ITSA20080036A1 - STERILIZATION OF BIO-MEDICAL INSTRUMENTS BY EXPANDING ORGANIC ACIDS - Google Patents

Description

PRODUCTION

The present invention relates to a procedure for the sterilization of biomedical devices through the use of organic acids in the form of "expanded liquids. In the technical literature, the term 'expanded liquid) "means an organic solvent (liquid at room temperature and pressure) added with a compressed gas solubilized in it. The purpose of the operation is to modify the diffusivity and voltage surface of the liquid component while retaining part of its characteristics, such as solvent power and oxidizing capacity. The present invention proposes the use of expanded organic acids as sterilizing agents of complex bio-medical devices, by virtue of their particular effectiveness both for the properties favorable transport (similar to those of a gas) and due to the oxidizing potentials which vary as the composition of the liquid-gas mixture varies.

Conventionally, medical devices (endoscopes, instruments for microsurgery, catheters, etc.) following contamination with bacteria, viruses and secretions from! human body require thorough cleaning and an equally meticulous sterilization procedure, without causing damage to the structure of the devices which must then be reused several times. In particular, during their use, endoscopes come into contact with mucous membranes and tissues and can be contaminated by pathogenic microorganisms such as, for example, HBV, HCV ilV, tuberculous bacilli, Pseudomomts uentghwsa, helìcobacter pylori and many others. These microorganisms have high levels of pathogens and are very resistant to disinfectants. Endoscopes, therefore, are quite complex devices to sterilize both because of their particular contamination and their characteristic micro-structure. It is widely shared by the entire scientific community on the subject that the sterilization process must include any process, physical or chemical, capable of destroying all forms of living microorganisms and / or biological agents. However, this definition simplifies the concept of sterility which, on the contrary, can only be defined on a statistical basis. In fact, conventionally a sterile product is declared if the treatment foresees the probability that at most one product is not sterile out of 1 million sterilized products, i.e. the safety level of sterility SAL (Sterility Assurance Level) is equal to 6 (i.e. 1 : 1,000,000 ^ IO <6>). To ensure this result, specific physical conditions must be guaranteed that take into account the variability of the species of microorganisms potentially present on the device to be treated e. above all, of their possible state: vegetative or spore-forming or other forms of non-classical biological agents. The spores, in fact, are by far the most resistant forms to sterilizing agents and, in order to be eliminated, they require, compared to the vegetative forms, higher temperatures (above 100 <C> C) and longer exposure times. Traditionally, sterilization is carried out with different conventional methods such as pressurized steam, ethylene oxide, oxidizing agents (peroxides or peracids), gamma or ultra-traction radiation. In the case of complex devices, however, repeated thermal stresses can generate distortions in the very delicate structure (e.g. that of the telescopic microlenses present inside them), while gamma radiation can compromise the mechanical properties of some of the polymers present. Ethylene oxide is toxic, mutagenic and carcinogenic and can be retained by some polymers while liquid organic acids, even if diluted, cannot reach some of the internal microstructures due to the surface tension and in any case are often too reactive with the constituent parts. of very delicate instruments.

The present invention proposes an innovative sterilization process which involves the use of acetic acid and peracetic acid or their "expelled" mixtures obtained by adding dense gases. BACKGROUND OF THE INVENTION

With the aim of overcoming the limitations of heat treatments and liquid oxidizing agents, many recently proposed patents use the supercritical carbon dioxide iSC-CO;) as a sterilizing fluid. Among these Dillow et al, (patent number: WO 99 66960; Applicant: MIT, MA, USA) suggest the use of SC-CCA as an alternative to existing sterilization technologies for various healthcare industry products with few harmful effects on the treated materials. In particular, the authors report the inactivation process of a wide range of microbes using this compressed gas at pressures between 100-250 bar and temperatures between 4G-60 ° C with repeated pressurization and depressurization cycles. However, in the patent the results obtained only on a sporulating bacterium (B. cereus) are reported, and there are no indications on the efficiency of the process on other standard bio-indicators.

Ranno et al., (Patent number: US 04/0120852; Applicant: Oliff & Berridgc, VA, USA) also report the effects of repeated cycles of pressurization and depressurization with CO: supercritical on bacteria and viruses establishing that rapid expansion can destroy bacterial cells after only 30 minutes of treatment.

The use of CO mixtures; solid, liquid or gaseous with small quantities of organic acids for applications in sterilization was then proposed by Fischer (patent number: US 07/0073081; Applicant: Air Uquid, TX, USA); the author reports combinations of CO: solid, liquid and possibly supercritical with peracetic acid in concentrations between 0.05 and 15% molar used as anhydrous sterilizers for their ability to treat solid surfaces. THE! patent mainly describes the different existing methods for the production of the proposed combinations with the aim of improving the sterilizing effects of carbon dioxide.

Christensen et al., (Patent number: US 07/0003432; Applicant: Welsh & Flaxman, VA. USA) have proposed a sterilization method that achieves a 6-log tn CFU (Colony Forming Unit) reduction of bacteria and spores using fluids under conditions of temperature and pressure close to those of the critical point. The proposed process uses SC-C02 with small percentages of additives such as peroxides, carboxylic acids in percentages between 0. i and 2% by volume.

Matthews et al, {patent number: WG 07/008618; Applicant: University of South Carolina, CO, USA) have recently proposed a similar process of high pressure sterilization, which consists of a treatment carried out with mixtures of C02 and oxidizing and non-oxidizing sterilizing agents in concentrations up to about 1000 ppm as well as various pressurization and depressurization cycles.

In conclusion, from the analysis of the patent literature, it was observed that all the various authors have described sterilization processes that make use of SC-CO; and SC ~ C02 modified with small amounts of additives to obtain new and proven sterilization methods.

A different approach is used in the present invention. A new sterilization process based on the controlled variation of the oxidizing properties of liquid organic acids is claimed. In particular, the invention relates to a sterilization process carried out with "expanded" organic acids (peracetic acid, acetic acid or mixtures of them in all proportions) carried out by adding a compressed gas in order to produce a solution (expanded liquid) which will have a low surface tension and a high diffusivity and, therefore, better material transport properties. These expanded acids allow a more thorough sterilization following an easier penetration into the microscopic surfaces of the equipment which would otherwise be too difficult to reach by a traditional liquid by virtue of the surface tension. In particular, the expanded solutions, formed by an organic acid and a compressed gas (for example C02 at operating conditions of 50-150 bar of pressure and 35-80 ° C) show a reduced surface tension and a high diffusivity such as to penetrate the microscopic interstices inside the most complex instruments, producing a steri! quick and easy implementation. In addition, the addition of a compressed gas in the formation of the "expanded liquid" is also useful for modulating the oxidizing activity of acid mixtures against different parts of medical devices that do not tolerate the oxidizing action of pure liquid oxidizing media. Surprisingly. The addition of compressed gases in relatively small quantities produces foamed liquids with a substantial modification of the diffusivity and surface tension, while maintaining part of their solvent power and oxidizing action. Therefore, these foamed liquids can be successfully used as sterilizing agents with the further advantage of an oxidizing action that can be adjusted by varying the amount of compressed gas added.

A specific procedure of this invention provides for the use of an organic acid and carbon dioxide in a percentage ranging from 99 to 15% by weight. Carbon dioxide appears to be the preferred compressed gas for this application, because it can further improve the sterilization process due to its bactericidal, although not oxidizing, properties. Furthermore, its strong modulating action of the oxidizing activity of the expanded acid solutions is linked to its use in conditions of pressure and temperature close to critical conditions, where small variations in the process parameters (mainly pressure and temperature) can lead to large variations in properties. of the fluids involved. However, other gases can also be successfully used to trap "expanded liquids". A non-exhaustive list includes: ethylene peroxide, nitrous oxide, propane and trifluoromethane,

The process in question consists of the following stages:

a) formation of the expanded acid solution in a high pressure mixer; b) sending the expanded solution to a pressurized autoclave previously loaded with the medical material to be sterilized;

c) sterilization of instruments by selecting pressure, temperature and process time;

d) elimination of organic acid residues from the autoclave, by washing with the same compressed gas;

e) depressurization of the solution at the exit of the autoclave to recover the organic acids in one or more separators located downstream of the autoclave.

The compounds selected as expanding components are preferably gaseous at room temperature and can be selected from: carbon dioxide, nitrous oxide, chopped uromethane, propane, but many other compounds can also be selected and used. The organic acids used in the proposed process are selected from a group consisting of: acetic acid, peracetic acid, and mixtures of them in all proportions.

The formed expanded solutions contain from 99 to 15% by weight of organic acids, preferably between 80 and 20% by weight. The operating conditions in the mixer and in the autoclave (operation a) and b)) concern pressures between 40 and 200 bar (preferably 80-100 bar) and temperatures between 25 and 80 ° C (preferably 30-60 ° C). The residence time in the autoclave can vary between 5 and 190 minutes (preferably 10-60 minutes).

A variant of the process involves the use of a static mixer, while a second variant involves the use of a dynamic mixer for the preparation of the expanded solutions.

The advantages of the process are: the fast and complete sterilization of medical devices due to the characteristics of the expanded solutions: very low surface tension and high diffusivity; the reduction of the time required for sterilization from many hours to a few minutes, a low environmental impact due to the fractional separation and the complete recovery of the organic acids used. Further aspects of the invention can be found by reading the results described in the following examples.

EXAMPLES

In the process in question, the solution is obtained in a mixer and then placed in the sterilization autoclave previously loaded with material to be sterilized. The microorganisms, bacteria and spores present on the surface of the devices are brought into contact with the expanded liquid of acetic acid or mixtures of acetic and peracetic acid with a dense gas (for example CCL) for a fixed period of time and a given flow rate . The mixture leaving the sterilization autoclave (organic solvent + CCL) is then fed into the separator, where, by changing the pressure and temperature conditions, the demixing of the organic solvent and C02 is obtained. The CO2 and the organic solvent can both be recycled.

The degree of de-activation can be calculated by measuring the number of microorganisms present on an untreated surface and those present on a treated surface with the following relationship:

All efforts have been made to ensure the accuracy of the numbers (quantities, temperatures. Eoe), but some errors and deviations should still be kept in minting. Unless otherwise indicated, parts are parts by weight, the temperature is in ° C and the pressure in bars.

EXAMPLE 1

STERILIZATION OF FORCEPS AND SCALPELS USING AN EXPANDED SOLUTION OF PERACETIC ACID ACETIC ACID AND CO

Parts of small medical devices, especially forceps and scalpels, are placed with a type B spore sample, Stearothermophilus (I mL) larger than I O6 CFU / mL in a stainless steel basket. The autoclave is loaded with materials contaminated with the spores previously tìnse on them. A solution of 20% peracetic acid (PA) in acetic acid (AA) and C02 in which the liquid and the gas have been mixed with ratios by weight between 12 and 10% of solution with C02 (preferably 9% of solution by weight ) in a mixer. The solution is used in a pressure range of 80-100 bar (preferably 90 bar) and temperatures in a range of 30-50 ° C (preferably 35 ° C) to produce the foamed liquid. The solution is introduced into the sterilization autoclave with a flow rate between 0.4 and 5 kg'h (preferably l kg / h).

The expanded solution, thanks to its characteristics of surface tension, viscosity and density, covers all the surfaces reaching all the internal parts of the devices to be sterilized, even the most difficult to reach. The process is completed over a period of time ranging from 10 to 90 minutes (generally 30 minutes). Downstream of the autoclave, the solution is sent to the separator which operates at pressures between 10 and 30 bar (preferably 20 bar) and temperatures between 0 and 25 ° C (preferably 10 CC). In the separator. PA and AA are precipitated and recovered following decompression, while C02 is recovered as a gas.

The number of CPUs on each Petri dish is calculated after 24-48 h of incubation at 30-35 ° C. The numerical average of the CPUs is calculated from 3 Petri dishes at each dilution and converted to the spore cone and the number of surviving spores on the medical devices using the corresponding dilution factor. Finally, the log reduction of type B. Stearothermophilus spores is calculated following the formula described above.

Operating under the process conditions of 90 bar. 35 ° C with a flow rate of 0.8 kg / h for 30 minutes with a 9% PA / AA solution in mass traction with CCh, the complete destruction of the bioindicator was achieved after evaluations on many experiments. These reductions correspond to a Log reduction between 6.2 and 6.6.

EXAMPLE 2:

STERILIZATION OF ENDOSCOPES USING AN EXPANDED SOLUTION OF PERACET1C ACID / ACETIC ACID AND C02

In this experiment, B. Airopheus and B. anfhracis bacteria, previously suspended in liquid medium, were swabbed onto the surface of two endoscopes (150 mm x 20 hymns) and left to act for approximately fifteen minutes.

The same procedure was used as illustrated in EXAMPLE I. 10% peracetic acid (AP) in acetic acid (AA) and CO; were mixed in a mixer in a weight ratio between 15 and 5% (preferably 5% solution by weight). The solution was used in a pressure range of 80-110 bar (preferably at 90 bar) and in a temperature range of 30-50 ° C (preferably at 35 ° C) to obtain the formation of the foamed liquid. The solution was then sent to the sterilization autoclave with a flow rate between 0.8 and 5 Kg / h (preferably 0.9 KgTi),

The high diffusivity and almost zero surface tension of the expanded solution meant that it reached all the internal parts of the endoseopium. The process was conducted for a period of time between 10 and 90 minutes (usually 25 minutes). At the exit of the auto key. the solution was sent to the separator which operated at a pressure between 10 and 30 bar (preferably 20 bar) and at a temperature between 0 and 25 ° C (preferably 20 ° C), In the separator, AP and AA are precipitated and recovered by decompression, while the C02 was separated in the form of gas.

The CFU number was calculated as in EXAMPLE 1. A Log reduction of 6.3 and 6.1, respectively, was measured for the spores of B Atropheus and B anthracis.

EXAMPLE 3:

STERILIZATION OF F1BROSCOPES FOR INTUBATION USING AN EXPANDED SOLUTION OF PERACETIC ACID ACETIC ACID AND C02

EXAMPLE 1 was repeated, with the difference that a sample of B. suhtilia spore / vegetative preparation (1 mL) was used to contaminate the medical instrument, which was an 80 mm long piece of intubation fiberscope.

The autoclave was loaded with the contaminated instrument on which the spores had previously been spread. A 25% solution of AP In A A was mixed with C (3⁄4 at a weight ratio between 10 and 8% of solution with CCK The experiment was conducted at a pressure of 60-100 bar and a temperature range of 30-50 ° C to obtain the formation of the expanding liquid The solution was sent to a sterilization autoclave with a flow rate between 0.8 and 5 Kg3⁄4 (preferably 1 Kg'h).

The trial was conducted over a period of 30-40 minutes. Upon exiting the autoclave, the solution was sent to! separator operating at a pressure between 10 and 30 bar (preferably 15 bar) and at a temperature between 0 and 25 <:> C (preferably 18 ° C). in the separator, AP and AA are precipitated and recovered by decompression, while the C02 is separated in the form of gas.

The number of CFUs was calculated as in EXAMPLE 1. By carrying out many experimental evaluations, log reductions in CFUs of 6.3-6.7 were observed.

Claims (11)

CLAIMS 1. A process that uses foamed liquids formed with organic acids and dense gases to sterilize medical instruments. The process consists of the following operations: a) formation of expanded acid solutions in a high-pressure mixer; h) sending the expanded solution to a high pressure autoclave previously filled with the medical instruments to be sterilized; c) sterilization for a fixed pressure, temperature and residence time; d) elimination of organic acid residues in the autoclave by washing with a gas; e) depressurization of the solution to recover the organic acids in one or more separators located at the exit of the autoclave. 2. A process according to claim 1, which consists of a further operation t) of precipitation of the extracted residues 3. A process according to claims 1 and 2, which consists of a further operation g) depressurization of the expanded solution to recover the organic acids; 4. A process according to claims 1 to 3. in which one or more gases of a group that can be formed by: carbon dioxide, nitrous oxide, ethylene peroxide, trifluoromethane, propane can be used. A process according to claims 1 to 4, in which one or more organic acids can be selected from a group consisting of: acetic acid, acid for acetic, and their mixtures. 6. A process according to claims 1 to 5, in which the foamed liquid is obtained by mixing some of the compounds described in claim 4 with some of the compounds described in claim 5 in a proportion of 1 to 20%; 7. A process according to claims 1 to 5, ne! which the foamed liquid is obtained by mixing some of the compounds described in claim 4 with some of the compounds described in claim 5 in a proportion of from 21 to 80%; 8. A process according to claims 1 to 5, in which the foamed liquid is obtained by mixing some of the compounds described in claim 4 with some of the compounds described in claim 5 in a proportion of 80 to 85%; 9. A process according to claims 1 to 6, in which in operations a) and b) the expanded solution operates in a pressure range between 50 and 350 bar, 10. A process according to claims 1 to 6, in which in operations a) and b) the expanded solution operates at a temperature in the range between 20 and 80 ° C. 11. A process according to claims 1 to 6, in which the process time varies between 5 and 120 minutes.