DE20211854U1 - Polymers with antibiotic, bioresistant and fungus-resistant properties - Google Patents

Description

GB

POLYMERS WITH ANTIBIOTIC, BIORESISTENT AND FUNGAL RESISTANT PROPERTIES

DESCRIPTION TECHNICAL AREA

This invention relates generally to the field of polymers and paints containing polymers, and more particularly to polymers having bioresistant and fungal resistant properties.

STATE OF THE ART
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The use of heavy metals in paints and marine coatings is prohibited in most industrialized countries. It is known that marine paints fail when attacked by microbes. Eventually the paint is completely destroyed. In the past, heavy metals were used in paints to prevent this attack. With the help of a polymer coating, this problem could be solved.

In addition, polymers are used in many applications that

antibiotic or antifungal properties, such as in medical equipment, contact lenses, plastic diapers, and numerous other applications. Covalently incorporating an antibiotic moiety into the main chain of the polymer that provides these properties would be of great benefit.

DESCRIPTION OF THE INVENTION

The present invention relates to a polymer containing an antibiotic moiety that is covalently linked into the main chain (backbone) of the polymer.

^ This moiety generally consists of a bromine atom and a nitro group (NO2),

that is, a bromonitro group which is linked to at least one carbon atom in the main chain of the polymer (the bromine atom and the nitro group on

J5 the same or different carbon atoms). The proportion can

in various levels from 5 ppm to 100%. The preferred proportion is approximately 1000 ppm. The invention therefore relates to polyurethane, polyurea, polyamide, polyester, polycarbonate, polyether, polysiloxane, epoxy, polyacrylic, polyacrylate, polyvinyl or all polymers in which the bromonitro group is linked to the main chain of the polymer. It is widely known that the reaction of an organic isocyanate (di- or polyisocyanate) with a polyol (polyalcohol) or polyol polymer in the presence of a suitable catalyst forms a polyurethane polymer. With this invention, a bromonitro-substitution diol or a bromonitro-substitution polyol is added to a standard polyol for polymer synthesis. The ratio of the substitution agent is selected to achieve the desired concentration of the proportion in the final polymer. A preferred diol for use is bromonitropropanediol or 2-bromo-2-nitropropane-1,3-diol (BNPD). This

&bull; · t <

particular diol is a solid material with varying degrees of solubility in other polyols and has proven antibiotic properties. In addition, BNPD has been shown not to have carcinogenic effects and is generally accepted for use in cosmetic products at levels up to 0.1%.

Since the active antibiotic component is directly covalently linked to the polymer main chain, such a ship paint is not leached out even under extreme conditions (repeated and long-term immersion). The component is also not sensitive to light and is not decomposed by daylight or mineral salts (such as the salt in sea water).

Because BNPD is a substitution diol, it forms a natural reactant for a polymeric chain with an isocyanate. As a diol, BNPD can be mixed directly with many polyols and other performance-enhancing additives. Mixing does not cause any problems or adverse reactions. In fact, it can be mixed in any ratio (as long as it is soluble) with any standard polyol used to synthesize polyurethane or other polymers. Furthermore, the bromine or nitro group does not appear to be able to form undesirable crosslinks in the resulting polymer.

Due to its proven properties and its beneficial effects on the environment and the human body, BNPD is considered the preferred antimicrobial agent. However, other diols or polyols containing bromine and nitro groups can also be linked to the same or different carbon atoms in the polymer's main chain to achieve an antibiotic or antifungal effect. The polyols used can be aliphatic, cycloaliphatic or, less preferably, aromatic diols or polyols to link to the bromonitro group, for example the isomeric butanediols, pentanediols, hexanediols, heptanediols, octanediols and nonanediols.

Tests with BNPD have shown that it is effective against various types of gram-positive and gram-negative bacteria at concentrations of 1-50 ppm. The minimum effective concentration is approximately 25 ppm. Other tests have shown that BNPD is resistant to fungi.

It is widely known that the combination of polyols or polyol prepolymers with organic isocyanate and other materials forms polymers and polymer resins (e.g. polyurethane). In particular, paints, including marine paints, contain high levels of polyurethane or other coating polymer materials. A generic urethane has the formula:

-2-

HI

R and R' can be identical or different.

A typical polyurethane polymer consists of chains in the form:

R-

or:

N I H

IS

&ogr; \

H H

R"

BNPD has the structure:

Br

HO

OH

NO ₀

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BNPD blended polyols can be combined with organic isocyanates to form polyurethane layers and polymers. This covalently bonds the active moiety into the polymer's main chain. BNPD and similar components containing the desired moiety can be blended with the polyol component of the known two-component systems. In the case of polyurethane, the bonded moiety resembles the following structure:

R-

'N

Br

&Lgr;,

NO,

N I H

^R1

In general terms:

oO

Br

NO,

Although BNPD is a preferred polyol starting point for linking the active moiety into a polymer, other materials containing a bromine atom and a nitro group can be used. Typically, the bromine and nitro group are linked to the same carbon atom. However, it is believed that a moiety in which the bromine and nitro group are not linked to the same carbon atom but are linked close together would have the desired properties. In addition, many other compounds are possible, such as bromonitromethanediol, bromonitroethanediol, bromonitrobutanediol. Bromonitromethane is known to be effective for the treatment of nematodes in soil (US Patent 5,013,762) and as a general biocide (US Patent 5,866,511). Bromonitro-methanediol and similar diols are believed to be equally effective.

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The invention also includes the use of a BNPD or BNPD equivalent as a term, as in the following example:

X

Br

^R1
NOo

R' can be CH ₂ OH, OH, CH ₃ or H (or any other combination).

Production methods for polyurethane paints are widely known. For example, US Patent 5,712,342 gives some examples of a process for producing a water dispersion of the polyurethane resin for paint with a prepolymer of approximately molecular weight 800 prepared from phenylpropane and various isocyanates such as isophorone diisocyanate, the result of which is polymers with average molecular weights of about 3200 for paints.

US Patent 3,936,409 describes a method for producing urea-urethane using organic solvents. The polymer is formed in solution by allowing the solvent to evaporate. The patent also describes instantaneous formation by using a spray nozzle.

The invention describes BNPD or a comparable hydrocarbon diol as a replacement agent which is dissolved into the polyols with or without the aid of a solvent or co-solvent to prepare the prepolymers to incorporate the active portion of the bromine and nitro in the range of 5 ppm to 100% into the main chain of the resulting polymer. The molecular weights of the resulting polymers can range from several thousand for paints to several hundred thousand for various other polymers.

US Patent 5,798,115 describes the incorporation of other antibiotic agents into the backbone of polymers used in medical applications. Specifically, dusocynate is reacted with an antibiotic agent such as ciprofloxacin to form polymeric materials. This produces a biodegradable polymer that releases antimicrobial substances as it is broken down by enzymes.

The invention results in polymers for the medical industry and for many other purposes, wherein the active part of the bromine and the nitro group are covalently linked to an aliphatic chain in the main chain of the polymer. The invention can be used wherever microbes are to be destroyed or decomposition caused by microbes or fungi is to be prevented.

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·

The invention applies to polyurethane, polyurea, polyacrylate, polymethacrylate, polyacrylic, polyester, polyamide, polyimide, polycarbonate, polyglycolic acid, polylactic acid, polyether, polysiloxane, epoxy adhesives and polymer structures of many other types.
5

Of particular interest are the polymers formed from polylactic acid (polylactic acid). These polymers have been known since 1932. Lactic acid is produced commercially by the fermentation of corn. The acid forms in two components called lactides, L-lactic acid and R-lactic acid. The physical properties of the final polymers can be controlled by the percentage of L and R isomers.

Polymers of polylactic acid are biodegradable. Since in many applications the natural rate of biodegradation is to be prevented or controlled, this invention also applies to these polymers. For example, lactic acid can be combined with BNPD to form a polylactic acid polymer on the principles of the invention. After the degradation of the water and the

Condensation polymerization forms a polymer with the bromonitro group. Fig. 1 shows the general steps of this process.
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Like polylactic acid, polyglycolic acid is also of particular interest. Polyglycolic acid is another biodegradable polymer that can benefit from the invention's control of its natural biodegradation rate.

The invention further relates to the group of polymethacrylate polymers used in contact lenses such as Polymacon. Fig. 2 shows the normal production method for Polymacon (trade mark) and two production methods for a modified Polymacon (trade mark) containing the desired proportion. Methacrylic acid or methyl methacrylate can be combined with the BNPD or a similar diol which is linked to a bromine and a nitro group on the same carbon atom. Generally, 2 moles of methacrylic acid are reacted with one mole of BNPD.

^ (however, equal molar amounts can also be used). The

" The resulting product can then be treated with ethylene glycol dimethacrylate (2-hydroxyethyl-

Methacrylate). Ethylene glycol monomethacrylate can also be added to achieve the desired properties.

US Patent 4,109,074 describes the basic process for forming such a hydrophilic polymer from the monomer. The basic polymer is prepared by heating a monomer such as ethylene glycol monomethacrylate for a specific time at a specific temperature. An initiator or catalyst is used for the initial process. This produces a polymer that is free of any toxic residues of an initiator or catalyst. This result is particularly desirable in medical products such as contact lenses.

Bacterial infection of contact lenses can lead to eye inflammation or even more serious infections that may cause blindness. Therefore, the production of a hydrophilic polymer that inhibits bacterial growth

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on the surface. The compound of the bromonitro group in this invention can produce a suitable polymer with bacterial resistant properties.

Figure 3 shows the treatment of BNPD with ammonium hydroxide to form a bromonitroamine or diamine, which can then be combined with an isocyanate compound such as TDI (toluene diisocyanate) to produce a polyurea. Figure 3 shows two possible structures of this type, one with two nitrogens linked to a carbonyl group and one with only one nitrogen.

Figure 4 shows the BNPD used to form a polyester, while Figure 5 shows a polyamide structure. Figure 6 shows the standard structure of the polyamide known as "Nylon Sixty-Six". The modified polyamide structure with the bromonitro group is clearly visible.

Fig. 6 shows a modified epoxy resin, and Fig. 7 shows a modified polyether and a modified polysiloxane. Both structural classes (polyether and polysiloxane) are within the scope of this invention.

The invention consists of a bromonitro moiety covalently linked into the backbone of various polymers to obtain bacterial or fungal resistant polymers or antibacterial/antifungal polymers of many different categories and types. The invention has many useful industrial applications.

EXAMPLES Example 1. Urethane:

6 g of BNPD was dissolved in 14 g of γ-butyrolactone (BLO) with vigorous mixing. Then 100 g of urethane grade castor oil was added, also with vigorous mixing. To this mixture 42 g of Bayer Mondur XP-744 aromatic isocyanate was added dropwise over twenty minutes and the whole was vigorously mixed for another 20 minutes. This prepolymer urethane of castor oil/BNPD shall be referred to as T-3IBR.

39 g of Chemoddities HP70 acrylic polyol, 0.12 g of Eagle Sales FB 100 Defoamer and 0.12 g of Eagle Sales FX-6 Slip-Aid were added to 15 g of T-3 IBR. This mixture shall be referred to as Component I.

To Component I, 11 g of Bayer Mondur XP-744 aromatic TIC isocyanate prepolymer and 10 g of BLO were added. The BLO is used to improve flow. A film sample produced an excellent urethane clear coat.

This acrylic urethane layer contained 0.85% BNPD.

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Example 2, acrylic resin

400 g (2 mol) of BNPD was combined with 344 g (4 mol) of methyl methacrylate and 150 g of xylene (reflux solvent) in a nitrogen-blanketed reaction vessel equipped with a water condenser/separator. The mixture was heated to 141°C. At this point, the water was released. The reaction vessel was maintained between 154° and 156°C until water loss was almost zero (3 hours and 7 minutes). The theoretical water loss was 72 g. 53 g was recovered and approximately 19 g of unreacted BNPD remained in the reaction vessel. The unreacted BNPD was removed. This conversion product shall be referred to as MAA/BNPD-002.

Then 360 g of xylene was added to a reaction vessel with shaking.

The vessel was blanketed with nitrogen and had a water condenser/separator and was heated to 141°C. A combination of 20 g of MAA/BNPD-002, 598 g of isobutyl methacrylate and 20 g of tert-butyl peroxybenzoate was then added dropwise over 3 hours. After this process was completed, the vessel was held at 142°C for 55 minutes. Then, 2 g of tert-butyl peroxybenzoate in 18 g of xylene was added and the mixture was held at 142°C for one hour. Then, another 2 g of tert-butyl peroxybenzoate in 18 g of xylene was added and the mixture was held at 142°C for one hour. Finally, 6 g of tert-butyl peroxybenzoate was added and the mixture was held at 142°C for one hour. After this, the vessel was removed from the heat to cool slowly.

The resulting polymer was the color of light straw with sufficient transparency to be used as a free coating. The material was stripped for confirmation. This resin contains 924 ppm BNPD.

Example 3. Polyester resin:

In a reaction vessel with nitrogen blanket and water condenser/separator, 400 g (2 mol) of BNPD, 616 g (4 mol) of 1,2-cyclohexanedicarboxlic anhydride (HHPA) and 150 g of xylene as reaction solvent were mixed with heating and shaking.

The container is heated to 162° C. At this point the reaction became exothermic and began to darken. The temperature was then reduced to 150° C and held at this temperature for one hour. 1162 g of a conversion product were obtained which was a strong, dark transparent

-8th-

liquid. This conversion product shall be referred to as MAA/BNPD-003.

In a reaction vessel with a nitrogen blanket and water condenser/separator, 416 g of neopentyl glycol (NPG) and 1.7 g of HHPA/BNPD-003 were heated under a slurry. The vessel was heated until the NPG began to melt. The stirrers were turned on and the temperature was maintained at 149°C for one hour and 38 minutes. Then 438 g of adipic acid [fatty acid] was added to the vessel and after two minutes the water began to be released.

The container was then kept between 156°C and 172°C for 3 hours until the release of water stopped and the temperature began to rise. A total of 108 g of water was released. The resulting resin had a brownish color and was very clear and transparent. It contained 896 ppm BNPD.

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Claims (10)

1. Polymer containing at least one bromonitro moiety of a formula


contains
wherein R and R' may be the same or different and are independently selected from the group consisting of linear or branched, saturated or unsaturated alkyl, alkenyl, alkylamine, NH or arylalkyl having 0 to 10 carbon atoms, and
wherein A and A' may be the same or different and are independently selected from the group consisting of [-(C=O)O-, - O(C=O)NH-, -HN(C=O)NH-, -O-, -OH, -CH ₂ OH, CH ₃ , -(C=O)OH, - O((C=O)CO) _m , -O((C=O)C=C) _m , -N(C=O)-, -O(C=O)C ₆ H ₄ (C=O)-, - O(C=O)D-, -OC(C-OH)D-, -(O-SiH ₂ ) _m -, -(CH ₂ ) _n -], and
wherein D consists of linear or branched, saturated or unsaturated alkyl, alkenyl, alkylamine or alkylaryl having 0 to 10 carbon atoms, and
where n and m represent numbers greater than 0. 2. Polymer according to claim 1, which contains at least one bromonitro moiety of a formula


contains,
wherein R and R' may be the same or different and are independently selected from the group consisting of [-(C=O)O-, - O(C=O)NH-, -HN(C=O)NH-, -O-, -OH, -CH ₂ OH, CH ₃ , -(C=O)OH, - O((C=O)CO) _m , -N(C=O)-, -(CH ₂ ) _n -], and
where n and m represent numbers greater than 0. 3. Polymer according to claim 1, characterized in that the polymer is a reaction product of a polyisocyanate with a polyamine prepolymer, and that the polyamine prepolymer contains the bromonitro moiety. 4. Polymer according to claim 1 or 2, characterized in that the polymer is a reaction product of a polyisocyanate with a polyol prepolymer, and that the polyol prepolymer contains the bromine moiety. 5. Polymer according to claim 1, characterized in that the polymer is a reaction product of a polyisocyanate with a polyamine, and that the polyamine contains the bromonitro moiety. 6. Polymer according to claim 1 or 2, characterized in that the polymer is a reaction product of a polyisocyanate with a polyol, and that the polyol contains the bromonitro moiety. 7. Polymer according to at least one of the preceding claims, characterized in that it contains the bromonitro content in the range between 5 ppm and 100%. 8. Polymer according to claim 7, characterized in that it contains the bromonitro content in the range 1000 ppm. 9. A polymer according to any one of the preceding claims, wherein the polymer is a resin in a layer. 10. The polymer of claim 9, wherein the polymer is a resin in a color.