WO2007135163A1

WO2007135163A1 - Use of poly(hexamethylene biguanide)hydrochloride as an antiviral agent

Info

Publication number: WO2007135163A1
Application number: PCT/EP2007/054973
Authority: WO
Inventors: Niklaus J. LÜTHI; Peter Stutte; Walter Bender
Original assignee: Sanitized Ag
Priority date: 2006-05-23
Filing date: 2007-05-23
Publication date: 2007-11-29

Abstract

The invention relates to the use of poly(hexamethylene biguanide)hydrochloride as an antiviral agent, in particular in the production or treatment of a polymer or textile article. The invention also relates to an article which has been treated with antiviral agent and to a method for the production of such an article. The article can be, for example, a textile or a plastic, in particular, a polyurethane.

Description

Sanitized AG May 23, 2007

SAN64634PC IB / YES / jhl

USE OF POLY (HEXAMETHYLENE BIGUANIDE) HYDROCHLORIDE AS ANTIVIRAL AGENT

The invention relates to the use of poly (hexamethylene biguanide) hydrochloride as an antiviral agent and to the preparation of various articles equipped with poly (hexamethylene biguanide).

The effects of a variety of agents against bacteria and other microorganisms such as microfungi or algae are well known and have been used technically in part for decades for a large number of articles on a large scale. Protection against the fouling of various everyday items, constructions, products and intermediates for industrial use, such as numerous aqueous products or intermediates, by microorganisms can often be ensured by known means.

The list of active ingredients and products made from them is long. As a source, please refer to Annex 1 of European Community Regulation no. 1048/2005 (dated 9.07.2005) and to the biocide lists of the Environmental Protection Agency in the USA, where such substances and formulations are included.

To name a few biocidal active substances as examples:

The family of isothiazolinones with the frequently used active compounds 1,2-benzisothiazol-3-one (CAS 2634-33-5), N-butyl-1,2-benzisothiazol-3-one, 4,5-dichloro-2-n octyl-4-isothiazolin-3-one (CAS: 64359-81-5), 2-methyl-4-isothiazolin-3-one (CAS: 2682-20-4) alone or in admixture with 5-chloro-2 -methyl-4-isothiazolin-3-one (CAS: 26172-55-4) or 2-n-octyl-4-isothiazolin-3-one (CAS: 26530-20-1); the group of pyrithiones, inter alia, with the representatives with the common names sodium pyrithione (CAS: 3811-73-2) or zinc pyrithione (CAS: 13463-41-7) or the last-mentioned example 2,4,4'-trichlor - 2'-Hydroxydipheny lether with the trivial name trichlosan (CAS: 3380-34-5). Also known are agents for disinfecting against all major germs and pathogens, including against viruses. This applies to the surface disinfection and the disinfection of equipment.

In addition to thermal methods for combating viruses, there are also chemical methods. For example, The Robert Koch Institute publishes a list of the tested procedures and approved disinfectants (see website of the Robert Koch Institute). Here are also a few examples called: formaldehyde, phenol compounds and peroxides.

All of these chemicals are characterized by the fact that they are intended to be used in liquid form, usually in solution, and to achieve a rapidly achieved complete kill of all germs and deactivation of viruses, but not to permanently protect articles against occupancy by active viruses or by to reach germinable microorganisms.

Viruses do not have their own metabolism and can not independently proliferate outside of host cells. Therefore, their control can not be carried out with the same methods and mechanisms as with the other microorganisms, where in the metabolism can be intervened so that the microorganisms can not reproduce or die.

However, viruses can only be deactivated. Depending on the structure of the virus, there are two fundamentally different types. Envelopeless viruses that consist of a genome, DNA or RNA, and a capsid, and viruses that still have a membrane envelope in addition to the genome and the capsid, and that are usually much larger than the non-enveloped viruses. Known is the fact that has already been found in textbooks and encyclopedias that viruses without shell are particularly difficult to deactivate, since the central point of attack for reagents, which is the membrane envelope is not present.

It was therefore the object to develop a product and / or formulations that makes a durable antiviral equipment, possibly in combination with antimicrobial effect, of everyday objects and articles in the manufacturing process technically possible. For this purpose, such substances come into consideration, which can already be incorporated in the industrial manufacturing process of such goods. However, this requires that the chemical and physical properties of such substances should allow this. This means, for example, that such materials should not be volatile and that they are chemically stable enough to survive the incorporation process and storage of the finished article until use.

Researchers and literature have searched for such active ingredients that are in principle suitable for being incorporated into textiles and plastics, and at the same time are effective against viruses. It has been found, for example, that bradophen, a quaternary aromatic ammonium compound (benzoxonium chloride), which is used among other things for the disinfection in animal husbandry, is classified as virucidal against large viruses.

WO 2006/029255 describes the use of numerous biocidal products which can be used for the disinfection of mucous membranes in mammals. These products are said to act against bacteria, as evidenced in the experimental part, but also against viruses that have been erroneously counted and subsumed into microorganisms. However, no test results are presented.

Some of the enumerated substances fulfill the technical conditions in order to be able to fulfill the task basically as permanently antiviral acting product on fabrics and in plastics, in particular in polyurethane foams. Some of these are already used today as antibacterial and / or antifungal agents for this purpose. Of these, the following products may be mentioned as examples: silver, silver salts and silver complexes, benzalkonium salt, quaternary ammonium compounds with C8 to C18 alkyl chains, polyhexamethylene biguanide (CAS: 27083-27-8). It would also be possible to consider compounds such as cetylpyridinium chloride or chlorhexidine, both of which are likewise enumerated in WO 2006/029255.

WO 2004/037115 discloses a medical dressing with an antimicrobial agent. The bandage consists of a fabric that combines three layers. The

Tissue may be impregnated or coated with the antimicrobial agent. The antimicrobial agent may also be polyhexamethylene biguanide. In this document however, the use of polyhexamethylene biguanide alone as an antiviral agent is neither described nor suggested.

WO 2004/087226 describes an antimicrobial substrate in which a combination of an organosilicon-quaternary ammonium salt with a cationic polymer, in particular polyhexamethylene biguanide, adheres to at least a part of its surface. WO 2004/087226 neither describes nor suggests the use of polyhexamethylene biguanide alone as an antiviral agent.

FR-A-2 769 228 describes a composition impregnated with a chemical composition. The entire composition has several properties (including virucidal properties). It contains polyhexamethylene biguanide. Also in this document, the use of polyhexamethylene biguanide alone as an antiviral agent is neither described nor suggested.

An object of the present invention is to achieve in a simple and cost effective manner a durable antiviral finish of various materials, such as plastics or textiles.

It has now been found that poly (hexamethylene biguanide) hydrochloride can be used as an antiviral agent. The invention relates to the use of poly (hexamethylene biguanide) hydrochloride as antiviral agent. Such an agent works even with viruses that have no shell and are very difficult to combat.

According to a first embodiment of the invention, the poly (hexamethylene biguanide) hydrochloride is incorporated in the finishing of an article.

According to a second embodiment of the invention, the poly (hexamethylene biguanide) hydrochloride is incorporated in the preparation of an article.

The invention also relates to an antiviral article (for example a plastic product or a textile) which is provided with poly (hexamethylene biguanide) hydrochloride or which contains poly (hexamethylene biguanide) hydrochloride. Another object of the invention is a method for producing an antiviral article, wherein the article is equipped with poly (hexamethylene biguanide) hydrochloride.

Another object of the invention is a process for the preparation of an antiviral Kunstoffes, wherein poly (hexamethylene biguanide) is present in the reaction mixture.

The antiviral active ingredient poly (hexamethylene biguanide) hydrochloride is usually in an amount of 0.1 to 10 wt.%, Preferably 0.1 to 5 wt.% And in particular 0.15 to 4 wt.% (Based on the equipped or offset object).

These and other features, objects and advantages of the present invention will be apparent from the following detailed description of the invention.

Equipment of textiles and PU foams

By "equipment" it is understood hereinafter that the antiviral agent is applied to at least part of the surface of the article.

Textiles, in particular of cotton, but also of other, preferably cellulose-containing fibers can be equipped with various active ingredients in different concentrations. The equipment can z. B. done in a padding process. The textile pattern can then z. B. dried on a tenter.

As an example, the antiviral agent can be used on a fabric of about 200 g / m ² , ie at 2 to 4% by weight, based on the weight of the textile. These concentrations of the drug are generally higher than the concentrations used for antimicrobial equipments (ie, 0.4 to 0.5% by weight).

The antiviral agent can also be used to finish plastics, such as polyurethane foam. Another object of the invention is a plastic composition containing poly (hexamethylene biguanide) as an antiviral component and additionally at least one polymer (P) selected from the group of polyurethanes, polycarbonates, polyester carbonates, polyesters and polyamides. Also, the production of a plastic composition and the use of a plastic composition containing poly (hexamethylenbiguanid) for the production of moldings and the moldings themselves, made of a poly (hexamethylenbiguanid) -containing plastic mass, are the subject of the invention. The suitable polyurethanes, polycarbonates or polyester carbonates may, for. B. be linear or branched. Branched products are preferably obtained by incorporation of from 0.05 to 2.0 mol%, based on the sum of the diphenols used, of trifunctional or more than trifunctional compounds, for example those having three or more than three phenolic OH groups ,

The polycarbonates or polyester carbonates may also contain aromatically bonded halogen, preferably bromine and / or chlorine. Preferably, however, they are halogen-free. Suitable polyesters are preferably polyalkylene terephthalates, i. Reaction products of aromatic dicarboxylic acids or their reactive derivatives (e.g., dimethyl esters or anhydrides) and aliphatic, cycloaliphatic or arylaliphatic diols, and mixtures of such reaction products. Preferred polyalkylene terephthalates can be prepared from terephthalic acids (or their reactive derivatives) and aliphatic or cycloaliphatic diols having 2 to 10 carbon atoms by known methods (see Kunststoff-Handbuch, Vol. VIII. P. 695 ff, Carl Hanser Verlag, Munich 1973).

Suitable polyamides are known homopolyamides, copolyamides and mixtures of these polyamides. They may be partially crystalline and / or amorphous polyamides. Polycrystalline polyamides which are suitable are polyamide-6, polyamide-6,6, mixtures and corresponding copolymers of these components. Also suitable are partially crystalline polyamides, the acid component of which wholly or partly consists of terephthalic acid and / or isophthalic acid and / or suberic acid and / or sebacic acid and / or azelaic acid and / or adipic acid and / or cyclohexanedicarboxylic acid, whose diamine component is wholly or partly from m- and / or p-xylylenediamine and / or hexamethylenediamine and / or 2,2,4-trimethylhexamethylenediamine and / or 2,2,4-trimethylhexamethylenediamine and / or isophoronediamine and their composition is known. Also to be mentioned are polyamides which are wholly or partly made of lactams having 7-12 carbon atoms in the ring, optionally with the concomitant use of one or more of the abovementioned starting components. Copolymers obtained by polycondensation of several monomers are also suitable for being provided with poly (hexamethylene biguanide).

In addition to the antiviral active ingredient poly (hexamethylene biguanide) as auxiliary and processing additives, various additives (D) in amounts of from 0 to 10% by weight, preferably 0 to 5% by weight, may be added to the synthetic compositions according to the invention. Suitable additives (D) are all those substances which are usually used for processing or finishing the polymers. Mention may be made, for example, of dyes, pigments, colorants, antistatic agents, antioxidants, stabilizers for improving the thermal stability, stabilizers for increasing the light stability, stabilizers for increasing the hydrolysis resistance and the resistance to chemicals, anti-thermal decomposition agents and especially lubricants / lubricants 1, which are suitable for the Production of moldings or moldings are appropriate. The dosing of these other additives can be done at any stage of the manufacturing process, but preferably at an early stage, to take advantage of the stabilizing effects (or other specific effects) of the additive at an early stage. With regard to other customary auxiliaries and additives, e.g. on "Plastics Additives Handbook", Ed. Gächter and Muller, 4th edition, Hanser Publ., Munich, 1996, referenced.

From the experiments carried out, surprisingly, poly (hexamethylene biguanide) hydrochloride (PHMB) has proven to be a substance which is very active against viruses. The PHMB is not a polymer in the strict sense. It is an oligomer with a degree of polymerization of from 4 to 12 units, but usually from 4 to 7 units of hexamethylene biguanide.

The product is marketed as hydrochloride in aqueous solution, usually with about 20% by weight of active ingredient, and also as a powdered active ingredient.

Production of PU foams

The production of PU foams is known and is described, for example, in "Ullmanns Enzyklopadie der technischen Chemie", 4th Edition, Volume 19, pages 301 to 341. The formulations of Th. Goldschmidt AG, for example in of the technical product documentation of the catalyst "Tegoamin 33" for the production of laboratory foams. In practice, a formulation in the range of about 20 wt .-% PHMB is particularly favorable because of the resulting viscosity. In principle, however, it is also possible to work with PHMB in any other concentration and even in powder form. Instead of polyethylene glycol, the polyol, both a polyether polyol and a polyester polyol used for the foam, or other organic solvents may be used.

The foam properties can also be changed very much by the choice of polyol, most significantly when changing from polyether polyol to polyester polyol, and of course also by the use of catalysts and other auxiliaries. Foam properties are z. As the density, the pore size, open and closed porous foam, etc. With the amount of water, the foam density can be adjusted. Thus, for example, it is also possible to work with an aqueous dissolved product, in particular if the amount of water is compensated for and the use concentration of the water present as solvent thus corresponds at most to the amount of water needed for the foam.

Preferably, then the water is added in the polyol stream before the Verschäumungskopf where often a static mixer ensures that the components are homogenized before as the last component then the isocyanate, often TDI, wherein other at least diisocyanates can also be used, is mixed, whereupon The formation of polyurethane foam starts immediately.

Examples

The invention is illustrated by the following examples wherein all percentages are expressed in weight percent.

A) Equipment of textiles

Experimental Example 1

With dimethyl-tetradecyl [3- (trimethoxysilyl) -propyl] ammonium chloride, 50% dissolved in methyltriglycol as the active ingredient formulation.

In tap water 25 g of drug formulation per liter are dissolved and this solution is then added to the padder chassis. The cotton fabric of 198 g / m ² is pulled through this bath and squeezed between the padder rolls so that the pick-up is 80%. This means that 2.0% drug formulation has been applied.

The wet textile is dried on the tenter for 2 minutes at 120 ⁰ C. As described, the experiment is carried out with 50 g of the active ingredient formulation per liter of water, so that a pattern with 4% of the active ingredient formulation is obtained.

Experimental Example 2

20 g of Bradophen are dissolved in 80 g of water. For the application, in each case 950 g of water are introduced, as a wetting agent is 0.3 g per liter of an ethoxylated fatty alcohol (eg.

B. Sandozin NRW manufacturer Clariant, Switzerland) was added and then 7 resp. 14 resp.

42 g of the Bradophenlösung stirred. The solution is in each case supplemented to 1000 g with water. These solutions are then as described in Example 1 by means of

Foulardverfahren applied.

With a pick-up of 71% patterns with 0.5, 1.0 resp. 3.0% of the solution, resulting in an active ingredient concentration of 1000, 2000 resp. 6000 ppm on the textile corresponds. Experimental Example 3

10 g of 3-iodo-2-propynyl butylcarbamate (IPBC) are dissolved in 60 g of isopropyl alcohol. 30 g of an ethoxylated fatty alcohol are added. From this formulation, as described above, 1, 2 resp. 5% applied, which in turn a drug concentration of 1000, 2000 resp. 6000 ppm on the textile corresponds.

Experimental Example 4

1, 2 resp. 5% of an aqueous dispersion containing 15% zinc pyrithione is applied as previously described by means of the padding process on cotton fabric and dried on the tenter.

example 1

From a 20% solution of poly (hexamethylene biguanide) hydrochloride (PHMB) in

Water is applied to cotton at concentrations of 1, 2 and 5%.

The active ingredient concentration is thus 2000, 4000 resp. 10000 ppm based on the weight of the finished textile.

The textiles obtained in Experimental Examples 1 to 3 and Example 1 are tested for their effectiveness against viruses (phages). Surprisingly, only the patterns equipped with PHMB showed a really good and above all fast action against viruses.

Experimental Example 4 - Equipment of PU Shapes

In this experiment foams are prepared based on Poletherpolyol and equipped with dimethyl-tetradecyl [3- (trimethoxysilyl) -propyl] ammonium chloride, 50% dissolved in methyltriglycol, wherein at the concentration of the formulated active ingredient up to 10% by mass of the polether polyol. The tests against viruses were negative.

Example 2 On the same basis as described in Experimental Example 4, PU foams were prepared and equipped with a product containing PHMB. The product was produced as follows:

30% poly (hexamethylene biguanide) hydrochloride, the powdered technically pure active ingredient, was taken up in 69% polyethylene glycol and treated with 1% Aerosil. The mixture was finely ground with a glass bead mill. The thus prepared disperse product was incorporated in the polyurethane foams as described below. A) Production of PU foams

Example 3

The following products were used for the production of a simply constructed laboratory foam

(the polyether polyol with the tertiary amine catalysts, stabilizers,

Plasticizer and water as blowing agent) together:

100.0 g of polyether polyol (Desmophen 7160 from Bayer)

0.2 g of dimethylbenzylamine (Desmorapid SO from Bayer)

0.1 g of bis (2-dimethylaminoethyl) ether in glycol (Niax Catalyst Al of

OSi Specialties Germany) 0.2 g 1,4-diazabicyclo- (2,2,2) -octane in dipropylene glycol (Dabco 33LV from Air Products)

1.0 g of polyether-modified polysiloxane (Tegostab B 3640 from Th. Goldschmidt)

3.5 g of water

2.5 g of the PHMB-containing ground mixture of Example 2. To this mixture are added at once with stirring

43.3 g of tolylene diisocyanate (TDI)

The foaming reaction starts immediately and you get a largely closed-pore PU foam. As described above, hand foams were made up to 10% of the PHMB formulation. This PHMB formulation was also prepared at various concentrations.

The tests against viruses (phages) were positive.

Claims

claims

1. Use of poly (hexamethylene biguanide) hydrochloride as antiviral agent.

2. Use according to claim 1, characterized in that the poly (hexamethylene biguanide) hydrochloride is incorporated as an antiviral agent in the finishing of an article.

3. Use according to claim 1 or 2, characterized in that the poly (hexamethylene biguanide) hydrochloride is incorporated as an antiviral agent in the equipment of an article in an amount of 0.1 to 5 wt .-%.

4. Use according to claim 1, characterized in that the poly (hexamethylene biguanide) hydrochloride is incorporated as an antiviral agent in the manufacture of an article.

5. Use according to claim 1 or 4, characterized in that the poly (hexamethylene biguanide) hydrochloride is incorporated as an antiviral agent in the preparation of an article in an amount of 0.1 to 5 wt .-%.

6. An antiviral finished article, characterized in that it is equipped with poly (hexamethylene biguanide) hydrochloride in an amount of 0.1 to 5 wt .-%.

7. Antiviral equipped article according to claim 5 or 6, characterized in that it is a textile.

8. A method of making an antivirally finished article, wherein the article is provided with poly (hexamethylene biguanide) hydrochloride.

9. An antiviral finished article, characterized in that it contains poly (hexamethylene biguanide) hydrochloride.

10. An antiviral finished article according to claim 9, characterized in that it contains poly (hexamethylene biguanide) hydrochloride in an amount of 0.1 to 5 wt .-%.

11. Antiviral equipped article according to claim 9 or 10, characterized in that it is a plastic.

12. Antiviral equipped article according to one of claims 9 to 11, characterized in that it consists largely of polyurethane.

13. A process for the preparation of an antivirally finished plastic, which comprises polymer

(Hexamethylenbiguanid) used in the reaction mixture with the monomers.