RU2189570C2 - Composition for thermal and time indicator of steam sterilization - Google Patents

Abstract

FIELD: units for monitoring temperature and time conditions of steam sterilizers, manufacture of indicators changing their color at integral action of definite temperature and pressure of water vapor during preset interval of time. SUBSTANCE: composition contains mixture of aminosulfonic acid (ureasulfonate, or thiourea, or guanidine) registering components which is just pH-indicator or mixture of pH-indicators changing its color in acid zone. Urea-sulfonic acid (sulfuric acid), sulfamic acid, sulfanilic acid or metanilic acid may be used as aminosulfonic acid, Basic urea sulfonates (sulfanilurea, urasulfane, etc.) or thioreas (badional, etc.) or guanidine sulgin, etc. ) as well as acid urea sulfonates (sulfanilic acid urea, etc.) or thioreas (sulfamic acid thiourea, etc.) or guanidine (sulfamic acid guanidine, etc. ) may be used salts aminosulfonic acid. One of the following pH-indicators or their mixture may be used as registering component in proposed composition; bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red and bromocresol green. EFFECT: avoidance of toxic components in reaction products; reduced rate of hydrolysis, if necessary, of components; retaining final color of composition during extended period of time. 8 cl

Description

 The invention relates to means of thermometry, and in particular to means of monitoring the operation of steam sterilizers, and can be used in the manufacture of chemical thermo-time indicators used in medicine, veterinary medicine, balneology, heat engineering, pharmaceutical and food industries.

 In the practice of monitoring the operation of steam sterilizers, various methods are used to register the sterilization process: physical, biological (tests based on microorganism strains), and chemical. The most widespread because of its simplicity, rapidity and cheapness are chemical control methods based on the use of chemical thermo-time indicators.

 Chemical thermo-time indicators are made on the basis of compositions in which, under the influence of temperature and steam, a color change is observed as a result of a chemical reaction. At the same time, after the exposure of these compositions in dry air at typical temperatures and time of steam sterilization, the color of the compositions should remain the original, or change slightly and noticeably differ from the final state achieved by exposure in a steam sterilizer.

 Known compositions for thermal indicators, in which the active components are salts of polyvalent metals and sulfur and / or sulfur-containing compounds (see, for example, UK patent 1132334, CL C 3 F, 1968).

 The disadvantages of this type of composition are as follows. The color change of the composition occurs in this case due to a chemical reaction between the active components of the composition, which leads to a gradual color change, while it is impossible to clearly indicate compliance with the sterilization parameters. The color change time of the compositions depends on the thickness of the layer, which requires strict control of compliance with the technology of applying the composition. The composition of the composition contains environmentally harmful components - salts of polyvalent metals. In addition, the formulation of the composition does not allow varying in a wide range of values of the recorded parameters (temperature and time).

 Compositions are also known, in which carboxylic acids and their salts, esters, pyridines are used as active components, which when hydrolyzed in steam are hydrolyzed, and a recorder component that shows the degree of hydrolysis of these components by color; these are acid-base (pH) or redox indicators (see, for example, UK patent 1,415,782, class G 1 B, 1975; US patent 4,880,466, class 106 / 31.32, 1989). In these compositions, the color change occurs due to the color transition of the recorder component, showing the depth of the chemical reaction between the active components of the composition.

 Closest to the proposed composition in terms of technical nature and the achieved result is a composition for a thermo-time indicator for monitoring steam sterilization processes, containing a mixture of organic acid and its salt and a component-recorder, which is a pH indicator or a mixture of pH indicators and changes color when changing from acidic region to alkaline (UK patent 1415782, CL G 1 B, 1975). The known composition contains, in particular, a mixture of 2,4-dihydroxybenzoic acid and its sodium salt, a mixture of pH indicators that change color when changing from an acidic to an alkaline region, for example a mixture of methyl red and bromothymol blue, are used as a recording component.

A disadvantage of the known composition is that the end product of the reaction in this composition is an environmentally harmful component - resorcinol. The hydrolysis rate of the carboxylic acids and their salts used in the composition of this composition is quite high, which does not allow for the manufacture of thermo-time indicators with long recording times of process parameters - more than 20 minutes at temperatures of about 130 ^o C. In addition, when the components of the composition are hydrolyzed, the pH of the medium changes from neutral (equilibrium) to an increase in alkalinity (unstable), as a result, the final color of the composition does not persist for a long time, which does not allow the use of chemically th thermal indicator based on this composition to document the operation of steam sterilizers.

 The technical results achieved by the implementation of the present invention are: elimination of environmentally harmful components from the reaction products, reducing, if necessary, the hydrolysis rate of the components used in the composition of the composition and ensuring the preservation of the final color of the composition for a long time.

These results are achieved in that the composition for a thermo-time indicator for monitoring steam sterilization processes, containing a mixture of an organic acid and an organic acid salt and a recorder component, which is a pH indicator or a mixture of pH indicators and changes color in the acidic region, as an organic mixture acids and salts, the composition contains a mixture of aminosulfonic acid and salts of aminosulfonic acid (urea or thiourea or guanidine sulfonate) in the following ratios of components, m ass.%:
Aminosulfonic acid - 5-79.9
Aminosulfonic acid salt (urea or thiourea or guanidine sulfonate) - 20-90
Recorder component - 0.1-10
As aminosulfonic acid, urea-sulfonic (sulfuric) NH ₂ CONHCO ₃ H, sulfamic NH ₂ SO ₃ H, sulfanilic NH ₂ C ₆ H ₄ SO ₃ H or methanyl C ₁₈ H ₁₄ N ₃ SO ₃ H acid can be used.

As salts of aminosulfonic acids can be used:
- the main urea sulfonates (ureides) - sulfonylurea NH ₂ CONHSO ₂ NHCONH ₂ , urasulfan NH ₂ C ₆ H ₄ SO ₂ NHCONH ₂ ;
- acidic urea sulfonates — sulfuric acid NH ₂ CONHCO ₃ H • NH ₂ CONH ₂ , sulfonyl acid NH ₂ C ₆ H ₄ SO ₃ H • NH ₂ CONH ₂ , sulfamic acid NH ₂ SO ₃ H • NH ₂ CONH ₂ urea;
- basic thiourea sulfonates - Badional NH ₂ C ₆ H ₄ SO ₂ NHCSNH ₂ and others;
- acid thiourea sulfonates - sulfonyl acid thiourea NH ₂ C ₆ H ₄ SO ₃ H • NH ₂ CSNH ₂ and others;
- the main sulfonates of guanidine - sulgin (sulfaguanidin) NH ₂ C ₆ H ₄ SO ₂ NHCNHNH ₂ and others;
- guanidine acid sulfonates - guanidine sulfamic acid NH ₂ C ₆ H ₄ S0 ₃ H • NH ₂ CNHNH ₂ and others.

 The recording component may be one of the following pH indicators or a mixture thereof: bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red, bromocresol green.

 The composition may, in the particular case, contain sulfuric acid as an aminosulfonic acid, urea sulfuric acid as a salt, and bromphenol blue as a recording component. In another particular case, the composition may contain sulfamic acid as an aminosulfonic acid, urasulfan as a salt, and a mixture of bromophenol blue with bromochlorophenol blue as a recording component. In another particular case, the composition may contain sulfanilic acid as an amino sulfonic acid, sulgin as a salt, and bromocresol green as a recording component.

 The composition is based on the principle of high-temperature hydrolysis of aminosulfonic acid and a salt of aminosulfonic acid (urea sulfonate, or thiourea, or guanidine), which leads to a change in the acidity (pH) of the composition, which is accompanied by a change in color of the acid-base indicator or a mixture of acid-base used in its composition indicators. This composition has under normal conditions a strongly acidic environment (pH <3), but with prolonged exposure to hot water vapor, the acidity changes towards its decrease (and increase the pH), which is accompanied by a change in the color of the pH indicator or mixture of pH indicators and ensures compliance steam heat treatment parameters (temperature, time). The absence of a corresponding color change indicates non-compliance with the exposure parameters in water vapor.

 Compliance with the proposed quantitative ratio of the components in the composition is due to the need to ensure the response parameters of the indicators, the necessary color characteristics in the initial and final states. Moreover, if the aminosulfonic acid in the composition will be more than 80 wt. %, a color change will not occur, no matter how long the indicator is paired. At the maximum salt content of this acid (90 wt.%), The minimum response time of the indicator is provided, while reducing its content to less than 20 wt. % indicator does not work. The content of the registrar component is determined by the necessary intensity and contrast of colors, exceeding its content of more than 10 wt.% Leads to an increase in the time interval for color change.

When urea-sulfonic (sulfuric) acid NH ₂ CONHSO ₃ H and sulfanylurea (NH ₂ CONН) ₂ SO _{2 are} used in the composition, the acid and ureide are hydrolyzed at the first stage to form sulfuric acid and urea, but only after complete destruction of these compounds does hydrolysis begin urea with the formation of ammonium sulfate. Due to the fact that urea is a very weak base, a high acidity (low pH) is maintained in the solution until the hydrolysis of urea begins. After the start of urea hydrolysis, a sharp (abrupt) decrease in acidity (increase in pH) of the composition occurs, which provides a contrasting color change in a narrow time interval.

Аналогичным образом происходит гидролиз уреида сульфуровой кислоты, с образованием сульфата аммония и аммиака:

Варьируя соотношением кислоты и уреида в композиции, можно получить регистрацию (за счет изменения цвета композиции) соблюдения параметров термообработки водяным паром в широком диапазоне времени (от 1 минуты до 5 часов) и температуры от 100 до 150^oС.The hydrolysis of sulfuric acid is described by the following equation:

Similarly, the hydrolysis of ureide sulfuric acid occurs, with the formation of ammonium sulfate and ammonia:

Varying the ratio of acid to ureide in the composition, it is possible to obtain registration (by changing the color of the composition) of compliance with the parameters of heat treatment with steam over a wide range of time (from 1 minute to 5 hours) and temperatures from 100 to 150 ^o C.

Using the composition of the composition of various pH indicators or mixtures thereof that change color in the pH range from 2.7 to 5.5, you can get different source and final colors of the composition, different nature (spasmodic or gradual) color transition and different transition points (according to pH of the medium). As pH indicators, you can use:
bromphenol blue - the transition of color from yellow to blue;
methyl yellow - transition from red to yellow;
methyl orange - the transition from red to yellow-orange;
bromochlorophenol blue - the transition from yellow to purple;
Congo red - transition from blue-violet to violet;
bromocresol green - transition from yellow to green (blue),
or mixtures thereof:
bromochlorophenol with bromphenol blue - the transition from yellow to black, etc.

 In the manufacture of a chemical thermal indicator, the present composition is introduced into the carrier (porous substrate, for example, filter paper) by impregnation from an aqueous or alcohol solution, or applied to the carrier or substrate by irrigation, printing, etc. as a mixture of a composition and a polymeric binder. Solutions of simple and complex polyesters - cellulose ethers, polyvinyl alcohol esters, malonic acid esters, polyvinyl alcohol, polyvinyl chloride, etc., can be used as a binder, water, alcohols and ethers, aliphatic, aromatic, chlorinated hydrocarbons and t .d.

 The mass ratio of the composition and the binder does not affect the response parameters of the indicator, but is determined by the technology of introducing the composition into the composition of the carrier.

 The most practical is the application of the composition by conventional printing. In this case, the composition is applied to the substrate in the form of spots, patterns or inscriptions. After drying, the indicator mark or inscription is covered with a transparent film to prevent mechanical damage and steam washing.

 Example 1

 28 g of sulfuric (urea-sulfonic) acid, 5 g of sulfuric acid urea (or thiourea) and 1.5 g of the recorder component are ground into fine powder. The resulting powder is added to 100 g of a 40% solution of polyvinyl chloride in carbon tetrachloride. The components are stirred until a homogeneous, thick mixture is obtained. The resulting paint is applied to the polymer substrate by printing in the form of a round indicator label. After evaporation of solvents, the indicator label is sealed with a polymer film resistant to water vapor and high temperature.

Exposure to dry air with a temperature of 140 ^o C for 30 minutes does not change the color of the indicator mark.

When the chemical thermo-time indicator is kept under pressure of saturated water vapor at 130 ^o С, the process of hydrolysis occurs, and the color of the label changes. The initial and final colors of the indicator label, the nature and time of the color change depends on the composition of the registrar component (Table 1).

 Example 2

 50 g of sulfamic acid, 14 g of badional, 2 g of the registrar component are taken, everything is mixed and ground in a mill until a homogeneous fine powder is obtained. A polymer binder (40% solution of cellulose ether in acetone) in an amount of 100 g is added to the obtained powder. The resulting mixture is triturated to a homogeneous state and applied by the method described in Example 1.

Exposure to dry air with a temperature of 140 ^o C for 30 minutes does not change the color of the indicator mark.

When holding a chemical thermal indicator at 120 ^o C under pressure of saturated vapor, the color of the indicator label changes. The nature of the color change of the indicator label is given in table.2.

Changing the ratio of the components of this composition, as well as in the case of the composition described in example 1, you can get the response time of the chemical thermal indicator in a wide range for temperatures of 100-150 ^o C.

 Example 3

 97 g of finely ground sulfamic acid powder is taken, 160 g of urasulfan and 3.5 g of a mixture of bromophenol and bromochlorophenol blue are added. An aqueous solution of 10% polyvinyl alcohol in an amount of 500 ml is poured into the resulting mixture and adjusted to a homogeneous state by the usual method.

 The paint is applied by the method described in example 1.

Drying of the paint is carried out by blowing with dry air, the temperature of which is increased from 35 to 100 ^o C. as it dries. In order to protect it from mechanical damage and wash out with steam, the indicator mark is closed with a film resistant to water vapor and high temperature.

Exposure to dry air with a temperature of 140 ^o C for 30 minutes does not change the color of the indicator mark.

When holding the thermal indicator at a temperature of 110 ^o C in an atmosphere of saturated steam, the color of the mark in the first 15 minutes remains the original - yellow, in the range of 15-18 minutes there is a change of yellow to black. With a further increase in exposure time, the color of the mark does not change.

By changing the ratio of components, you can vary the response time of the indicator in a wide range:
at 100 ^o C - from 2 minutes to 4 hours;
at 110 ^o C - from 5 minutes to 3 hours;
at 120 ^o C - from 5 minutes to 2 hours;
at 132 ^o C - from 2 minutes to 60 minutes.

 Example 4

 200 g of finely ground sulfanilic acid powder is taken, 90 g of sulgin, 3.5 g of bromocresol green powder are added, mixed and ground to a fine powder, poured into 500 ml of a 2% solution of polyvinylpyrrylidone in water. The resulting mixture is stirred until a homogeneous solution is obtained.

The paper base is impregnated with this solution, dried with a gradual increase in temperature from room temperature to 100 ^o C. The impregnated and dried paper is cut into separate strips and hermetically sealed in a transparent polymer film based on polyolefins, polyesters, fluorinated polymers, polyamides. For impregnation, the manufacture of a solution without a polymer binder is allowed.

Exposure to dry air with a temperature of 140 ^o C for 30 minutes does not change the color of the indicator mark.

When holding the thermal indicator at a temperature of 132 ^o С under saturated steam pressure, the paper color in the first 18 minutes remains the original - yellow, in the range of 18-20 minutes, the color changes to blue. With a further increase in the exposure time, the color does not change.

By changing the ratio of components, you can vary the response time of the indicator in a wide range:
at 100 ^o C - from 15 minutes to 5 hours;
at 120 ^o C - from 5 minutes to 3 hours;
at 132 ^o C - from 2 minutes to 60 minutes.

 Example 5

 100 g of finely ground sulfamic acid powder is taken, 120 g of urea sulfamic acid (or thiourea) and 7 g of alizarin red are added. The resulting mixture is added to 100 g of a 40% solution of polyvinyl chloride in carbon tetrachloride and carefully rubbed to a homogeneous state.

 The paint is applied by the method described in example 1. The paint is dried by blowing with warm air. In order to prevent mechanical damage and steam washing, the indicator mark is sealed on top with a polymer film that is resistant to water vapor and sterilization temperature.

Exposure to dry air with a temperature of 140 ^o C for 30 minutes does not change the color of the indicator mark.

When holding the thermal indicator at a temperature of 120 ^o C in an atmosphere of saturated steam, the color of the mark in the first 35 minutes remains the original - yellow, in the range of 35-45 minutes, the color changes to purple. With a further increase in exposure time, the color of the mark does not change.

By changing the ratio of components, you can get the time interval of color change in a wide range from 2 minutes to 5 hours at temperatures of 100-150 ^o C.

Thus, the above examples show that in all variants, the main component in the final product is ammonium sulfate, which is an environmentally friendly compound. Using this composition allows you to significantly extend the time interval for the operation of indicators, allows you to make indicators with a short time (5 minutes at 120 ^o C), and with a long time (more than 30 minutes at 132 ^o C) of operation. In all the examples cited, the preservation of the final color of the indicators was more than one year in a heated room, which allows the use of indicators to archive sterilization control results.

Claims (7)

1. A composition for a thermo-time indicator for monitoring steam sterilization processes, comprising a mixture of an organic acid and an organic acid salt and a recorder component, which is a pH indicator or a mixture of pH indicators and changes color in the acidic region, characterized in that as an organic mixture acid and salt, the composition contains a mixture of aminosulfonic acid and salts of aminosulfonic acid (urea sulfonate, or thiourea, or guanidine) in the following ratio, wt. %:
Aminosulfonic acid - 5-79.9
Aminosulfonic acid salt (urea or thiourea or guanidine sulfonate) - 20-90
Recorder component - 0.1-10
2. The composition according to p. 1, characterized in that urea-sulfonic (sulfuric), sulfamic, sulfanilic or methanilic acids are used as amino sulfonic acid.  3. The composition according to paragraphs. 1 and 2, characterized in that the main urea sulfonates (sulfanylurea, urasulfan, etc.), or thiourea (badional, etc.), or guanidine (sulgin, etc.) are used as the amino sulfonic acid salt.  4. The composition according to paragraphs. 1 and 2, characterized in that as the salt of the aminosulfonic acid are used acidic urea sulfonates (sulfonylate urea, etc.), or thiourea (sulfamic acid thiourea, etc.), or guanidine (guanidine sulfamic acid, etc.).  5. The composition according to paragraphs. 1-4, characterized in that the registration component is one of the following pH indicators or a mixture thereof: bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red, bromocresol green.  6. The composition according to paragraphs. 1, 2, 4 and 5, characterized in that it contains sulfuric acid as an aminosulfonic acid, urea sulfuric acid as a salt, and bromphenol blue as a recording component.  7. The composition according to PP. 1-3 and 5, characterized in that it contains sulfamic acid as an aminosulfonic acid, urasulfan as a salt, and a mixture of bromophenol blue with bromochlorophenol blue as a recording component.  8. The composition according to PP. 1-3 and 5, characterized in that it contains sulfanilic acid as an aminosulfonic acid, sulgin as a salt, and bromocresol green as a recording component.

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