in combination with NaOH and heat lead to a high foaming composition. The formation of foam lowers in particular the cleaning properties, due to the loss of mechanical agitation. Further, pumping of foam dramatically reduces the liquid flow rates, thus causes dosing and transport problems in the sump, liquid conduits, as well as in the dispensing drawer. Thus, foam is not acceptable in an automated washer. Cleaning efficacy tests have shown that that the results without polyethylene glycol in the formula were not as good as with polyethylene glycol in the formula.

To achieve a good level of cleaning efficacy it was successfully tried to add a small amount of polyethylene glycol to the NAOH based formulation. With this addition of a minor amount of polyethylene glycol (PEG) the composition has a surprising cleaning efficacy due to none or practical none foam formation, if mixed with water, as sump solution or in the dispensing drawer and can be used according to the invention for irreversible destruction of infectivity and/or reducing

unconventional infectious agents, such as prions. Example

The following examples were carried out to illustrate the superior prion activity of the composition of the present invention in more detail.

The following alkaline concentrates were provided in a solid form:

All components of table 1 and 2 are mixed together. Then the slurry is mixed and heated to temperature of about 80° C for about 30 minutes. Thereafter, the mixed slurry is casted and allows cooling to room temperature, whereby a casted alkaline solid is formed.

Table 1

Solid alkaline concentrate of the invention

Components El E2 E3 E4 E5 E6 E7

Wt.-% Wt.-% Wt.-% Wt.-% Wt.-% Wt.-% Wt.-%

Polyethylene glycol (PEG 2 3 5 6 9 10 12 8000)

Hexylene glycol — — — 0.6 0.6 0.6 0.6

Polyacrylic acid 6 6 5 5 5 5 4

NaOH 37 35 33 30 28 25 25

1 ,2,3-Benzotriazole 6 5 4 7

Disilicate 4 5 3

N,N-bis(carboxylate methyl) 25 22 22 -L-glutamate (GLDA)

Water Add. Add. Add. Add. Add. Add. Add.

100 100 100 100 100 100 100

Components E8 E9 E10 El l E12 E13 E14

Wt.-% Wt.-% Wt.-% Wt.-% Wt.-% Wt.-% Wt.-%

Polyethylene glycol (PEG 2 4 6

4000)

Polyethylene glycol (PEG 2 6 8 10 10000)

Hexylene glycol 0.6 0.5 0.4

Polyacrylic acid 6 6 5 6 5 5 5

NaOH 37 33 30 28 26 26 25

1 ,2,3-Benzotriazole 6 6 5

Disilcate 6 5 4 4

N,N-bis(carboxylatemethyl) 28 24 24 -L-glutamate (GLDA) Water Add. Add. Add. Add. Add. Add. Add.

100 100 100 100 100 100 100

Table 2

Solid alkaline concentrate provided for comparison

Invitro test for inactivating of unconventional infectious agents

This test method provides a basis to assess the inactivating properties of the liquid alkaline cleaning composition against unconventional infectious agents.

All tests have been done according to the protocol of the French authority ANSM. The test design is shown below:

a) Phase 0 (prescreening): in vitro test - Western Blot

b) Phase la + lb (mode of action): in vitro test - Western Blot of surface and suspension c) Phase la + lb (additional strains): in vitro test - Western Blot

d) Phase 2: in vivo test - animal test with hamsters

Materials and methods An aqueous alkaline ready-to-use solution is formed, wherein first a 5 percentage concentrated solution of examples El to El 4 by dissolving in deionized water is obtained each. The concentrated solution is than dissolved with deionized water to a 1 percentage aqueous alkaline ready-to-use solution.

Assessment in two independent runs of the ready-to-use solutions of El to E14 against Scarpie strain adapted to hamster, 263K strain (phase O qualitative runs in duplicate).

Then for the ready-to-use solutions of El to E14, tested in suspensions and on surfaces against the Scrapie strain adapted to hamster, 263K strain (Adjou et al. 1995); Scrapie strain adapted to mouse, 22L strain (Carp et al., 1998); another Scarpie strain adapted to mouse, C506M3 strain (Lasmezas et al. 1996); Bovine spongiform encephalopathy (BSE) strain adapte to mouse, 6PB1 strain (Lasmezs et al., 1996); Gerstmann-SrausslerScheinker sysndrome (GSS) strain adapted to mouse, Fukuoka starin (Tateishi et al., 1988); and Human strain of variant of Creuzfeldt- Jakob disease (vCJD); phases la for suspension study and lb for surfaces, experiments done in triplicates, except for vCJD in duplicate.

Neat brain contaminated brain homogenates or contamination of stainless stell wires with brain homogenates or direct;

Treatment of artificially contaminated wires or directly brain homogenats for 10 min at 55° C; Reference treatment sodium hypochlorite at 20000 ppm for 1 hour at ambient temperature;

Rinsing of wires with water;

Desorption and detection of any residual PrPres using western blot;

Calculation of PrPres50% titres using Sperman-Karber formula and of reduction factor (RF). Assessment of activity

Stainless steel wires (Stainless steel reference: 316) were artificially contaminated with 10% brain homogenates obtained from rodents at the ultimate stage of diseases caused by these different prion strains in these animals. Then, these wires were treated with the ready-to-use solutions of El to E14 for 10 minutes at 55° C. These sheets were rinsed once using water for 2 minutes at room temperature (23° C). In parallel, contaminated wires were not treated and kept at these previous defined conditions to be the untreated controls.

Only for the 263K strain, an "high efficiency" control sodium hypochlorite at 2% i.e. 20000 ppm of active Clorine for 1 hour at room temperature (23° C) and "partial efficiency" control sodium hypochlorite at 2% i.e. 20000 ppm of active Clorine for 15 minutes at room temperature (23° C) where performed also in parallel.

Wires were then desorbed and possible residual PrPres was detected by western blot in desorption solutions. The presence of any residual PrPres on wires was then assessed using the method described by Lemmer et al. Journal of General Virology, Dec 2004, Vol. 85 No. 12, 3805 - 3816). Prions strains and preparation of inoculums

Brains of hamsters infected with the 263K strain, of mice infected with the C506M3 strain and of mice infected with the 6PB1 BSE strain were controlled after euthanasia at the PBS using a ribolysor.

These brain homogenates generated corresponded to inocula "263K", "C506M3" and "6pBl" used for the artificial contaminations of wires and solutions.

Concerning 22L and Fukuoka strains, 10% brain homogenate (w/v in PBS) were provided by the Human Genetics Institute in Montpellier (Pr. Sylvain Lehmann). Last vCJD strain, 10% brain homogenate (w/v in PBS) was provided by the Hopital Neurologique de Lon (Pr Armand Perrer- Liaudet).

Artificial contamination of stainless steel wires

Stainless steel wires length 5 mm; Steelex monofilament B Braun, 0 0.30 mm, ref G0094137 were artificially contaminasted with the prion strains. Forty wires were immersed for 1 hour in 100 μL· of each inoculums, prepared as described. These wires were then dried individualized flat for 16 hours under flow at room temperature. For the prescreening study (phase 0), only the 263K strain was evaluated).

Treatment of solutions (phase 1 a suspension study)

For each strain 90 μΐ_^ of the ready-to-use solutions of El to E14, preheated to 55° C were contaminated with 10 μΕ inoculums and then incubated for 10 minutes at 55° C. In parallel 90 μΕ of water were also contaminated with 10 μΕ inoculums (untreated control). After treatment, proteins in these solutions were immediately precipitated with phosphotungstic acid using the method described by Wadsworth et al. The Lancet, Volume 358, Issue 9277, Pages 171 - 180, 21 July 2001.

Desorption of wires

Wires were desorbed using the methodology described above by Lemmer et al.. Supports were incubated in TBS - Sarkosyl (50 mM Tris-HCL, 150 mM NaCl pH 7.5, 1% Sarkosysl) buffer supplemented with 150 μg/ml of proteinase K for 1 hour at 37° C.

For wires, after inactivation of proteinase K, desorption solutions were 1 :2 diluted in western blot buffer, concentrated twice, in final volume of 104 μΕ.

Precipitation of Treatment solutions

Solutions issued from "treatment solutions" (El to El 4) were precipitated using

phosphotungstic acid method. Then, they were resuspended in 50 μΕ of PBS - Sarkosysl 0.1%> buffer supplemented with 50 μg/ml proteinase K and, incubated for 1 hour at 37° C. After proteinase K inactivation, solutions were then 1 :2 diluted in western blot buffer (final volume: 100 μΕ). Detection of PrPres by Western blot

Limit dilutions (successive 1:10) were performed for each sample and 10 μΐ. of each dilution were tested on 12% polyacrylamide gel and a transfer on nitrocellulose membrane. Samples were immunoblotted using HRP-conjugated Sha31 monoclonal antibody (anti-PrP antibody). PrPres signal were visualized using ECL hyperfilms (Amersham) and the Super Signal R-West Extended Duration Substrate kit (Pierce).

Data analysis

PrPres 50% titres (PrPres50) were determined usind the Spearman-Karber formula. The amount of PrPres coated on supports or in solution was then calculated by comparing the titre to the final volume of the samples generated after desorption and precipitation. The reduction factor (RF) for each treatment was calculated as follows:

RF = logio(PrPres50 for the treated group/PrPres50 for the untreated control group)

Table 3

Log reduction of tested strains

Strains 263K 6PB1 22L C506M3 Fukuoka vCJD

50% PrPres 5 4 2 2 2 2 titre (loglO)

Untreated

control

El >5 >4 >2 >2 >2 >2

E2 >5 >4 >2 >2 >2 >2

E3 >5 >4 >2 >2 >2 >2

E4 >5 >4 >2 >2 >2 >2

E5 >5 >4 >2 >2 >2 >2

E6 >5 >4 >2 >2 >2 >2

E7 >5 >4 >2 >2 >2 >2

E8 >5 >4 >2 >2 >2 >2

E9 >5 >4 >2 >2 >2 >2

E10 >5 >4 >2 >2 >2 >2

Ell >5 >4 >2 >2 >2 >2

E12 >5 >4 >2 >2 >2 >2

E13 >5 >4 >2 >2 >2 >2

The El to El 4 ready to use compositions significantly reduce the risk associated with prions and reusable medical devices such as surgical stainless steel.

Invivo Test

To measure the efficiency of the composition of the invention to eliminate and/or to inactivate the 263K scrapie strain invivo.

Introduction

This bioassay was the animal model of Syrien Golden hamsters infected with the scrapie 263K strain accordance with the general principles enunciated in the "Prion Standard Protocol" (PSP) of the "Agence Nationale da Securite du Medicament et des produits de sante" (ANSM; formerly "Agence Franchise de Securite Sanitaire des Produits de Sante" (Afssaps)).

Material & methods

Artificial contamination of stainless steel wires with the 263K scrapie strain

Treatment of these wires with each solution of E8

Measurement of the residual infectivity on the surface of wires by implantation of these wires in brains of Syrian Golden hamsters

Clinical and biological (detection of PrPres by Western-Blot) monitoring

Calculation of infectious titers and of the reduction factors (RF)

Stainless steel wire segments (Aesculap", 5 mm x 0.30 mm) were artificially contaminated by incubation in a suspension containing a known load of TSE (strain 263K). After drying, they were treated with 3 different decontamination procedures under study

After decontamination, these wires were individually implanted in brains of hamsters.

Results

- Fifty% infectious dose per wire: 5.5 logslO

Example E8: efficiently reduced the infectious load on wire, with a RF > 5.5 and a transmission rate of 0%, their efficiencies are considered as "Complete". Animals

Wires were inoculated into Syrian Golden hamsters (Mesocricetus auratus), which are sensitive to TSE strain used (experimental scrapie 263K strain).

The groups and sub-groups and number of animals per group or sub-group are shown in table 4:

Table 4

Negative control group

Negative controls were composed of 3 hamsters in 3 groups. Among them, two hamsters were not implanted (NN) and the others were implanted with wires coated with negative brain homogenate treated or not with E8 product (NW group for untreated wires and NT2W and group for E8 product).

Standard curve and positive control groups Standard curves were composed of 1 of 8 hamsters for the highest dilution, 2 groups of 4 hamsters for the two following dilutions, 4 groups of 8 hamsters for the next four dilutions, and 2 groups of 4 hamsters for the last two dilutions (SCIW toSC9W sub-groups). The SCIW group corresponded also to the untreated or positive group (PCW). For each group, 12 steel wires were contaminated by respective incubations in serially 10-fold dilutions of positive homogenate. Practically, a 10% (weight/volume) homogenate of brains from terminal stage- infected hamsters was serially 10-fold diluted in a 10 % (weight- volume) homogenate of brains from healthy hamsters. Each wire was individually implanted into one hamster by the intracerebral route.

Reference treatment groups

For each reference treatment (sodium hypochlorite 20,000 ppm for 1 hour at 20° C (RT1 W), sodium hypochlorite 5,000 ppm for 15 min at 20° C (RT2W) and sodium hydroxide IN 1 hour at 20° C (RT3W), a group of 12 hamsters was formed. Each wire was individually implanted into one hamster by the intracerebral route.

Water control group

In this water group (WW; 12 hamsters), treatment was replaced by water. Each wire was individually implanted into one hamster by the intracerebral route.

Composition of the invention E8

Twelve hamsters were for E8 tested as a group T2W. Each wire was individually implanted into one hamster by the intracerebral route.

Animal housing

The hamsters were housed in the biosafety level 2 animal facilities (INRA Centre de Ours, Plate-forme d'lnfectiologie Experimentale, 37380 Nouzilly, France). Animals were stabilized one week and identified by an electronic tag before starting the experiments. Food (Rodent food RMl from SDS) and drink (Tap water) was ad libitum.

The hamsters were randomly housed four per cage in a same room and litter was changed once a week. Experimentations

Strain of Transmissible Spongiform Encephalopathy agent

Wires were contaminated using 10% brain homogenates obtained from 263K-infected hamsters at the terminal stage of TSE disease.

Brain homogenates were previously obtained from brains of 263K-infected hamsters at the terminal stage of the disease. These brains were homogenized using a ribolyser, at 20% weight/volume (w/v) in a sterile 5% glucose solution. The unconventional transmissible agent 263K strain is used in our laboratory for validation purpose of inactivation/elimination process. This TSE strain was manipulated in CEA Level-2 high-security facilities. The 263K strain is a laboratory scrapie strain with a titre of 10¹¹ infectious units per gram of brain. It was selected and propagated in the Syrian golden hamster in which it had been stabilized. The model of infection of the hamster by strain 263K yields quick results. The average period of incubation is 70 days and death occurs between 80 and 90 days for an intracerebral injection of 10 infectious units.

Artificial contamination of wires

Stainless-steel wires were artificially contaminated with the 263K strain by an incubation of 1 hour under gentle agitation in the 263K-infected brain homogenate previously described in the section "Strain of Transmissible Spongiform Encephalopathy agent" above. These stainless-steel wires were dried for 16 hours under a class II microbiological safety cabinet at ambient temperature (23° C).

Treatment of wires

Each of the following treatments applied to at least 15 wires; wires were treated in batches of five.

E8 composition

- composition E8 heated to 55° C ± 1° C.

Added 5.0 ml of E8 to 5 inoculated wires in a glass vial containing a small magnetic stir bar and equilibrated to 55 ± 1° C (for 1 min) (3 batches). Mixed at 55° C ± 1° C for 10 minutes.

Rinsed each 5 wires batch with 1 mL distilled water. After treatment, treated wires were stored frozen at -80° C until inoculation.

As mentioned in the following table 5 different treatment processes were performed and compared to a water treatment (WTW). The inoculum was titrated in parallel.

Inoculation and monitoring of animals

The anaesthetized animals were implanted intracerebral with an individual wire. The infectious titre was determined on the basis of the physical examination, the dates of death, and observation of the terminal stage. The physical examination included observation of the pathognomonic signs of transmissible sub acute spongiform encephalopathy. The physical examinations were practiced once or twice a week along the study. There are four types physical signs:

- Behavioral disorders (excitability, nesting and grooming disorders);

Cerebellar ataxia, abnormal gait, prostration;

- Obesity followed by weight loss;

Paraplegia then tetraplegia. Undings were examination.

The findings were written up after each physical examination. Clinical signs and deaths were recorded. At the terminal stage of the disease, euthanasia was performed to minimize the animal suffering.

Twelve months (i.e. four times the incubation period of the disease for an intracerebral injection of theoretically 10 infectious units) after the inoculation (end of the study) of the various wires, all surviving animals were subjects to euthanasia. The brains of these animals were removed and any PrPres present was estimated biochemically by Western blot. The brains of that died during the study also examined biochemically.

Biochemical detection of PrPres by Western blot

Brain homogenates from hamsters were homogenized using a ribolyser at 20% weight/volume (w/v) in a sterile 5% glucose solution. PrPres was then purified from these brain homogenates using the Biorad's "BSE purification kit" according to the Bertin Pharma's in-house methodology. All these samples were run on 12 % polyacrylamide gels and transferred onto a nitrocellulose membrane. Immunoblotting was performed with the monoclonal peroxidase-conjugated anti-mouse PrP Sha-31 antibody. Immuno-reactivity was revealed using ECL hyperfilm (Amersham) and the "Super Signal R-West Extended Duration Substrate" (Pierce), visualized by autoradiography.

Data analysis

Hamsters from SC groups ware implanted with successive 10-fold dilutions of brain homogenate adsorbed on wires. The 50% infectious dose (ID50), that is the pathogen dose which infects 50% of the animals, was then determined using the Spearman-Karber formula (5) as follows:

M = X_k + d / 2 +∑_Pi

where M is logarithm (loglO) of the dilution at which half the mice are infected, relative to the tested volume; X_k is the log 10 of the highest dilution with the 100 % of infected mice; d is the log 10 of the dilution factor, pi is the ratio between the number of infected mice per dilution and the number of inoculated mice per dilution;∑ p_t is the sum of pi (starting with the highest dilution giving 100 % of positivity).

The standard error (SE) is calculated according to the following formula: d^l

SE r 1 ( Ir_! ² + , r₂ ² + , r₃ ² + , ...J

n(n - \) n where d is the log 10 of the dilution factor;

n is the number of mice inoculated at each dilution;

r is the total number of mice infected counting all dilutions;

rl , r2 are .. . the numbers of mice infected at each dilution.

The 95 % confidence interval is reported as: Mean ID50 ± 1.96 SE.

For each group of animals, standard curve controls or wires groups, the mean duration was calculated including both TSE infected and healthy animals sacrificed at the end of the study, to take into account these values both the incubation periods of TSE disease and the transmission rate. The mean duration for different groups of the standard curve was plotted to define a 4- parameter standard curve. For each group of treated wires, the mean duration was reported on the curve to determine the dilution of adsorbed inoculums presenting an equivalent infectivity.

The RF related to each treatment was calculated as follows:

RF = logio (corresponding dilution of the treated group / corresponding dilution of the water control group)

Results

Results for the "standard curve" groups 365 days post-implantation (p.i.) are presented in Table 5.

All animals of the 10^"1, 10^"2 , 10^"3 and 10^"4 sub -groups died with TSE signs with a mean period incubation of respectively 91 ± 4, 99 ± 9, 109 ± 12 and 126 ±17 days p.i.. All these animals were confirmed as positive with PrPres detected in their brains.

In the 10^"5 dilution sub-group, 4 out of 8 animals presented clinical TSE signs and were confirmed to be PrPres positive by western blot with an incubation period of 230 ± 72 days p.i..

In the 10^"6 dilution sub-group, 1 out of 7 animals presented clinical signs and was confirmed to be PrPres positive by western blot with an incubation period 261 days p.i..

Table 5

Dilution Intercurrent Animals Brains Brains Transm. Incub.

Subanimals recorded tested in positive for Level Period groups'¹ with the WB PrPres

TSE signs

10 ¹ 2 6/6 6/6 6/6 6/6 - 100% 91 ± 4

10^" 1 3/3 3/3 3/3 3/3 - 100% 99 ± 9

10^"J 0 4/4 4/4 4/4 4/4 - 100% 109 ± 12 lo-⁴ 1 7/7 7/7 7/7 7/7 - 100% 126 ± 17 io-° 0 4/8 4/8 8/8 4/8 - 50% 230 ± 72

10^"b 1 1/7 7/7 1/7 1/7 - 14% 261 lo-⁷ 1 0/7 7/7 0/7 0/7 -0% > 173^b

10 " 1 1/3 3/3 1/3 1/3 - 33% 182

10 ^y 0 0/4 4/4 0/4 0/4 -0% > 365

Results for the "standard curve" group. ^a Dilution of inoculum. ^b In the 10^"7 subgroup, 1 out of the 7 animals died at day 173 p.i. without TSE signs and its brain was negative for PrPres. All other animals from the subgroup were sacrified at day 365 p.i. and were negative for PrPres.

In the 10^"7 dilution sub-group, none of the animals presented clinical TSE signs. One animal died at day 173p.i. but its brain was negative for PrPres. For all other animals in this sub-group, brains were negative for PrPres at 365 days p.i..

-8

In 10^" dilution sub-group, 1 out of 3 animals presented clinical TSE signs and was confirmed PrPres positive by Western blot with an incubation period of 182 days p.i.. A PrPres aggregate on the surface of the wire could explain this positivity. One other animal died at day 207 post-implantation but was PrPres negative.

In the 10-⁹ dilution sub-group, none of the presented clinical TSE signs at 365 days p.i.; all these animals were PrPres negative.

Several intercurrent animals were excluded in the "standard curve" group as presented in table 6. They mostly died just after implantation or in the early phase post implantation. In the 10^"6 sub -group, one animal died at day 97 post-implantation but its brain was tested for PrPres by western blot and was negative.

Using these data and the Spearman-Karber formula, the 50% infectious dose (ID50) coated on each wire was of 5.5 ± 0.7 log 10. It is of interest to note that this titre per wire is consistent with those previously described for this scrapie 263K strain.

Table 6

Justification of intercurrent animals in the "standard curve" group

Dilution SubDeath (day p.i.) Recorded TSE Brains tested in Comments groups signs WB

lo-¹ 1 No No Immediate p.i.

toxicity

1 No No Immediate p.i. toxicity

10^" 4 No No Immediate p.i.

toxicity lo-⁴ 97 No No Immediate p.i.

toxicity

10^"b 97 No No PrPres negative

10-' 1 No No Immediate p.i.

toxicity

10 " 1 No No Immediate p.i.

toxicity

Water Control Group

Table 7

Water Control Group

All animals of the "Water Control" died with TSE signs with a mean period incubation of 91 ± 7 days p.i.. All these animals were confirmed positive for PrPres in brains.

Negative Control groups

Table 8

Results for different negative control groups at day 365 p.i. are presented

Groups Intercurrent Animals Brains Brains Transm.

animals recorded tested in positive for Level

with the WB PrPres

TSE signs

NN 0 0/2 2/2 0/2 0/2 - 0%

NW 0 0/1 1/1 0/1 0/1 - 0% NT2W 0 0/3 3/3 0/3 0/3 -0%

(E8)

All animals from the "negative control" groups were negative for PrPres at the end of the study.

Reference treatment groups

Table 9

Results for reference treatment groups at day 365 p.i. are presented

All animals in these three "reference control" groups were negative for PrPres at the end of the study. The NaOCl partial efficacy treatment also led to 0% of transmission rate.

Several intercurrent animals were excluded in the "reference treatment" groups as presented in table 10. As for other groups, they mostly died just after implantation or in the early phase post-implantation. In the RTW2 group, one animal died at day 100 post- implantation but brain was tested for PrPres by western blot and was negative. In the RTW3 group, one animal died at day 216 post-implantation but its brain was tested for PrPres by western blot and was negative.

Table 10

Justification of intercurrent airmails in 3 " reference control" groups

Groups Death (day p.i.) Recorded TSE Brains tested in Comments signs WB

RT1W 1 No No Immediate p.i.

toxicity

1 No No Immediate p.i. toxicity

RT2W 1 No No Immediate p.i.

toxicity

1 No No Immediate p.i.

toxicity

30 No No Death unrelated to TSE

100 No No PrPres negative

RT3W 1 No No Immediate p.i.

toxicity

15 No No Immediate p.i.

toxicity

216 No Yes Death unrelated to TSE

Composition of the invention E8

Results for the "composition of the invention E8" group 365 days post-inoculation (p.i.) are presented in Table 11. There was no intercurrent animal in these 3 groups.

Table 11

Results obtained for composition of the invention E8

All animals implanted with wires treated with product (TW2 group) were alive and negative for PrPres at the end of the study (365 days p.i). Conclusion

The composition of the invention E8 efficiently reduced the infectious load on wire. With a RF > 5.5 and a transmission rate of 0 its efficiency considered as "Complete" by PSP.

Foam Formation Test

This test method provides a basis to assess the foam formation properties of the liquid alkaline cleaning composition of the invention.

Foam testing equipment

250 ml long-necked glass cylinder

Rubber stopper to close the long-necked glass cylinder

Test method

An aqueous alkaline ready-to-use solution is formed, wherein 1.0 g of examples 1 to 14 and VI to V7 are dissolved in 100 ml of deionized water each.

100 ml of said aqueous alkaline ready-to-use solution of examples El to E14 and VI to V7 are added to a graduated 250 ml long-necked glass cylinder.

The long-necked glass cylinder was then turned up and down 20 x times in 20 seconds.

Thereafter the glass cylinder was placed and the foam depth of each cylinder was scaled in ml to determine the foam formation. This test was carried out at a temperature of the cleaning solution at ambient temperature, 20° C and 55° C.

The foam hight of about > 0 ml and about < 0.1 ml are considered to be excellent (++) and in line with the invention. The foam hight of about > 0.1 ml to about < 5 ml are considered to be good (+) and in line with the invention. The foam hight of about > 5 ml are considered to be insufficient (-) thus not in line with the invention, i.e. non-inventive.

The table 12 shows the result of the foam formation caused by the aqueous alkaline ready-to- use solution of examples El to E14 and VI to V7 obtained by the foam formation test.

Table 12

Foam Formation Test-Results

Exampels

El ++ E8 ++ VI -

E2 ++ E9 ++ V2 -

E3 ++ E10 ++ V3 -

E4 ++ El l ++ V4 -

E5 + E12 + V5 - E6 + E13 + V6 -

E7 + E14 + V7 -

Material Compatibility Test

This test method provides a basis to assess the enhanced metal-surface-safeness of the liquid alkaline cleaning composition with respect to corrosion.

Corrosion testing equipment

350 ml wide -necked screw cap flasks for each test condition

Acetone

Aluminum test plates of 100 mm x 50 mm x 1.5 mm

(The aluminum test plates are cleaned with acetone before use)

Clean paper toweling

Stop watch

Drying oven

Analytical balance capable of weighing to the 0.0001 place. Test method

The cleaning compositions El to E14 were diluted with deionized water to a 0.8 wt.-% ready- to-use solution. The weights of aluminum test plates of 100 mm x 50 mm x 1.5 mm were recorded and then placed in the center area of the bottom of a 350 ml wide -necked screw cap flask each. The aluminum test plates were completely submerged. Subsequently, each wide -necked screw cap flask was filed to the top with said 0.8 wt.-% ready-to-use solution El to E14 having a temperature of 23° C. The wide -necked screw cap flasks were closed with the cap and allow staying for 7 days at a temperature of 23° C. Thereafter, the aluminum test plates were removed, rinsed with deionized water, placed on a clean paper towel and allowed to dry at a temperature of 23° C. The aluminum test plates were then weighted and the weight was taken to the fourth place. Subsequently the aluminum test plates were returned in there wide-necked screw cap flasks for another 7 days. Thereafter, the aluminum test plates were removed, rinsed with deionized water, placed on a clean paper towel and allowed to dry at a temperature of 23° C. The aluminum test plates were then weighted and the weight was taken to the fourth place. Subsequently the aluminum test plates were returned again in there wide -necked screw cap flasks for another 7 days. The weight loss was calculated. Three tests were run for each experiment and the average weight loss was determined. The average weight loss for each aluminum test plates after treatment with said ready-to-use solution obtained from El to El 4 were about < 0.34 wt.-%.

Metal surfaces and/or plastic surfaces in need of cleaning are found in several locations.

Exemplary locations include surgical instruments, medical instruments, and dental instruments, sinks, cookware, utensils, machine parts, vehicles, tanker trucks, vehicle wheels, work surfaces, tanks, immersion vessels, spray washers, and ultrasonic baths.

The compositions can be used for inactivating and/or reducing unconventional infectious agents, such as prions and for removing residues including blood, greases, cutting fluids, drawing fluids, machine oils, antirust oils such as cosmoline, carbonaceous soils, sebaceous soils, particulate matter, waxes, paraffins, used motor oil, fuels, etc..

Metal surfaces that can be treated with the composition for inactivating and/or reducing unconventional infectious agents, such as prions include iron-based metals such as iron, iron alloys, e. g. steel, tin, aluminum, copper, tungsten, titanium, molybdenum, etc., for example. The structure of the metal surface that can be treated with the composition for inactivating and/or reducing

unconventional infectious agents, such as prions, can vary widely. Thus, the metal surface and/or plastic surface can be as a metal and/or plastic part of complex configuration, sheeting, coils, rolls, bars, rods, plates, disks, etc..

More preferred is the use of the liquid alkaline solution, in particular the ready-to-use-solution on metal and/or plastic articles, especially metal instruments, plastic instruments, instruments with a plastic surface and/or instruments with a metal surface for inactivating and/or reducing unconventional infectious agents, such as prions, thereon.

Most preferred is the use of the liquid alkaline cleaning solution, in particular the ready-to-use- solution, in an automated instrument processing metal and/or plastic articles, especially metal instruments, plastic instruments, instruments with a plastic surface and/or instruments with a metal surface for inactivating and/or reducing unconventional infectious agents, such as prions, thereon.

As used herein, the term "about" refers to variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients used to make the compositions or carry out the methods; and the like. The term "about" also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalents to the quantities.

It should be noted that, as used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise.

Thus, for example, reference to a composition containing "a compound" includes a mixture of two or more compounds. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise. All publications and patent applications in this specification are indicative of the level of ordinary skill in the art to which this invention pertains. The invention has been described to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.

Claims

What is claimed is:

1. Use of a solid alkaline composition for cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents, comprising at least one alkaline source and at least one polyethylene glycol, wherein the ratio of alkaline source to polyethylene glycol is in the range from about 30 : 1 to about 2 : 1.

2. Use of the solid alkaline composition according to claim 1, wherein the composition comprises at least one corrosion inhibitor, preferably the composition comprises at least one corrosion inhibitor in an amount of > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, wherein the weight- % of the corrosion inhibitor are based on the total weight of the solid composition and more preferred the corrosion inhibitor is free of a silicate.

3. Use of the solid alkaline composition according to claims 1 or 2, wherein the ratio of alkaline source to polyethylene glycol can be in the range from about 25 : 1 to about 5 : 1, further preferred about 22 : 1 to about 8 : 1, also preferred about 20 : 1 to about 10 : 1 and in addition preferred about 18.5 : 1 to about 16 : 1.

4. Use of the solid alkaline composition according to claims 1 to 3, comprising:

- about > 10 wt.-% to about < 50 wt.-%, preferably about > 15 wt.-% to about < 45 wt.-%, further preferred about > 20 wt.-% to about < 40 wt.-%, also preferred about > 30 wt.-% to about < 38 wt.-%and more preferred about > 35 wt.-% to about < 37 wt.-%, of at least one alkaline source;

- about > 0.1 wt.-% to about < 15 wt.-%, preferably about > 0.5 wt.-% to about < 10 wt.-%, further preferred about > 1 wt.-% to about < 5 wt.-%, and more preferred about > 2 wt.-% to about < 3 wt.-%, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of 4.000 to 12.000; and

- > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is free of a silicate;

- a solvent, preferably water, is added add. 100 wt.-%; wherein the weight-% of the components are based on the total weight of the solid composition.

5. Use of the solid alkaline composition according to claims 1 to 4, wherein the composition

comprises a threshold inhibitor/crystal modifier component.

6. Use of the solid alkaline composition according to claims 1 to 5, wherein the composition comprises at least one sequestering agent composition.

7. Use of the solid alkaline composition according to claims 1 to 6, wherein the composition

comprises at least one alkaline source selected from the group of sodium hydroxide, sodium carbonate, potassium hydroxide, and lithium hydroxide.

8. Use of the solid alkaline composition according to claims 1 to 7, wherein the composition

comprises at least one corrosion inhibitor selected from the group comprising silicate, sodium silicate, calcium acetate, calcium chloride, calcium gluconate, calcium phosphate, calcium borate, calcium carbonate, calcium citrate, calcium lactate, calcium sulfate, calcium tartrate,

benzotriazole, 1,2,3-benzotriazole and mixtures thereof.

9. Use of the solid alkaline composition according to claims 1 to 8, wherein the composition

comprises at least one threshold inhibitor/crystal modifier selected from the group comprising salts of phosphonocarboxylic acids, phosphonates, salts of 1 -hydroxyethylidene -1,1,- diphosphonic acid (HEDP), salts of acid substituted polymers, and mixtures thereof, preferably salts of acid substituted polymers of monomers of acrylate, methacrylate, salts of polyitaconic acid, salts of polymaleic acid, and mixtures thereof.

10. Use of the solid alkaline composition according to claims 1 to 9, wherein the composition

comprises at least one sequestering agent composition selected from the group of sodium gluconate, pentasodium salt of diethylenetriamine pentaacetic acid, sodium glucoheptonate, salts of ethylene diamine tetraacetic acid, salts of ethylene diamine tetraacetic acid, salts of hydroxyethyl ethylene diamine triacetic acid, salts of hydroxy ethyl ethylene diamine triacetic acid, salts of nitrilotriacetic acid, salts of nitrilotriacetic acid, diethanolglycine sodium salt, ethanoldiglycine disodium salt, salts of hydroxymonocarboxylic acid compounds, salts of hydroxydicarboxylic acid compounds, salts of amine containing carboxylic acids, terasodium N,N-bis(carboxylatomethyl)-L-glutamate and mixtures thereof.

11. Use of the solid alkaline composition according to claims 1 to 10, wherein the composition

comprises at least one solvent selected from the group comprising water, alcohols, ethanol, isopropanol, 2-butoxy ethanol, 1 -decanol, benzyl alcohol, glycerin, monoethanolamine, glycols, ethylene glycol, diethylene glycol, propylene glycol, butoxy diglycol, triethylene glycol, tetraethylene glycol, glycerin, propylene glycol, dipropylene glycol, hexylene glycol, glycol ethers, esters, or combinations thereof. Suitable alcohols include, but are not limited to, ethanol, isopropanol, 2-butoxy ethanol, 1 -decanol, benzyl alcohol, glycerin, monoethanolamine, or combinations thereof; preferably the composition comprises at least two solvents and more preferred the composition comprises water and hexylene glycol.

12. Use of the solid alkaline composition according to claims 1 to 11, comprising:

- about > 10 wt.-% to about < 50 wt.-%, preferably about > 15 wt.-% to about < 45 wt.- %, further preferred about > 20 wt.-% to about < 40 wt.-%, also preferred about > 30 wt.-% to about < 38 wt.-%and more preferred about > 35 wt.-% to about < 37 wt.-%, of at least one alkaline metal hydroxide, preferably sodium hydroxide;

- about > 0.1 wt.-% to about < 15 wt.-%, preferably about > 0.5 wt.-% to about < 10 wt.-%, further preferred about > 1 wt.-% to about < 5 wt.-%, and more preferred about > 2 wt.-% to about < 3 wt.-%, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of 4.000 to 12.000;

- > 2 wt.-% to about < 10 wt.-%, preferably about > 3 wt.-% to about < 9 wt.-%, further preferred about > 4 wt.-% to about < 8 wt.-%, and more preferred about > 5 wt.-% to about < 6 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is a heterocyclic compound and more preferred a benzotriazol;

13. Use of a solution of the solid alkaline composition according to claims 1 to 12 for the cleaning of and/or destruction of prions on surfaces contaminated with unconventional infectious agents.

14. Use of the solution of claim 13, wherein the solution is a concentrated liquid composition or a ready-to-use solution.

15. Use of the solution of claim 13 or 14, wherein the ratio of the solvent, preferably water, to solid, to provide a concentrated liquid composition, preferably an aqueous solution, of the solid alkaline composition is in the range from about 200 : 1 to about 10 : 1, preferably about 100 : 1 to about 12 : 1, further preferred about 50 : 1 to about 15 : 1, also preferred about 40 : 1 to about 17 : 1 and in particular preferred about 30 : 1 to about 20 : 1; or the ratio of the solvent, preferably water, to solid, to provide a ready-to-use solution, preferably an aqueous solution, of the solid alkaline composition is in the range of from about 10,000 : 1 to about 100 : 1, preferably about 5000 : 1 to about 300 : 1, further preferred about 3000 : 1 to about 500 : 1, also preferred about 2500 : 1 to about 750 : 1 and in particular preferred about 2000 : 1 to about 1000 : 1.

16. Use of a ready-to-use liquid composition according to claims 1 to 15, comprising:

- about > 0.001 wt.-% to about < 0.1 wt.-%, preferably about > 0.002 wt.-% to about < 0.08 wt- %, further preferred about > 0.003 wt.-% to about < 0.05 wt.-%, and more preferred about > 0.004 wt.-% to about < 0.03 wt.-%, of at least one alkaline source;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0003 wt.-% to about < 0.005 wt.-%, further preferred about > 0.0004 wt.-% to about < 0.004 wt.-%, and more preferred about > 0.0005 wt.-% to about < 0.003 wt.-%, of at least one corrosion inhibitor; and a solvent, preferably water, is added add 100 wt.-%; wherein the weight-% of the components are based on the total weight of the composition.

17. Use of a ready-to-use liquid composition according to claims 1 to 16, comprising:

- about> 0.001 wt.-% to about < 0.1 wt.-%, preferably about > 0.002 wt.-% to about < 0.08 wt- %, further preferred about > 0.003 wt.-% to about < 0.05 wt.-%, and more preferred about > 0.004 wt.-% to about < 0.03 wt.-%, of at least one alkaline source, preferably sodium hydroxide;

- about > 0.00008 wt.-% to about < 0.01 wt.-%, preferably about > 0.0001 wt.-% to about < 0.003 wt.-%, further preferred about > 0.00015 wt.-% to about < 0.002 wt.-%, and more preferred about > 0.0002 wt.-% to about < 0.001 wt.-%, of at least one polyethylene glycol, preferably a polyethylene glycol with a MW in the range of about 4000 to about 12000;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0003 wt.-% to about < 0.005 wt.-%, further preferred about > 0.0004 wt.-% to about < 0.004 wt.-%, and more preferred about > 0.0005 wt.-% to about < 0.003 wt.-%, of at least one corrosion inhibitor, preferably the corrosion inhibitor is a heterocyclic compound and more preferred a benzotriazol;

- about > 0.0001 wt.-% to about < 0.01 wt.-%, preferably about > 0.0002 wt.-% to about < 0.01 wt.-%, further preferred about > 0.0003 wt.-% to about < 0.005 wt.-% and more preferred about > 0.0004 wt.-% to about < 0.0035 wt.-% of at least one threshold inhibitor/crystal modifier, preferably the threshold inhibitor/crystal modifier is a salt of a polyacrylic acid; - about > 0.001 wt.-% to about < 0.01 wt.-%, preferably about > 0.002 wt.-% to about < 0.05 wt.-%, further preferred about > 0.003 wt.-% to about < 0.02 wt.-%, and more preferred about > 0.004 wt.-% to about < 0.014 wt.-% of at least one sequestering agent, preferably the sequestering agent is a salt of an amine containing carboxylic acid; and

18. Use of the solution of claims 13 to 17 to irreversibly destroy infectivity and/or to reduce

unconventional infectious agents on surfaces comprising metal and/or plastic articles, metal surfaces and/or plastic surfaces, further preferred metal instruments, plastic instruments, instruments with a plastic surface and/or instruments with a metal surface, and more preferred clean hard and/or soft surfaces in an automated processing.

19. Use of the solution of claims 13 to 18 to irreversibly destroy infectivity and/or to reduce

unconventional infectious agents on surfaces in hospitals, industrial facilities and research laboratories, particularly selected from surfaces of instruments employed in medical, dental, and pharmaceutical procedures, surfaces of equipment, processing facilities or containers used in the food service, food processing, butchery, dairy, beverage, brewery, and pharmaceutical industries, work surfaces, walls, floors, ceilings, fermentation tanks, and fluid supply lines.