JPS6144842B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a method for producing a non-medical disinfectant containing an organic iodine-containing composition, and particularly relates to a method for producing a non-medical disinfectant containing the composition that releases active iodine. . [Prior Art] In general, methods for producing iodine-containing compositions are widely known from literature and the like. For example, US Pat. No. 1,676,554 to Hoopman discloses pharmacologically effective compositions containing iodine along with various glycerins. This composition is not manufactured by the method of the present invention and does not contain all of the ingredients used in the present invention.
In addition, Bryant's U.S. patent no.
No. 1,596,651 discloses a mucilage composition containing iodine, phenol, thymol and mineral oil, and thus differs from the present invention in its scope of ingredients and in particular the use of thymol to reduce the iodine content of the composition. It's different. US Pat. No. 1,719,523 to Stevens discloses compositions of iodine and alcohol. The patentee has thereby obtained a composition containing ethylene iodide, which can be clearly distinguished from the composition of the invention. Bommarito U.S. Patent No.
No. 1580400 relates to a composition consisting of elemental iodine, potassium iodine, guaicol, distilled water and glycerin, which is used for the treatment of thyroid cancer by injection into patients. In this composition, the glycerin acts as a solvent and is intended to reduce the irritation that can occur with injection procedures.
The elemental iodine in Bommarito is considered to be pure iodine that is recognized as a crystalline state.
The presence of iodine and potassium iodine distinguishes Bommarito's invention from the present invention. Gray, US Pat. No. 1,767,667, relates to a germicidal compound using the following components: zinc iodide, iodine in resublimated form, menthol, glycerin, alcohol, and water. Gray manufactures the composition by combining these components at low temperatures maintained below 40°C. Such limitations allow Gray's compositions to be clearly distinguished from those of the present invention. US Pat. No. 1,013,913 to Wemer specifically relates to iodine-containing compositions consisting of iodine mixed with glycerite of tannic acid. Uehma claims that the crystalline iodine is virtually dissolved in the tannins and glycerin without changing their properties or properties. However, Uehmer does not mention how to make the solution, and more importantly does not suggest heating it in the manner disclosed by the present invention. Furthermore, since the composition of Ueyma uses a tannic acid component, it is classified from the composition of the present invention. Finally, Harry's U.S. Patent No.
No. 1896171 relates to iodine-containing compositions in which iodine is used in admixture with glycerin and/or glycerol and tannic acid. The Hurley disclosure suggests that the tannic acid component is intended as a key ingredient. (page 2, line 126 - page 3, line 6
(see line). Even more importantly, Hurley discloses and claims that its compositions contain free iodine, which is clearly distinct from the teachings of the present invention. In addition to each of the cited patents cited above, the applicant is aware of references related to the subject matter of the present invention. In particular, a paper by Osol and Pines on the solubility of iodine in glycol-water solutions was published in the Journal of American
(Pharmaceutical Association), Volume 41, Page 634, in which the authors examine the solubility of iodine and various glycols, including ethylene and propylene glycol, on the effect of adding water to a solution of iodine in a solvent. We are considering this together. However, all of these tests were conducted at 25°C and are not intended to be the method of preparing Applicant's compositions in this respect. Furthermore, the bonds proposed by the above-mentioned authors as existing between iodine and the respective glycols, including the presence of complexes similar to the triiodide ion, are present in the compositions of the invention described below. It is different from Recent research on the interaction of iodine with various glycols was conducted in 1971 at Auburn University.
University) G.D.Fail (GD)
Doctor of Pharmacy Dissertation (Ph.D. Faile)
dissertation). The author has carried out extensive UV spectroscopy studies on various glycol-iodine systems, including the ethylene glycol-iodine system, all prepared at 25°C, and has
It is speculated that a complex bond described as a transition complex is formed. In particular, ultraviolet spectroscopic analysis of ethylene glycol-iodine shows an absorption maximum at 231 nm, which according to the authors is clearly indicative of the complex. However, similar to the above literature, Feil has not yet realized the present invention and its particular method of production, which uses much higher temperatures during mixing.
For reasons further discussed below, the differences between that study and the unexpected properties of the compositions of the present invention are significant. [Structure of the Invention] According to the present invention, a composition is disclosed that comprises a glycol component including ethylene glycol, a polymer thereof, and a mixture thereof, and iodine, and the composition comprises ultraviolet rays between the glycol and the iodine. It is characterized by the absence of spectroscopically identifiable complex compounds, the absence of free iodine in the solution, and the absence of water. Specifically, glycols include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol and mixtures thereof, and the iodine content of the compositions varies from 5 to 10%.
Contains the following titratable iodine content: In a preferred embodiment, the compositions of the present invention contain ethylene glycol and no more than about 5% iodine, preferably about 5% or less iodine.
Contains 0.5-5% iodine. In the composition of the present invention, an appropriate amount of iodine is added to the glycol component while stirring, and the resulting mixture is mixed with approx.
It is produced by a method consisting of heating to 180° C. and then allowing the resulting solution to cool to room temperature.
In a preferred embodiment, the process of the present invention is conducted under substantially anhydrous conditions without any moisture, and is then maintained under anhydrous conditions. The compositions of the present invention have a variety of utilities including use as non-medical disinfectants with utility in any application requiring the presence and activity of iodine, environmental applications and other industrial maintenance applications. have. This composition acts in response to moisture to release free iodine in molecular form, while in the absence of moisture it retains iodine, in which case the addition of an iodine indicator to the composition has negative consequences. arise. Furthermore, spectroscopic analysis of the composition of the present invention,
In particular, according to observation of the ultraviolet spectrum, there is no reaction exhibiting an iodine-glycol complex compound at a wavelength where such a complex compound is known to exhibit an absorption peak. Furthermore, the compositions of the present invention can be formulated into a variety of formulations, including incorporating various dispersants, vehicles, mucilages, etc., depending on the nature of their desired end use. [Object of the Invention] Therefore, the main object of the present invention is to maintain iodine as a stable solution so that when it comes into contact with a moist environment,
The object of the present invention is to provide a method for producing a non-medical disinfectant containing an iodine-containing composition that releases iodine in an amorphous molecular form. Another object of the present invention is to provide a method for producing a non-medical disinfectant containing the above-mentioned iodine-containing composition, which facilitates rapid release of molecular iodine and is non-toxic to the human body. Yet another object of the present invention is to provide a method for producing a non-medical disinfectant comprising said iodine-containing composition which exhibits suitably increased storage stability. Yet another object of the present invention is to provide a method for producing a non-medical disinfectant containing the iodine-containing composition, which exhibits significantly improved antimicrobial activity. Yet another object of the present invention is to provide a method for making a non-medical disinfectant comprising an iodine-containing composition that produces a composition that retains iodine in a stable solution. Other objects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description taken in conjunction with the accompanying drawings. According to the present invention, the above objects and advantages can be easily achieved. [Means for Solving the Problems] The present invention relates to a method for producing a non-medical disinfectant comprising a composition comprising a glycol component including ethylene glycol, polymers thereof and mixtures thereof, and iodine, the composition comprising: It is characterized by the absence of spectroscopically identifiable complex compounds between glycol and iodine and the absence of free iodine. Specifically, the glycol component of the present invention comprises a compound selected from the group consisting of ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, and mixtures thereof, and in preferred embodiments, the glycol component consists of ethylene glycol. . The compositions of the present invention differ from conventional compositions by their negative response to ultraviolet spectroscopy indicating the presence of glycol-iodine complexes as reported in the prior art by Feil's dissertation already mentioned. distinguished. Furthermore, the compositions of the present invention when prepared by the method of the present invention respond negatively to tests for free iodine in solution, indicating that iodine is less common to alcohol than suggested by the prior literature. This shows that iodine is retained in a complex compound that is different from the charge transfer complex compound. It is believed that this form of the composition retains the iodine almost completely in solution for an extended period of time, thereby providing a desirable increased shelf life. Furthermore, in addition to the feature of the present invention that effectively retains iodine in unique complex bonds, the compositions also contain amorphous molecular iodine upon direct contact with moist environments, including moisture. Can be released from solution. Finally, the compositions of the invention have improved antimicrobial activity with reduced irritation to the human body. As already mentioned, the composition of the invention is unique in that it is characterized as a reactive microorganism in that the compounds contained therein react with each other after they have been combined by the method according to the invention. It is thought to consist of a mixture. That is, it is considered that the iodine component is not obtained in a free state and does not form a complex compound with the alcohol moiety of glycol in the usual manner. According to the above discussion of Feil's paper, the author used various iodine-alcohol systems, especially systems consisting of ethylene glycol and iodine, to determine the reactions that were thought to exist between alcohol substitutes and iodine. It is shown that an experiment was conducted on The authors further conducted tests, including ultraviolet spectroscopy, and determined that the absorption bands observed were indicative of the presence of complexes between alcohol and iodine, referred to by the authors as charge transfer complexes. Applicants have conducted comparative tests to determine whether the compositions of the present invention have a structure of the type characterized by Fail, or whether different structures exist. . This comparative test is described below. Experiment 1 Dry by contact with magnesium sulfate,
The composition containing distilled ethylene glycol was then placed in an aqueous solution and exhibited an alcohol concentration of less than 1.0 molar. 100 ml of this solution was brought to 10 ^-4 M in HClO ₄ to inhibit triiodide formation. Next, 3 ml of the obtained charging solution was placed in a sample cell of an ultraviolet spectrophotometer and its ultraviolet spectrum was observed. Three crystals of resublimed iodine were added to this sample cell containing the charge solution and stirred. This stock stock solution was placed in the comparison chamber to run the spectrum. The above steps are part 11 due to fail.
The experiments were carried out as described on pages 1-15. Curve 1 of the resulting spectrum shown in Figure 1 is ethylene glycol;
Curve 2 shows that an absorption peak occurred in the 231 nm region as observed by the author, indicating the existence of a charge-transfer complex between the alcohol substituted product of ethylene glycol and iodine. Experiment 2 For comparison, ethylene glycol and iodine components were reacted in the absence of moisture by heating these components at a temperature of approximately 160°C in a commercially available reaction vessel, and the resulting solution was then exposed to air. The composition of the present invention was prepared by cooling to room temperature while maintaining the composition in a moisture-free atmosphere. A sample of this solution was then placed in an ultraviolet spectrophotometer and ethylene glycol prepared by Feil was used as a comparison sample. The observed spectrum shows the absence of absorption in the region described by the authors, especially from 230 to 240n
A significant increase in transmittance was shown in the region of m. As seen in FIG. 2, the spectra of the two curves 2 and 3 of each of the prepared products of the composition according to the invention containing 3% iodine, as well as the spectrum of curve 1 of the ethylene glycol comparison sample, were simultaneously generated. It is clear from the foregoing that the precise structure of the compositions of the present invention differs in practice from that known or expected in the prior art, as exemplified by Feil. . In addition to the structural features already discussed, the foregoing experiments have shown that there is no free iodine in the solutions prepared according to the invention. In particular, the appearance of an absorption band at 203 nm was indicative of the presence of free iodine in the glycol solution, as Feil describes on page 67 of his paper. However, referring again to FIG. 2, since there is an increase in the transmittance of the sample at these wavelengths, it appears that such absorption does not exist. Therefore, the above experiment is considered to establish that there is no complex compound between the alcohol substituted glycol and iodine and no free iodine is present in the solution containing the composition of the present invention. . As previously mentioned, the compositions of the present invention are prepared with varying iodine concentrations to suit the intended end use thereof. That is, the iodine content of the compositions of the invention can be varied up to the saturation point of iodine in the glycol component, including, for example, from 5 to 10% iodine content. More specifically, compositions containing about 5% iodine are prepared for non-medical use, and in yet another example such compositions contain 0.05-5% iodine. Also disclosed in accordance with the present invention is a manufacturing method that is believed to impart distinctive properties to the compositions of the present invention. That is, an important requirement of the method of the present invention is to heat the glycol and iodine component at 180°C while stirring.
It is heated to a certain temperature. Once this temperature is reached, the resulting product is removed from the heating source and allowed to cool to room temperature. In a preferred embodiment, the glycol component is substantially anhydrous and is prepared by removing all moisture, eg, with magnesium sulfate. The glycol is then kept substantially anhydrous, either by keeping it in an inert atmosphere or under vacuum, and a suitable amount of iodine in crystalline form is added thereto, and the resulting mixture is stirred to remove the iodine. Dissolve the crystals. The resulting solution is then heated to said temperature while maintaining anhydrous conditions and then cooled to room temperature to form the complete reaction product. An important feature of the method of the invention is that the composition is
It is heated to a temperature of 180℃. According to the applicant, whereas compositions containing higher alcohols such as glycerol produce non-hydrolyzable compounds upon reaction within this temperature range, the compositions of the present invention It was found that iodine readily hydrolyzes to generate free iodine in the molecular form when it comes into contact with a moist environment. That is, the process of the present invention is carried out at temperatures ranging from about 140°C to about 180°C, and in a preferred embodiment a reaction temperature of 160°C is used. Another feature of the method of the invention is the use of anhydrous reaction conditions to produce a substantially water-free composition. It was unexpectedly discovered that greater stability could be added to the resulting compositions by using anhydrous reaction conditions, since the retention of iodine by binding to the glycol resulted in negative iodine indicator tests. This is because it is accelerated to such an extent that it shows a positive result and shows the absence of free iodine from the solution. Although it is preferred to form and maintain anhydrous reaction conditions, the compositions of the present invention may also be produced under conditions that allow access to air and therefore moisture while still yielding compositions having all of the above properties. ,
Anhydrous conditions are not necessarily required. Therefore, this invention is not limited to the use of anhydrous reaction conditions; such conditions are believed to represent the best mode of carrying out the invention. As mentioned above, the compositions of the present invention are specifically used in various applications, and are therefore formulated with various additives, dispersants, carriers, etc. to facilitate use in such applications. Thus, the compositions of the present invention have been found to have significant antibacterial and antimicrobial properties and are mixed with suitable dispersants such as propylene glycol for application in liquid form. Such a mixture is preferably prepared, for example, by combining 1 part by volume of the composition of the invention and 3 parts by volume of propylene glycol. Alternatively, the composition of the present invention and an appropriate amount of an excipient or carrier such as mannite or a polyethylene glycol having a high molecular weight of about 6000 may be formulated so that each of these ingredients has a consistency of cream or thick paste. Mix in proportions that vary over a range of things. Additionally, other materials may be used that act to provide a suitable medium for presenting the compositions of the invention according to the desired use. That is, the composition of the present invention can also be used as a liquid additive in environmental and water purification such as fish water, tooth sterilization, and hard surface cleaning applications. The compositions according to the invention are used in each case on their own or in combination with suitable additives. The scope of the present invention will be explained below with reference to Examples. [Example] Example 1 2 g of iodine crystals were added to 100 g of ethylene glycol in a 500 ml beaker at room temperature with stirring. The ethylene glycol-iodine mixture was then heated to a temperature of about 160 DEG C. while stirring, and immediately after reaching this temperature, it was removed from the heat source and allowed to cool to room temperature. During cooling, the beaker was sealed and no further stirring was performed. Example 2 9.0 g of iodine was placed in a loosely sealed 500 ml beaker at room temperature and then 450 g of ethylene glycol was added with stirring. The ethylene glycol-iodine mixture was then heated to a temperature of 160 DEG C. with continued stirring. When the temperature reached 160° C., the beaker containing the composition was immediately removed from the heat source, and the solution was allowed to gradually cool to room temperature in a sealed state without stirring. One part by volume of the composition was then mixed with three parts by volume of propylene glycol at room temperature. The mixture was then tested for free iodine by dipping a starch indicator paper into a portion of the resulting mixture. The starch indicator paper showed no reaction, indicating the absence of free iodine from this solution. Example 3 This example demonstrates the preparation of a composition of the invention in which the glycol component consists of diethylene glycol. Therefore, 5.37 g of iodine was placed in a loosely sealed 250 ml Erlenmeyer flask, and then 263.0 g of diethylene glycol was added with stirring. The resulting mixture having an iodine content of approximately 2% by weight was heated with stirring to a temperature of 160°C. When the temperature reached 160°C, the flask was removed from the heat source, sealed, and allowed to cool gradually to room temperature without further stirring. The resulting composition was then titrated with a 1N Na ₂ S ₂ O ₃ standard solution and found to contain 1.35% available iodine. The above composition compares well with a comparative composition prepared using monoethylene glycol which yields 1.30% available iodine upon titration. Furthermore, the composition of Example 3 responded similarly to the compositions of Examples 1 and 2 in all other respects. Example 4 A composition of the present invention was prepared in which the glycol component consisted of polyethylene glycol. That is, 3g
of iodine was placed in a loosely sealed 500 ml container at room temperature, and then 97 g of polyethylene glycol having a molecular weight of 400 was added with stirring. This glycol-iodine mixture is then heated to a temperature of 160°C with stirring,
Thereafter, the container was removed from the heat source and the solution was allowed to gradually cool to room temperature in a sealed state and without further stirring. The product was then titrated with a 1N Na ₂ S ₂ O ₃ standard solution and found to contain approximately 1.915% available iodine. The composition thus prepared gave a negative response to the available iodine test, but when mixed with water gave a positive response to the iodine indicator test. The compositions of the present invention are characterized by their ability to release molecular iodine upon contact with an aqueous medium and are therefore useful for the oxidation of iodine for fixed-term compounds. Additionally, the composition has antimicrobial properties and is therefore useful as a preservative and disinfectant in industrial applications. Moreover, this composition is not toxic to living tissues. In order to confirm the above-mentioned usefulness, the following several tests were conducted. Experiment 3 A composition of the invention containing 0.3% free iodine by titration was prepared and this was applied to a series of concentrations of free _I2 of 0.0003
Trypticase was diluted in soy broth (TBS) to span ~0.075%. Although the composition of the present invention does not contain free iodine, free iodine is released when diluted with a TBS solution. Next, each of the prepared media was inoculated with the following microorganisms, and these were cultured at 35°C for 16 to 18 hours. Staphylococcus aureus #6538, Staphylococcus aureus
−Gregg strain, Staphylococcus
Albus (Staphyloccus albus) 914-4-1A,
Pseudomonas cepacia
cepacia) 153, Sarcina lutea (Sarcina
lutea) ATCC #9341RR, Escherichia coli ATCC #10536, Pseudomonas aeruginosa
aeruginosa) 568-18-1A and Enterobacter cloacae (Enterobacter cloacae) 603-1
−1B. Inoculation was performed by adding 0.05 ml (1 drop) of overnight aged broth medium to 10 ml of antimicrobial in TBS. The transfer tube used to determine the bactericidal activity end point of the titrated compound contains a neutralizing agent,
Tween (0.5%), lecithin (0.07%) and sodium thiosulfate (1%)
was prepared by adding to TBS. 35 of these inoculum tubes containing dilutions of test compound
C. for 48 hours and the presence of growth (+) was recorded for each tube. 1.0 ml of solution from tubes showing no growth (-) was transferred to 10 ml of neutralized broth, and the tubes containing this neutralized broth were then incubated at 35° C. for 48 hours. The bactericidal activity endpoint was determined for each sample by the absence of growth in these tubes. The results of these tests are shown in Table 3.

[Table] From the above tests, it was determined that the composition of the present invention requires a concentration of 0.03% free iodine to kill Gram-positive bacteria, and a concentration of 0.05% free iodine to kill Gram-negative bacteria. Ta. The fungicidal activity of the compositions of the invention is thus clearly demonstrated. Experiment 4 The skin toxicity of the composition of the present invention was determined under the Hazardous Substances Labeling Act.
Regulation) Part 191, Chapter 1, Title 21, Code of Federal Regulations, Section 191, Section 10, a dose of 2.2 g/Kg of naked skin from six rabbit subjects was placed in gauze pads. The gauze pad was tested by holding the gauze pad in place for 24 and 72 hour measurement times. According to the test results, this composition did not cause mortality, and therefore, this composition was determined to be non-toxic to the skin. Experiment 5 A further toxicity study was conducted consisting of an eye irritation test. According to this, a 0.1 ml sample of the composition tested in Experiment 4 was prepared under Part 191, Chapter 1, Title 21, Code of Federal Regulations of the Hazardous Materials Labeling Regulations.
It was applied to the eyes of albino rats according to the method described in Section 191, 12. That is, the composition was applied to one eye of a rabbit while the other eye was left alone for control. These eyes were then examined daily for a total of 7 days for eye response. Six rabbit subjects were used in this test and the results are shown in Table 5 below.

【table】

From the above tests, the compositions of the invention do not cause irritation to the eyes of rabbits and are therefore considered non-irritating in this respect. The foregoing data suggest that the compositions of the present invention have utility in non-medical and general industrial applications requiring bactericidal properties. It will be clear that the above-described composition can be used for a variety of other useful uses in addition to those specifically described above, and therefore the scope of the present invention is not limited to these only.

[Brief explanation of the drawing]

FIG. 1 shows the ultraviolet spectral curves for ethylene glycol (curve 1) and a mixture of ethylene glycol and iodine according to the prior art (curve 2); FIG. This is an ultraviolet spectral curve obtained by the analysis of 3).

Claims (1)

[Claims] 1. In a method for producing an iodine-containing composition free of free iodine, a titratable amount of 10% or less of a certain amount of a glycol component selected from the group consisting of ethylene glycol, polymers thereof, and mixtures thereof. of iodine, heating said mixture to a temperature in the range of 140°C to 180°C, after which said mixture is cooled to room temperature and maintained under anhydrous conditions. method for producing the agent. 2. A method for producing a non-medical disinfectant comprising the iodine-containing composition according to claim 1, wherein the temperature is in a range of about 160° C. or less. 3. A method for producing a non-medical disinfectant containing the iodine-containing composition according to claim 1, characterized in that the glycol component and the iodine are stirred during mixing and heating. 4 The glycol component is ethylene glycol,
A method for producing a non-medical disinfectant containing the iodine-containing composition according to claim 1, wherein the iodine-containing composition is selected from the group consisting of diethylene glycol, triethylene glycol, polyethylene glycol, and mixtures thereof. 5. Claim 1, wherein the glycol component consists of ethylene glycol.
A method for producing a non-medical disinfectant comprising the iodine-containing composition described in 1. 6. A method for producing a non-medical disinfectant comprising the iodine-containing composition according to claim 1, wherein the iodine component is in a range of about 5% or less. 7. Claim 6, wherein said iodine content is in the range of about 0.05% to about 5%.
A method for producing a non-medical disinfectant containing an iodine-containing substance as described in 1.