WO2014170858A1

WO2014170858A1 - Process for the purification of anesthesia gases using membrane contactors and its applications

Info

Publication number: WO2014170858A1
Application number: PCT/IB2014/060797
Authority: WO
Inventors: Luísa Alexandra GRAÇA NEVES; Isabel Maria RÔLA COELHOSO; Carlos Alberto Mateus Afonso; JOãO PAULO SEREJO GOULÃO CRESPO
Original assignee: Graça Neves Luísa Alexandra; Rôla Coelhoso Isabel Maria; Carlos Alberto Mateus Afonso; Serejo Goul O Crespo Jo O Paulo
Priority date: 2013-04-19
Filing date: 2014-04-17
Publication date: 2014-10-23
Also published as: WO2014170858A4; PT106902A

Abstract

The present application describes a process for removing toxic compounds, namely carbon dioxide, present in gas streams in anesthesia circuits, using membrane contactors. The present process allows for the recirculation of anesthesia gases, C0₂ free, to the anesthetized subject, aswell as the recirculation of the receiving absorber liquid phase, from which the CO₂ is removed. The present application also describes the use of this procedure in the field of medicine, namely its in-situ use during medical interventions, in which the subject is anesthetized.

Description

DESCRIPTION

"ANESTHESIA GAS PURIFICATION PROCESS USING MEMBRANE CONTACTORS AND THEIR APPLICATIONS"

Technical Domain

The present application relates to a process of removal of toxic compounds, namely carbon dioxide, present in gas streams in anesthesia circuits.

Background

An anesthesia gas is generally composed of about 70% nitrous oxide (N ₂ 0), 22-29% of oxygen and 1-8% of halogenated hydrocarbons. After breathing, the carbon dioxide (CO ₂ ) present in the gas mixture reaches a content of 5% and should be removed below 0.5%, making it possible to recirculate this gas to the patient under anesthesia.

Currently the removal of CO ₂ from anesthetic gas streams is done through the use of an absorbent composed of calcium hydroxide (CaOH ₂ ). This absorbent promotes the following reaction with CO ₂ :

CaOH ₂ (s) + CO ₂ (g) ► Ca (C ₃ ) (s) + H ₂ 0 (g, 1) in which calcium hydroxide reacts with carbon dioxide to form calcium carbonate and water. Although the most used circuits in anesthesia absorbent for the removal of C0 _2, the calcium hydroxide has a high sensitivity to reactive anesthetic agents.

The most commonly used anesthetic agents are fluorinated hydrocarbons, such as sevoflurane, isoflurane, desflurane, which may react chemically with the calcium hydroxide, which may form potentially toxic by-products for the patient.

Some solutions have been proposed in the literature to minimize the occurrence of side reactions between the absorbent and the anesthetic agent. MX 2009006916A suggests the use of a CO ₂ absorber with the composition 70-90% calcium hydroxide (free of potassium hydroxide and sodium hydroxide), 0.1-17% lithium hydroxide and 5-25%. % of water. US 5,390,667 suggests the use of a CO ₂ absorber consisting of magnesium oxide, magnesium hydroxide, or magnesium hydrocarbon with a small amount of water.

All solutions mentioned above are based on absorption systems, ie there is no simultaneous regeneration of the absorbent, which implies the replacement of the absorbent when saturated and a high cost associated with the disposal of contaminated hospital waste.

More recently, US 2004/0103898 suggests the construction of a tube for adapting to anesthesia circuits, which should contain a membrane and a CO ₂ absorbent (without specifying what the composition of this absorbent or the membrane material is). however, once again, an absorption only system which does not ensure its in-situ regeneration.

As mentioned above, the most commonly used anesthetic agents are fluorinated hydrocarbons, which may lead to the formation of potentially toxic compounds when combined with the absorbent. Xenon, on the other hand, is considered the ideal anesthetic gas. Its use causes virtually no side effects (particularly on the cardiovascular system) to occur, is odorless, and allows rapid induction. Moreover, it does not react chemically with any substance and does not present the problem of formation of potentially toxic compounds for the patient. However, the high cost of surgery when using Xenon compared to other anesthetic agents has limited its use. It is therefore urgent to find efficient alternative processes for recovering and recycling anesthetic gases, and in particular Xenon, in an efficient and inexpensive manner.

Recent studies propose the use of membranes for absorption of C0 ₂ using solutions of amino acids with polyethylene glycol and glycerol salts, but these processes require heat regeneration, which determines its use in hospital environment (Portugal, AF, DF Magellan , A. Mendes, Carbon dioxide removal from anesthetic gas circuits using hollow fiber membrane contactors with amino acid salt solutions J. Memb Sci. 339 (2009) 275-286).

Some Ionic Liquids (Lys) have a high solubility to CO ₂ , which makes them good candidates as gaseous CO ₂ absorbers, as well as having a very low vapor pressure, which ensures no evaporation losses. to the atmosphere.

There are also eutectic mixtures that ensure high affinity for CO ₂ and negligible volatility. The present invention proposes an integrated process (in situ absorption and regeneration) for the purification of anesthetic gases and CO ₂ removal by combining the ability of ionic liquids or eutectic mixtures with specificity to solubilize carbon dioxide with the use of an enzyme. carbonic anhydrase, which catalyzes the reaction of converting CO ₂ to bicarbonate according to the following reaction:

C0 ₂ + H ₂ 0 ₄ ^► HC0 ₃ ^~ + H ⁺

Thus, in addition to the selective liquid phase transport of CO ₂ , the additional mechanism of enzymatic conversion to bicarbonate increases the transport driving force, considerably improving the total CO ₂ transfer. Carbonic anhydrase is recognized by the scientific community as having the ability to reversibly catalyze the carbon dioxide to bicarbonate conversion reaction.

summary

It is the object of the present application to describe a gas purification process of anesthesia circuits using membrane contactors. This process is characterized by contacting a gaseous stream comprised of anesthetic gases and gases exhaled by the anesthetized subject into a membrane contactor, ensuring solubilization and diffusion of toxic gaseous compounds into a receptor liquid phase comprising the dispersed carbonic anhydrase enzyme. in an ionic liquid or a eutectic mixture with affinity for carbon dioxide, allowing its subsequent removal of this liquid phase in a second membrane contactor. So the Said method allows the recirculation of the purified anesthetic gas stream to the subject under intervention and the recirculation of the CO ₂ free receiving liquid phase (exiting the second contactor) to the first contactor.

The main advantages are:

The. Elimination of toxicity problems caused by current gas purification systems in anesthesia circuits.

B. In situ and room temperature regeneration of the liquid phase used for solubilization of toxic gases.

ç. Compact equipment (membrane contactors) suitable for use in a hospital environment.

In this context, the present application describes a process of removal of carbon dioxide present in the gas stream in anesthesia circuits, comprising the following steps:

admission of a gaseous stream comprising anesthetic gases and gases exhaled by the anesthetized subject to at least one first membrane contactor in which the solubilization and diffusion of carbon dioxide to a receiving liquid phase occurs;

admitting the receiving liquid phase from the first contactor to at least one second membrane contactor in which carbon dioxide desorption occurs;

recirculation of the gas stream from the first contactor to the anesthetic gas stream to be administered to the subject; - recirculation of the receiving liquid phase from the second contactor to the first contactor.

In a preferred embodiment, the receiving liquid phase comprises an ionic liquid or a eutectic mixture.

In another preferred embodiment, the receiving liquid phase further comprises an immobilized carbonic anhydrase enzyme, wherein the concentration ranges from 0.001% (w / w) to 0.1% (w / w).

In yet another preferred embodiment, the ionic liquid has a Q ⁺ structure X ^~, wherein the cationic moiety Q ⁺ is selected from the group comprising imidazolium, pyrazolium, pyridinium, pyrrolidinium, ephedrinium, morfolineo, piperazineo, triazolium, thiazolium, benzotriazólio , oxazolium, tetrazolium, sulfonium, ammonium, phosphonium or guanidinium salts or containing a pendant tertiary amine groups and wherein anionic moiety ^X- is selected from the group comprising halide, aluminum tetrachloride, iron tetrachloride, perchlorate, nitrate, cyanide, dicyanamide, thiocyanate, tricyanomethane, formate, acetate, trifluoroacetate, trichloroacetate, propionate, butanoate, octanoate, methylsulfate, ethylsulfate, propylsulfate, butylsulfate, octylsulfate, tosylate, benzenesulfonate, mesylate, triflate, sulfate, hydrogen sulfide, bisulfonate, carbonate, carborane, saccharinate, acesulfanate, hexafluorophosphate, phosphate, dihydrogen phosphate, hydrogenophos fact, tetrafluoroborate, tetrafenylborate. In a preferred embodiment, the eutectic mixture comprises a combination of choline with a compound selected from the group comprising urea, thiourea, methylurea, 1,3-dimethylurea, 1,1-dimethylurea, acetamide, benzamide, ethylene glycol, glycerol, 2, 2,2-trifluoroacetamide, imidazole, adipic acid, benzoic acid, citric acid, malonic acid, oxalic acid, phenylacetic acid, phenylpropionic acid, succinic acid, levulinic acid, xylitol, sorbitol, tartaric acid or isosurbide or by the combination of urea methylurea, 1,3-dimethylurea, or 1,1-dimethylurea, and choline, triethylchlorethylammonium chloride, dimethylbenzylhydroxyethylammonium chloride triphenyl methylphosphonium chloride and zinc dichloride.

In another preferred embodiment, the operating temperature of the receiving liquid phase ranges from 10 ° C to 100 ° C, preferably at room temperature.

In yet another preferred embodiment, the two contactors are membrane contactors whose pore diameter is between 20nm and 500nm.

In a preferred embodiment, the membranes of the two contactors are polymeric or inorganic or simultaneously comprising polymeric and inorganic materials, being tubular, capillary fiber, hollow fiber, flat or spiral modules. It is also the objective of this application to use this process in the medical field, preferably in medical interventions in which the subject is anesthetized.

General description

The present application proposes an integrated process (simultaneous absorption and regeneration) using membrane contactors in order to obtain a compact medical system that allows the patient to recycle anesthetic gases during the medical intervention process.

In this configuration, the CO ₂ -containing gas stream contacts a solution consisting of ionic liquids or eutectic mixtures of suitable water activity and the carbonic anhydrase enzyme. CO ₂ is selectively transported from the anesthetic gas stream through the solution consisting of ionic liquids or eutectic mixtures containing the carbonic anhydrase enzyme.

This solution is regenerated at room temperature which results in no accumulation of CO ₂ in the absorbent solution, avoiding its saturation (as in the previously proposed solutions). Elevated temperatures are not required to regenerate the ionic liquid or eutectic mixture because the reduced pressure or carrier gas used in the permeate circuit permits the release of the captured carbon dioxide. On the other hand, the treated gas stream having a suitable carbon dioxide content may be recirculated to the patient. This system completely prevents contamination of the treated gas as the ionic liquid or the eutectic mixture has negligible vapor pressure. Recently the capacity of ionic liquid ([C ₄ ME] [f ₂ N]) has been demonstrated in the literature. solubilization of the carbonic anhydrase enzyme, with an increase in the CO ₂ solubility coefficient by 30% for a small enzyme concentration (0.1 mg / g ionic liquid) (Neves, Luisa, C. Afonso, IM Coelhoso, J. Crespo, CO Integrated _Σ Capture and enzymatic bioconversion in supported ionic liquid membranes _r Sep. Purif. Tech. (2012), 97, 34-41).

In this process, it is proposed to disperse the enzyme, carbonic anhydrase in ionic liquids or high affinity eutectic mixtures to selectively remove CO ₂ . By adjusting the appropriate activity in water it is possible to disperse the carbonic anhydrase (AC) enzyme in an ionic liquid or eutectic mixture. The ionic liquid composed entirely consisting of ionic species have a general structure Q ⁺ ^X-, chiral or achiral, with an organic cation Q ⁺ ^X- , and an inorganic or organic anion. The cationic moiety Q ⁺ is preferentially unit imidazolium type, pyrazolium, pyridinium, pyrrolidinium, ephedrinium, morfolíneo, piperazíneo, triazolium, thiazolium, benzotriazólio, oxazolium, tetrazolium, sulfonium, ammonium, phosphonium or guanidinium salts, and anionic moiety ^X- is a halide, aluminum tetrachloride, iron tetrachloride, perchlorate, nitrate, cyanide, dicyanide, thiocyanate, tricyclomethane, formate, acetate, trifluoroacetate, trichloroacetate, propionate, butanoate, octanoate, methylsulfate, ethylsulfate, propylsulfate, butylsulfate, benzylsulfate, , mesylate, triflate, sulfate, hydrogen sulfate, carbonate, bis (trifluoromethyl sulfonyl) imide, carborane, saccharate, acesulfanate, hexafluorophosphate, phosphate, dihydrogen phosphate, hydrogen phosphate, tetrafluoroborate, tetrafenylborate. Because of their very low vapor pressure, they can be used in both supported liquid membranes and membrane contactors, providing extremely stable membranes or solutions when in contact with gaseous streams. The use of ionic liquids or eutectic mixtures with very low vapor pressure, with the particularity of concentrating and solubilizing CO2, promotes the perfect environment for the enzyme, ensuring a high local concentration of CO2 and the required water level that ensures adequate activity. and enzyme stability. Thus, in addition to the greater solubility of CO2 in an IL or selective eutectic mixture, the additional mechanism of enzymatic conversion of CO2 to bicarbonate increases the transport driving force, and significantly improves overall CO2 mass transfer. This design also allows to overcome the evaporative absorbent loss problems that occur when using aqueous solutions. The use of a membrane contactor characterized by a high mass transfer area in a small volume allows the development of a compact equipment suitable for hospital use and allows the patient to recirculate anesthetic gases.

Highly affinity CO2 ionic liquids or eutectic mixtures are preferably used in this process. In recent experiments a range of high affinity CO2-affixed imidazole cation based ionic liquids has been developed. The eutectic mixture comprises a combination of choline one or more compounds selected from the group comprising urea, thiourea, methylurea, 1,3-dimethylurea, 1,1-dimethylurea, acetamide, benzamide, ethylene glycol, glycerol, 2,2,2-trifluoroacetamide, imidazole, adipic acid, benzoic acid, citric acid, malonic acid, oxalic acid, phenylacetic acid, phenylpropionic acid, succinic acid, levulinic acid, xylitol, sorbitol, tartaric acid or isosurbide by the combination of urea, methylurea, 1,3-dimethylurea, or 1,1-dimethylurea, and choline, triethylchlorethylammonium chloride, dimethyl benzylhydroxyethyl ammonium triphenyl methylphosphonium chloride and zinc dichloride. This affinity can be further enhanced by synthesizing ionic liquids based on the imidazole, pyrazol, pyridinium, pyrrolidinium, ephedrinium, morpholine, piperazine, triazole, thiazole, benzotriazole, oxazole, tetrazolium, sulfonium, ammonium, phosphonium, or guanidinium cation. tertiary amine group pending. The use of these cations allows for selective CO ₂ absorption due to the presence of the organic cation and to ensure that the tertiary amine containing group acts as a counterion of the enzymatically produced bicarbonate anion.

This technology makes it possible to solve the problem of removing toxic compounds from anesthesia circuits, preferably CO ₂ , in an efficient and sustainable manner, with the ionic liquid or eutectic mixture being regenerated by desorption of CO2 using reduced pressure or a drag (Figure 1).

Brief Description of the Figures

For an easier understanding of the invention, attached the figure, which represents embodiments of the invention which, however, are not intended to limit the object of the present application.

Figure 1. Integrated process for capturing toxic gases present in anesthesia circuits with two membrane contactors in series. In the first contactor the CO2 present in the anesthesia gas is preferably removed and in the second contactor the receiving liquid phase is regenerated in the circuit with a carrier gas or with reduced pressure. Reference numbers are:

1 - anesthesia gas intake current;

2 - subject or patient;

3 - anesthetic gases and gases exhaled by the subject

anesthetized, rich in C0 _2, N ₂ 0 or Xe;

4 - CO2 free gas stream;

5 - first contactor;

6 - dissolved liquid phase current with dissolved CO2;

7 - receiving liquid phase;

8 - second contactor;

9 - CO2 free receiver liquid phase current;

10 - condenser;

11 - vacuum pump;

12 - CO2 recovery;

13 - chain with carrier gas.

Description of embodiments

Referring to the figures, some embodiments will now be described in more detail, which are not, however, intended to limit the scope of the present application. The present application describes a process for the efficient removal of toxic compounds, namely carbon dioxide, present in the gas stream in anesthesia circuits, combining the ability of ionic liquids or eutectic mixtures with specificity to solubilize carbon dioxide with the use of an enzyme, carbonic anhydrase, that catalyzes the reaction of converting CO2 to bicarbonate.

In this process, the carbonic anhydrase enzyme is dissolved in an ionic liquid or eutectic mixture which has high solubility to CO2. In order to ensure the stability and activity of the enzyme, it is necessary that this liquid or mixture contains a certain activity in water, with optimum values between 0.2 and 0.8.

In this process, a membrane contactor is used characterized by a high mass transfer area in a small volume. In the integrated process two contactors (5 and 8) are provided, with membranes which may be polymeric or ceramic, with pore sizes ranging from 0.02 micrometers to 0.5 micrometers. This process is characterized by contacting a gaseous stream, consisting of anesthetic gases and gases exhaled by the anesthetized rich in CO2, N2O or Xe (3), in a membrane contactor (5) ensuring the solubilization and diffusion of toxic gaseous compounds. a receptor liquid phase (7) incorporating the carbonic anhydrase enzyme dispersed in an ionic liquid or a eutectic mixture with affinity for CO2. The liquid phase in which the CO2 is dissolved (6) is fed to a second operated membrane contactor (8). at reduced pressure using a condenser (10) and a vacuum pump (11), or using a controlled flow carrier gas (13). In this second contactor (8), the CO ₂ is captured (12) and separated from the receiving liquid phase stream, which contains the enzyme and the CO ₂ free ionic or eutectic mixture (9), the latter being recirculated to the first contactor (5). The treated gas stream in the first carbon dioxide free contactor (4) can be recirculated to the patient (2). A controlled addition of anesthesia gas (1) is also possible to replace the composition of anesthesia gas to be administered to the patient. This system completely prevents contamination of the treated gas (and carbon dioxide stream) as the ionic liquid or eutectic mixture has negligible vapor pressure. High temperatures are not required to regenerate the ionic liquid or eutectic mixture because the use of reduced pressure or the use of carrier gas in the permeate circuit allows the release of the captured carbon dioxide.

Example 1

In the 1-butyl-3-methylimidazolium bis (trifluoromethanosulfonyl) imide ionic liquid, [C ₄ ME] [f ₂ N] with water activity of 0.753, the lyophilized enzyme carbonic anhydrase was dissolved at a concentration of 0.01% (w / w). P) . The liquid phase consisting of ionic liquid and enzyme was immobilized on a hydrophobic PVDF membrane with a pore size of 0.22 micrometers. Pure gas, carbon dioxide and xenon permeability tests were performed at 30 ° C for the hydrophobic membrane immobilized with ionic liquid and the hydrophobic membrane immobilized with ionic liquid. and enzyme. Experimental results demonstrated an average 90% increase in optimal C0 ₂ / Xe selectivity when the enzyme is present in the immobilized liquid phase in the membrane pores.

Claims

1. A process of removing carbon dioxide from the gaseous stream in anesthesia circuits, comprising the following steps:

admission of a gaseous stream comprising anesthetic gases and gases exhaled by the anesthetized subject to at least one first membrane contactor in which carbon dioxide solubilization and diffusion to a receiving liquid phase occurs;

recirculation of the gas stream from the first contactor to the anesthetic gas stream to be administered to the subject;

- recirculation of the receiving liquid phase from the second contactor to the first contactor.

The process according to the preceding claim, wherein the receiving liquid phase comprises an ionic liquid or a eutectic mixture.

The process according to the preceding claim, wherein the receptor liquid phase further comprises an immobilized carbonic anhydrase enzyme.

The process according to the preceding claim, wherein the concentration of the carbonic anhydrase enzyme immobilized in the receiving liquid phase ranges from 0.001% (w / w) to 0.1% (w / w).

5. The process according to any one of claims 2-4, wherein the ionic liquid has a structure ^X-Q ^+, wherein Q ⁺ is cationic moiety selected from the group comprising imidazolium, pyrazolium, pyridinium, pyrrolidinium, ephedrinium, morfolineo, piperazineo, triazolium, thiazolium, benzotriazólio, oxazolium, tetrazolium, sulfonium, ammonium, phosphonium or guanidinium salts or containing a pendant tertiary amine groups and wherein anionic moiety ^X- is selected from the group comprising halide, aluminum tetrachloride, iron tetrachloride , perchlorate, nitrate, cyanide, dicyanamide, thiocyanate, tricianomethanide, formate, acetate, trifluoroacetate, trichloroacetate, propionate, butanoate, octanoate, methylsulfate, ethylsulfate, propylsulfate, butylsulfate, octylsulfate, tosylate, benzenesulfonate, sulfate, sulfate bis (trifluoromethyl sulfonyl) imide, carborane, saccharate, acesulfanate, hexafluorophosphate, phosphate, dihydrogen phosphate, hydrogen phosphate, tetrafluoroborate, tetrafenylborate.

The process according to any one of claims 2-4, wherein the eutectic mixture comprises a combination of choline with a compound selected from the group comprising urea, thiourea, methylurea, 1,3-dimethylurea, 1,1-dimethylurea , acetamide, benzamide, ethylene glycol, glycerol, 2,2,2-trifluoroacetamide, imidazole, adipic acid, benzoic acid, citric acid, malonic acid, oxalic acid, phenylacetic acid, phenylpropionic acid, succinic acid, levulinic acid, xylitol, sorbitol, tartaric acid or isosurbid or by the combination of urea methylurea, 1,3-dimethylurea, or 1,1-dimethylurea, and choline, triethylchlorethylammonium chloride, chloride dimethyl benzyl hydroxyethyl ammonium triphenyl methylphosphonium chloride and zinc dichloride.

The process according to any preceding claim, wherein the operating temperature of the receiving liquid phase ranges from 10 ° C to 100 ° C.

The process according to any preceding claim, wherein the operating temperature of the receiving liquid phase is at room temperature.

The process according to any preceding claim, wherein the two contactors are membrane contactors whose pore diameter is between 20nm and 500nm.

The process according to any preceding claim, wherein the membranes of the two contactors are polymeric or inorganic or simultaneously comprising polymeric materials and inorganic materials.

The process according to the preceding claim, wherein the membranes are tubular, capillary fiber, hollow fiber modules, flat modules or spiral modules.

Use of the process described in claims 1-11 in the field of medicine.

Use of the method according to the preceding claim, in medical interventions in which the subject is anesthetized.