UA72588C2 - Composite material for a temperature-and-time indicator used in steam sterilization - Google Patents

Abstract

The proposed composite material for a temperature-and-time indicator used in steam sterilization contains acidic component, allkali, and recording component. As the acidic component, acid amine is used. As the recording component, pH indicator or a mix of such indicators is used that changes its color in acidic medium. The content, in percent by weight, of the components of the composite material is as follows: Acid amine: 19.9 ... 89.9 % Alkali:9.0 ... 80 % Recording component: 0.1 ... 15.0 %

Description

The invention relates to means of thermometry, namely to means of controlling the operation of autoclaves and steam sterilizers and can be used in the manufacture of chemical thermo-time indicators, to control sterilization and disinfection processes used in medicine, veterinary medicine, balneology, pharmaceutical and food industry, as well as to control technological processes in heat engineering.

According to the European Pharmacopoeia (Epgoreap RiPaptasoroeia, 3rd eijop, 1997 Zigazrygo, Egapse (European Pharmacopoeia, 3rd edition, 1997, Strasbourg, France))| (1), the most reliable method of sterilization is sterilization with saturated steam. With steam sterilization, the reliability of sterilization is 1059, that is, out of 106 sterilized products, 1 product may turn out to be non-sterile. By

by the European Pharmacopoeia (1| and according to the European standard EM554 | Eishgoreap biapdaga EM554: 1994 "Bgepiygayop oi teaisa! demisez - Maiiidayop apa goshiipe sopigo! oi viepiygayop ru toivy Neai" / European standard EM554:1994 "Sterilization of medical devices - Validation and current control of sterilization moist heat") (2| for reliable steam sterilization, the following minimum values of saturated water vapor parameters are sufficient: a temperature of 1217C for 15 minutes or a temperature of 134"C for 3 minutes, i.e., for reliable sterilization, these conditions must be provided in any hard-to-reach point sterilized product.

In practice, the reliability of sterilization depends both on the equipment used and on the methods of monitoring compliance with critical sterilization parameters (temperature of saturated steam and holding time), both in the sterilization chamber and inside the sterilized products. Chemical indicators that change color under the action of a sterilizing agent are mainly used for operational visual control.

At the same time, the color of the indicator when the values of the critical parameters are observed must clearly differ from the color of the indicator when the parameters of sterilization are not observed. The shorter this interval of changing the state of the indicator, the smaller the deviations of the parameters of the sterilization mode can be recorded by the indicator.

Indicators are divided into 6 classes according to the interval of temperature values and color transition time (GOST R IBO 11140-1-2000. State standard of the Russian Federation. Sterilization of medical products. Chemical indicators. Part 1. 2000)

ISI

Compositions for indicators of higher classes should provide a change in color in a narrow temperature-time interval. In addition, there are additional requirements for indicators of class 6 - an indicator of one composition must be used for a series of sterilization modes.

In chemical thermo-time indicators of sterilization, the activation time is provided by the kinetics of the chemical reaction between the components and the sterilizing agent (for steam sterilization - water vapor). The kinetics of a chemical reaction obey the Arrhenius law, which is expressed by the equation:

I pK-A-Edkt/AT (1), where I pK is the natural logarithm of the chemical reaction constant, which in this case can be taken as the indicator's activation time; A is a constant; Edkt - activation energy of a chemical reaction, A - gas constant; T is the temperature in degrees Kelvin.

It can be seen from equation (1) that the dependence of the logarithm of the activation time of the indicators (I pK) on the inverse temperature (1/7) is linear, and the slope of the line is determined by the value of the activation energy of the chemical reaction. Accordingly, the activation energy of the chemical reaction between the components of the indicator composition should be such that the indicator activation line is parallel to the line that passes through the two points -1217C, minutes and 134"C, C minutes, which will allow using an indicator with one composition for the 2 most For this, the value of the activation energy should be equal to 34-35 kcal/mol.

In compositions for chemical indicators of this type, colorless salts, acids, ethers or pyridines are used as active components, which hydrolyze when kept in steam, and a recorder component that shows the degree of hydrolysis of these components by changing its color; these are acid-base (pH) or oxidation-reduction indicators | see, for example, British patent Me1415782, class C18B; US patent Mo4880466, class 106/31.32, 1989, US patent Mo5.254.473, class (01М31/10, 1993). A small amount of the registrar component (from 0.1 to 109 omas) is enough to fix qualitative changes in the composition of the composition.

The closest to the proposed composition in terms of technical essence and possible to achieve the result is a composition for a thermo-time indicator of control of steam sterilization processes, containing a mixture of acid and its salt and a recorder component, which is a pH indicator or a mixture of pH indicators and changes its color during the transition from an acidic environment to an alkaline one (British patent Me1415782, class SI, 19751.

The known composition contains, in particular, a mixture of 2,4-dihydrobenzoic acid and its sodium salt. A mixture of methyl red and bromothymol blue is used as a recorder component. The color of the composition changes when the pH changes from 6 to 7.5.

The disadvantage of this composition is that with long-term storage of indicators treated with water vapor (which have changed color), color inversion is observed over time. The color of the thermo-time indicators is returned to the original or brightened, which does not allow the use of thermo-time indicators for documenting the operation of steam sterilizers and archiving these documents, that is, for long-term storage of steam-processed indicators or their fragments in work logs or as part of archived documents. Color inversion in this composition becomes possible due to the fact that the activation of the indicator occurs as a result of a reversible reaction with a change in pH to an alkaline area. As is known, the synthesis of dihydrobenzoic acid is carried out from resorcinol in the presence of carbonates or CO" in the alkaline region. In the final state, this composition in the form of reaction products contains resorcinol, CO? and meadow

The second disadvantage of this composition is the mismatch of the temperature dependence of the color change time with the temperature dependence of the minimum sterilization time defined in the European standard EM554 |2) (121"C, 15 minutes - 134"C, 3 minutes), that is, the activation energy of the chemical indicator based on of this composition is 28 kcal/mol instead of 34-35 kcal/mol. This does not allow using the same composition of the indicator composition for the entire sterilization temperature range of 12170-134"С. For this reason, the indicator needs its own original composition for each sterilization mode, or in this case, one composition is used for two unequal modes: for example, 121"С, 15 minutes and 134"7С for 5.5 minutes.

The technical result achieved by the implementation of the invention is to ensure the preservation of the color of the composition for a long time of storage and the possibility of using the same composition for the entire temperature range of sterilization.

The specified results are achieved due to the fact that the composition, which is a mixture of an acid, a base and a registrar component, which is a pH indicator or a mixture of pH indicators and changes its color in the acidic region, as acid contains an acidic amine at this ratio of components, Uo mass:

Acid amine 19.9-89.9

Base 9.0-80

Recorder component 0.1-15.0

As a basis, this composition may contain urea and/or its analogues: urea, thiourea, diphenylthiourea. As an acidic amine, the composition may contain acidic urea and/or acidic guanidine: sulfuric acid, sulfuric acid, acetic acid, citric acid, oxalic acid, oxaluric acid, oxamine urea (urea, thiourea, diphenylthiourea) or guanidine, as well as acidic salts of urea or guanidine with carboxylic acids (succinic , malon, benzoin, etc.) As a registrar component, the composition may contain one of the following pH indicators or their mixture: bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red, bromocresol green, naphthyl red, dinitrophenol , lacmoid, methyl red, iodeosin, hematoxylin. In one particular case, the composition may contain urea sulfate as an acidic amine, urea as a base, and bromophenol blue as a registrar component. In another separate case, the composition may contain sulfamine guanidine as an acidic amine, urea as a base, and bromophenol blue as a registrar component. In the third separate case, the composition may contain acetic acid thiourea as an acidic urea, urea as a base, and hematoxylin as a registrar component. In another separate case, the composition may contain guanidine hydrochloride as an acidic amine, urea as a base, and bromophenol blue as a registrar component.

In Fig. the experimental dependence of the logarithm of the activation time of the steam sterilization indicator, made on the basis of a composition of urea sulfate, urea and bromophenol blue (Example 1), on the reverse temperature of its processing is presented.

As an acidic amine, sulfuric acid МНг.СОМН»На25О»х, hydrochloric acid МНГСОМНаеНСИ, phosphoric acid МНГСОМН»-НзРох, sulfamino acid МНГСОМН».МНаБО zn, sulfanilic acid can be used.

MnSOMN».MNoSeNaVOzZN, sulfuric acid MNaSOMN».MNa.SOMNOOzZN acetic acid MNgSOMN»SNzCOOH, citric acid MN»SOMN».C2OzNa(SgO with З)», oxalic acid MNgSOMN».C2Oz4H», oxalic acid

МНгСОМН»МНа.СОМНОогО zn, oxaminoacid МН»СОМН»МНа.С2ОзН urea (urea, thiourea, diphenylthiourea) and/or guanidine and other acidic salts of urea and/or guanidine with carboxylic acids (succinic, malonic, benzoic, etc. )

As a registrar component, the composition may contain one of the following pH indicators or their mixture: bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red, bromocresol green, naphthyl red, dinitrophenol, lacmoid, methyl red, iodeosin, hematoxylin.

Depending on the strength of the acid in the composition in the initial and final states, a different pH value is provided, accordingly, it is necessary to use different pH indicators for different groups of acids. The correct combination of acidic amine and pH-indicator allows you to obtain a change in the color of the composition in a narrow time interval.

Possible combinations of acidic amines and the registrar component are listed in Table 1.

Table 1 of analogues and final states of indicator 1. Acidic amines with strong acids: Bromophenol blue

Sulfuric acid amine Methyl yellow

Hydrochloric amine Methyl orange,

Sulfamic acid amine Bromochlorophenol blue 50-55

Sulfuric amine Congo red t

Alizarin red

Bromocresol green

Dinitrophenol 2. Acidic salts of amines with weak and medium strength acids: Lachmoid

Oxalic acid amine Methyl red

Citric acid amine Iodeosin

Oxaluric acid amine

Oxaminoacid amine 5.5-6.5

Phosphoric acid amine

Acetic acid amine

Acid salts of urea and guanidine with other carboxylic acids - succinic, benzoic, malonic, etc.

Table 2 shows a list of pH indicators with the main characteristics: color change interval, initial and final colors. Depending on the type of pH indicator used, different colors of chemical indicators are provided. The colors of the indicators can be varied by adding inert organic and inorganic dyes and pigments to the composition, for example, rhodamine - red, malachite green - in combination with the yellow color of the pH indicator gives green, etc.

Table 2

Preservation of the final color of the indicator during its long-term storage is ensured by the fact that the activation of the indicator occurs as a result of an irreversible reaction - the hydrolysis of an acidic amine.

The possibility of applying one component of the composition to a series of equivalent regimes is provided by the fact that the activation energy of the activation process of the indicator composition is 35 kcal/mol. As a result, the indicator trigger line passes through the points corresponding to the following modes: 1217C and 15 minutes, 1342 and C minutes or 1212 and 20 minutes, 1342 and 5 minutes.

The action of the chemical indicator of steam sterilization is based on the neutralization reaction of acid (HB), as a result of which the pH changes, and a change in the color of the pH indicator is observed. Neutralization of the acid takes place in two stages - in the first stage, the hydrolysis of urea (2) and acidic amine (3) occurs with the formation of ammonia:

МНгСОМН»гНГО-з2МНзазСОО» (2)

MnHgSOMnNoNANgO-z2MNHzuSO2ANA (3)

At the second stage, the acid is neutralized:

NAAMNIi-MNaA (4)

As a result of neutralization of the acid, there is a change in the pH of the composition, which is immediately fixed by the recorder component (pH-indicator) by a change in color. For example, in a composition with urea sulfate, urea and bromophenol blue, upon neutralization of the acid, the original yellow-orange color changes to blue-violet. The figure shows the temperature dependence of the color change time in the interval 118-1347C for this composition for the mixture given in example 1. As can be seen from the graph, all experimental points lie on a straight line that passes through the points corresponding to the regimes - 121702 15 minutes, 134 "From 3 minutes.

The tangent of the angle of inclination of this straight line is equal to the activation energy of the activation of the chemical indicator and corresponds to the process of acid amine hydrolysis (35kcal/mol).

When the content of urea (base) in the composition increases, the rate of reaction 2 increases, the acid neutralization time decreases, and the time required for the color of the chemical indicator to change decreases.

By changing the ratio of urea and acidic amine, it is possible to obtain different activation times of the indicators at the same temperature. For example, in a specific case, when using hydrochloric acid urea in a mixture with urea, the activation time at a temperature of 120"C is: with a urea content of less than 9 omas, the color change occurs in a period of more than 3 hours, at 1295 mass - in 60 minutes, at 1595 mass - in 50 minutes, at 20905 - in 45 minutes, at 309 mass - in 35 minutes, at 5095 mass - in minutes, at 8095 mass - in 4 minutes.

Modes of steam treatment at 120"C for less than 4 minutes are of no practical interest.

When the content in the described composition of the registrar component is less than 0.190 mass. the resulting colors of the chemical indicator are very pale, as a result, sufficient contrast of the color transition is not provided. The content of the registrar component, greater than 159 omas, also worsens the contrast of the transition due to obtaining very dark colors.

In the manufacture of a chemical thermo-time indicator, this composition is introduced into the composition of the carrier (porous base, for example, filter paper) by impregnation from an aqueous solution, or it is applied to the carrier or base by watering, printing, etc. in the form of a mixture of the composition and a polymer binder. Solutions of simple and complex polyesters - cellulose ethers, polyvinyl alcohol ethers, malonic acid ethers, polyvinyl alcohol, polyvinyl chloride, polyvinylpyrrolidone, polystyrene, etc. can be used as a binder, and water, alcohols and ethers, aliphatic, aromatic and chlorinated carbohydrates, etc. as a solvent. Emulsifiers, defoamers, thickeners (for example, white or colorless metal oxides), stabilizers can be added to the composition of the bond to improve its technological properties. In order to give different colors to the original indicator spot, inert organic and inorganic pigments can be added to the composition, such as rhodamine - which gives the original indicator spot a pink-red color, or malachite green - which gives a green shade, or iron ocher - which gives a red-brown shade.

The ratio of the mass of the binder and the composition does not affect the temperature-time parameters of the indicator activation and is determined by the technology of introducing the composition into the carrier.

The most practical is to apply the composition using the usual printing method on a polymer base in the form of spots, patterns or inscriptions. When applying the printing method, films made of vinyl, polyolefin, polyester, polyamide, organochlorine and organofluorine polymers can be used as a polymer base. To prevent mechanical damage, washing with hot steam and to protect sterilized products from dye contamination after drying the composition, the indicator mark is covered with a transparent polymer film from the above mixtures.

Example 1. 100 g (549 by mass) of urea sulfate, 80 g (43.390 by mass) of urea, 5 g (2.79 by mass) of bromophenol blue pH indicator are weighed on a balance, everything is thoroughly crushed and mixed. The resulting composition is introduced into 500 g of a 1090-weight aqueous solution of polyvinyl alcohol. Porous filter paper is impregnated with the resulting solution, the produced indicators are dried and packed in a polyamide film.

When the thermo-time indicator is kept in a steam sterilizer at 121"C, the initial yellow color changes to a dark blue-violet color in 15 minutes, at 134" - in 3 minutes. The temperature dependence of the activation time of this indicator is shown in Fig. It can be seen that all indicator activation values in the entire temperature range lie on a straight line that passes through the points corresponding to the minimum values of steam sterilization parameters and defined by the EM554 standard.

At the same temperature and time values, the indicator does not change color in dry air.

Both discolored and non-discolored indicators processed in a steam sterilizer retain their colors during long-term storage (over 5 years), allowing the indicators to be used for documentation purposes.

Example 2. 100 g (78.190 wt.) of acetic urea, 20 g (15.695 wt.) of thiourea, g (6.39 wt.) of hematoxylin are weighed on a scale. The mixture is thoroughly mixed and ground. The resulting composition is poured into

ZbOg of a 1095 (wt.) aqueous solution of polyvinylpyrrolidone. There, 1 g of rhodamine is added to give a pink color to the initial indicator, polyethylene oxide is added as a stabilizer, and 50 g of titanium dioxide is added as a thickener. The resulting paint is thoroughly ground in a paint grinder and applied in the form of spots using a printing method on a polypropylene film, dried and sealed with a polymer film resistant to high temperature and water vapor.

When keeping the thermo-time indicator in a steam sterilizer at 1217C, the pink color changes to dark purple in 22 minutes: at 126"C - in 14 minutes, at 134" - in 6 minutes, in water with a temperature of 757C - in 28 hours.

At the same temperature and time values in dry air, the indicator does not change color.

Both discolored and non-discolored indicators processed in a steam sterilizer retain their colors during long-term storage (over 5 years), allowing the indicators to be used for documentation purposes.

Example 3. 100g (46.590 by mass) of sulfanilic urea, 100g (46.590 by mass) of diphenylthiourea, 15g (79Uomabs.) of bromophenol blue indicator are weighed on a scale. Everything is thoroughly mixed and crushed, 0.01 g of malachite green indicator is added to give the initial indicator a salad color. A 595% aqueous solution of rosin ester of malonic acid is added to the resulting mixture, as a thickener - zinc titanate, everything is thoroughly ground in a paint grinder. The resulting paint is applied by a printing method to a polyethylene terephthalate film and is sealed with a polymer film resistant to water vapor and high temperature.

When the thermo-time indicator is kept under the pressure of water vapor in the temperature range of 118-140"С, a change in the initial salad color to the final blue-violet color is observed. Moreover, the color from the initial to the final color changes in the interval of 1-2 minutes. The time values for reaching the final color are given in Table 3 .

Table C

Time tet Trees of final color, min.

Exposure to dry air at the same temperature and time values does not lead to a change in color.

Example 4. 89 g (8990 mass) of thiourea hydrochloride, 9 g (995 mass) of urea, 2 g (295 mass) of bromophenol blue are weighed on a balance, thoroughly mixed and ground. 200 g of 5095 (wt.) solution of polystyrene (in organic solvents) is added and thoroughly ground in a paint grinder to a homogeneous state. The paint is applied by a printing method in the form of marks on a film made of polyethylene terephthalate, dried and glued with a film with the same composition.

Keeping the chemical indicator in a steam sterilizer at the following temperatures and time periods leads to a color change: 120"C - in 90 minutes, 126"7C - in 58 minutes, at 1342C - in 37 minutes, 1407C - in minutes, 1507 - in 9 minutes .

Both discolored and non-discolored indicators processed in a steam sterilizer retain their colors during long-term storage (over 5 years), allowing these indicators to be used for documentation purposes.

Example 5. 19.9 g (19.990 wt.) of sulfamic acid, 80 g (8090 wt.) of urea, 0.1 g (0.190 wt.) of bromocresol green are weighed on a balance, thoroughly mixed and ground. 200 g of a 1595 (wt) solution of polyvinyl butyral in butanol is poured into the resulting mixture. The mixture is thoroughly ground to a homogeneous state in a paint grinder. The paint is applied to a polymer base made of polypropylene by a printing method in the form of marks, dries and is glued with a polypropylene film with a sticky layer.

Holding the chemical indicator in a steam sterilizer leads to activation under the following parameters: 11570 - 2 minutes, 1207С - 1 minute, at 130"С - 30 seconds. Holding in dry air at the same temperature and time values does not lead to a change in color.

Both discolored and non-discolored indicators processed in a steam sterilizer retain their colors during long-term storage (over 5 years), allowing the indicators to be used for documentation purposes.

Example 6.

God (509 by mass) of guanidine sulfate, 43 g (439 by mass) urea, 7 g (79 by mass) bromophenol blue pH-indicator is weighed on a balance, everything is thoroughly crushed and mixed. The resulting composition is introduced into 120 g of a 6095 (wt.) solution of polystyrene in tetralin and ground in a paint grinder to a homogeneous state. Indicator marks are applied to the polymer film with the obtained paint using the printing method. After drying, lamination with a polymer film is carried out.

The resulting indicator retains its original yellow color when kept in a steam sterilizer at a temperature of 1327°C for 20 minutes, turns green after 22 minutes, and turns blue-violet after 23 minutes. Keeping it in dry air at the same temperature and time values does not change the color .

Both discolored and non-discolored indicators processed in a steam sterilizer retain their colors during long-term storage (over 5 years), allowing the indicators to be used for documentation purposes.

Our research showed that the proposed compositions make it possible to produce chemical indicators in a wide range of temperature and time parameters of activation: from temperatures of 75"7C (up to 28 hours) to 150"C (up to 9 minutes). 2.8 th

I21C, 15 min

F in: - ов «fra

My J e 2 - Ky 18 rai 18 r and her r, 1,3

Euhkt - 35 kcal/mol

By

G and in BZHS, min 2.45 2.5 2.5 2.525 2.58 1/7, P/gradk)

Fig.

Claims (9)

1. A composition for a thermo-time indicator of steam sterilization, which contains a mixture of acid and base and a recorder component, which is a pH indicator or a mixture of pH indicators and changes its color in an acidic environment, which differs in that, as an acid, an acidic amine contains to the following ratio of components, Uomabs.: acidic amine 19.9-89.9 base 9.0-80 component-registration 0.1-15.0. 2. The composition according to claim 1, which differs in that it contains urea and/or its analogues as a basis: urea, thiourea, diphenylthiourea. 3. The composition according to claims 1 and 2, which differs in that it contains acidic urea and/or acidic guanidine as an acidic amine: sulfuric acid, hydrochloric acid, phosphoric acid, sulfamic acid, sulfanyl acid, sulfuric acid, acetic acid, citric acid, oxalic acid, oxaluric acid, oxamic acid amine (guanidine , urea and its analogues) and other acidic salts of urea and/or guanidine with carboxylic acids (succinic, malonic, benzoic, etc.). 4. The composition according to claims 1-3, which differs in that the registrar component contains one of the following pH indicators or their mixture: bromophenol blue, methyl yellow, methyl orange, bromochlorophenol blue, Congo red, alizarin red, bromocresol green, naphthyl red, dinitrophenol, lacmoid, methyl red, iodeosin, hematoxylin. 5. The composition according to claim 1, which differs in that it contains urea sulfate as an acidic amine, urea as a base, and bromophenol blue as a registrar component. 6. The composition according to claim 1, which differs in that it contains sulfamine urea as an acidic amine, thiourea as a base, and bromophenol blue as a registrar component. 7. The composition according to claim 1, which differs in that it contains thiourea acetic acid as an acidic amine, urea as a base, and hematoxylin as a registrar component. 8. The composition according to claim 1, which differs in that it contains urea hydrochloric acid as an acidic amine, urea as a base, and bromophenol blue as a registrar component. 9. The composition according to claim 1, which differs in that it contains guanidine sulfate as an acidic amine, urea as a base, and bromophenol blue as a recording component.