FIELD OF THE INVENTION

The present invention is concerned with providing stable compositions which can be used to treat water through the release of an active chlorine ion. The present invention is also concerned with a convenient and advantageous method of providing treated water (e.g. , drinking water) .

BACKGROUND OF THE INVENTION

Various derivatives of allantoin, such as for example 5-ureido-hydantoin and 2,5-dioxo-4-imidazoli- dinyl urea, have long been known and have been used for various applications. U.S. Patent No. RE 32,848 des¬ cribes the reaction product of allantoin with formalde¬ hyde, which exhibits bactericidal activity, and is effective against molds and yeasts, and which can be used as a conservation additive for substances susceptible to microbial contamination. U.S. Patent No. 3,830,908 describes a mixture of allantoin as a carrier for a bactericidal component, (e.g. Ag citro- allantoinate) or fungicidal component, (e.g. Zn-sulf- hydroxy-allantoinate) . This medium is disclosed as being used to treat the surface of splints, bandages and packing material to ensure sterility. German Patent No. DD 158,357 describes a protective medium for cosmetic emulsions containing allantoin and ascorbic acid.

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British Patent No. GB 2,108,840 describes derivatives of allantoin with bactericidal and bacteriostatic activity for the treatment of illnesses and disorders of the skin. Anti-inflammatory activity (Japanese Patent No. 59-055874; anti-tumor activity (Japanese Patent No. 57- 050969; and bleaching and disinfectant activity (U.S. Patent No. 4,654,424 and U.S. Patent No. 4,560,766) exhibited by allantoin derivatives have also been described. Allantoin has been used in medicine to facilitate the healing of wounds. Allantoin itself is also used as a component of cosmetics because of its biocompatibility.

The halogenated derivatives of substituted hydantoin are generally known for their disinfectant activity, chlorination and bleaching properties, poly¬ merization catalytic properties, and industrial deodorant properties. Commercially manufactured substances of this type include, for example, 1,3- dichloro-5,5-di-methylhydantoin (Halane) . Allantoin itself is known for its ability to regenerate damaged tissues in poorly healing, festering wounds. Its chlorinated derivatives have not yet been described in the literature.

Glycoluril compounds are known compounds which have been used in connection with disinfecting and bacteri¬ cidal applications as disclosed by U.S. Patent No. 3,019,160, U.S. Patent No. 3,161,521, and U.S. Patent No. 3,019,075, as well as, Great Britain Patent No. 831,853. Chloroglycoluril compounds have been disclosed as being useful as chlorine liberators in ointments as disclosed by U.S. Patent No. 2,638,434 and as anti- vesicants as disclosed by U.S. Patent No. 2,649,389, U.S. Patent No. 2,934,451, and U.S. Patent No. 2,988,526. Additional processes for preparing halogenated glycoluril compounds are disclosed by U.S. Patent No. 3,147,259 and U.S. Patent No. 3,345,371.

TIT TE H ET

Natural surface waters are utilized to an increasing degree to cover increasing needs for drinking and service water, and humic substances represent a major portion of the organic pollution in natural surface waters.

Depending on their physical and chemical properties, humic acids can be classified as humus acids (humic acids, fulvoacids, hymatomelanic acids) , humines and humus coal. (Kalavska D. , Holoubek J. : Analyza vόd. Alfa, Bratislava, 1989) Of the humic substances in natural surface waters, only humic acids are important in water treatment as humines and humus coal are insoluble in water and not hydrolyzable. Since humic acids differ in their solubility in acidic media, basic media and in ethanol, this property can be utilized in the separation of the individual groups. For example, humic and hymatomelanic acids can be precipitated from acidified solutions as dark precipitates, while fulvoacids remain in solution. In contrast to humic acids, hymatomelanic acids are soluble in ethanol.

In practice, it is difficult to isolate the individual groups of humic substances as they do not have precisely defined structures, and moreover, their composition depends on the nature of the natural materials that were decomposed in their formation. Even so, the results of research work have indicated that humic substances are high molecular weight polycyclic compounds containing aromatic and aliphatic components. Hypothetical structural formulae for humic acids and fulvoacids have been given in the literature. (Kalavska D. , Holoubek J.: Analyza vόd. Alfa, Bratislava, 1989; 2aδek L. : Huminove latky v pfirozenych vodach a mo≥nosti jejich odstraήovani. Works and studies VUV, Prague, 1976) The presence of a number of functional groups (carboxylic, hydroxylic - phenolic and alcoholic, methoxylic, quinoid) affects their physical and chemical properties. The -C00H and -OH groups lead to acidity.

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an exchange capacity and weakly polar character, while the presence of guinoid structures together with hydroxyls leads to redox properties.

Humic substances are present in natural surface waters in concentrations from about 10 mg/1 to about 120 mg/1, with extreme values (backwaters) of up to about 500 mg/1. (Kalavska D. , Holoubek J. : Analyza vόd. Alfa, Bratislava, 1989; sorm J. , 2aδek L. , Vyu≥iti spektroskopichy metod k hodnoceni organickeho zneδistδni pfi procesech ύpravy vody. Publication VUV, No. 16, SZN, Prague 1987) A concentration of 100 mg/1 is considered to be harmful to man. Humic substances are not directly toxic but their presence can considerably decrease the appearance and taste properties of water. The presence of humic substances cannot only effect drinking water but also service waters (e.g., in the textile industry) where products could be damaged by the presence of such substances. An increase in corrosive properties is also associated with the presence of such substances.

The presence of humic substances is also very detrimental in water treatment processes. In commonly empi /ed procedures, increased contents of these substances can lead to a number of difficulties (break- through of humic substances and coagulants, high corrosiveness in the treated water and a decrease in water quality in water mains) . (Vagner V. , Janda V. , Havel L. , Rudovsky J. : Vodni hospodafstvi No. 12, 315 (1989)). However, the greatest danger to health comes from the formation of trihalogen-methanes during chlorination.

Harmful compounds can appear in water treatment in the presence of humic substances not only through the action of chlorine, but also through the action of chlorine dioxide and ozone. (Havlik B. , Hanusova J.: Vodni hospodafstvi No. 4, 85 (1989)). The reaction between humic acids and chlorine primarily leads to the

SUBSTITUTESHEET

formation of chloroform, while mono-, di-, and tri- chloroacetoni-triles and cyanobutanic acids have also been found. Chloropicrin has even been found in alkaline medium in the presence of nitrites. Ozcnation of humic acids leads to splitting of the polymer chains to yield aliphatic acids, ketones and aromatic compounds such as tetra-, penta- and hexachlorobenzene. Ozonation can also lead to release of substances formerly bonded in humate complexes, (e.g., some pesticides and heavy metals) .

Consequently, considerable research work has been directed to a search for an effective and economically reasonable procedure for treating humic waters. This subject was studied in detail by 2aδek. ( _a_ek L. : Huminove latky v pfirozenych vodach a mo≥nosti jejich odstraftovani. Works and studies VUV, Prague, 1976; sorm J. , 2aδek L. , Vyu≥iti spektroskopichy etod k hodnoceni organickeho zneδistδni pfi procesech ύpravy vody. Publication VUV, No. 16, SZN, Prague 1987; 2aδek L. : Vodni hospodafstvi No. 1, 5 (1989)). He carried out complex studies of humic substances in water, evaluated separation processes and studied optimization of the technology of clarification with ferric and aluminum compounds. (2aδek L. : Huminove latky v pfirozenych vodach a moέnosti jejich odstraftovani. Works and studies VUV, Prague, 1976; sorm J., Eaδek L. , Vyu2iti spektroskopichy metod k hodnoceni organickeho zneδisteni pfi procesech ύpravy vody. Publication VUV, No. 1 6 , SZN, Prague 1987. Vagner et al (Vagner V., Janda V., Havel L. , Rudovsky J. : Vodni hospodafstvi No. 12, 315 (1989)) considered the use of active carbon for the sorption of humic substances and measured the sorption capacity of several types of active carbon. He measured the organic substance content as the chemical oxygen demand, C0D _Mn , in an oxidation by permanganate. Mention is also made of the removal of humic substances using ion-exchangers XAD1, XAD7, XAD8 (Kalavska D. , Holoubek

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J.: Analyza vόd. Alfa, Bratislava, 1989) and XAD4 (Havlik B. , Hanusova J. : Vodni hospodafstvi No. 4, 85 (1989)) or ion-exchangers based on DEAE cellulose (Kalavska D. , Holoubek J.: Analyza vόd. Alfa, Bratislava, 1989) . Tested inorganic sorbents included aluminum oxide, silica gel and calcium carbonate (Kalavska D. , Holoubek J.: Analyza vόd. Alfa, Bratislava, 1989) .

SUMMARY OF THE INVENTION The present invention provides advantageous compositions which can be used to readily convert a quantity of untreated water into sanitized water which is suitable for drinking or other potable water uses. The compositions possess the ability to release an active chlorine ion in an aqueous environment and yet remain stable until used for their intended purpose. Exemplary of such compositions, but not limited thereto, are water sanitation tablets such as described in the Detailed Description Section hereof. The present invention also provides advantageous water treatment compositions which not only release an active chlorine ion in aqueous environments, but which also contain activated carbon for the absorption of humic substances in the waters treated with the inventive compositions. Advantageously, the active carbon is impregnated with a metal containing ion (e.g. Fe) so as to maximize the absorption of such humic substances.

The water treatment compositions of the present invention contain one of the following chlorinated allantoin or glycoluril derivatives of Formula I or II, respectively.

SUBSTITUTE SHEET

In Formula (I) , R ₁ and R ₂ , which can be identical or different, denote chlorine or hydrogen atoms, an alkyl group with 1-5 carbon atoms or a phenyl group, wherein at least one of these substituents is chlorine; R ₂ , R ₄ and R ₅ , which can be identical or different, denote chlorine or hydrogen atoms, an alkyl group with 1-5 carbon atoms or a phenyl group; and R ₆ denotes a hydrogen atom, an alkyl group with 1-5 carbon atoms or a phenyl group.

In Formula (II), R ¹ , R ² , R ³ and R ⁴ are the same or different, and denote chlorine or hydrogen atoms, with the proviso that at least one of R ¹ -R ⁴ is chlorine.

The compositions of the present invention contain low residual amounts of moisture therein, and advantageously remain stable prior to their introduction into an aqueous environment.

The present invention is also concerned with a method of providing potable water, which comprises treating water with one or more of the present inventive compositions, as well as a water treatment kit for carrying out this method.

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DETAILED DESCRIPTION OF THE INVENTION

The following Detailed Description is not limiting to the present inventive discovery. Instead, the following description is provided as an aid to those desiring to practice the present invention, since it discloses preferred and advantageous ways in which the present invention can be practiced. It should at all times be understood that minor changes and/or variations can be made in the inventive processes and compositions herein described without departing from the spirit or scope of the present inventive discovery. In this respect, such changes and variations are considered to be those that would be generally and/or readily understood by those of ordinary skill in the art. The inventors' ability to prepare the present inventive water treatment compositions results from their ability to produce compositions containing low residual amounts of moisture therein (less than about 2 to 3% w/w) . This is because the release of an active chlorine ion from a Formula I or II compound requires one of two initiators. One of these is moisture (or water) , the other is heat (temperatures above about 60°C) . As such, if either one of these conditions is reached prematurely, there can occur a premature release of an active chlorine ion from the present inventive water treatment compositions.

In order to insure that the present inventive compositions maintain a residual amount of moisture therein of below about 2 to 3% w/w, certain procedures should be utilized. First, each component utilized in the present inventive compositions should be tested for moisture (e.g. , gravimetrical analysis) , and once the moisture thereof is ascertained, the same component should be dried (if needed) to a moisture content below about 0.2 to 0.3% w/w and thereafter be placed in a relatively moisture free environment. Exemplary of such

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a moisture free environment is a desiccator containing a suitable desiccant, or an environmentally controlled room containing extremely low amounts of moisture therein (e.g., the air therein containing less than 1% w/w moisture) . Moreover, when preparing the present inventive compositions, it may be necessary to take pre¬ cautions such as protecting ingredients from moisture inherently present in the preparer's exhaled breaths (typically containing 80% w/w moisture) . Nonetheless, the present inventive compositions, if prepared under suitable conditions, will contain less than about 2 to 3% w/w moisture.

In order to insure that the present inventive compositions contain residual amounts of moisture less than 2 to 3% w/w, the production of the present inventive compositions and packaging thereof should occur under extremely low humidity or moisture conditions. Moreover, the packaged compositions themselves must be capable of remaining moisture free for prolonged periods of time, prior to their intended use. It is fully envisioned that those of ordinary skill in the art will readily recognize procedures which are applicable to the preparation of the present inventive compositions without being unduly burdensome. The use of such techniques to control the moisture content of the present inventive compositions is fully encompassed hereby.

As noted previously, heat can destabilize the Formula I and II compounds used herein (at a temperature above about 60°C) . Thus, it is suggested that temperatures above about 60°C not be utilized in preparing the present inventive compositions whenever a Formula I or II compound is present therein, since such elevated temperatures can easily cause the release of an active chlorine ion. Even so, preparation of a suitable anhydrous vehicle may utilize elevated temperatures, if

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thereafter, the vehicle is allowed to cool before com¬ bining a Formula I or II compound therewith.

As indicated in the Background Section hereof, a reduction in the level of humic substances in water treatment is often highly desirable. Thus, in addition to the presence of a Formula I or II compound, the present inventive compositions may also optionally contain activated carbon(s) for the absorption of humic substances occurring in a water sample. Such activated carbon may be impregnated with a metal ion (e.g., Fe ⁺³ ) , if so desired.

The inventors hereof have discovered that certain ion impregnated activated carbons are extremely efficient and valuable in removing humic substances from water samples. For example, activated carbons impregnated with an ion such as Fe ⁺³ in an amount of about 0.5 to 15% w/w based on the weight of the final absorbent can effectively and easily be used to remove humic substances from a water sample. Activated carbons and ion-impregnated activated carbons when utilized in the compositions herein described are preferably in a powdered or granular form. However, activated carbons can be spatially separate from the present inventive compositions and still be used in the present inventive methods. Moreover, the inventive water treatment kits herein provided can advantageously contain a spatially separate activated carbon component, if so desired. When an activated carbon component is spatially separate from the compositions herein provided, it is thought preferable that it should exist in the form of a fabric, a fleece, or in a granular form in a tea-bag like configuration. Such forms would allow waters to be effectively treated for humic substances while being easily removed from the water after treatment. Filter pads containing activated carbons can also be utilized if so desired. In such an instance, one would recirculate a water sample through

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an activated carbon filter, until an acceptable level of humic substances occurred in the sample.

As an example of preparing an ion impregnated activated carbon, the following illustrative preparation is provided wherein an activated carbon absorbent is impregnated with iron (3% w/w) .

Exemplary Ion-Impregnated Activated Carbon An activated carbon absorbent which is impregnated with iron was prepared by impregnation of a fraction of ground granulated active charcoal (AC) , size 100 - 160 microns by a spraying method. As an impregnation solution, the inventors used 0.4M Fe ₂ (SO ₃ • 9 H ₂ 0 in water at a volume equal to the sum of pores volume (1.0 1/kg) of the used AC. The formed substrate was kept at 30°C in a closed vessel in the incubator. After repeatedly washing the substrate with distilled water (approximately 40 1/kg) until no ferric ions (Fe ³⁺ ) were detected in the extract, the product was dried at 100°C. The content of iron (Fe) was 3.0 weight percent. The original active charcoal (AC) and the sorbent activated with ferric hydroxide (AC/Fe) were tested for adsorption isotherms, and for kinetics of adsorption of humic acids (HA) from an aqueous solution at 25°C. Test results obtained showed a significant and substantial increase of sorption capacity for the iron impregnated activated charcoal when compared with the original activated charcoal.

The compositions of the present invention are described herein as being stable prior to their intended use. This stability results primarily from the in¬ ventors' use of compositions which contain low amounts of residual moisture therein.

The compositions of the present invention are preferably formulated into a form which can be easily handled, and which may be used advantageously to practice the present inventive methods. Exemplary of

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such forms would include the following, a tablet, a capsule, a powder, a suspension or a dispersion. It only being necessary that whatever the form chosen, it should appropriately disinfect and/or sanitize the water, while at the same time remaining stable prior to its intended use. Nonetheless, it is thought preferable if the compositions of the present invention are manufactured into a tablet-like form.

Tablets are thought preferable in the present invention, due to their ease of manufacture, and their ease of use. In this regard, tablets could easily be prepared and placed in a format such as a blisterpack container, if so desired, which includes instructions for practicing the water sanitizing methods of the present invention. Similarly, tablets are thought preferable in the present invention, since those of ordinary skill in the art would realize that this would include the use of effervescent tablets.

If tablets are prepared according to the present invention, suitable excipients may be utilized therein. Exemplary of such excipients are fillers, lubricants, stabilizers, dyes, anti-caking agents, and the like. Nonetheless, whatever excipients are utilized in a given tablet formulation, the same should result in a tablet which remains stable until its intended use, and which produces the desired effect in the water to be treated. Of course, all excipients utilized in such a tablet formulation should be physiologically acceptable and should not adversely effect taste characteristics associated with the treated water.

Having described different inventive compositions which are encompassed hereby, the following exemplary formulations are provided as an aid to those skilled in the art practicing the present invention. Each of the following formulations can be utilized to prepare a tablet composition of the present invention. Similar

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formulations can also be utilized, if desired, to form powders or capsules utilizing readily known techniques.

EXEMPLARY TABLET COMPOSITIONS

The following water sanitation tablets were formulated and achieve the objects of the present invention, and are thus illustrative of compositions which are encompassed by the present invention, and processes for the manufacture thereof.

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TABLET FORMULATION #1 PER TABLET FORMULA

A. Chlorinated derivative of 10.00 mg

Formula I or II Magnesium carbonate (heavy) , 50.00 mg

PVP(polyvinylpyrrolidone-P-6755) .... 10.00 mg

Stearyl alcohol (powdered) 10.00 mg

B. Sodium bicarbonate 100.00 mg

Glycine 4.00 mg Calcium phosphate, monobasic 3.00 mσ

TOTAL TABLET WEIGHT = 187.00 mg

Mixing Directions for component A: 1. Gently blend the first two ingredients and pass through a #40 sieve. Let air dry in low humidity at least an hour.

2. Add the polyvinylpyrrolidone and blend gently.

3. Powder the stearyl alcohol (#40 sieve) and in- corporate into the mixture.

4. V-blend the mixture.

Mixing Directions for component B:

1. Blend all the ingredients of B.

2. Place in drying oven at about 40°C for about two to three hours, then let cool to room temp, in low humidity.

3. Pass through #20 sieve and V-blend with component A mixture.

The resulting mixture of components A and B is thereafter tableted IN A LOW HUMIDITY area.

SUBSTITUTE SHEET

TABLET FORMULATION #2

PER TABLET FORMULA

A. Chlorinated derivative of 10.00 mg

Formula I or II Magnesium carbonate (heavy) 50.00 mg

PVP(polyvinylpyrrolidone-P-6755) .... 10.00 mg

Magnesium stearate 10.00 mg

Sodium lauryl sulfate 10.00 mg B. Sodium bicarbonate 100.00 mg

Glycine 4.00 mg

Calcium phosphate, monobasic 3.00 mg

TOTAL TABLET WEIGHT = 197.00 mg

Mixing Directions for component A:

1. Gently blend the first two ingredients and pass through a #40 sieve. Let air dry in low humidity at least an hour.

2. Add the polyvinylpyrrolidone and blend gently. 3. Add the magnesium stearate and sod. laur. sulfate (#40 sieve) and incorporate into the mixture. 4. V-blend the mixture.

Mixing Directions for component B: 1. Blend all the ingredients of B.

2. Place in drying oven at about 40°C for about two to three hours, then let cool to room temp, in low humidity.

3. Pass through #20 sieve and V-blend with component A mixture.

The resulting mixture of components A and B is thereafter tableted IN A LOW HUMIDITY area.

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TABLET FORMULATION *3

PER TABLET FORMULA

A.

Sodium bicarbonate 100.00 mg

Mannitol powder 40.00 mg

Binder solution (wt. contribution).... 46.00 mg PVP(polyvinylpyrrolidone-P-6755) 30.00 mg

Magnesium carbonate (heavy) 30.00 mg

B.

Chlorinated derivative of 10.00 mg

Formula I or II Impregnated active carbon 15.00 mg

Stearic acid 10.00 mg

Magnesium stearate 10.00 mg

Sodium lauryl sulfate 7.00 mg

Glycine 7.00 mg TOTAL TABLET WEIGHT = 305.00 mg

Mixing Directions for component A:

1. Gently blend the component A ingredients making a wet granulation using the binder solution and sieve #20.

2. Dry in oven at 50°C for about two hours.

3. Sieve #20 the dry granulation. (May rework fines if necessary) .

Mixing Directions for component B: 1. Mix the stearic acid, magnesium stearate, sodium lauryl sulfate and the glycine.

2. Add to this mixture the impregnated active carbon and mix well.

3. Add the chlorinated derivative of Formula I or II to this mixture and mix well.

4. Add this mixture (B) to the granulation (A)and V-blend the final m .ture.

Tablet at this stage IN LOW HUMIDITY area using 9/16 standard concave punch/die. Thereafter, preferably strip-wrap package in foil lined air-tight wrap.

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BINDER SOLUTION FORMULATION FOR ADDITION TO TABLET FORMULATION

Per Tablet Amounts:

Acacia powder, U.S.P 12.000 mg

Gelatin 34.000 mg

Distilled water q.s. and 0.157 L

WEIGHT CONTRIBUTION PER TABLET = 46.0 mg

The compounds of Formulas I and II encompassed hereby were tested for their disinfectant properties and may be prepared as follows.

Disinfectant Properties of Formula I Compounds

The chlorinated derivatives of allantoin encompassed by Formula I hereof have a high and instantaneous oxidative disinfectant effect and thus can be expected to act as bactericides and virocides.

The bactericidal effectiveness of the chlorinated derivatives of allantoin were determined by inhibition tests of agar plates. For illustration, the testing of 1,3-dichloroallantoin together with the comparative standard "RLA", a complex of sodium chlorite with citric acid (a chlorite solution acidified with citric acid at the instant of testing) is described.

Test I - effectiveness against Staphylococcus aureus Test II - effectiveness against Escherichia coli Test III - time dependence of the effectiveness Text IV - stability in solution Test V - effectiveness in nonaqueous medium

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Test I

A disk of filtration paper with a diameter of 6 mm applied to an agar plate with inoculated culture of Staph. aureus and 20 μl of the test sample pipetted to the plate in a concentration of 1 mg and 0.5 mg (in 20 μl) . Size of inhibited zone determined after 1 day after incubation at 37°C.

concentration size of inhibited zone (mm) mg/plate d ^a Δr ^b

1,3-dichloroallantoin

RLA streptomycin 0.01 16 5

^a d = diameter of the inhibited zone. ^b Δr = radius of the inhibited zone - radius of the filter paper disk (3 mm) .

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Test II

Filter paper disk with a diameter of 6 mm applied to an agar plate with inoculated culture E. coli and 20 μl of the test sample pipetted to the plate at the given concentrations. Size of the inhibited zone determined after 1 day incubation at 37°C.

concentration size of inhibited zone (mm) mg/plate d ^a Δr ^b

1,3-dichloroallantoin

RLA

^a d = diameter of the inhibited zone. ^b Δr = radius of the inhibited zone - radius of the filter paper disk (3 mm) .

SUBSTITUTE SHEET

Test III

Filter paper disk saturated with 10 μl of standard solution of the substance (25 mg/ml) applied to an agar plate with a culture of E. coli, repeatedly at regular time intervals transferred to a new agar plate.

time diameter of the inhibited zone (cm)

1,2-dichloroallantoin

RLA

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Test IV

10 μl of standard solution of the substance (25 mg/ml) applied to a filter paper disk and effectiveness tested at regular intervals. Results indicate the stability of the test solution stored in a sealed test tube at laboratory temperature for 200 hours.

time diameter of the inhibited zone (cm)

1,3-dichloroallantoin

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Test V

100 mg of anhydrous paste (PEG, cetyl alcohol) containing 1% of the test substance applied to a 6mm plastic disk and the coated side applied to an agar plate inoculated with 10 ⁷ E. coli. Incubated at 37°C; size of inhibited zone determined after 18 hours of incubation on the next day.

1, 3-dichloroallantoin - zone size 5.5 and 6.0 cm

(duplicate determination) 100 mg of anhydrous paste was also incorporated in a 1 x 1cm ² porous film (melt blown) , applied to an agar plate inoculated with E. coli and incubated at 37°C. After 18 hours of incubation, the 1, 3-dichloroallantoin prevents the growth of E. coli over the whole agar plate with a diameter of 7 cm.

Based on experimental tests carried out, the inventors have determined that of the allantoin derivatives of Formula I, the best results are obtained for 1,3-di- chloroallantoin, for which it was found that (a) optimal bactericidal activity is exhibited in an amount of 200/μg/6 mm disk;

(b) on contact with agar gel, all the active chlorine is released within 2 hours;

(c) it is active in the form of a 1% ointment (in anhydrous base - PEG 4000 47.5%, PEG 400 47.5%, cetyl alcohol 5%) ; and

(d) it is most effective incorporated in a "meltblow" film with a porosity of < 1 micron.

Preparation of Formula I Compounds The preparation of various allantoin derivatives encompassed by Formula I is described below.

Generally, the chlorinated derivatives of allantoin of the general Formula I, in which R.,-R ₆ have the above designations, may be prepared by first providing derivatives of allantoin of the general Formula IA:

SUBSTITUTE SHEET

in which R_, and R ₂ are the same or different and each denote a hydrogen atom, an alkyl group with 1-5 carbon atoms or a phenyl group wherein at least one of the substituents R ₁ and R ₂ is a hydrogen atom; and R ₃ ~R ₆ are the same or different and each denote a hydrogen atom, an alkyl group with 1-5 carbon atoms or a phenyl group. These compounds of Formula IA are allowed to react in a suitable solvent and with cooling in an ice bath with chlorine, optionally in the presence of a sodium hydrogen carbonate, wherein the reaction product is obtained either by filtration under vacuum, washing with ice water and drying or by removal of the organic salt by filtration, evaporation of the solvent and drying. Varying the conditions and/or starting materials appropriately allows for the production of the various chlorinated allantoin compounds of Formula I as illustrated by the examples below.

Example l

Preparation of 1,3-dichloroallantoin (R, = R ₂ = CI, R ₃ , R ₄ , R^ , R ₆ = H) .

1.4 g (8.77 mol) of allantoin is mixed in 50 ml dichloromethane with 3 g of sodium hydrogen carbonate with cooling in an ice bath, with introduction of 4 g of gaseous chlorine over 30 minutes. After completion of addition of chlorine, the reaction mixture is stirred for an additional 3 hours, the product is drawn off and washed with ice water until disappearance of a positive reaction for chlorine. The product is dried in the vacuum of a water pump at 45°C. The yield is 70-75% of

B TITUTESH ET

theoretical. The product contains 31.5% chlorine (theo¬ retical 31.23%). Melting point 119-120°C decomp.

IR^ - 3352, 1750, 1691, 1329, 1235, 1177, 1100, 500 cm ^"1

Example 2 Preparation of 3-chloroallantoin (R ₂ = Cl, R ₁ , R ₃ , R^, R _j , R ₆ = H) .

1.4 g (8.77 mmol) of allantoin is mixed in 25 ml water with cooling in an ice bath, with addition of 2 g of gaseous chlorine over 30 in. After completion of addition of chlorine, the reaction mixture is stirred for a further 1 hour, the product is drawn off and washed with ice water, followed by drying in the vacuum of a water pump at 45°C. The yield is 55% of theoretical. The product contains 18.3% chlorine (theoretical 18.41%). Melting point 155-157°C decomp.

IR _KBr - 3440, 3340, 3320, 3244, 3067, 1790, 1739, 1655, 1538, 1328, 1275, 1187, 1103, 590, 520 cm ^"1 .

Example 3

Preparation of l-chloro-3-methyl allantoin (R, = Cl, R ₂ = CH ₃ , R ₃ , R ₄ , R^ R ₆ = H) .

1.5 g (8.78 mmol) of 3-methylallantoin is mixed in 50 ml of dichloromethane with 1.5 g of sodium hydrogen carbonate with cooling in an ice bath. 2 g of gaseous chlorine is introduced over 30 min. and the mixture is stirred for a further 3 hours; the product is drawn off, washed thoroughly with ice water and dried at a temperature of 45°C in the vacuum of a water pump. The yield is 67% of theoretical. The product contains 17.7% chlorine (theoretical 17.16%). Melting point 170-172°C decomp.

I ,^ - 3308, 3232, 1716, 1544, 1473, 1305, 1094, 556 cm ^"1 .

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Example 4

Preparation of 1,3-chloro-5-methyl allantoin (R, = R ₂ = Cl, R ₆ = CH ₃ , R ₃ , R,, ₅ = H) .

0.5 g (2 ₌ 92 mmol) of 5-methyl allantoin is mixed in 15 ml of dichloromethane with 1 g of sodium hydrogen carbonate with cooling in an ice bath. 2 g of gaseous chlorine is added over 30 min. and the reaction mixture is stirred for a further 2.5 hours. The product is filtered, dichloromethane evaporated in vacuo on a rotating evaporator and the residue is dried at 45°C in the vacuum of a water pump. The yield is 71% of theoretical. The product contains 30.11% chlorine (theoretical 29.41%). Melting point 89-91°C decomp. IR^ - 3386, 1758, 1727, 1687, 1616, 1337, 1280, 1206, 1132 cm ^"1 .

Bactericidal Properties of Formula II Compounds

Dichloroglycoluril was supplied by Professor

Zahradnik as a white fine powder, forming few globules.

A solution containing 50 mg of dichloroglycoluril per ml water was prepared. At this concentration, most of the substance did not dissolve. The addition of ethanol (up to 15%) only minimally affected the solubility. Therefore, the suspension was pipetted, as shown below, into 1 liter of distilled water, contaminated with known counts of E. coli culture.

The following dilutions of dichloroglycoluril were tested:

1. 50 ppm 3. 12.5 ppm

2. 25 ppm 4. 6.25 ppm It was found that the original suspension of the dichloroglycoluril drug once transferred into 1 liter of the contaminated water formed a clear solution within 1- 2 minutes.

Samples of 100 μl were collected at times 0, 5, 10 and 15 minutes of incubation, placed in sterile Petri dishes with agar, the solution spread with round glass

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(bottom of a test tube) over the whole 10 cm diameter area of the agar. Samples were incubated for 14 hours at 37°C. The number of growing colonies forming units were counted.

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Results are shown in the following Table.

Sample ppm

50

25

12.5

6.5

Conclusion

At 6.25 ppm final concentration of dichloroglyco¬ luril there is 100% kill in 5 minutes.

The substance is very effective as a bactericidal agent and does not require an activator. It is a convenient drug to use. The sporadic E. coli growth shown at 10 min. at 12.5 or 6.25 ppm dichloroglycoluril reflects external contamination of the plate by spreading the 100 μl over the agar plate.

Preparation of Formula II Compounds

The glycoluril derivatives of Formula II may be prepared according to conventional processes known in the art, such as those disclosed by U.S. Patent No. 3,019,160, U.S. Patent No. 3,161,521 and U.S. Patent No.

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3,019,075, which are all expressly incorporated herein by reference.

While the tablets and other compositions provided herein remain stable prior to their introduction into an aqueous environment, it is thought preferred that the formulations used to prepare such compositions, and moreover, the compositions themselves be maintained and stored under low humidity conditions. In the case of tablet composition, it is thought preferred that the tablets be provided in a container which can maintain the composition in a low humidity environment. For example, the tablets could be provided in a hu idically- sealed container such as in a blisterpack arrangement, or even in a bottle type container in combination with a desiccant packet, etc. The ability to manufacture and thereafter store tablets and similar compositions under low humidity conditions is readily understood by those skilled in the art; thus such considerations do not limit the present discovery.

Water Treatment Kit

Another embodiment of the present invention is that of a water treatment kit which generally includes a water treatment composition containing less than about 2-3% w/w residual moisture therein constituting an effective water disinfecting or sanitizing amount of a compound of Formula I or II, as described above, and a container for storing the water treatment composition in a low humidity environment. The water treatment kit may further optionally include an activated carbon component or ion-impregnated activated carbon component which may each be optionally spatially separated from the water treatment composition for combination therewith at a predetermined time. The kit may further optionally contain instructions for producing potable water by employing the water treatment composition.

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The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims. Each of the publications and patents referred to herein above is expressly incorporated herein by reference in its entirety.

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