KR100216957B1 - Antimicrobial dialdehyde composition and methods of use - Google Patents

Abstract

Stable solid or semisolid antimicrobial compositions are provided that include polyols such as sugar alcohols, carbohydrates such as sugars, and dialdehyde antimicrobials such as glutaraldehyde. The composition can be used to prevent, disinfect, sterilize, and preserve a contaminated surface or area. The composition may also be combined with an absorbent to produce a water absorbing antimicrobial composition used to sterilize and absorb biological leaks, such as body excretion leaks.

Description

[Name of invention]

Antimicrobial Dialdehyde Compositions and Their Uses

[Field of Invention]

The present invention relates generally to antimicrobial compositions, more particularly to stable antimicrobial compositions comprising adducts of dialdehyde antimicrobials and carbohydrates or polyols, which generate dialdehydes in active form upon addition of an aqueous liquid.

[Background of invention]

Antimicrobial compositions have been used so far and can be made of a variety of different chemical compounds. Sodium hypochlorite is an active ingredient in many household and hospital antimicrobial products. Bactericidal disinfectants usually suffer some loss of activity in the presence of organic substances, but hypochlorite loses particularly significant amounts of bactericidal activity due to the strong reactivity of hypochlorite and hypochlorite ions with organic substances generally present at the site of use. do. Therefore, in most cases it is necessary to first remove the organic contaminants in order to use the hypochlorite cleaning composition correctly. In addition, bactericidal disinfectants containing chlorine leave an unpleasant odor upon use.

Saturated C ₂ to C ₆ dialdehydes, such as glutaraldehyde, are known to be particularly effective as fungicides and do not have the disadvantages of other chemicals such as chlorine containing compounds. Dialdehydes and more particularly glutaraldehyde are used in hospitals, clinics and dental clinics for the sterilization of surgical instruments, catheters and the like, and if heat sterilization is inconvenient or impractical, for example when the instruments do not withstand heat. It has been used so far as a cold sterilant for other uses. Glutaraldehyde is most active as an antimicrobial agent above pH 7.

However, there are some disadvantages that limit or reduce the use of glutaraldehyde. Glutaaldehyde generates a severe tear gas and also has an unpleasant odor in the absorbed or blue phase. At high concentrations, ie at least about 50%, glutaraldehyde tends to homopolymerize and consequently lose its microbicidal effect. In addition, the tendency for glutaraldehyde to polymerize in the neutral to alkaline pH range with maximum antimicrobial activity is increased. Adjusting the pH of aqueous glutaraldehyde to pH 7 or above or evaporating water will cause glutaraldehyde to polymerize rapidly and lose antimicrobial activity. Thus, glutaraldehyde should be stored at a concentration of less than 50% in water, below pH 7, preferably below pH 5.

Commercially available glutaraldehyde is sold at 25 and 50 percent concentrations buffered on the acidic side, ie pH 3.1 to 4.5, to minimize homopolymerization on storage. However, the antimicrobial activity is poor in this pH range and should be adjusted to pH 7,5 to 8.5 before use. To overcome this problem, some manufacturers have developed a two part system, a first part as an active solution, typically 2 to 3% glutaraldehyde, buffered to pH 3.1 to 4.5, and a second part consisting of an activated alkalizer. It has been commercially available. However, the shelf life of the mixed solution is only a few weeks, so the two parts should be mixed just before use. This mixing increases the pH to an appropriate level and activates glutaraldehyde.

This two-part system is not only inconvenient to use but also puts an economic burden on the end consumer in terms of shipping costs for distributing the active solution. Due to the instability of aqueous glutaraldehyde above pH 7, the use of additional activators was inevitable.

Several attempts to formulate glutaraldehyde compositions continue from the past.

For example, US Pat. No. 3,968,250 to Boucher describes the preparation of 2% liquid glutaraldehyde compositions at pH 6-7.4 using sodium citrate and alcohols or diols to stabilize glutaraldehyde at pH 7. It is describing. Glutaraldehyde absorbed in a solid inert carrier and added to an anhydrous alkalizing agent is disclosed in Fellows, US Pat. No. 4,122,192, which has been demonstrated to have bactericidal and duster activity. In another attempt, Warner et al., US Pat. No. 4,448,977, focuses on the synthesis of mixtures of liquid acetals and acid (s) that release glutaraldehyde after water is added to the formulation, where glutaraldehyde The conversion takes several hours.

EP 046 375 typically discloses a formulation containing 20% diol and 2.5% glutaraldehyde with reduced odor. German Patent DE 3517548 describes a bactericidal disinfectant containing 18% of anhydrous adducts of glycerin and glutaraldehyde, absorbed onto a mixture of the surfactants sodium tripolyphosphate, sodium sulfate and sodium cumene sulfonate. . The adduct was formed after neutralizing glutaraldehyde to pH 6.5. Although the above patents seek to improve the stability of glutaraldehyde in various formulations, they do not provide a method or formulation that is practical and ensures the stability of the formulation.

British Patent No. 2,017,124 discloses the reaction of bifunctional aldehydes such as glutaraldehyde with polyols such as carbohydrate sugars or certain polyhydric alcohols in the presence of water to produce dendritic adducts. However, there is no mention or teaching regarding the use of such compositions as antimicrobial agents.

Public health administrators around the world have common knowledge about leaked fluids contaminated with pathogenic agents of the AIDS virus, hepatitis or other infectious diseases. National health authorities continue to recommend the use of sterile income compounds in leaking fluids that may be contaminated, such as blood, soil, manure and feces. These biological excretion leaks can occur in many places, including schools, hospitals, day care centers, airplanes, restaurants, day care centers, and the like.

For the removal of biological excretion, moisture absorbent compositions are useful that rapidly absorb liquids and convert them into semi-solid states that can be easily processed. Such moisture absorbent compositions are useful in hospitals and other places where biological leakages such as body fluids can occur. The importance of antimicrobial compositions that can be used on biological excretion to absorb before human reach and to disinfect around leaks is on the rise. Moisture absorbing compositions containing chlorine as bactericidal agents are known. However, moisture absorbent products containing antimicrobial dialdehydes, such as glutaraldehyde, are not currently available.

Accordingly, there is a continuing need for stable antimicrobial compositions that can be used in a variety of ways and capable of exhibiting antimicrobial action on demand.

[Summary of invention]

It has been found that solid dialdehyde hemiacetals with high melting points, i.e. above normal storage temperatures, have excellent stability and offer the possibility of never being possible with liquid glutaraldehyde or syrupy glutaraldehyde derivatives absorbed on the formulation flexibility and solid support. It was revealed by the present invention. The present invention includes a stabilizing effective amount of a polyhydroxy compound, such as an antimicrobial dialdehyde, a carbohydrate compound or a polyol compound, such as glutaraldehyde, which can be used to prevent, disinfect, sterilize or sterilize a contaminated surface. To a stable solid or semisolid antimicrobial composition. The carbohydrate compound is preferably a monosaccharide compound, a disaccharide compound, an oligosaccharide compound, a polysaccharide compound, a derivative thereof or a mixture thereof, and is used in an amount effective to make the composition into a stable solid form.

The polyol compound is preferably a sugar alcohol and will change the composition into a stable semisolid or viscous liquid. The antimicrobial composition of the present invention may also include other ingredients such as an effective amount of a buffer to maintain a pH range that exhibits proper antimicrobial activity when the composition is used in an active antimicrobial form. Antimicrobial dialdehydes are released in antimicrobial active form when the compositions of the invention are in contact with an aqueous liquid.

The composition of the present invention is prepared by mixing aqueous glutaraldehyde with a polyol or carbohydrate. Water is removed under reduced pressure and / or heating to form an adduct which is a colorless viscous liquid. A portion of the liquid solidifies upon cooling so that the solid can be powdered or formed into a solid block. The adducts prepared immediately release glutaraldehyde when dissolved in water under acidic, neutral or basic conditions. The compositions of the present invention may be formed as a mixture of antimicrobial dialdehydes and carbohydrates or polyols, or may be reaction condensation products between the -CHO group of the dialdehyde antimicrobial agent and the -OH group of the carbohydrate or polyol.

The antimicrobial composition of the present invention has excellent antimicrobial activity and does not have problems related to storage instability, loss of activity, tear gas, odor and the like of liquid glutaraldehyde. The stability in storage of the inventive muscles and the activity upon contact with aqueous liquids is of an amazing level. The composition is always particularly useful if an effective amount of a dialdehyde microbial agent such as glutaraldehyde is urgently needed.

The composition of the present invention can be made water absorbent by adding an absorbent of an aqueous liquid such as an inorganic or organic particulate carrier material. The resulting solid, finely separated, moisture absorbent composition will effectively absorb and disinfect the aqueous liquid, such as excretion leaks, when placing the composition on a biological leak.

The antimicrobial composition is preferably a dialdehyde such as glutaraldehyde, but can be used in various products that provide antimicrobial activity wherever stability of the liquid form, which is a conventional product, impedes its use. For example, the moisture absorbent compositions of the present invention can be effectively sealed when used in leaking excretion by sealing them in packets or pouches made of water-soluble, water-sensitive or moisture-absorbing polymeric materials. Disinfectant antimicrobial products can be made.

As used herein, "antimicrobial" means having the ability to prevent, disinfect, sterilize or sterilize a contaminated surface or area by killing microorganisms. "Anti-corruption", "disinfection", "sterilization" and "sterilization" refer to the ability of a composition to gradually kill microorganisms, from low lethality (anti-corruption) to "sterilization," which is a complete destruction of all microorganisms.

One aspect of the present invention includes antimicrobial compositions that can be used for various sterilization purposes on contaminated surfaces. Another aspect of the invention is a finely divided, water absorbing antimicrobial composition in the solid phase. Another aspect of the invention is a product comprising an antimicrobial composition or water absorbent composition contained in a packet or pouch made of a water soluble, sensitive or absorbent polymer material. The invention also relates to processes and methods of using the compositions and products in antiseptic, income, sterilization or sterilization of contaminated surfaces or areas.

[Brief Description of Drawings]

1 is a graph showing the relative stability of the sucrose-glutaraldehyde hemiacetal of the present invention as compared to glycerol-glutaraldehyde hemiacetal of the prior art at 25 ° C. in a closed bottle.

2 is a graph showing the relative stability of the sucrose-glutaraldehyde hemiacetal of the present invention as compared to the prior art glycerol-glutaraldehyde hemiacetal at 40 ° C. in a closed bottle.

3 is a graph showing the relative stability of sucrose-glutaraldehyde hemiacetal compared to the prior art glycerol-glutaraldehyde hemiacetal at 40 ° C. in opened bottles.

4 is a graph showing the relative stability of sucrose-glutaraldehyde hemiacetal according to the present invention under various storage conditions.

Detailed description of the invention

The present invention has a broad spectrum of microorganisms in anti-corruption, disinfection, sterilization and sterilization (e.g., has spreader and bacteriostatic properties) and is particularly used as a cold sterilizer in hospitals, clinics, dental clinics and veterinary medicine. It relates to useful antimicrobial compositions. The composition of the present invention is a stable compound comprising an antimicrobial dialdehyde and a polyhydroxy compound such as a carbohydrate compound or a polyol compound, which immediately releases a dialdehyde such as glutaraldehyde upon dissolution in an aqueous solvent.

[Antimicrobial agent]

Antimicrobial agents used in the compositions of the present invention may be included in effective amounts without inducing undesirable interactions or chemical reactions that occur between the main components of the compositions of the present invention. Antimicrobials provide bactericidal action that kills harmful microorganisms.

The antimicrobial agent used in the compositions of the present invention is an antimicrobial dialdehyde. In general, such dialdehydes have the general formula OHC-R-CHO, wherein R is a C ₁ to C ₄ alkylene group or one single covalent bond. In more detail, the R group may be selected from residues comprising lower alkylene consisting of methylene, ethylene, propylene and butylene or may be a single covalent bond between two bilateral carbonyl groups. Preferred antimicrobial agents are saturated C ₂ to C ₆ dialdehyde compounds. Examples of suitable compounds include succinaldehyde, malonaldehyde, adialdehyde, glyoxal and glutaraldehyde.

Glutaraldehyde is particularly preferred as an antimicrobial and has the formula OHC (CH ₂ ) ₃ C HO. Eucaside 225 and 250 (Ucarcide 225 and 250, product of Union Carbide) are commercial glutaraldehyde compositions that are 25% and 50% active solutions, respectively. Glutaraldehyde is stable in solution in the acidic pH range but less active as a bactericide. Typical glutaraldehyde solutions are in the most stable pH range of 3.1 to 4.5. Glutaraldehyde solutions in the alkaline pH range are more effective as fungicides, but are less stable and tend to polymerize.

Glutaraldehyde is one of the few microbial agents that have sterile properties, that is, substances that can destroy all forms of microorganisms containing tuberculosis bacteria, viruses and spores, as well as feeder cells. Glutaraldehyde is used to sterilize surgical instruments and supplies, more particularly in situations where heat sterilization is not practical or heat may cause damage to the product to be sterilized.

As stated, glutaraldehyde tends to be homopolymerized in the pH range in which it is most active. Thus, glutaraldehyde for microbial use has a pH range of 3.1 to 4.5 for end use to avoid homopolymerization from manufacture to use, generally having 25 to 50 percent active strength for commercial use and concentration of use. Has been sold as an aqueous solution which is generally two to three percent active strength. This means that an alkalizing agent should be added immediately before use to adjust the pH of the solution used in the range of pH dir 8 to 9. Because of this, the conventional product was marketed as a two-part system, which was inconvenient to use and also had the inconvenience of measuring and mixing the amount of each part in advance in order to adjust the pH within the correct range.

Adjusting the pH of glutaraldehyde is a very important factor. For example, mortality at pH 8.5 is approximately 20 times faster than mortality at pH 5.0. This difference is presumably due to the slower reaction rate of these biocides when the surface amine groups on the cell wall protonate at acidic pH or form amine salts. In this state, glutaraldehyde is thought to induce its activity by reacting with free amine residues in the cytoplasm through the cell wall where the internal pH is more neutral. The lower the pH, the more protonated surface amine will be and therefore the more biocidal activity will be delayed.

To explain the mechanism of antimicrobial action Mechanisms for bacterial inactivation by antimicrobial agents such as glutaraldehyde have been studied. One mechanism is that the ultimate bactericidal effect is due to the ability of these fungicides to release bacterial cell components into the surrounding medium. There is also a view that the interaction of antimicrobial agents with cell walls interferes with the metabolic processes of the organism and leads to mortality.

Compositions exhibiting an antimicrobial effect of the present invention are about 1 to 90% by weight, preferably about 20 to 70% by weight and most preferably about 50 to 60% by weight, based on the antimicrobial composition, of glutaraldehyde. Such antimicrobial dialdehydes.

[Carbohydrates and Polyols]

The antimicrobial composition of the present invention further comprises an amount effective to stabilize a polyhydroxy compound comprising a carbohydrate compound such as a sugar or a polyol compound such as a sugar alcohol.

Sugars are a group of organic compounds linked by a molecular structure that includes simpler compounds of the general kind of carbohydrates. Each sugar consists of a chain of 2 to 7, usually 5 or 6 carbon atoms. One of the carbons carries aldehyde or ketone oxygen, which can be combined in acetal or ketal form, and the other carbon atoms usually carry hydrogen atoms and hydroxyl groups. In general, sugars are somewhat sweet, water-soluble, colorless, odorless, and optically active, which lose water, caramelize, or charize when heated.

Some sugars exist as discrete single units called monosaccharides or monosaccharides. Other sugars are coupled to di, tri and more saccharides. Carbohydrates that hydrolyze and decompose to produce two molecules of monosaccharides are called disaccharides. Disaccharides are produced by the condensation of two molecules of monosaccharides through one or both of the carbonone groups. New bonds are acid labile and often alkali labile. Acids hydrolyze disaccharides to their constituent monosaccharides, and disaccharides with free carbo groups are reducible. As used herein, "oligosaccharide" means a sugar polymer of 3 to 15 units, and a higher sugar polymer having at least 10 units is referred to as "polysaccharide".

The carbohydrate component of the composition according to the invention preferably comprises one or more monosaccharides, disaccharides, oligosaccharides, polysaccharides, derivatives thereof or mixtures thereof. Monosaccharides preferably used include fructose, glucose, or mixtures thereof. Preferred disaccharides include sucrose, lactose, maltose or mixtures thereof. The carbohydrate component of the compositions of the present invention may also comprise disaccharides, oligosaccharides, polysaccharides or mixtures thereof composed of glucose repeating units. Carbohydrates make the composition of the present invention a stable solid phase when used.

Glucose (dextrose) is commercially known as corn sugar and is present in fruit juices in glass and with honey in fructose. Commercial sources of glucose are acid or enzyme digested corn starch.

The most common form of glucose is the alpha form of monohydrate called dextrose hydrate. (Melting point 80 to 85 ° C.) Fructose (rebloose) is present with glucose in honey, but is more commonly bound in sucrose. In the form of fructose polymers, fructose is a storage carbohydrate present in the tubers of dahlias and Jerusalem artichoke, as well as Hawaiian ti plants. D-fructose is the most soluble in common sugars and crystallizes into hygroscopic anhydrous beta form (melting point 102-104 ° C.).

Sucrose is a disaccharide consisting of glucose and fructose monosaccharides in which alpha-D-glucosyl residues in the six-membered ring form are bonded to beta-D-fructoside residues in the five-membered ring form. Sucrose is found in the juice of all land plants investigated and is produced primarily from sugar beets and sugar cane.

Sucrose is crystallized from water to a characteristic monoclinic form (melting point 184 ° C.). Lactose, or lactose, is a disaccharide that has been found to comprise about 2 to 6% of the milk of all primates studied. Commercially available products are alpha monohydrate (melting point 201.6 ° C.). Crystallization at temperatures above 93.3 ° C. yields anhydrous beta form (melting point 252.5 ° C.). In lactose, the beta-galactosyl moiety binds to hydroxyl oxygen on the fourth carbon of the glucose unit (both of which are in the six-membered ring form), making lactose a reducing sugar. Maltose or maltose is a disaccharide present in the maltosemination step of the sprouted grain kernels and brewing process. Maltose is produced commercially by breaking down starch into beta-amylase. Maltose is a reducing disaccharide in which the alpha glucosyl moiety is bound to hydroxyl oxygen on the fourth carbon of the other glucose unit in glucose in both six-membered ring form. Maltose is crystallized from water with beta form monohydrate (melting point 102-103 ° C.).

Various oligosaccharides and polysaccharides may also be used in the compositions of the present invention. Preferred oligosaccharides are derivatives of sucrose. Polysaccharides are widely distributed in the flora and fauna and function as edible storage materials and structural materials. Suitable polysaccharides include starch and cellulose composed of D-glucopyranosyl units bound by alpha- and beta-1.4 bonds, respectively. Corn starch is a preferred polysaccharide for use in the present compositions.

The carbohydrate compounds used in the compositions of the present invention may also include various derivatives of the sugars, preferably ester or ether derivatives of the sugars.

Esters of carbohydrates are typically produced by treating carbohydrates with acid chlorides or acid anhydrides in the presence of a base. All hydroxyl groups of the carbohydrate, including anmeric hydroxyl groups, react. Carbohydrates can be converted to ethers by treatment with alkyl halides in the presence of a base. Complete etherification is achieved only after repeated treatments.

Esters and ether derivatives of carbohydrates can be used because they are easier to process than free sugars. Monosaccharides are very soluble in water because of many hydroxyl groups, but insoluble in organic solvents.

They are also difficult to purify and tend to form syrups rather than crystallize when water is removed. However, ester and ether derivatives behave like most other organic compounds in that they tend to dissolve in organic solvents and can be easily purified and crystallized.

Polyols that may be used in the compositions of the present invention are polyhydroxyl alcohols having 3 or more hydroxyl groups per molecule. Polyols having four or more hydroxyl groups are generally known as sugar alcohols and have the general formula CH ₂ OH (CHOH) _n CH ₂ OH, where n may be 2-5. Examples of suitable polyols include xylitol, maltitol, pentaerythritol, mannitol, sorbitol, inositol, glycerol, ethylene glycol, 1.4-cyclohexane diol and the like. When polyols are used in the compositions of the present invention, they make the antimicrobial agent semi-solid or viscous liquid.

The antimicrobial composition comprises about 10 to 99 wt%, preferably about 30 to 80 wt%, most preferably about 40 to 50 wt% carbohydrate or polyol compound based on the antimicrobial composition. The solid form of the antimicrobial composition of the present invention may be formed into a particle form having a desired particle size. The compositions of the present invention may also be formed into solid blocks.

[Buffer]

The antimicrobial composition of the present invention may comprise a buffer so that the composition maintains an alkaline pH when used in active antimicrobial form. It is preferable to use a buffer that maintains the pH at an appropriate alkaline level for the antimicrobial activity of dialdehydes such as glutaraldehyde when the composition is in contact with an aqueous liquid.

The pH range beneficial for the antimicrobial activity of the compositions of the present invention is about 3 to 11, preferably about 7 to 9.

Typical buffers that may be used include sodium bicarbonate / sodium carbonate, acetic acid / sodium acetate, potassium dihydrogen phosphate / disodium monohydrogen phosphate, cacodylic acid / sodium cacodylate, tris (hydroxymethyl) aminomethane hydrochloride / tris (hydroxy Methyl) aminomethane, bobbyton / barbitone sodium, potassium para-phenolsulfonate / potassium sodium para-phenolsulfonate, 2-amino-2-methyl propane-1,3-diol hydrochloride / 2-amino-2- Methylpropane-1,3-diol, hydrochloride / 2-amino-2-methylpropane-1,3-diol, ammonia / ammonium chloride, glycine / sodium glycinate, maleate trisate / sodium hydroxide, potassium dihydrogen Phosphate / sodium hydroxide, hydrochloric acid / collidine, hydrochloric acid / tris (hydroxymethyl) aminomethane, hydrochloric acid / 2-amino-2-methylpropane-1,3-diol, boric acid / potassium chloride / sodium hydroxide, and disodium monohydrogen phosphorus Acid salt / sodium hydroxide. Other suitable inorganic buffers include borax (sodium borate), calcium carbonate, ferrous lime hydroxide (calcium carbonate), sodium bicarbonate, sodium hydrogen phosphate, sodium hydroxide, sodium dihydrogen phosphate, sodium metasilicate, sodium sesquicarbonate, Sodium oxide and trisodium phosphate. Suitable organic buffers include sodium benzoate, sodium citrate, sodium fumarate, sodium glutarate, sodium lactate, sodium laurate, sodium oleate, sodium oxalate, sodium salicylate, sodium stearate, sodium succinate, sodium tartarate, monoethanolamine, di Ethanolamine and triethanolamine.

The antimicrobial composition may comprise about 0 to 30 wt%, preferably about 1 to 20 wt%, most preferably about 1 to 5 wt% buffer, based on the composition.

[Absorbent]

The antimicrobial compositions in solid form according to the invention can be mixed with absorbents for aqueous liquids comprising anhydrous inorganic or organic particulate carrier materials for producing water absorbent compositions.

The antimicrobial composition is preferably finely separated and mixed with anhydrous powdered carrier material to form a flowable bactericidal powder mixture. The absorbent allows the antimicrobial composition to effectively absorb the excretion leak when contacting the composition with the same aqueous liquid when contacting the composition with an aqueous liquid such as a biological excretion leak.

Carrier material absorbents that may be used in the present invention include silica, alkali metal silicates, polyacrylates, diatomaceous earth, ground corncobs or mixtures thereof.

Silica or silicon dioxide (SiO ₂ ), which can be used as the absorbent, is preferably amorphous. Amorphous silica is substantially dehydrated and polymerized silica, which can be viewed as a condensation polymer of silicic acid. Amorphous silica that is preferably used in the composition of the present invention is precipitated silica. Precipitated silica is a very finely divided silica whose polymerization degree is limited by the manufacturing technique.

Precipitated silica is usually prepared by destabilizing soluble silicates by acid neutralization. Destabilization is carried out in a solution containing a polymerization inhibitor, such as an inorganic salt, which allows the formation of extremely fine particles of hydrated silica. The precipitate thus formed is filtered, washed to be substantially free of attached salts, and then dried to the desired degree.

The final silica particles are about 20 to 50 microns (millimeter microns) in size, and form aggregated particles of about 1 to 5 microns (microns). The surface area of precipitated silica is about 100 to 200 m 2 per gram and is often contaminated with calcium or other cations from the salt to precipitate. The percentage of silicon dioxide (SiO ₂ ) in the precipitated silica is 85 to 90 and the pH may be about 4 to 8.5.

Another absorbent that can be mixed with the antimicrobial composition of the present invention is an alkali metal silicate. Alkali metal silicates are synthetic inorganic silicates formed of alkali metal bases. Preferred alkali metal silicates for use in the compositions of the present invention are sodium silicates in anhydrous powdered or crystalline hydrate form. Other silicates that can be used include potassium or lithium silicates. Sodium silicate is the pH of the basic medium, it may be changed to about 0.5 SiO ₂ / Na ₂ O to 4SiO ₂ / Na ₂ O. Commercially available crystalline products are anhydrous sodium metasilicate and hydrated metasilicate. Typically, sodium and potassium silicates are prepared in conventional glass furnaces by melting sand with soda ash at about 1450 ° C. The proportion of the components is determined by the ratio of sand to alkali applied to the furnace. Commercial soda ash is so pure that it hardly contains any impurities in the final product. Anhydrous crystalline products can be prepared by melting sodium carbonate and sand in the desired proportions. Such glasses crystallize very rapidly, but the higher the proportion of sodium carbonate, the greater the proportion of carbon dioxide remaining in the molten glass. Thus, anhydrous solids that are more alkaline than hydrated metasilicate are often mechanical or overall mixtures of sodium metasilicate and caustic soda. Hydrated crystalline products are generally prepared by making solutions of the hydration composition at temperatures above the melting point, cooling and crystallizing them.

Another absorbent that can be mixed with the antimicrobial composition of the present invention to produce a water absorbent antimicrobial composition is a porous polymeric water absorbent composition such as polyacrylate. Acid wet (available from Sanwet, Hoechst Celanese) is a preferred polyacrylate polymer composition. Another preferred moisture absorbent composition is diatomaceous earth, which is a soft, bulky solid material (about 88% silica) composed of the support of small prehistoric aquatic plants belonging to algae (diatoms). Celatom FW-80 from Eagle-Picher is a preferred diatomaceous earth. Crushed corncob can also be used as an absorbent.

In formulating the water absorbent composition of the present invention, the absorbents may be used alone or in the form of several mixtures. The water absorbent antimicrobial composition comprises about 0 to 99% by weight, preferably about 50 to 99% by weight and most preferably about 70 to 99% by weight, based on the composition.

[Other Ingredients]

In addition to the above components, the compositions of the present invention may contain conventional additives such as pigments, perfumes, preservatives, stabilizers such as triethylene glycol and surfactants.

Surfactants that can be used in the compositions of the present invention include quaternary ammonium compound nonionic and anionic surfactants. Quaternary ammonium compounds not only act as surfactants but also support antimicrobial activity. Nonionic surfactants provide increased stability to antimicrobial compositions.

Preferred nonionic surfactants include water insoluble alcohols such as octanol, decanol, dodecanol and the like; Phenols such as octyl phenol and nonyl phenol; Alcohols or phenols, which are preferably 1 to 10 moles of ethylene oxide per mole, are oxylates of the alcohols and petols. Other nonionic surfactants that may be used may include ethylene oxide / propylene oxide block copolymers. When using surfactants, they may comprise about 0 to 89%, preferably about 1 to 50%, by weight of the composition of the present invention.

Preferred solid phase antimicrobial compositions comprise about 1 to 90 weight percent antimicrobial agent of the general formula OHC-R-CHO, wherein R is a C ₁ to C ₄ alkylene group or one single covalent bond; Carbohydrate compounds (which are selected from the group consisting of monosaccharide compounds, disaccharide compounds, oligosaccharide compounds, polysaccharide compounds, derivatives thereof or mixtures thereof) and sugar alcohols or mixtures thereof About 10 to 99% by weight of a polyhydroxy compound comprising a polyol compound; And from about 0 to 30 weight percent of a buffer that maintains the composition at pH DIR 3 to 11, which is the pH for proper antimicrobial activity of the composition in its active form.

Particularly preferred stable antimicrobial hemiacetal compositions in solid phase comprise from about 1 to 90 weight percent glutaraldehyde and from about 10 to 99 weight percent sucrose.

Preferred solid phase finely separated water absorbing antimicrobial compositions comprise from about 2 to 50% by weight of an antimicrobial dialdehyde compound; Carbohydrate compounds (which are selected from the group consisting of monosaccharide compounds, disaccharide compounds, oligosaccharide compounds, polysaccharide compounds, derivatives thereof and mixtures thereof) and sugar alcohols or mixtures thereof About 1 to 50% by weight of a polyhydroxy compound comprising a polyol compound; And about 10 to 97% by weight of an absorbent for an aqueous liquid, selected from the group consisting of precipitated silica, silicates, polyacrylates, diatomaceous earth, ground corncobs or mixtures thereof. The moisture absorbent composition effectively absorbs aqueous liquids, such as aqueous leakage emissions.

The present invention provides a stable solid phase dialdehyde donor which rapidly releases dialdehyde when dissolved in an aqueous solvent.

The compositions of the present invention are believed to be formed as a mixture of antimicrobial agents and carbohydrates or polyols which act as carriers or as condensation products. It is believed that the -CHO group of dialdehydes, such as glutaraldehyde, reacts with the -OH group of carbohydrates or polyols to bind the antimicrobial agent to the carbohydrates or polyols in a condensation reaction to form the compositions of the present invention.

Glutaraldehyde may form hydrates, hemiacetals or acetals in aqueous sucrose solution. It is assumed that hemiacetal is formed between glutaraldehyde and sugars because water is removed to produce the composition of the present invention. Because of the large number of hydroxyl groups in sugars such as sucrose and the dialdehyde groups of glutaraldehyde, both intramolecular and intermolecular hemiacetals can be formed. Intramolecular hemiacetals will form molecules and intermolecular hemiacetals will form polymers. In the composition of the present invention, a mixture of the above structures may be present.

It has been found according to the invention that the hemiacetal of the present invention is very stable and any solid form of hemiacetal is one of the most stable forms. Particularly preferred hemiacetals are solid phase glutaraldehyde- sucrose hemiacetals. It has also been found that such hemiacetals readily form free glutaraldehyde when dissolved in an aqueous system and are equally active as glutaraldehyde when compared to ppm phase for glutaraldehyde.

The solid phase glutaraldehyde hemiacetals of the present invention can be formulated without interacting with other solid phase alkalizing agents or additives such as buffers, solid phase surfactants and other solid components, thus providing a one-part system, ie fully active use. It is particularly advantageous and advantageous in that it provides a system in which only a measured portion of the solution to obtain a solution is dissolved in a given volume of water. Another advantage over previously developed products is that no inert, undesirable support material is required and the concentrated product can be adjusted; In other words, the present invention has the economic advantage that no fillers (supporting materials) are necessary and therefore the shipping and storage costs are reduced. Such a stable system thus meets unmet needs not disclosed by the prior art. The composition of the present invention has excellent microbial activity and does not have the problems that liquid glutaraldehyde has in terms of storage instability, loss of activity, tear gas, odor and the like.

The present invention also has a safer toxicity level than conventional glutaraldehyde formulations. In oral ingestion, in all cases, the lethal dose (LC) is the same, but since the solid is not absorbed through the skin, the composition of the present invention provided in solid form has reduced skin toxicity. For example, when oral intake in mice LD ₅₀ of the aqueous glutaraldehyde is a LD ₅₀ of the case through the 2.38㎖ / kg or skin 2.56㎖ / kg. When the composition of the present invention in solid form is in contact with the skin, the mortality is much higher and thus a stable product for treatment.

[Manufacturing method]

The antimicrobial composition of the present invention may be a solid source of antimicrobial dialdehydes, such as glutaraldehyde. Hard, clean crystalline solids can be produced by dehydrating glutaraldehyde-sugar aqueous solution at high temperature (eg, 80 ° C.). The antimicrobial composition can be baked to be odorless, stable in warm air and having a melting point of 60 to 80 ° C.

As a typical synthesis method, water can be removed without any problem using a absorber at a temperature of 50 to 100 ° C. under reduced pressure. In the preparation of the glutaraldehyde- sucrose adduct composition, the mixture becomes very viscous and the conditions In use, removal of water is stopped. Two methods have been found for preparing glutaraldehyde-suscrose compositions and overcoming these obstacles. The high viscosity appeared to be localized in the center of the resin polarsk, which was related to the temperature gradient in the resin flask. Viscosity reducing agents (eg, glycerin) or higher reduced pressures can be used to keep the viscosity uniform so that a more uniform temperature is maintained throughout the resin flask. Methods that can be used to prepare stable compositions of the present invention with high activity are sensitive to pH and temperature. When the composition is prepared above pH 6, the measured glutaraldehyde activity is low. The most active compositions are made from 25% to 50% commercial glutaraldehyde with a pH of 3.1 to 4.5.

After preparation, the composition of the present invention has high glutaraldehyde activity and the ability to immediately release glutaraldehyde in water. However, the ability of the composition to release glutaraldehyde decreases over time. The glutaraldehyde-suscrose composition has a surprisingly long term sustained ability to release an amount of glutaraldehyde.

Antimicrobial studies of the compositions of the present invention (in dissolved form in water) show that the compositions work the same as liquid glutaraldehyde. The composition of the present invention is completely soluble in water, and the results of nuclear magnetic resonance (NMR) studies indicate that only sugar and glutaraldehyde are present in the aqueous solution. This means that the solid phase composition readily releases glutaraldehyde into water.

The compositions of the present invention may be provided in various solid forms. This includes powders, tablets (cured liquid drops), granules and solid blocks of various sizes. Solid forms of the invention can be higher than 50% activity and as high as 80% activity. The water absorbent antimicrobial composition may be made by mixing the previously prepared antimicrobial dialdehyde composition with an absorbent, finely divided into solid particles. Unlike liquid glutaraldehyde, the compositions of the present invention, either alone or in the form of a formulated product, are excellently stable and exhibit antimicrobial activity in the presence of anhydrous base. Thus, the composition may mimic glutaraldehyde, although glutaraldehyde is preferred but its stability or liquid phase is impeded. For example, solid phase antimicrobial compositions can be used in many products where antimicrobial agents are useful, such as lubricants as well as urinals or toilet edge blocks.

The dialdehyde-sugar composition may be mixed with anhydrous base and / or absorbent without losing antimicrobial activity. The dialdehyde-sugar composition may also be shaped into blocks. The block itself has a use as a disinfectant or bactericide. Blocks or powders may be formulated with anhydrous bases, dissolved in aqueous liquids and used as cold sterilizers for medical devices.

The antimicrobial composition mixed with the absorbent to make the water absorbent antimicrobial composition can be contained in a container of water soluble, sensitive or absorbent polymer material shaped into a packet or pouch to provide an absorbent bactericidal product. Absorbent antimicrobial products can be used to clean up biological excretion leaks, such as contaminated body fluid leaks found in hospitals and other areas.

Preferred water absorbing antimicrobial products include about 2-50% by weight of antimicrobial saturated C ₂ to C ₆ dialdehyde compounds; About 10 to 97% by weight absorbent for aqueous liquids; And a solid phase microseparated water absorbent antimicrobial composition comprising from about 1 to 50 weight percent of a carbohydrate compound comprising a disaccharide compound, an oligosaccharide compound, a polysaccharide compound, or a mixture thereof. The product also includes a water soluble, water soluble or absorbent polymeric material molded into a cachet or pouch containing a water absorbent antimicrobial composition. When the product is used for leaking feces, it effectively absorbs and sterilizes the leaking feces, which are aqueous liquids. Preferred components of the water absorbent composition are as described above. The polymeric material, which is preferably used in articles and shaped into packets or pouches, consists of polyvinyl alcohol polymers.

[How to use]

Anti-corruption, disinfection of contaminated surfaces or areas using stable antimicrobial compositions comprising an effective amount of an antimicrobial dialdehyde compound and an effective amount of a polyhydroxy component comprising a carbohydrate compound, a polyol compound, or a mixture thereof The method of sterilization or sterilization comprises contacting the activated form of the composition with a contaminated surface or area for a time effective to prevent decay, income, sterilization, or sterilization.

The water absorbent composition and the product containing the water absorbent composition are particularly useful for cleaning and sanitizing the aqueous biological excretion leak areas created by body fluid excretion leaks.

Such excretion leaks may include aqueous biohazards or biocontaminants.

The water absorbent compositions and articles of the present invention provide a method for safely and easily treating biological excretion that may be harmful. The compositions and products of the present invention provide a safe means to wash out biological excretion, because if a composition is sprayed on or placed on the excretion prior to human contact, the excretion is absorbed and sterilized before it is received and treated. .

The method of washing and sterilizing biological excretion using the solid phase water absorbing antimicrobial composition described above comprises contacting the antimicrobial composition with the biological leak excretion for a time effective to absorb and sterilize the biological excretion. do.

Washing or removing biological excretion leaks using a water absorbent antimicrobial product comprising the solid phase water absorbent antimicrobial composition and a water soluble, sensitive or absorbent polymeric material molded into a packet or pouch containing the water absorbent antimicrobial composition. The method of sterilization includes contacting the antimicrobial product for a time effective to absorb and sterilize the biological excretion leak and the biological excretion leak.

Antimicrobial solutions can also be prepared using compositions of the present invention comprising dialdehyde antimicrobials such as glutaraldehyde and carbohydrate or pulliol compounds. The composition can be mixed with an aqueous liquid to produce an anti-corruption, disinfection, sterilization or sterile solution that can come into contact with contaminated objects and articles. Examples of such objects and articles include contaminated clothing or other textiles, contaminated medical instruments and tools.

Water-sensitive antimicrobial agents that can be used to prepare anti-corruption, disinfection, sterilization or sterilization solutions include about 1 to 90% by weight of antimicrobial saturated C ₂ to C ₆ dialdehydes, and drugs comprising carbohydrate compounds or polyol compounds. 10 to 99 weight percent polyhydroxy component. The antimicrobial composition is contained in a water soluble, sensitive or absorbent polymeric material molded into a packet or pouch. The product may be added to an aqueous liquid to produce an aqueous anti-corruption, disinfection, sterilization or sterilization solution. The polymeric material used is preferably a polyvinyl alcohol polymer.

Methods for preventing, disinfecting, sterilizing or sterilizing a contaminated object or article include preparing an aqueous antimicrobial solution by adding the antimicrobial product to an amount of an aqueous liquid that can effectively dissolve the antimicrobial product. The contaminated object or article is then contacted with the antimicrobial solution for a time effective to prevent, disinfect, sterilize or sterilize the object or article.

The following examples illustrate the invention and include the best mode.

Example 1

The antimicrobial composition of Example 1 was prepared as follows. In a round bottom flask, 34 g of deionized water was added to 30 g of 50% aqueous glutaraldehyde, followed by 34 and 23 g of sucrose. The solution was heated in a steam bath until all sucrose was dissolved to form a clarified homogeneous solution. The volatiles were degassed from the reaction solution at 80 ° C. on a rotary evaporator. The product obtained was a hard, clear and brittle bubble comprising glutaraldehyde and sucrose.

The antimicrobial activity of Example 1 was tested as well as the glutaraldehyde release properties as compared to the eucaside 250 (50% aqueous glutaraldehyde). Several experiments were conducted to test the antimicrobial activity of Example 1. The first experiment involved dissolving the solid composition of Example 1 in neutral unbuffered water to produce a theoretical 1250 ppm concentration of glutaraldehyde. Active solution microorganism s. Oreus and S. aureus. E. coli was inoculated respectively to determine the rate of population reduction over time (see Table 1).

The second experiment was performed in the same manner as the first experiment except that the pH of the active solution was buffered to pH8 (see Table 2). The data in Table 1 and Table 2 show that the composition of Example 1 has the same antimicrobial activity as aqueous glutaraldehyde, and Example 1 releases 100% glutaraldehyde.

The test concentration was theoretically 1250 ppm glutaraldehyde. This assumes that eucaride 250 contains 50% active glutaraldehyde and Example 1 contains 30.5% available glutaraldehyde. Actual values were obtained from titration assays (see Table 3).

In theory, Example 1 should contain 30.5% of active glutaraldehyde.

As shown in Table 3, Example 1 contained most of the glutaraldehyde even after two weeks of exposure at 50 ° C.

Samples of Example 1 with different concentrations of glutaraldehyde were further prepared. The stability of this sucrose-glutaraldehyde addition product was tested and the results are summarized in Table 4 below.

Change in theoretical activity: (absolute) change in activity between final activity and theoretical activity (related to process)

Initial activity change: The change between final and initial activity in (absolute) activity

As shown in Table 4, samples 5 and 8 actually gained activity after 6 weeks, while the remaining samples showed minimal loss in activity over the same period.

[Examples 2 to 10]

The following examples were prepared in a similar manner as described for Example 1.

Examples 2 to 10 were addition products of various polyhydroxy compounds which are glutaraldehyde, carbohydrates and polyols. Various polyhydroxy components and the characteristics of these compositions are listed in Table 5 below.

Room temperature

Llauric ester of sucrose, L1695 (Ryoto Sugar Esters, Inc.)

The antimicrobial activity of Examples 2, 3 and 6 was tested with the Eucaside 250 stock sample for their antimicrobial activity. The examples were tested by buffering at pH 8 similar to the method described in Example 1. The results are shown in Table 6 below. The data in Table 6 shows that the compositions of Examples 2,3 and 6 have the same antimicrobial activity as aqueous glutaraldehyde.

1-50% aqueous glutaraldehyde

Example 2 (Glutaraldehyde / Sucrose) was compared with Eucasside 250 (50% aqueous glutaraldehyde) at natural pH (pH 4) and buffered pH 8. The data for this experiment is described in Table 7 below. As shown in Table 7, Example 2 is similar to eucaside 250 at both natural pH (pH 4) and buffered pH (pH 8) for antimicrobial activity.

[Examples 11 to 19]

The composition of Example 2 was prepared by mixing the composition of Example 2 (32.9 g glutaraldehyde-sucrose) with polyacrylate (20.0 g Sanwet 3500 p) and diatomaceous earth (147.1 g Celatom FW-80) absorbent I was. The final composition component content (% by weight) is listed in Table 8 below. Examples 12-19 mix the components listed in Table 8 for comparative testing with the composition of Example 1 to form an absorbent mixture containing eucide 250 and 530 g (glutaraldehyde absorbed on silicate). Was prepared.

A disinfection test on the dry samples of Examples 11-19 was performed by contacting S. orureus for 5 minutes. The ratio of absorbent to inoculum was tested to be 1: 1. The results are shown in Table 9. As shown in Table 9, Example 11 had good activity after 6 weeks at all three temperatures. The three-week and one-week samples of Example 14 (Yucaside 530G) did not show significant differences between Yuccaides 250 and 530g, but required triethylene glycol (TEG) or TEG and nonylphenol ethoxylate to remain active. It became.

Glutaraldehyde Absorbed on Silicon Dioxide

Room temperature

Disinfection tests for Examples 11, 12, 13 and 16-18 were performed by contacting S. oreus for 5 minutes. The ratio of absorbent to inoculum was tested to be 1: 1.

The results are shown in Table 10 below. As shown in Table 10, the stability of the composition of Example 11 continued for 10 weeks showing good activity regardless of temperature. The 4-week stability sample of the other examples showed good activity with a log reduction of 2.5 or more for S. aureus.

Room temperature

Example 20

Example 20 was prepared in the same manner as in Example 1 except that the absorbent was mixed with the composition of Example 1 to prepare a water absorbing antimicrobial composition.

The composition of Example 1 was prepared by mixing Hubersorb, ie, a medium basic sodium silicate in the amounts described in Table 11. The composition of Example 20 was tested for antimicrobial activity in the same manner as in Example 1 except that the composition of Example 20 was used in a polyvinyl alcohol packet. Example 20 was compared with eucasside 250 (the eucaside mixture) absorbed on sodium silicate in the amounts described in Table 11. Test samples were aged at 50 ° C. and 50% relative humidity in a weakly sealed container for 2 weeks.

As shown in Table 12, the absorbed yucamide mixture lost most of its activity, while the water absorbent mixture of Example 20 was markedly resistant to both Gram negative (E. coli) and positive (S. orreus) bacteria. Microbial activity was shown.

Aqueous glutaraldehyde mixed with sodium silicate and used at a theoretical concentration of 11250 PPM.

Aqueous glutaraldehyde absorbed on sodium silicate and used at 1250 PPM.

Example 21

A glutaraldehyde / sucrose adduct was prepared in a similar manner to Example 1. The composition contained 26% by weight glutaraldehyde as a result of titration (similar to Example 1). This composition was used as 0.602 g in a packet made of polyvinyl alcohol (PVA) material. The composition was used at 0.602 g. The composition was used alone in the packet, mixed with Cipherate 50 (silicate, pH7) and also with Hooversorb 600 (sodium silicate, pH9-10). The packet was dissolved in 125 mL of water to make a 1250 ppm (theoretical) aqueous glutaraldehyde solution. The solutions were tested for S. aureus and E. coli with exposure times of 30 seconds, 60 seconds, 120 seconds and 300 seconds. The packets were aged at 50 ° C. and 50% relative humidity in a loose lid oven.

One sample contained 0.602 g of glutaraldehyde / sucrose composition (Example 1) dMF, used alone in the PVA packet. The other sample contained 0.602 g glutaraldehyde / sucrose composition mixed with 3.3 g cipheratite 50.

Another sample contained 3.3 g of Hooversorb 600 and 0.602 g of glutaraldehyde / sucrose composition. The samples were compared to the eucaside 250 / absorbent composition.

The results of the antimicrobial test are listed in Table 13 below.

As can be seen from Table 13, the adsorbed yuccaide mixture lost most of its activity over time. However, the glutaraldehyde / sucrose absorbent mixture showed significant antimicrobial activity against both E. coli and S. aureus even after 6 weeks with Hubersorb as the absorbent.

When the glutaraldehyde / sucrose composition was used alone in PVA packets, significant antimicrobial activity was seen within 2 to 5 minutes.

[Examples 22 to 34]

The hemiacetals of Examples 22-34 were prepared in a similar manner as described in Example 1. Table 14 summarizes the products of Examples 22-34, and provides a brief description of the products including the hemiacetal of dialdehydes and the physical state of the material, stability after 6 weeks storage at 40 ° C. Two important criteria from a practical point of view are stability, the percent loss of glutaraldehyde and the glutaraldehyde content of the product. Loss factors are necessary to determine the shelf life that ensures reliability in performing efficacy upon aging, and the high glutaraldehyde content offers the possibility of producing economical products in concentrated form. In general, the most ideal form of the dialdehyde donor is in solid form in that it can reduce the tendency of interaction with other components in the final product. According to Table 14, although Neodol 25-12 (tradename) hemiacetals provide adequately stable hemiacetals, sucrose hemiacetals not only are more stable but also have substantially higher dialdehyde content. Since it has, it is more preferable. Pentaerythritol hemiacetal is also preferred because it has a very high dialdehyde content with good stability.

solid

Liquid

While not wishing to be bound by theory, it has generally been shown that solid hemiacetals are more stable than liquid hemiacetals. Stereochemical structures also appear to be a factor of stability in that they exist at different points between the different hemiacetals in both groups. The most preferred hemiacetal tested is sucrose hemiacetal, which is a solid, high dialdehyde content and sucrose is a chemical that can be purchased cheaply in a very pure form such that no further purification is required. Because.

Example 35

1, 2 and 3 show the relative stability of the sucrose-glutaraldehyde hemiacetal of the present invention compared to the prior art glycerol-glutaraldehyde hemiacetal under membrane layer storage conditions. In FIG. 1, no loss of glutaraldehyde was detected after 8 weeks at room temperature for sucrose-glutaraldehyde hemiacetal, while glycerol-glutaraldehyde hemiacetal lost about 10% glutaraldehyde. . The relative stability of sucrose-glutaraldehyde hemiacetal and glycerol-glutaraldehyde hemiacetal at 40 ° C. is shown. FIG. 2 shows data on storage in closed bottles and FIG. 3 shows data on storage in open bottles. These two conditions, that is, the conditions in the open and closed bottles, will show some effect of humidity on hemiacetal. Sucrose derivatives in closed bottles showed very weak and almost undetectable loss of glutaraldehyde after 8 weeks, whereas the comparative composition glycerol derivatives lost approximately 40% of glutaraldehyde content. (See Figure 2).

In the open jar, the sucrose derivatives showed no loss of glutaraldehyde, while the glycerol derivatives lost approximately 50% after 8 weeks. As such, the sucrose derivatives showed surprising and unexpected stability at 40 ° C. storage conditions. Storage at 40 ° C. is the actual temperature at shipment and storage, unless the product is stored under an air conditioner.

A long term storage test was performed in which sucrose-glutaraldehyde hemiacetal samples were stored for 6 months at 40 ° C. and room temperature. 40 ° C. samples were stored in open and closed bottles as before. 4 is a summary of the data in which the ordinate is expanded to recognize the minute differences between the samples. The data show no significant loss of glutaraldehyde at room temperature (in a closed bottle). There was also no loss of glutaraldehyde even at 40 ° C. and in open bottles. Approximately 5 to 6 percent of glutaraldehyde was lost in the sealed bottle at 40 ° C. These stability data confirm that the sucrose-glutaraldehyde hemiacetal is very stable.

Example 36

In order to test the bactericidal effect of various polyol-glutaraldehyde hemiacetals, various hemiacetals were synthesized and compared with glutaraldehyde itself at the same active glutaraldehyde concentration. The sterilization test method used is standard A.O.A.O. It was a test method. The test microorganisms used were S. aureus and E. coli. The test was carried out at natural pH, pH 8, where glutaraldehyde products are generally tested because they are suitable conditions for bactericidal activity. Table 15 is a summary of the bactericidal effect data of glutaraldehyde hemiacetal derivatives of pentamerititol, sucrose and lactose at the natural pH of the derivative compared to 50% aqueous glutaraldehyde (yucamide 250).

Within experimental error limits, these derivatives were identical to glutaraldehyde in bactericidal effect. Table 16 is a repeated test performed in the same manner as the test method of Table 15 except that the pH was adjusted to pH 8.

These hemiacetals show the same bactericidal properties as free glutaraldehyde without exception within the limits of experimental error.

* Concentration: 1250ppm based on glutaraldehyde

* 1250 ppm based on glutaraldehyde

Example 37

A commercially available aqueous sample of glutaraldehyde was analyzed using 13-CNMR by whiffle. At room temperature, 70% of the active material was excavated into a 2,6-dihydroxy pyran structure with the remainder in the form of free glutaraldehyde and its hydrate. Glutaraldehyde tends to be hydrated and closed in this ring structure.

Concentrated aqueous or anhydrous solutions of low molecular weight alcohol, polyol or carbohydrate mixed glutaraldehyde have been shown to contain equilibrium mixtures. The mixture contained an adduct having a structure similar to glutaraldehyde, its hydrate, and aqueous glutaraldehyde. Alcohols, polyols or carbohydrates replace the water of glutaraldehyde hydrate in 2,6-dihydroxy pyran and adducts to form hemiacetal derivatives.

The mixture became rich in adducts when water was removed or the molar ratio of alcohol, polyol or carbohydrate to glutaraldehyde was increased.

The structure of this adduct was determined by 13-C NMR. Several C NMRs were adopted on the sucrose-glutaraldehyde adduct. In the solid phase 13-C NMRDP of the anhydrous sucrose-glutaraldehyde hemiacetal adduct, a near complete absence of carbonyl absorption was observed near 200 ppm. This indicates that all glutaraldehyde is complexed with sucrose. The 13-C NMR spectrum in dimethylsulfoxide-d6 of anhydrous sucrose glutaraldehyde adduct showed a significant increase in carbonyl absorption (near 200 ppm), indicating the presence of free glutaraldehyde.

Hemiacetal bonds are certainly weak enough to release some free glutaraldehyde in the dimethylsulfoxide solution.

The spectra in dimethylsulfoxide-d6 also showed a broader absorption corresponding to hemiacetal-carbon.

Wet chemical analysis of these adducts was performed to aid the NMR spectral method.

The activity of sucrose-glutaraldehyde was measured using a chemical analysis method similar to the process of glutaraldehyde of Union Carbide using sodium bisulfite (BB-TL-2004).

A small amount of solid adduct was dissolved in water to make a 500 ppm solution.

This solution was analyzed for its glutaraldehyde content and this value was used to calculate the activity of the solid. This method can be used to measure hemiacetal adducts. Hemiacetal type is hydrolyzed and free from water. While the glutaraldehyde is formed, the acetal adduct does not hydrolyze under these conditions and therefore the analytical method can only be used to determine hemiacetal form.

[Examples 38 to 42]

In order to test the sterilant activity of the compositions of the invention, Examples 38-42 were prepared in a similar manner as described in Example 1. Table 17 is a summary of the components of Examples 38-42. Each example contained the glutaraldehyde-sucrose hemiacetal of the present invention, the buffer used in Examples 39-42 (sodium bicarbonate), and the nonionic surfactants used in Examples 40 and 42. Each sample made was placed in a water soluble polyvinyl alcohol packet and the examples were tested for their sterilant activity.

The test method used to determine the sterilization activity of Examples 38-42 is described in Spiciicidal Activity of Disinfectants, A.O.A.C. Methods of Analysis, 15th Edition, 1990. The test was performed at 20 ° C. The test tail used was Bacillus Subtilis. All analyzed examples, including a control sample of commercial liquid glutaraldehyde, provided 20,000 ppm active glutaraldehyde when diluted in deionized water. The results of the sterilization test are summarized in Table 18 below.

The control is a commercial liquid glutaraldehyde product.

As shown in Table 18 above, the glutaraldehyde-sucrose composition provides sterile activity equivalent or better than commercial glutaraldehyde and can be supplied in a water soluble packet. All 30 of the 30 tubes tested were negative, ie no growth in the tubes. Thus there was complete lethality or sterilization of the microorganisms tested.

As can also be seen in Table 18, the use of the composition as a sterilant is not PH dependent since the exposure time was several hours to completely kill all microorganisms.

The above description and examples are intended to illustrate the invention.

However, since various other aspects of the invention can be devised without departing from the spirit and scope of the invention, the invention resides in the appended claims.

Claims (35)

(a) an effective amount of an antimicrobial dialdehyde compound; (b) polyhydroxy compounds including carbohydrate compounds selected from the group consisting of monosaccharide compounds, disaccharide compounds, oligosaccharide compounds, derivatives thereof and mixtures thereof, polyol compounds comprising sugar alcohols, or mixtures thereof Stabilizing effect amount; And (c) an effective amount of a buffer to maintain a pH that exhibits optimal antimicrobial activity when the composition is used in an active antimicrobial form, wherein the composition is in contact with an aqueous liquid. An antimicrobial composition in a solid phase, wherein the sexual dialdehyde is released in an active antimicrobial form. The composition of claim 1, wherein the -CHO group of the antimicrobial dialdehyde reacts with the -OH group of the polyhydroxy compound to bind the antimicrobial dialdehyde and the polyhydroxy compound. The composition of claim 1, wherein the carbohydrate compound comprises an ester derivative or an ether derivative of the carbohydrate. The composition of claim 1, wherein the antimicrobial dialdehyde comprises glutaraldehyde. The composition of claim 4 comprising 1 to 90% by weight of said glutaraldehyde. The composition of claim 1, wherein the carbohydrate compound comprises disaccharides, oligosaccharides or mixtures thereof composed of repeating units of glucose. The composition of claim 1, wherein said monosaccharide compound comprises fructose, glucose, derivatives thereof, or mixtures thereof. The composition of claim 1 wherein said disaccharide compound comprises sucrose, lactose, maltose, or derivatives thereof. The composition of claim 1 wherein said polyol comprises pentaerythritol, mannitol, sorbitol, inositol or mixtures thereof. The composition of claim 1 comprising 10 to 99% by weight of a polyhydroxy compound. The composition of claim 1 wherein the pH in the activated form is between 3 and 11. The composition of claim 1 wherein the buffer is selected from the group consisting of sodium bicarbonate, sodium carbonate, acetic acid, sodium acetate, potassium dihydrogen phosphate and disodium monohydrogen phosphate. The composition of claim 1 in the form of a solid block. (a) 1 to 90 weight percent glutaraldehyde; And (b) 10 to 99% by weight of sucrose, wherein the glutaraldehyde is released in an active antimicrobial form when the composition is contacted with an aqueous liquid. . (a) an effective amount of an antimicrobial dialdehyde compound; And (b) a polyhydroxy compound comprising a carbohydrate compound selected from the group consisting of monosaccharide compounds, disaccharide compounds, oligosaccharide compounds, derivatives thereof and mixtures thereof, polyol compounds comprising sugar alcohols, or these A surface or area contaminated with a stable antimicrobial composition in activated form, wherein the antimicrobial dialdehyde is released in an active antimicrobial form when the composition is contacted with an aqueous liquid. Contacting for a period of time effective to prevent, disinfect, sterilize or sterilize the method. . The method of claim 15, wherein the -CHO group of the antimicrobial dialdehyde reacts with the -OH group of the polyhydroxy compound to bind the antimicrobial dialdehyde and the polyhydroxy compound. The method of claim 15, wherein the carbohydrate compound comprises an ester derivative or an ether derivative of the carbohydrate. The method of claim 15, wherein the antimicrobial dialdehyde comprises glutaraldehyde. 19. The method of claim 18, wherein said composition comprises 1 to 90 weight percent of said glutaraldehyde. The method of claim 15, wherein the carbohydrate compound comprises disaccharides, oligosaccharides, or mixtures thereof composed of repeating units of glucose. The method of claim 15, wherein said monosaccharide compound comprises fructose, glucose, derivatives thereof, or mixtures thereof. The method of claim 15, wherein said disaccharide compound comprises sucrose, lactose, maltose, derivatives thereof, or mixtures thereof. The method of claim 15, wherein the polyol comprises pentaerythritol, mannitol, sorbitol, inositol or mixtures thereof. The method of claim 15, wherein the composition comprises 10 to 99 weight percent polyhydroxy compound. The method of claim 15, wherein the antimicrobial composition further comprises a buffer. The method of claim 15, wherein the pH of the composition is from 3 to 11 when the composition is in activated form. The method of claim 15, wherein said composition is in the form of a solid block. (a) 2 to 50 weight percent antimicrobial saturated C ₂ -C ₆ dialdehyde compound; (b) 1 to 50% by weight carbohydrate compound selected from the group consisting of monosaccharide compounds, disaccharide compounds, oligosaccharide compounds, derivatives thereof and mixtures thereof; (c) 1 to 30% by weight of a buffer that can maintain a pH that exhibits optimal antimicrobial activity when the composition is in an activated form; And (d) contacting for a time effective to absorb and sterilize the aqueous microbial effluent with a solid, finely divided, absorbent, antimicrobial composition comprising from 10 to 97% by weight of an absorbent to the aqueous liquid. A method of purifying and sterilizing an aqueous microbial effluent using an antimicrobial composition. The method of claim 28, wherein the antimicrobial dialdehyde comprises glutaraldehyde. 29. The method of claim 28, wherein said monosaccharide compound comprises fructose, glucose or mixtures thereof. The method of claim 28, wherein said disaccharide compound comprises sucrose, lactose, maltose, or mixtures thereof. 29. The method of claim 28, wherein said absorbent comprises silica, alkali metal silicates, polyacrylates, diatomaceous earth, corn cobs, or mixtures thereof. The method of claim 28, wherein said absorbent comprises precipitated silica, sodium silicate, or mixtures thereof. 29. The method of claim 28, wherein said antimicrobial composition is in anhydrous powder form. The method of claim 28, wherein the aqueous microbial effluent comprises an aqueous biohazard or an aqueous contaminant.