WO2012028196A1

WO2012028196A1 - Disinfectants based on glucoprotamin with efficacy against prions

Info

Publication number: WO2012028196A1
Application number: PCT/EP2010/062912
Authority: WO
Inventors: Bernhard Meyer
Original assignee: Ecolab Inc.
Priority date: 2010-09-02
Filing date: 2010-09-02
Publication date: 2012-03-08

Abstract

The present invention relates to the use of at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) with glutamic acid or glutamic acid derivatives corresponding to formula (II) for the cleaning and/or disinfecting of surfaces contaminated with unconventional infectious agents such as prions. Also disclosed are compositions usable for the cleaning and/or disinfecting of surfaces contaminated with unconventional infectious agents such as prions and methods of using the compositions.

Description

DISINFECTANTS BASED ON GLUCOPROTAMIN WITH EFFICACY AGAINST

PRIONS

FIELD OF THE INVENTION

The present invention relates to the field of biological decontamination and disinfectants. In particular, the present invention refers to the use of the active substance known as

glucoprotamin® for the cleaning and/or disinfecting of surfaces contaminated with

unconventional infectious agents such as prions.

BACKGROUND OF THE INVENTION

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 instruments, particularly neurosurgical and ophthalmo logical 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 advise 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.

Therefore, the object underlying the present invention was to provide means that are effective against prions and are less destructive.

It is known from document EP 0 156 275 to use at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) R¹-NH-(CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 12 to 14 carbon atoms, with glutamic acid or glutamic acid derivatives corresponding to formula (II) R²-0- CO-(CH₂)₂-CH(NH₂)-COOH in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, as disinfectants. This active ingredient of disinfectants is known under the tradename glucoprotamin®.

The present invention provides a novel use of the active substance and respective

compositions for the cleaning and/or disinfection of surfaces contaminated with

unconventional infectious agents such as prions.

SUMMARY OF THE INVENTION Surprisingly it was discovered that the products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) with glutamic acid or glutamic acid derivatives corresponding to formula (II) which are known as glucoprotamin® provide a good efficacy against unconventional infectious agents such as prions.

In accordance with one aspect of the present invention is provided a novel use of at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I)

R¹-NH-(CH₂)₃-NH₂ (I) in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with compounds corresponding to formula (II)

R²-0-CO-(CH₂)₂-CH(NH₂)-COOH (_Π) in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents.

In accordance with another aspect of the present invention is provided a liquid concentrate composition for the cleaning and/or disinfection of surfaces contaminated with

unconventional infectious agents comprising at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I)

R²-0-CO-(CH₂)₂-CH(NH₂)-COOH (II) in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, in an amount in the range of > 20 wt.-% to < 50 wt.-%, preferably in the range of > 25 wt.-% to < 45 wt.-%, more preferably in the range of > 30 wt.-% to < 40 wt.-%, based on the weight of the composition.

In accordance with another aspect of the present invention is provided a method of cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents wherein the surface is treated with a cleaning and/or disinfecting composition containing at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I)

R²-0-CO-(CH₂)₂-CH(NH₂)-COOH (_Π) in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms.

A big advantage of the present invention is that it is compatible with a wide variety of materials and devices, especially sensitive instruments with aluminum parts or anodized protective coating. So it inflicts less damage on delicate medical instruments. Detailed Description of the Invention

Surprisingly it has been discovered that the products which are obtainable by reacting an alkyl propylenediamine with glutamic acid or glutamic acid derivatives which are known as glucoprotamin® provide a good efficacy against unconventional infectious agents such as prions.

Accordingly, one aspect of the present invention provides a novel use of at least one active substance from the group of products which are obtainable by reacting an alkyl

propylenediamine corresponding to formula (I) R¹-NH-(CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with compounds corresponding to formula (II) R²-0-CO-(CH₂)₂-CH(NH₂)-COOH, in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, for the cleaning and/or disinfection of surfaces contaminated with

unconventional infectious agents.

The products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) with glutamic acid or glutamic acid derivatives corresponding to formula (II) are known as glucoprotamin®.

Preferably, the alkyl propylenediamine corresponding to formula (I) R¹-NH-(CH₂)3-NH₂, comprises R¹ which is a linear alkyl group containing 12 to 18, more preferably 12 to 14 carbon atoms. More preferably the alkyl propylenediamine corresponding to formula (I) is cocospropylene-l,3-diamine. Cocospropylene-l,3-diamine is obtainable by derivatisation of coco oil. Coco oil contains a mixture of fatty acids most of which have a linear alkyl group containing 12, 14, 16 or 18 carbon atoms, the majority having 12 or 14 carbon atoms.

Preferably the glutamic acid or glutamic acid derivatives corresponding to formula (II) is glutamic acid. Most preferred, the products are obtainable by reacting cocospropylene-1,3- diamine with glutamic acid. Preferably, the alkyl propylenediamine corresponding to formula (I) is reacted with compounds corresponding to formula (II) in a molar ratio of 1 : 1 to 1 :2 at temperatures of 60°C to 175°C. If required, the active substance or the group of products obtained in this way may be reacted with ethylene oxide and/or propylene oxide and, if required, further reacted with organic or inorganic acids.

The terms "group of products" or "products" according to the invention refers to the reaction mixture obtainable by reacting an alkyl propylenediamine corresponding to formula (I) R¹- NH-(CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with glutamic acid or glutamic acid derivatives corresponding to formula (II) R²-0-CO-(CH₂)₂- CH(NH₂)-COOH in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms.

Preferably the active substance or the "group of products" or "products" comprise glucoprotamin®, N,N-bis(3-aminopropyl)-laurylamine, N-dodecyl-l,3-propanediamine, N- cocos-l,3-propanediamine and mixtures thereof.

No efficacy of glucoprotamin® against unconventional infectious agents such as prions was expected so far.

The term "unconventional infectious agent" according to the invention refers to distinctive, transmissible infectious agents that do not fit the classic definition of viruses or bacteria or funghi. One such unconventional infectious agent is the non-viral "proteinaceous, infectious" particle, or prion. Prions have been strongly implicated as the causative agent of a group of diseases called transmissible spongiform encephalopathies (TSEs). Transmissible spongiform encephalopathies or human prion infections occurring in humans include rare dementing diseases like kuru, Creutzfeldt- Jakob disease (CJD), Gerstmann-Straussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI). In animals these include scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease in deer and elk. The prion agent appears not to have any recognizable nucleic acid component, and is resistant to conventional inactivation techniques for infectious agents.

In some embodiments, the at least one active substance is used for cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents such as prions comprised in a composition, wherein the composition comprises the at least one active substance in the range of > 0.001 wt.-% to < 50 wt.-%, preferably in the range of > 20 wt.-% to < 30 wt.-%, more preferably of 25 wt.-%, based on the weight of the composition.

More preferred, the at least one active substance is used for cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents such as prions comprised in a composition, wherein the composition comprises the at least one active substance in the range of > 20 wt.-% to < 50 wt.-%, preferably in the range of > 25 wt.-% to < 45 wt.-%, more preferably in the range of > 30 wt.-% to < 40 wt.-%, based on the weight of the composition.

Advantageously, a composition comprising the at least one active substance in the range of > 20 wt.-% to < 50 wt.-%, based on the weight of the composition, can provide a good efficacy against unconventional infectious agents such as prions.

In some embodiments, the at least one active substance is used for cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents such as prions comprised in a composition having a pH in the range of > 7 to < 11, preferably in the range of > 8 to < 10. Advantageously, a wide variety of especially sensitive medical instruments with aluminum parts or anodized protective coating can be treated. Especially delicate medical instruments often include anodic coating and will benefit from the invention.

The products may be used together with additional functional and/or additive ingredients that may further increase the effectiveness or provide an additional functional benefit. In preferred embodiments the at least one active substance may be used together with an alcohol, preferably selected from the group consisting of alcohols comprising a CI to CIO alkyl group that is straight or branched, substituted or non-substituted, and/or aromatic alcohols. Preferably, the alcohol is selected from the group consisting of ethanol, 1-propanol, and 2-propanol. The alcohol preferably is comprised in an amount in the range of > 1 wt.-% to < 80 wt.-%, preferably in the range of > 20 wt.-% to < 60 wt.-%, more preferably in the range of > 20 wt.-% to < 40 wt.-%, based on the weight of the composition.

The aromatic alcohol preferably is a phenoxy alcohol, or a phenyl monoglycol ether of an oligoglycol with up to 20 ethylene oxide units. Suitable phenoxy alcohols are 2-phenoxy ethanol, l-phenoxy-2-propanol, 2-phenoxy- 1-propanol, 3 -phenoxy- 1-propanol, l-phenoxy-2- butanol, 2-phenoxy-l-butanol, or a mixture of two or more of these compounds. Preferred are phenoxy ethanol, phenoxy propanol and phenyl oligoglycol ether with 2 to 8, in particular 4 to 6 and especially 4 ethylene oxide units. It is particularly preferred if the aromatic alcohol is selected from the group consisting of benzyl alcohol, 2-phenoxyethanol, 1-phenoxypropanol, and mixtures thereof. Also suitable are phenyl oligoglycol ethers with preferably 4 ethylene oxide units, which have the advantage to be miscible with water. Further, phenyl oligoglycol ethers are effective in cleaning.

In further embodiments, the products may be used together with cationic and/or non-ionic surfactants, preferably selected from the group consisting of fatty alcohol ethoxylates and alkylpolyglycosides.

The products may be used together with further compounds and/or additional functional ingredients, depending on the specific application that increase the effectiveness of the composition or provide an additional functional benefit. Suitable ingredients include antimicrobial agents, heavy metal salts, enzymes, and additives. In preferred embodiments the at least one active substance may be used in combination with one or more compounds selected from:

- an antimicrobial agent, preferably selected from the group consisting of an oxidizing or non-oxidizing compound selected from the group consisting of quaternary ammonium compounds particularly benzalkonium chloride, phenolic derivatives, and mixtures thereof;

- a heavy metal salt, preferably selected from the group consisting of copper (II) salts, silver (I) salts, copper (II) complex ions, and silver (I) complex ions;

- an enzyme, preferably selected from the group consisting of lipases, amylases, proteases particularly a serine endopeptidase, and mixtures thereof;

- an enzyme stabilizer selected from the group consisting of a boron compound, a calcium salt, glycols, and mixtures thereof;

- additives such as detergents, surfactants, builders, sequestering agents, defoamers, thickening agents, gelling agents, complexing agents, clear rinsing agents, corrosion inhibitors, perfumes, and mixtures thereof, and/or

- a solvent, preferably selected from the group consisting of water, ether, aromatic alcohol, benzyl alcohol, dialkyl diester, alkyl glycols and mixtures thereof.

The quaternary ammonium compound is preferably of formula (III) N R⁴R⁵R⁶R⁷X^~, in which R⁴ and R⁵ independently of one another represent alkyl radicals containing 1 to 3 carbon atoms or benzyl radicals or halogenated or alkylated benzyl radicals, R⁶ and R⁷ independently of one another represent alkyl or benzyl radicals or halogenated or alkylated benzyl radicals containing 6 to 22 carbon atoms, and X^" is an anion, preferably a halide such as chloride and bromide, or a carboxylate. Preferably, the anion is chloride.

Preferred examples of quaternary ammonium compounds include benzalkonium chloride, benzethonium chloride, behentrimonium chloride, cetrimonium chloride, dimethyldidecylammoniunchloride, and/or dimethyl-dioctylammonium chloride and derivatives thereof. Most preferred the quaternary ammonium compounds include

benzalkonium chloride also known as alkyldimethylbenzylammonium chloride.

Advantageously, quaternary ammonium compounds show a disinfecting capacity which will further improve the disinfectant effect.

Preferably, enzymes are selected from the group consisting of lipases, amylases, proteases particularly a serine endopeptidase, and mixtures thereof. More preferably, the enzyme is one or more of the commercially available serine endoproteases. The enzymes provide the benefit to break down adherent proteinaceous materials typically found on instruments after use, into forms that are readily dispersed into a water-based wash solution. Proteins left in or on instruments that cannot be mechanically scrubbed may prevent cleaning or disinfecting agents to perform in an efficient way. Preferred enzyme stabilizers are a boron compound selected from the group consisting of boronic acid, boric acid, borate, polyborate and combinations thereof. Also preferred enzyme stabilizers are glycols.

Preferred copper (II) salts include copper(II) sulphate, copper(II) hydroxide, and copper(II) chloride. Preferred copper complex ions include gluconate and other organic acids. Especially preferred is copper (II) gluconate.

A preferred alkyl glycol is butyldiglycol. A preferred glycol is propylenglycol.

Further, the products may be used as a first part of a two-part system together with a second part comprising an oxygen composition selected from the group consisting of hydrogen peroxide, organic peroxides, peracids, peracetic acid, performic acid, percitric acid, perglycolic acid, perlactic acid, perbenzoic acid, active halogen compounds, hypochlorous acid, chlorine dioxide, peroctanoic acid, and mixtures thereof. Preferably the oxygen composition is selected from the group consisting of hydrogen peroxide, peracetic acid, peroctanoic acid, and mixtures thereof.

The products and/or a composition containing the products may be applied to a wide variety of surfaces, especially as compared to conventional prion treatment such as strong alkaline or hydroxide. Accordingly, in preferred embodiments the surfaces are of metal or alloys which are susceptible to alkaline corrosion.

The substrate preferably may include any hard surface. In some embodiments, the surfaces are potentially contaminated 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.

Surfaces that especially may benefit from cleaning and/or disinfecting include surfaces of instruments employed in medical, dental, and pharmaceutical procedures. Surfaces in need of effectively removing or substantially reducing the prion contamination include surgical instruments, and surfaces of hospital rooms, especially surfaces in operating rooms.

Preferred instruments are implements employed in human or veterinary patient contact during the practice of surgery, medicine, ophthalmology, dentistry, podiatry, pathology for e.g., therapeutic, diagnostic and/or research purposes. Examples include surgical instruments, e.g., scalpels, probes, clamps, etc., endoscopes, operating room or dental handpieces, ventilation tubes, and the like. Surgical instruments and equipment inevitably may come into contact with prion contamination while being employed in operations on infected humans or animals. Further surfaces that especially may benefit from cleaning and/or disinfection include equipment used in butchery such as cutlery, containers which contact animal parts contaminated with prions or other meat contact surfaces. Further examples include the treatment of rooms, cages, and the like used for housing animals known or suspected to be infected with prions, and the decontamination of BSE infected areas, including

slaughterhouses, food processing facilities, and the like.

A further aspect of the present invention relates to a liquid concentrate composition for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents such as prions comprising at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) R'-NH- (CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with compounds corresponding to formula (II), R²-0-CO-(CH₂)₂-CH(NH₂)-COOH, in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, in an amount in the range of > 20 wt.-% to < 50 wt.-%, preferably in the range of > 25 wt.-% to < 45 wt.-%, more preferably in the range of > 30 wt.-% to < 40 wt.-%, based on the weight of the composition.

The liquid concentrate composition according to the invention preferably contains glucoprotamin®, N,N-bis(3-aminopropyl)-laurylamine, N-dodecyl-l,3-propanediamine, N- cocos-l,3-propanediamine and mixtures thereof.

The liquid concentrate composition preferably has a pH in the range of > 7 to < 11, more preferably in the range of > 8 to < 10.

The liquid concentrate composition may include additional functional and/or additive ingredients that increase the effectiveness of the composition or provide an additional functional benefit.

In preferred embodiments the composition comprises an alcohol, preferably selected from the group consisting of alcohols comprising a CI to CIO alkyl group that is straight or branched, substituted or non-substituted, and/or aromatic alcohols. Preferably, the alcohol is soluble or miscible with water. Preferably, the alcohol is selected from the group consisting of ethanol, 1-propanol, and 2-propanol.

The aromatic alcohol preferably is a phenoxy alcohol, or a phenyl monoglycol ether of an oligoglycol with up to 20 ethylene oxide units. Suitable phenoxy alcohols are 2-phenoxy ethanol, l-phenoxy-2-propanol, 2-phenoxy-l-propanol, 3-phenoxy-l-propanol, l-phenoxy-2- butanol, 2-phenoxy-l-butanol, or a mixture of two or more of these compounds. Preferred are phenoxy ethanol, phenoxy propanol and phenyl oligoglycol ether with 2 to 8, in particular 4 to 6 and especially 4 ethylene oxide units. It is particularly preferred if the aromatic alcohol is selected from the group consisting of benzyl alcohol, 2-phenoxyethanol, 1-phenoxypropanol, and mixtures thereof. Also suitable are phenyl oligoglycol ethers with preferably 4 ethylene oxide units, which have the advantage to be miscible with water. Further, phenyl oligoglycol ethers are effective in cleaning.

The alcohol preferably is comprised in an amount in the range of > 1 wt.-% to < 80 wt.-%, preferably in the range of > 20 wt.-% to < 60 wt.-%, more preferably in the range of > 20 wt.- % to < 40 wt.-%, based on the weight of the composition.

In preferred embodiments, the composition comprises cationic and/or non-ionic surfactants. The non- ionic surfactants preferably are selected from the group consisting of fatty alcohol ethoxylates and alkylpolyglycosides.

The cationic and/or non-ionic surfactants preferably is comprised in an amount in the range of > 1 wt.-% to < 20 wt.-%, more preferably in the range of > 2 wt.-% to < 15 wt.-%, even more preferably in the range of > 4 wt.-% to < 12 wt.-%, based on the weight of the composition.

The liquid concentrate composition may also include further compounds and/or additional functional ingredients, depending on the specific application that increase the effectiveness of the composition or provide an additional functional benefit. Suitable ingredients include antimicrobial agents, heavy metal salts, enzymes, and additives.

The further compounds and/or additional functional ingredients may provide an improved cleaning and/or disinfectant efficacy.

The liquid concentrate composition in preferred embodiments comprises one or more compounds selected from: - an antimicrobial agent, preferably selected from the group consisting of an oxidizing or non-oxidizing compound selected from the group consisting of quaternary ammonium compounds particularly benzalkonium chloride, phenolic derivatives, and mixtures thereof;

Advantageously, such a composition comprising further antimicrobial agents, preferably quaternary ammonium compounds, can provide complete elimination or at least substantially reduction of microbial or viral populations on a surface or object.

The quaternary ammonium compound is preferably of formula (III) N R⁴R⁵R⁶R⁷X^~, in which R⁴ and R⁵ independently of one another represent alkyl radicals containing 1 to 3 carbon atoms or benzyl radicals or halogenated or alkylated benzyl radicals, R⁶ and R⁷ independently of one another represent alkyl or benzyl radicals or halogenated or alkylated benzyl radicals containing 6 to 22 carbon atoms, and X^" is an anion, preferably a halide such as chloride and bromide, or a carboxylate. Preferably, the anion is chloride. Preferred examples of quaternary ammonium compounds include benzalkonium chloride, benzethonium chloride, behentrimonium chloride, cetrimonium chloride, dimethyldidecyl ammonium chloride, and/or dimethyl-dioctylammonium chloride and derivatives thereof. Most preferred the quaternary ammonium compounds includes benzalkonium chloride also known as alkyldimethylbenzylammonium chloride.

Advantageously, quaternary ammonium compounds show a good disinfecting capacity which will further improve the disinfectant effect of the composition.

The quaternary ammonium compound can be comprised in an amount in the range of > 5 wt.- % to < 50 wt.-%, preferably in the range of > 5 wt.-% to < 30 wt.-%, more preferably in the range of > 10 wt.-% to < 30 wt.-%, even more preferably in the range of > 10 wt.-% to < 25 wt.-%, based on the weight of the composition.

The enzyme preferably is comprised in an amount in the range of > 0.001 wt.-% to < 10 wt- %, more preferably in the range of > 0.001 wt.-% to < 5 wt.-%, even more preferably in the range of > 0.01 wt.-% to < 5 wt.-%, based on the weight of the composition. Preferred copper (II) salts include copper(II) sulphate, copper(II) hydroxide, and copper(II) chloride. Preferred copper complex ions include gluconate and other organic acids. Especially preferred is copper (II) gluconate.

The heavy metal salt preferably is comprised in an amount in the range of > 0.001 wt.-% to < 10 wt.-%, more preferably in the range of > 0.01 wt.-% to < 5 wt.-%, even more preferably in the range of > 0.01 wt.-% to < 1 wt.-%, based on the weight of the composition. Alternatively, the heavy metal salt preferably can be comprised in an amount in the range of > 0.001 wt.-% to < 1 wt.-%, based on the weight of the composition.

Suitable additives are detergents, surfactants, builders, sequestering agents, defoamers, thickening agents, gelling agents, complexing agents, clear rinsing agents, corrosion inhibitors, perfumes, and mixtures thereof.

The concentrate composition preferably further comprises defoamers. Such an anti-foam component preferredly is a silicone-based anti-foam component.

Builders and complexing agents help boost the cleaning performance of surfactant systems and are typically associated with materials that are capable of complexing with polyvalent cations, such as calcium and magnesium. Thickening agents such as alkyl celluloses, alkoxy celluloses, xanthan gum, guar gum, and polyacrylamide derivatives, such as the polymer of 2- acrylamido-2-methylpropane sulfonic acid, hectorite, synthetic hectorite, magnesium aluminum silicate, bentonite, montmorillonite, and amorphous silicon dioxide can affect retention, flow and lubricity. Additives can be comprised in an amount in the range of > 0.01 wt.-% to < 30 wt.-%, preferably in the range of > 0.1 wt.-% to < 29 wt.-%, more preferably in the range of > 0.1 wt.-% to < 20 wt.-%, even more preferably in the range of > 0.1 wt.-% to < 5 wt.-%, based on the weight of the composition.

In other embodiments the liquid concentrate composition is a first part of a two-part system comprising a second part comprising an oxygen composition which comprises an oxygen component selected from the group consisting of hydrogen peroxide, organic peroxides, peracids, peracetic acid, performic acid, percitric acid, perglycolic acid, perlactic acid, perbenzoic acid, active halogen compounds, hypochlorous acid, chlorine dioxide, peroctanoic acid, and mixtures thereof. A preferred oxygen component is selected from the group consisting of hydrogen peroxide, peracetic acid, peroctanoic acid, and mixtures thereof.

Advantageously, a combination of the liquid concentrate composition and an oxygen composition can have a synergistic effect on efficacy against microorganisms, without rendering both components ineffective. Such additive efficacy against microorganisms will further improve the disinfecting effect of the composition. The liquid concentrate composition and an oxygen composition at least are compatible for a limited period of time. Specifically, a combination has been found to maintain antimicrobial efficacy for a time period of at least 15 minutes, preferably for at least about 60 minutes, but up to 4 hours after mixture.

The oxygen composition preferably is comprised in an amount in the range of > 1 wt.-% to < 30 wt.-%, more preferably in the range of > 3 wt.-% to < 20 wt.-%, even more preferably in the range of > 4 wt.-% to < 15 wt.-%, based on the total weight of the composition.

In a preferred embodiment, the liquid concentrate composition for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents such as prions comprises, based on the weight of the concentrate composition: > 20 wt.-% to < 50 wt.-% of at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) R¹-NH-(CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 6 to 18, preferably 12 to 14, carbon atoms, with compounds corresponding to formula (II) R²-0-CO-(CH₂)₂-CH(NH₂)-COOH, in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms;

> 1 wt.-% to < 20 wt.-% cationic and/or non-ionic surfactants; and/or

> 0.1 wt.-% to < 29 wt.-% additives such as cleaning boosters, carriers, detergents, builders, sequestering agents, defoamers, foam inhibitors, thickening agents, gelling agents, complexing agents, clear rinsing agents, corrosion inhibitors, dyes, perfumes, and mixtures thereof.

In a further preferred embodiment, the liquid concentrate composition for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents such as prions comprises, based on the weight of the concentrate composition:

d) optional > 1 wt.-% to < 80 wt.-% alcohol selected from the group consisting of alcohols comprising a CI to CIO alkyl group that is straight or branched, substituted or non-substituted and/or aromatic alcohols;

e) optional > 5 wt.-% to < 30 wt.-% quaternary ammonium compounds of formula (V) N⁺R⁴R⁵R⁶R⁷X^", in which R⁴ and R⁵ independently of one another represent alkyl radicals containing 1 to 3 carbon atoms or benzyl radicals or halogenated or alkylated benzyl radicals, R⁶ and R⁷ independently of one another represent alkyl or benzyl radicals or halogenated or alkylated benzyl radicals containing 6 to 22 carbon atoms, and X^" is an anion; and/or

f) optional > 0.001 wt.-% to < 1 wt.-% heavy metal salts, preferably selected from the group consisting of copper (II) salts, silver (I) salts, copper (II) complex ions, or silver (I) complex ions, and mixtures thereof. The term "liquid concentrate composition" refers to a composition that is diluted to form a cleaning composition which is used for cleaning and/or disinfecting and which also is called use composition. The concentrate is preferably a liquid. The cleaning or use composition refers to the composition that is applied to a surface to clean the surfaces from contamination with unconventional infectious agents such as prions.

It may be beneficial to dilute a concentrate to a use composition since a concentrate is often easier and less expensive to ship than the use composition. Further, a low amount of water contributes to the stabilization of the concentrate composition during storage.

A further aspect of the present invention relates to a cleaning and/or disinfecting composition for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents obtainable by diluting the concentrate composition according to the invention to form a use composition comprising the concentrate composition in the range of > 1 wt.-% to < 15 wt.-%, preferably in the range of > 2 wt.-% to < 8 wt.-%, more preferably in the range of > 3 wt.-% to < 6 wt.-%, based on the weight of the cleaning and/or disinfecting composition.

The concentrate composition preferably is diluted with water to a percentage ranging from about 1 wt.-% to about 15 wt.-% to yield the cleaning or use composition. Such a cleaning composition is effective in the reduction or elimination of hazardous prions.

The cleaning and/or disinfecting composition may be a liquid or may be formulated in the form of a thickened or gelled solution, or a foam. Thickened or gelled solutions and foams can provide a longer contact time.

Further, the cleaning and/or disinfecting composition according to the present invention has good efficacy over a broad temperature range, especially from 20°C to about 60 °C and shows good material compatibility. The cleaning composition is employable for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents such as prions especially for medical and surgical instruments, dental hand piece, and the like, for both human and veterinary practice. The cleaning composition is particularly useful for manual, mechanical and ultrasonic cleaning and disinfection of surgical instruments and endoscopes contaminated with unconventional infectious agents such as prions, especially instruments with anodic coating.

To be added to ultrasonic baths and to automatic washer, for cleaning more elaborate medical equipment, preferably a concentrate can also be readily used.

Further, the present invention provides a method of cleaning or pre-cleaning, disinfection or pre-disinfection of surfaces contaminated with unconventional infectious agents, especially medical, surgical, ophthalmo logical or dental instruments, or endoscopes.

A further aspect of the present invention relates to a method of cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents wherein the surface is treated with a cleaning and/or disinfecting composition containing at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine

corresponding to formula (I) R¹-NH-(CH₂)3-NH₂, in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with compounds corresponding to formula (II) R²-0-CO- (CH₂)₂-CH(NH₂)-COOH, in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms.

Preferably the method of cleaning and/or disinfecting surfaces contaminated with

unconventional infectious agents such as prions includes that the surface is treated with a cleaning and/or disinfecting composition obtainable from a liquid concentrate composition according to the invention. The cleaning and/or disinfecting composition may be applied to a surface in a variety of ways including wiping, immersing, flooding, spraying or foaming. Further, the method may be carried out either manually or in ultrasonic application or as automated application in washers.

Particularly, the cleaning and/or disinfecting composition according to the present invention can be used for automated application in washers at a temperature up to about 55°C to 60 °C. Further, the cleaning composition is particularly useful for manual cleaning of delicate instruments, for example by soaking or foaming methods.

Generally, the method may be performed by contacting the items with an effective amount of the cleaning composition according to the present invention as described above, for a sufficient time to reduce or eliminate hazardous unconventional infectious agents especially prions, and then removing the cleaning composition from said surfaces and instruments.

For a more complete understanding of the invention, the following example is given to illustrate some embodiment. This example and experiments are to be understood as illustrative and not limiting.

EXAMPLES

Example 1

Example 1 tested the effectiveness of glucoprotamin® against prions. For this example, a quantitative evaluation of prion inactivation by glucoprotamin® 50, an active ingredient used for disinfectants manufactured by Ecolab which contains 50 wt.-% of products obtained by reacting cocospropylene-l,3-diamine with glutamic acid in a solution of butyldiglycol and water, was tested against the mouse-adapted C506M3 scrapie strain. Prion strain

The mouse-adapted scrapie strain C506M3 was obtained in C5781/6 brain inoculated mice after 150 to 180 days. 10 ml of test homogenate were prepared by mixing 3.4 g of infectious brains with 4.7 ml of 5 % glucose solution for injection, and added to 2 ml of foetal bovine serum. 25 μΐ of the homogenate were aseptically deposited in 13 mm diameter sterilized glass tubes, then dried and congelated at -80°C.

Serial decimal dilutions of 10^"1 to 10^~7 from brain homogenate glass tubes were carried out, and an end point titration was performed by intracerebral inoculations of 20 μΐ per mouse into 6-week-old mice, 8 mice per dilution.

Table 1 : Titration of C506M3 infectivity in untreated brain-homogenates

Table 1 shows the number of deaths of the total number of 8 inoculated mice for each dilution. It can be taken from table 1 that a dilution of 10^"5 of the injection preparation causes one death of a total number of 8 inoculated mice. Glucoprotamin® 50 water solutions were tested at concentrations of 9 g/1 and 18 g/1

Glucoprotamin® 50. The contact time was 60 minutes at 20°C. 2 ml of each dilution of the product were added to 3 infectious glass tubes. After the contact, inoculated glass tubes were immediately rinsed three times with 2 ml of sterile water for injection. A control was done with 2 non-infectious brain homogenate glass tubes.

After exposure, the liquid-treated rinsed tubes of 3 tests and 2 controls were recovered by 200 μΐ of 5 % glucose solution for injection. After scratching using the pipette tip, the suspension were heated at 80°C for 10 minutes, and aliquots were inoculated intra-cerebrally into 6 week-old-mice, in order to detect residual infectivity.

For each tested dilution of glucoprotamin® 50, the 3 test-preparations of 20 μΐ were inoculated into 8 mice. 24 mice per test were on control. For negative controls 8 mice were injected with untreated non-infectious preparations, to verify the absence of laboratory contamination. Rinsing controls were performed by injection of treated non-infectious preparations on 4 mice, to verify the elimination of the disinfectant.

Assay animals were regularly monitored for clinical neurological disorder signs, the survival times were noted or the mice were euthanized at least at the end of the study after 14 months. Scrapie was confirmed by detection of the pathological prion protein, using immunoblot techniques in brain by western blot. The survival time was the interval between the first inoculation and the death. Table 2: Effect of various Glucoprotamin® concentrations on prion infectivity

As can be seen in Table 2, a 18 g/1 glucoprotamin® solution is able to reduce the tested preparation by an evaluated factor of 10⁵, as is 3/24 compared to 1/8.

These experiments show that tested after 420 days, 18 g/1 glucoprotamin® solutions were effective against the test preparations, reducing the infectivity by a factor equal to or higher than 10⁵ which was the infectivity titer of C506M3 in brain homogenates, being the first dilution for 1 death/8 mice.

Consequently, these experiments show that glucoprotamin® can be effectively used for the disinfection of surfaces contaminated with unconventional infectious agents such as prions.

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 at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I)

R²-0-CO-(CH₂)₂-CH(NH₂)-COOH (_Π) in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms,

for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents.

2. The use according to claim 1, characterized in that the alkyl propylenediamine corresponding to formula (I) is reacted with compounds corresponding to formula (II) in a molar ratio of 1 : 1 to 1 :2 at temperatures of 60°C to 175°C.

3. The use according to claim 1 or 2, characterized in that the at least one active substance is used for cleaning and/or disinfection comprised in a composition, wherein the composition comprises the at least one active substance in the range of > 0.001 wt.-% to < 50 wt.-%, preferably in the range of > 20 wt.-% to < 30 wt.-%, more preferably of 25 wt.-%, based on the weight of the composition.

4. The use according to any of claims 1 to 3, characterized in that the at least one active substance is used for cleaning and/or disinfection comprised in a composition having a pH in the range of > 7 to < 11, preferably in the range of > 8 to < 10.

5. The use according to any of claims 1 to 4, characterized in that the surfaces are of metal or alloys which are susceptible to alkaline corrosion.

6. The use according to any of claims 1 to 5, characterized in that the surfaces are potentially contaminated 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.

7. A liquid concentrate composition for the cleaning and/or disinfecting of surfaces contaminated with unconventional infectious agents comprising at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I)

R²-0-CO-(CH₂)₂-CH(NH₂)-COOH (_Π) in which R² is hydrogen or an alkyl group containing 1 to 4 carbon atoms, in an amount in the range of > 20 wt.-% to < 50 wt.-%, preferably in the range of > 25 wt.-% to < 45 wt.-%, more preferably in the range of > 30 wt.-% to < 40 wt.-%, based on the weight of the composition.

8. The liquid concentrate composition according to claim 7, characterized in that the composition has a pH in the range of > 7 to < 11, preferably in the range of > 8 to < 10.

9. The liquid concentrate composition according to claim 7 or 8, characterized in that the composition comprises an alcohol, preferably selected from the group consisting of alcohols comprising a CI to CIO alkyl group that is straight or branched, substituted or non- substituted, and/or aromatic alcohols, wherein the alcohol preferably is comprised in an amount in the range of > 1 wt.-% to < 80 wt.-%, preferably in the range of > 20 wt.-% to < 60 wt.-%, more preferably in the range of > 20 wt.-% to < 40 wt.-%, based on the weight of the composition.

10. The liquid concentrate composition according to any of claims 7 to 9 characterized in that the composition comprises cationic and/or non-ionic surfactants, wherein the non-ionic surfactants preferably are selected from the group consisting of fatty alcohol ethoxylates and alkylpolyglycosides.

11. The liquid concentrate composition according to any of claims 7 to 10 characterized in that the composition further comprises one or more compounds selected from:

- a heavy metal salt, preferably selected from the group consisting of copper (II) salts, silver (I) salts, copper (II) complex ions, and silver (I) complex ions; - an enzyme, preferably selected from the group consisting of lipases, amylases, proteases particularly a serine endopeptidase, and mixtures thereof;

12. The liquid concentrate composition according to any of claims 7 to 11 characterized in that the composition is a first part of a two-part system comprising a second part comprising an oxygen composition which comprises an oxygen component selected from the group consisting of hydrogen peroxide, organic peroxides, peracids, peracetic acid, performic acid, percitric acid, perglycolic acid, perlactic acid, perbenzoic acid, active halogen compounds, hypochlorous acid, chlorine dioxide, peroctanoic acid, and mixtures thereof.

13. A cleaning and/or disinfecting composition for the cleaning and/or disinfection of surfaces contaminated with unconventional infectious agents obtainable by diluting the concentrate composition according to any of claims 7 to 12 to form a use composition comprising the concentrate composition in the range of > 1 wt.-% to < 15 wt.-%, preferably in the range of > 2 wt.-% to < 8 wt.-%, more preferably in the range of > 3 wt.-% to < 6 wt.-%, based on the weight of the cleaning and/or disinfecting composition.

14. A method of cleaning and/or disinfecting surfaces contaminated with unconventional infectious agents characterized in that the surface is treated with a cleaning and/or disinfecting composition containing at least one active substance from the group of products which are obtainable by reacting an alkyl propylenediamine corresponding to formula (I) R¹-NH-(CH₂)₃-NH₂ (I) in which R¹ is a linear alkyl group containing 6 to 18 carbon atoms, with compounds corresponding to formula (II)

15. The method of cleaning and/or disinfecting surfaces contaminated with

unconventional infectious agents according to claim 14 characterized in that the surface is treated with a cleaning and/or disinfecting composition obtainable from a liquid concentrate composition according to any of claims 7 to 12.