JPS6023302A - Dialdehyde/phenol solution as disinfectant and sporicidal - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to sterilizing aqueous solutions, and more particularly, to highly sterilizing,
It concerns an aqueous solution of a dialdehyde/phenol mixture with sporicidal and tuberculous action.

Description of the Prior Art Aqueous solutions containing saturated dialdehydes, particularly glutaraldehyde, have been widely used as disinfectants, microbicides, disinfectants, and the like. Glutaraldehyde is effective as a disinfectant or microbicide when used in alkaline aqueous solutions. This is because it exerts a faster antimicrobial action than glutaraldehyde sleeves. however,
U.S. Patent No. 3,016,328 (Pepper et al.
al.) Microbicide preparations such as those disclosed herein lack stability, resulting in reduced microbicidal efficacy. Moreover, such preparations are published in the Journal of
Applied Bacteriology)' C 3
Vol. 0, No. 1 (1967)] pp. 0788-87, especially 85
(Rubbo et al.) and American Jo
urnal of I (hospital Pharma)
cy (Volume 31 (June 1974)), 5546-55
7 pages%, 553 pages) (R, M, G, Bouche
r), exhibiting inconsistent effects in certain microbicidal applications, such as mycobacterial efficacy.

To overcome such limitations, dialdehyde disinfectant solutions have been developed in US 1. ! Il! +! f permit No. 4,103,001
No. 5 (ch-attner), it was modified to contain a mixture of phenol and metal phenate. Such preparations suffer from undesirable corrosivity, toxicity and odor problems which limit their utility due to the essential phenol concentrate disclosed.

Also, U.S. Patent No. 3,917,850 (Bouche
r ) and British Patent Specification No. 1,432,324 (
Dialdehyde disinfectant baths, such as those disclosed by Eggensber-Germ et al., have been utilized.

Although phenol derivatives generally have substantially greater microbicidal activity when compared to phenol, many phenol derivatives, such as 0-phenylphenol, have limited solubility in aqueous solutions, which makes them less desirable. This will result in an unpleasantly cloudy bath solution. The presence of such suspended materials in the solution also acts to worsen the disinfecting action. Many such solutions are often contaminated with toxic by-products and there are problems with undesirable odors.

Therefore, it is essential to provide microbicidal aqueous solutions that have high efficacy over a wide range of practical applications, have minimal odor, corrosiveness and toxicity, and are sterile, i.e., solubilized, compositions in solution. There is.

SUMMARY OF THE INVENTION The present invention provides from about 0.5% to about 3.5% by weight of glutaraldehyde having 2 to 8 carbon atoms, preferably glutaraldehyde.
and from 0.1 to about 0.5 coulometric percent of phenol, metal phenate, and mixtures thereof.

3. Detailed description of the invention The present invention relates to microorganism spores, mycobacteria, viruses,
The present invention provides an improved sterilizing aqueous solution that is effective against a wide range of microorganisms, including bacteria. Such solutions also have low corrosivity and toxicity, are relatively odorless, and are essentially completely solubilized, clear compositions.

The sterilizing aqueous solution of the present invention mainly consists of a mixture of a saturated dialdehyde of a specific degree of harshness and a specific phenolic compound.

Saturated dialdehydes can be either straight-chain or branched and have from 2 to 8 carbon atoms, preferably from 3 to 5 carbon atoms, and include glyoxal (ethanedial),
Contains at least one of the following: malonaldehyde (propanedial), succinic aldehyde (butanedial), glutaraldehyde (pentanedial), adibaldehyde (hexanedial), etc. The most preferred dialdehyde is glutaraldehyde.

The phenolic compounds used in this invention are phenol, ie hydroxybenzene; metal phenates, ie metal salts of phenol; and mixtures of phenols and metal phenates. The metal phenates that can be used are those of groups 1, 11 or transition metals of the periodic table. Preferred metal phenates are alkali metal phenates of phenols, such as sodium or potassium phenates. Phenates of the type included in this invention include those formed by adding phenol to a sterile aqueous solution containing a metal cation that reacts with the phenol to form a total concentration of 7-enate salts.

A particularly preferred phenolic compound is phenol.The concentration of the mixture of dialdehyde and phenolic compound in the aqueous compositions of the invention is within a critical concentration range. The aqueous composition comprises about 0.5% to about 3.5% by weight dialdehyde;
Preferably from about 1.5 to about 2.5% by weight and from 0.1 to about 0.5% by weight of phenolic compounds, preferably about 0.2%.
~0.4% by weight. Aqueous compositions containing dialdehydes at concentrations lower than about 0.5% by weight do not have sufficient bactericidal activity, while compositions containing dialdehydes greater than about 3.5% by weight limit their utility. It has an undesirable odor and a poisonous odor. Additionally, aqueous compositions containing less than about 0.1% by weight of phenolic compounds do not have the desired broad range of bactericidal action, and compositions containing greater than about 0.5% by weight of phenolics do not have the desired broad range of bactericidal action. Has undesirable corrosive, toxic and odor properties.

The majority of aqueous compositions consist primarily of water, but may optionally include other additives commonly added to such compositions and known to those skilled in the art. Representative additives include, among others, U.S. Patent Application No. 477.593 (1983
buffering agents; chelating agents; coloring agents; fragrances; and U.S. Pat. No. 4,103,0
There are surfactants such as those described in No. 11 (5chattner). These additives may be prepared directly in the liquid phase of the aqueous solution, or they may be added prior to use as a liquid or surface phase and mixed with the aqueous composition to form an isolated disinfectant formulation. You can also get it.

The aqueous disinfectant composition v/4 of the present invention is useful as a disinfectant and sporicidal agent for laboratory, medical, dental and other equipment, supplies or objects.

A method of disinfecting such an object comprises contacting the object with a disinfecting amount of the aqueous composition of the invention for a sufficient period of time.

In a typical embodiment, the dialdehyde and selected phenolic compound(s), introduced in conventional manner as a bath solution, are added to water to form a liquid phase. This liquid phase is
It usually contains additives such as surfactants, fragrances or chelating agents. Other additives including buffers and colorants,
Usually provided in a solid or liquid phase, this phase or liquid phase is then added to and mixed with the bulk liquid phase before use as a disinfectant or sporicidal agent.

As a result of research, the inventors have discovered that the aqueous compositions of the present invention exhibit a broad range of combined disinfecting/sporicidal activity. This aqueous composition acts as a disinfectant to inhibit proliferative pathogenic organisms including Mycobacterium tuberculosis. This range of action is particularly surprising. This is because higher concentrations of dialdehyde alone cannot provide such a wide range of action. These results disclose that the use of all known phenol-conductors to have a minimum effective concentration of phenol that is substantially higher than that of the present invention and a much higher potency than the phenolic compounds of the present invention. This is unexpected in view of the prior art.

EXAMPLES The following examples are intended to specifically illustrate the practice of the present invention, and are not intended to limit the scope of the present invention.

Chemical nomenclature used in the Examples is defined as follows.

Name Description Buffer I Disodium phosphate buffer ■ Disodium phosphate 7H10 sluggish agent ■
Sodium carbonate buffer ■ Sodium carbonate buffer ■ Sodium formaldehyde sulfoxylate buffer ■ Sodium phosphate chelating agent I Ethylenediaminetetraacetic acid [(EDTA) 40% aqueous solution colorant of IJium salt I D+CGreen#8 Interface Activator ■ Union Carbide Corp. is an ethoxylated nonylphenol with an average of 9 moles of ethylene oxide.

TERGITOL, TPA SurfactantP manufactured by
-9 yf active agent ■ α-olenoin sulfur salt 40
% Water Bath Liquid Surfactant 111 TERGITOLTM Surf from Union Carbide Corp, H which is a linear etll alkoxylate with an average of 3 moles of ethylene oxide
actant 25-L-3 Examples 1 and 2 An aqueous disinfectant composition of the present invention was prepared using all of the chain components listed in Table 1. The preparations were made by mixing the components in phase and then adding the in phase mixture to the liquid phase. Then, using the standard child side as described in the notes to Table I,
SIl! The total bactericidal activity of the I product was tested.

A killing virus test using the viruses listed in Table 3 was conducted as follows. Polio virus.

Type■(Strain Brunhilde ATCC#VR
-58) was inoculated into Vero cells. When the cytopathological effect became apparent, a second group of Vero cells was added to the
The flasks were frozen and thawed in the fluid used to freeze and thaw the contents of these flasks by freezing-w4 cryocentrifugation after approximately 2 hours, as soon as cytopathological effects became apparent. The supernatant fluid was stored frozen at t--70±10°C. Kokisatsky virus.

Type I (strain Conn, ATCC #VR-103
2) Oyohiherpes symbrex A-,
Type■ (strain F, ATCC#VR-733) kP
Prepared with Jl;j5. The time between Vero cell inoculation and emptying was longer for these two viruses. Influenza virus.

Type A2 (Hong Kong Kakyuu, ATCC#VR-544
) was prepared in hen eggs. Virus was applied to the embryonic eggs, and after 48 hours, allantoic fluid was removed. This fluid was stored at -70±10° C. until use.

The test article was supplied as a powder, and each batch was fully activated by dissolving the contents of a small vial with a liquid Oya pin attached to the vial.

The activation was conducted on the 28th prior to the actual exam. The pH of the test article was measured immediately prior to testing.

The vial of test virus was removed from storage at -70°C, thawed, and kept on ice until ready for use. Sterilized benzylinda made of stainless steel was charged to Virus Q, 8ruJ aliquots and allowed to absorb for 30 minutes at room temperature. The cylinders were then removed and placed on top of a paper disc in a bedding dish with the cover open. The cylinders were dried for approximately 30 minutes at 30±5° C. in an incubator at 40±5% relative humidity.

The test solution was brought to 20°C before testing. The dried cylinders were loaded into 10 m samples of activated and negative test articles. Virus-free Pe/nijilinda was loaded into a sample of the test article for use as a cytotoxic control. All cylinders were exposed to 20°C for 10 minutes. The cylinder was then removed from the test solution, placed in tryptose phosphate broth 1.8- and
Stir intermittently for minutes. Arch, Exptle, Path, P
harmakol (vol. 162, pp. 480-483 (19
31)) by Karbers G-r Beitra
g zur kollektivin Behandl
ungPharnakologischer Re1h
Viral titers were calculated by the method disclosed in J. Enversuchi.

When compared to controls, compositions of the invention can exhibit significant bactericidal activity superior to compositions containing an equivalent or higher concentration of dialdehyde alone at a concentration that exceeds the total concentration of the dialdehyde/phenol mixture. it is obvious. The results demonstrate that the compositions of the invention exhibit significant tuberculicidal activity even when containing relatively low concentrations of phenol, down to 0.2% by weight. This result is particularly unexpected when compared to Control B, which contains a higher total concentration of active substance.

Examples 3 and 4 These examples demonstrate the production of liquid concentrates to be diluted before use in the production of compositions of the invention, which compositions contain 10 times the amount of active substance. do. first,
Such concentrates were made by adding the surfactant and perfume to water and then dissolving the chelating agent.

The solution was then heated to 45° C. and phenol was added to fully adjust the pIf to 4.5. The solution was stirred at 45°C for approximately 1 hour. Glutaraldehyde was added and the solution was rapidly cooled to room temperature. The cloudiness in the solution cleared within 24 hours.

Other suitable additives, including buffers, are added to the diluted solution prior to use.

Table I Aqueous sterilizing formulation solid phase: Buffer V 13.853 69.265 Buffer It 3
2.187 Buffer Vl 1.020 Buffer m 3.380 15.407 Buffer IV 1.884 Buffer I 85.226 Colorant I O,0160,080 Liquid phase bichelating agent I 20.0 20.0 2.0 Fragrance 0.
378 6.25 6.25 6.25 Surfactant I
O,757 Surfactant II 12.5 12B Surfactant ■125 Phenol; 7.571 100.0 100.0
100.0 (electricity%) (0,2) (0,4) (4
,0) (4,0)Glutaraldehyde' 18927
0 1250.0 1250.0 1250.0 (wt%) (2,5) (2,5) (25) (25) Water Q, s'a~1 gallon 23611.25 111
1.25 1111.25 total □25000.0 2
500.0 2500.0 The notes on clothing 1 are as follows.

a: using 50% water bath solution b: all i (r) per gallon of bath solution C: all i (f) per gallon of phase for a homophasic mixture 34.37 f d: all it (f ) e: Q, s, is a sufficient electric charge.

Takashi Fatemoto The notes in Table ■ are as follows.

a Nigertaraldehyde b: AOAC Test Procedures, Volume 13, Chapter 4, 56-6
Based on page 8 (1980) C: Test box 5 (Cff 4.018-4.022) d: Test box 4 (Cff 4.015-4.017) e: Test box 9, 11 parts (test tube test ) ((rI 4.048
~4.050) f: Test box 2 (ql 4.007~4.011) g:
Same procedure as described above Correction layer Showa! February 3, 1936, Commissioner of the Patent Office Mujiri Yo Tono Incident Showa 12, 1932 n iy Application No. 1 No. 423z
No. g-q no s name s74 column 4 fLIF! , 3-1'l as Schiff tv 7-"l:, ('"/7e/-
2 p-4 Person who makes the amendment Relationship with the case 1'f +
'f applicant number # number = 4-7. l)-Paihako-
Shown by J.J.

Claims (1)

[Scope of Claims] 1. Saturated dialdehyde having 2 to 8 carbon atoms from about 0.5 to
an aqueous disinfecting, tuberculicidal and sterilizing agent comprising about 3.5% by weight and 0.1 to about 0.5% by weight of a phenolic compound selected from the group consisting of phenols, metal phenates and mixtures thereof. Spore composition. 2. The composition of claim 1 containing from about 1.5 to about 2.5 weight 51 dialdehydes. 2. The composition of claim 1 containing from 0.2 to about 0.4% of 3.7 enolic compounds. 4. The composition according to claim 1, wherein the dialdehyde is glutaraldehyde. 5. Composition according to claim 'IJS1, characterized in that the phenol is selected from the group of monohydroxybenzene, sodium phenate or mixtures thereof. 6. The composition according to claim 1, further comprising a buffering agent, a chelating agent, a coloring agent, a fragrance, a surfactant, or a combination thereof. 7. Number of carbon atoms: 2 to 8 of saturated dialdehyde from about 0.5 to
an aqueous disinfection comprising about 3.5% by weight and 0.1 to about 0.5% by weight of a phenolic compound selected from the group consisting of phenols, metal phenates and mixtures thereof;
A method for disinfecting an object, the method comprising bringing the object into contact with a tuberculicidal composition and a sporicidal composition. 8. An aqueous disinfecting, tuberculicidal and sporicidal composition comprising a saturated dialdehyde having 2 to 8 carbon atoms, a phenolic compound selected from the group consisting of phenol, metal phenates and mixtures thereof, and water. An improved composition comprising about 0.5 to about 3.5 weight percent of the dialdehyde in combination with 0.1 to about 0.5 weight percent of the phenolic compound present in the composition. thing. 9. Glutaraldehyde about 1.5 to about 2.5 blood ft%
and from about 0.2 to about 0.4% by weight of a glaze of one of the group consisting of phenol, sodium phenate, or mixtures thereof. thing.