DIALDEHYDE CONTAINING COMPOSITIONS

Abstract: Described herein are aqueous compositions compris­ ing a saturated dialdehyde containing from 2 to 6 carbon atoms, an alkali metal bicarbonate and/or carbonate, and one or more additional buffers such that the initial aqueous solution has a pH of greater than 7.0 to about 9.0. These compositions are suitable for use as disinfectants and/or sporicides.

Description: This invention is directed to an aqueous composition comprising a saturated dialdehyde containing from 2 to 6 carbon atoms, an alkali metal bicarbonate and/or carbonate, and one or more additional buffers such that the initial aqueous solution has a pH of greater than 7 to about 9.0. These compositions are suitable for use as disinfectants and/or sporicides, particularly for laboratory, surgical, dental and other equipment. Saturated dialdehydes, particularly glutaraldehyde, are widely used as sterilizers, biocides, disinfectants and the like. Glutaraldehyde is more effective as a sterilant or microbiocide when used as an alkaline solution, since it exerts faster antimicrobal activity. It is commercially available as an aqueous acidic solution, which is sometimes alkalinated to a pHof from abqut 7.8 to about 8.5, since it is most effective at such a pH range. The pH of the solution is generally maintained at from about 7.8 to about 8.5 by the use of buffers. Giutaraldehyde solutions are stored in containers which may be opened and closed many times during use or the container may be left open while the glutaraldehyde solution is being used. It has been found that during such periods when the gluaraldehyde solution is exposed to air, the pH changes or "drifts't. If the pH of the solution changes so that it becomes acidic, its rate of microbiocidal activity becomes substantially slower. If the pH of the solution drifts to become more basic, the rate of polymerization of the glutaraldehyde accelerates, which results in a lowering of the effective amount of glutaraldehyde in solution, and hence a decrease in its biological activity. Thus, there is a need to formulate the dialdehyde solution so as to minimize the pH drift. U. S. Patent 3,016,328 describes a dialdehyde sporicidal composition comprising a mixture of a saturated dialdehyde, a lower alkanol, and an alkali metal carbonate or bicarbonate alkalinating agent. The examples in the patent describe the use of alkalinating agents such as alkali metal carbonates or bicarbonates. The patent also describes that the composition may be used without the lower alkanol which permits the addition of larger quantities of alkalinizing agents, such as alkali metal bicarbonates. However, aglutaraldehyde solution, as encompassed by U. S. Patent 3,016,328, demonstrates a pH drift when the container in which it is stored is open and closed or left open during use. It'has now been found that the pH drift of an aqueous solution containing a saturated dialdehyde may be controlled b adding to the dialdehyde solution a particular amount of an alkali metal bicarbonate and/or carbonate and one or more additional buffers, such that the initial aqueous solution has a pH of greater than 7 to about 9.0. The compositions of this invention maintain pH stability for a longer time, and thus the biological activity of the glutaraldehyde solution is prolonged. It has further been found that the pH stability of a solution containing a saturated dialdehyde may be controlled by reducing the alkali metal bicarbonate and/or carbonate level therein to less than about 0.018 molar and adding an additional buffer thereto. THE INVENTION This¯invention is directed to an aqueous composition comprising a saturated dialdehyde containing 2 to 6 carbon atoms, an alkali metal bicarbonate and/or carbonate and one or more additional buffers such that the initial aqueous solution has a pH of greater than 7.0 to about 9.0, and wherein the alkali-metal carbonates are used in amounts such that the composition contains from about 0.006 to about 0.018 molar bicarbonate in solution. The compositions as described herein are suitable for use as disinfectants and/or sporicides for laboratory, surgical, dental, and other equipment. The saturated dialdehydes which may be used in this invention contain from 2 to 6 carbon atoms and include at least one of the following: malonaldehyde, succinaldehyde, glyoxal, adipaldehyde, and preferably, glutaraldehyde. The alkali metal bicarbonates used in this invention may be formed in solution by adding either bicarbonate or carbonate species alone or in combination to form primarily the bicarbonate at the desired pH of the solution. The alkali metal bicarbonate which may be used herein include one or more alkali metal bicarbonates, such as sodium and potassium bicarbonate. The alkali metal carbonate which is suitable for use herein includes one or more alkali metal carbonates, such as sodium carbonate or potassium carbonate. The bicarbonate and/or carbonate is used in such amounts so as to yield an initial aqueous solution which is from about 0.006 to about 0.018 molar. Additional buffer salts may be added so that the initial combination of buffers in the aqueous solution have a pH of greater than 7.0 to about 9.0, preferably from about 7.8 to about 8.5. These additional buffers include phosphates, such as alkali metal phosphates, i.e., sodium phosphate, and the like; sulfoxylates; secondary or tertiary amines, i.e., diethylaminoethanol, triethylamine, and the like; acetates, such as alkali metal acetates, i.e., sodium acetate, and the like. The compositions of this invention may include other ingredients, such as colorants, surfactants, chelating agents, and the like. In a preferred embodiment of this invention, from about 0.01 to about 5.0 weight percent of a nonionic, cationic or anionic surfactant is added to the composition. Preferred surfactants include nonionic, anionic, and cationic, or amphoteric agents, such as ethoxylates of isomeric linear alcohols or alkyl aryl sulfonates, nonyl phenol ethoxylates, etc. These are well known and described in, for example, U. S. Patents 3,912,450; 3,282,775; and 4,093,744. EXAMPLES The following examples serve to give specific illustrations of the practice of this invention but they are not intended in any way to limit the scope of this invention. - Control A The following ingredients were mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldehyde solution: 2.68 grams of sodium bicarbonate, (Initial concentration: 0.032 molar) 4.80 grams-of sodium hydrogen phosphate, and (Initial concentration: 0.032 molar) 0.03 grams of sodium dihydrogen phosphate monohydrate (Initial concentration: 0.002 molar) The pH of the initial mixture was measured as well as the percent of glutaraldehyde in the mixture. Portions of the mixture were stored in an open container and portions stored in a closed container at room temperature (about 250C). The pH and percent of glutaraldehyde in the solution were measured after 1, 2 and 5 weeks. The results in an open container are shown in Table I and in a closed container in Table IIz Example 1 The following ingredients were mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldehyde solution: 0.893 grams of sodium bicarbonate, (Initial concentration: 0.011 molar) 4.80 grams of sodium hydrogen phosphate, and (Initial concentration: 0.032 molar) 0.03 grams of sodium hydrogen phosphate monohydrate (Initial concentration: 0.002 molar) The pH and percent of glutaraldehyde in the mixture were measured as described in Control A. The results are shown in Tables I and II. Control B The following ingredients were mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldehyde solution: 2.68 grams of sodium bicarbonate, (Initial concentration: 0.032 molar) 4.76 grams of sodium acetate trihydrate, and (initial concentration: 0.035 molar) 0.04 grams of sodium hydroxide, (Initial concentration 0.001 molar) The sodium hydroxide was added to the solution to adjust its¯pH to 8.0. The pH and percent of glutaraldehyde in the mixture were measured as described in Control A. The results are shown in Tables I and II. Example 2 The following ingredients were mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldehyde solution: 0.893 grams of sodium bicarbonate, (Initial concentration: 0.011 molar) 4.76 grams of sodium acetate trihydrate, and (Initial concentration: 0.035 molar) 0.04 grams of sodium hydroxide, (Initial concentration: 0.001 molar) The sodium hydroxide was added to its solution to adjust its pH to 8.0. The pH and percent of glutaraldehyde in the mixture were measured as described in Control A. The results are shown in Tables I and II. The data show that in closed containers:(Table II) with the concentrations of bicarbonate shown, the pH of the resulting aged aqueous solutions are relatively stable. However, in open containers (Table I), with high levels of- bicarbonate, there is a dramatic increase of pH with time which results in a substantial decline in the concentration of glutaraldehyde. TABLE I Buffers in the Composition (grams) Sodium Sodium Sodium Data in open container Sodium hydrogen dihydrogen acetate Initial One Week Example bicarbonate phosphate phosphate trihydrate pH Glutaraldehyde (%) pH Glutaraldehyde (%) Control A 2.68 4.80 0.03 - 7.9 2.4 - 0.893 4.80 0.03 - 7.8 2.4 - Control B 2.68 - - 4.76 8.0* 2.4 8.8** 1.0 2 0.893 - - 4.76 8.0* 2.4 8.0** 1.9 Data in open container Two Weeks Five Weeks Example Ph Glutaraldehyde(%) pH Glutaraldehyde(%) Control A 8.5 1.0 8.4 0.5 Control B 8.1 1.7 7.8 1.2 2 8.8 0.8 - 8.0 1.8 - * Initial pH adjusted to 8.0 with sodium hydroxide. ** These samples were measured after 9 days. TABLE I Buffers in the Composition (grams) Sodium Sodium Sodium Data in open container Sodium hydrogen dihydrogen acetate Initial One Week Example bicarbonate phosphate phosphate trihydrate pH Glutaraldehyde (%) pH Glutaraldehyde (%) Control A 2.68 4.80 0.03 - 7.9 2.4 7.7 0.893 4.80 0.03 - 7.8 2.4 7.8 Control B 2.68 - - 4.76 8.0* 2.4 8.8** 1.9 2 0.893 - - 4.76 8.0* 2.4 7.5** 2.2 Data in open container Two Weeks Five Weeks Example Ph Glutaraldehyde(%) pH Glutaraldehyde(%) Control A 7.7 1.9 7.6 1.6 1 7.7 1.9 7.5 1.3 Control B 7.9 1.8 7.6 1.7 2 7.6 2.1 7.3 2.0 * Initial pH adjusted to 8.0 with sodium hydroxide. ** These samples were measured after 9 days. In the following Examples and Control varying amounts of sodium bicarbonate were added to a 2 percent aqueous glutaraldehyde solution. To the solution of the Examples and Controls were added constant additional amounts of sodium buffer salts to control the initial pH. Control C The following ingredient was mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldehyde solution: 0.30 weight percent of sodium bicarbonate (initial concentration: 0.036 molar) The pH of the mixture was measured after preparation. Portions of the mixture was stored in an open container and portions in a closed container at room temperature (about 250C) for four weeks. The pH was measured at the end of four weeks. The results are shown in Table III. Example 3 The following ingredient Was mixed into one liter of water containing glutaraldehyde to yield a 2 percent aqueous glutaraldhyde solution: 015 weight percent of sodium bicarbonate (Initial concentration: 0.018 molar) The mixture was tested as described in Control C. The results are shown in Table III. Example 4 The following ingredient was mixed into one liter of water containing glutaraldelhyde to yield a 2 percent aqueous glutaraldehyde solution: 0.08 weight percent of sodium bicarbonate (Initial concentration: 0.011 molar) The mixture was tested as described in Control C. The results are shown in Table III. Control D This was a- 2 percent aqueous glutaraldehyde solution containing no sodium bicarbonate. The glutaraldehyde solution was tested as described in Control C. The results are shown in Table III. The data in Table III shows that the pH change between the open and closed container is dramatically reduced when using the preferred bicarbonate range as shown in Examples 3 and 4. Higher levels of bicarbonate, as shown in Control C, result in a larger pH drift whereas without bicarbonate, Control D, the pH drifts to an unacceptable acidic pH in open containers. TABLE III pH after 4 pH after 4 weeks pH Sodium bicarbonate Iniftial weeks in in closed Example (wt.%) pH* open container container (Open-Closed) Control C 0.30 7.9 8.6 7.3 1.3 3 1.15 7.9 8.2 7.2 1.0 4 0.80 7.9 7.5 7.0 0.5 Control D - 7.9 5.3** 6.8 - In the following Table IV, which simulates use conditions, the effect of opening and closing a container on the pH of a 2 percent glutaraldhyde solution containing different amounts of sodium bicarbonate is demonstrated. The formulation of Example 5 contained 2.68 grams of sodium bicarbonate (Initial concentration: 0.032 molar) while the formulation of Control E contained 0.893 grams of sodium bicarbonate (Initial concentration 0.011 molar). The formulations of Example 5 and Control E contained constant additional amounts of sodium buffer salts to control the initial pH. - The container was stored at room temperature (about 250C) for 14 days. The days the container remained opened and closed is shown in Table IV. The pH of the solution was measured at that point in time. zpH in Table IV is the difference between the highest and lowest pH values. The data shows that the drift in pH, i.e., hpH, is lower with the bicarbonate levels of this invention. TABLE IV Container Closed Opened Closed Opened Closed Opened #pH Time (days) 0 3 2 2 3 2 2 Elapsed Time (days) 0 3 5 7 10 12 14 Example pH 5 8.05 7.86 8.05 7.86 8.05 7.86 7.98 0.19 Control E 8.05 7.80 8.58 8.14 8.60 8.05 8.44 0.80

Claims: WHAT IS CLAIMED IS: 1. An aqueous composition comprising a saturated dialdehyde containing 2 to 6 carbon atoms, an alkali metal bicarbonate and/or carbonate and one or more additional buffers such that the initial aqueous solution has a pH of greater than 7.0 to about 9.0, and wherein the alkali metal carbonates are used in amounts such that the composition contains from about 0.006 to about 0.018 molar. bicarbonate in solution. 2. A composition as defined in claim 1 wherein the dialdehyde is glutaraldehyde. 3. A composition as defined in claim 1 wherein the additional buffer is selected from one or more of the following: a phosphate, a sulfoxylate, a secondary or tertiary amine, or an acetate. 4. A composition as defined in claim 1 wherein the alkali metal carbonate is selected from sodium bicarbonate and potassium bicarbonate ar mixtures thereof. 5. A composition as defined in claim 1 wherein the pH is from about 7.8 to about 8.5. 6. A composition as defined in claim 1 which contains a surfactant. 7. A method for disinfecting and/or sterilizing medical, dental, surgical or other objects by contacting said object with an aqueous sporicidal composition comprising a saturated dialdelhyde containing from 2 to 6 carbon atoms, an alkali metal bicarbonate and/or carbonate and one or more additional buffers such that the initial aqueous solution has a pB of greater than 7.0 to about 9.0, and wherein the alkali metal carbonates are used in amounts such that the composition contains from about 0.006 to about 0.018 molar bicarbonate in solution.

Inventors: EAGAR, ROBERT GOULDMAN, JR., FREID, MARVIN GEORGE, JR.
Applicants: UNION CARBIDE CORPORATION
Application year: 1982
Main classification: A01N35
IPC codes: A01N35, A61L2, C07C45, A01N25