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WO2024028975A1 - Agent de refroidissement de l'œsophage - Google Patents

Agent de refroidissement de l'œsophage Download PDF

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Publication number
WO2024028975A1
WO2024028975A1 PCT/JP2022/029643 JP2022029643W WO2024028975A1 WO 2024028975 A1 WO2024028975 A1 WO 2024028975A1 JP 2022029643 W JP2022029643 W JP 2022029643W WO 2024028975 A1 WO2024028975 A1 WO 2024028975A1
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WO
WIPO (PCT)
Prior art keywords
cooling agent
esophageal
compound
weight
esophageal cooling
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2022/029643
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English (en)
Japanese (ja)
Inventor
聡 杣本
邦彦 木内
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kobe University NUC
Sanyo Chemical Industries Ltd
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Kobe University NUC
Sanyo Chemical Industries Ltd
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Filing date
Publication date
Application filed by Kobe University NUC, Sanyo Chemical Industries Ltd filed Critical Kobe University NUC
Priority to PCT/JP2022/029643 priority Critical patent/WO2024028975A1/fr
Publication of WO2024028975A1 publication Critical patent/WO2024028975A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • the present invention relates to an esophageal cooling agent.
  • An object of the present invention is to provide an esophageal cooling agent that enables cooling of the esophagus with a relatively small burden on the patient by a simple means.
  • the present invention provides an esophageal cooling agent comprising a solvent and compound (A),
  • the esophageal cooling agent at 25° C., at least a part of the compound (A) is an undissolved substance that is not dissolved in the solvent,
  • DSC differential scanning calorimetry
  • the esophageal cooling agent of the present invention enables cooling of the esophagus with a relatively small burden on the patient by a simple means.
  • FIG. 1(a), FIG. 1(b), and FIG. 1(c) are diagrams each schematically showing a DSC curve of an esophageal cooling agent.
  • FIG. 2 is a cross-sectional view schematically showing a cross section of the esophagus.
  • FIG. 3 shows the DSC measurement results of the esophageal cooling agent of Example 3.
  • FIG. 4(a) is a photograph showing a state in which a temperature sensor is inserted in evaluation 1 of the cooling effect in the example.
  • FIG. 4(b) is a photograph showing a state in which the esophagus was filled with an esophageal cooling agent in evaluation 1.
  • FIG. 4(c) is a perspective view schematically showing the insertion position of the temperature sensor in the evaluation 1.
  • FIG. 5 is a diagram schematically showing the insertion position of the temperature sensor in evaluation 2 of the cooling effect in the example.
  • the esophageal cooling agent of the present invention contains a solvent and compound (A). Moreover, in the 25° C. esophageal cooling agent, at least a portion of the compound (A) is an undissolved substance that is not dissolved in the solvent.
  • the compound (A) in the present invention is preferably a compound having a polyoxyethylene chain, a compound having a sugar chain, a sugar alcohol, or the like.
  • a compound having a polyoxyethylene chain the following general formula (1): HO-(CH 2 CH 2 O) n -H (1)
  • n is an integer from 40 to 230, preferably from 50 to 220, more preferably from 60 to 211, from the viewpoint of influence on the human body (safety).
  • Examples include compounds represented by (polyethylene glycol), ethylene oxide adducts of compounds having active hydrogen and having 1 to 20 carbon atoms, and the like.
  • Compound (A) represented by general formula (1) can be obtained from the market as PEG-4000N, PEG-6000P, Macrogol 4000, Macrogol 6000SP [manufactured by Sanyo Chemical Industries, Ltd.], etc. .
  • Examples of the compound having 1 to 20 carbon atoms and having active hydrogen in the ethylene oxide adduct of the compound having 1 to 20 carbon atoms having active hydrogen include hydroxyl group-containing compounds (methanol, ethanol, 1,6-hexanediol, glycerin, etc.); Selected from hydroxyl groups, primary or secondary amino groups, carboxyl groups, and mercapto groups of amino group-containing compounds (methylamine, ethylamine, etc.), carboxyl group-containing compounds (succinic acid, etc.), and thiols (ethanethiol, ethanedithiol, etc.) Examples include compounds having at least one type of group.
  • Alkylene oxide other than ethylene oxide may be further added to the compound, and examples of the alkylene oxide include 1,2- or 1,3-propylene oxide, 1,2-, 1,3-, 1,4 - or 2,3-butylene oxide.
  • the total number of additions of ethylene oxide and other alkylene oxides is preferably 40 to 230, more preferably 50 to 220, and particularly preferably 60 to 211.
  • Examples of the compound having a sugar chain include carboxyalkyl (alkyl has 1 to 5 carbon atoms) cellulose (carboxymethyl cellulose, etc.) or a salt thereof (alkali metal salts and alkaline earth metal salts are preferred).
  • Examples of sugar alcohols include erythritol, xylitol, sorbitol, mannitol, maltitol, and lactitol.
  • Compound (A) may be used alone or in combination of two or more.
  • Compound (A) preferably satisfies the following (i) or (ii).
  • the heat of dissolution in water is less than 0 J/g.
  • the melting point is 10 to 50°C.
  • the heat of dissolution in water is less than 0 J/g can be confirmed, for example, by DSC described below.
  • DSC liquid crystal display
  • the DSC curve curves downward in the temperature range where compound (A) dissolves in water. If so, it can be determined that the heat of melting is less than 0 J/g.
  • the melting point of compound (A) is preferably 10 to 300°C, more preferably 10 to 50°C, even more preferably 25 to 50°C, and particularly preferably 30 to 40°C.
  • the melting point of compound (A) can be measured by DSC as described below.
  • the specific heat of compound (A) is preferably 0.8 kJ/kg ⁇ K or more, more preferably 1.0 kJ/kg ⁇ K or more, and 1.5 kJ/kg ⁇ K. It is particularly preferable that it is above.
  • the boiling point of compound (A) is preferably 39° C. or higher from the viewpoint of cooling efficiency.
  • the number average molecular weight (Mn) of compound (A) is preferably 500 to 9,000 from the viewpoint of cooling efficiency.
  • Mn is preferably 3,000 to 9,000.
  • Mn is preferably 500 to 2,000.
  • the number average molecular weight is a value measured using gel permeation chromatography (hereinafter abbreviated as GPC) under the following conditions.
  • GPC gel permeation chromatography
  • Examples of the solvent in the present invention include water, ethanol, and the following general formula (2): HO-(CH 2 CH 2 O) m -H (2) (In the formula, m is an integer from 1 to 39) Compounds represented by the following are preferred.
  • the solvent preferably contains water from the viewpoint of cooling efficiency.
  • Water may be contained in the form of physiological saline; Ringer's solution containing sodium chloride, potassium chloride, and calcium chloride; a buffer solution containing a buffer component, and the like.
  • buffer components include organic acids (such as phosphoric acid) and Good's buffer.
  • the buffer components may be used alone or in combination of two or more.
  • the content of the buffer component in the esophageal cooling agent is preferably 0 to 50 mM, more preferably 0 to 10 mM.
  • the weight proportion of water in the solvent is preferably 50 to 100% by weight, more preferably 70 to 100% by weight, particularly preferably 90 to 100% by weight, based on the weight of the solvent.
  • the content of the compound represented by the general formula (2) is preferably 10% by weight or less, more preferably 5% by weight or less, and 1% by weight or less based on the weight of the esophageal cooling agent. It is more preferable that the amount is at least 0.1% by weight or less, particularly preferably 0.1% by weight or less.
  • the specific heat of the solvent is preferably 0.8 kJ/kg K or more, more preferably 2.0 kJ/kg K or more, and 4.0 kJ/kg K or more. It is particularly preferable.
  • the boiling point of the solvent is preferably 39° C. or higher from the viewpoint of cooling efficiency.
  • the DDSC is negative in the temperature range of 10 to 50°C and in the region where the heat flow is 0 (W/g) or less. An endothermic signal with a value of can be observed.
  • DSC is measured by the following method.
  • ⁇ DSC measurement method> The esophageal cooling agent of the present invention is subjected to DSC using, for example, "DSC Q20" (manufactured by TA instruments) under the following conditions according to JIS K7122-2012.
  • a measurement sample previously cooled to 4°C is heated to 10 to 50°C under the following conditions, and then cooled to 10°C. Thereafter, the measurement sample is heated again under the following conditions and DSC is performed.
  • ⁇ Measurement start temperature 10°C
  • ⁇ Measurement end temperature 50°C
  • Nitrogen gas inflow rate 50mL/min
  • the amount of heat that can be calculated from the area area surrounded by the following lines (I) to (IV) is From the viewpoint of cooling efficiency, it is preferably -4 J/g or less, based on the weight of the esophageal coolant, and from the viewpoint of cooling efficiency, it is more preferably -5 J/g or less, -5.5 J. /g or less is more preferable, and -6J/g or less is particularly preferable.
  • the amount of heat that can be calculated from the area surrounded by lines (I) to (IV) is determined by adjusting the heat of dissolution of compound (A) in the solvent, the weight percentage of undissolved matter of compound (A) contained in the esophageal cooling agent, etc. By doing so, it is possible to adjust to the above-mentioned preferable range.
  • the heat of dissolution in water can be reduced to -4 J/g or less. Can be adjusted.
  • the area area below line (III) is calculated.
  • the sum of the amount of heat (negative value) calculated from the area above the line (III) (positive value) is preferably -4 J/g or less. That is, in the range of 25 to 40° C., the absolute value of the total endothermic amount is preferably 4 J/g or more greater than the absolute value of the total calorific value.
  • the sum of the heat amounts is more preferably -5.5 J/g or less, particularly preferably -6 J/g or less.
  • "Area area below line (III)" and “Area area above line (III)” refer to, for example, the total area of area a3 and area a4, and area b1 in FIG. 1(b), respectively. is the area of
  • the esophageal coolant of the present invention has a kinematic viscosity of 100 to 5,000 mm 2 /s at 25°C.
  • the kinematic viscosity of the esophageal coolant is preferably 100 to 4,500 mm 2 /s from the viewpoint of cooling efficiency.
  • the kinematic viscosity at 39° C. is preferably 5,000 mm 2 /s or less, more preferably 4,500 mm 2 /s or less.
  • the kinematic viscosity of the esophageal coolant is a value measured using an Ubbelohde viscometer in accordance with JIS-Z8803 (2011).
  • the weight percentage of undissolved matter that is not dissolved in the solvent of compound (A) is preferably 1 to 95% by weight based on the weight of the esophageal coolant from the viewpoint of cooling efficiency. It is preferably 5 to 80% by weight, more preferably 10 to 80% by weight, and most preferably 25 to 80% by weight.
  • the difference between the weight of the undissolved compound (A) contained in the esophageal coolant at 25°C and the weight of the undissolved compound (A) contained in the esophageal coolant at 40°C is the difference in cooling efficiency. From this point of view, it is preferably 1 to 95% by weight, more preferably 5 to 80% by weight, particularly preferably 10 to 80% by weight, based on the weight of the esophageal cooling agent at 25°C. Most preferably, it is between 80% and 80% by weight.
  • the "undissolved matter of compound (A) that is not dissolved in the solvent" contained in the 25°C esophageal cooling agent is the dried filtration residue obtained by the following method, and its weight percentage is calculated by the following formula: It can be calculated.
  • suction filtration of esophageal coolant previously cooled at 4°C and then temperature-controlled to 25°C
  • weight W (g) is carried out through cellulose filter paper (particle retention capacity: 1 ⁇ m) with weight W1 (g).
  • the cellulose filter paper carrying the filtration residue is dried for 15 hours, and the total weight W2 (g) of the dried filtration residue and the cellulose filter paper is measured.
  • the weight percentage of compound (A) contained in the filtration residue is preferably 50 to 100% by weight, more preferably 70 to 100% by weight, and more preferably 90 to 100% by weight, based on the weight of the filtration residue. Particularly preferred is 100% by weight. Note that the weight percentage of undissolved matter of compound (A) contained in the esophageal cooling agent at 40°C can be obtained by changing "25°C" in the above calculation method to "40°C".
  • the weight proportion of compound (A) is preferably 30 to 95% by weight, based on the weight of the esophageal cooling agent, from the viewpoint of cooling efficiency, and preferably 50 to 95% by weight. is more preferable, still more preferably 60 to 90% by weight, particularly preferably 70 to 90% by weight.
  • the esophageal cooling agent of the present invention may contain components other than the solvent and compound (A).
  • Components other than compound (A) include additives such as antioxidants.
  • the type and content of components other than the solvent and compound (A) are determined so that the amount of heat calculated from the area surrounded by the lines (I) to (IV) and the kinematic viscosity of the esophageal coolant will be the desired values. You can select it as appropriate.
  • Components other than compound (A) are preferably soluble or miscible in the solvent.
  • the esophageal cooling agent of the present invention preferably has a turbidity of 0.1 or more, more preferably 2 or more, as measured by the following method.
  • the method for producing the esophageal cooling agent of the present invention is not particularly limited, and for example, it can be produced by mixing compound (A) and a solvent at 20 to 30°C.
  • a method for cooling the esophagus using the esophageal cooling agent of the present invention includes a method of filling the esophageal cooling agent into the esophagus.
  • Methods for filling the esophagus include direct oral administration (swallowing), or inserting a gastric tube into the esophagus (preferably using a balloon during insertion; the gastric tube described above has the function of a balloon). Examples include a method of injecting the drug through a gastric tube. Among these, direct oral administration is preferred because it is simple and causes relatively little burden on the patient.
  • the filling amount of the esophageal cooling agent is preferably 5 to 20 ml per time.
  • the temperature of the esophageal cooling agent is preferably adjusted to 1 to 15° C. before filling.
  • the esophageal cooling agent of the present invention exhibits an excellent cooling effect on the esophagus with a simple operation such as having the patient swallow the esophageal cooling agent. Therefore, it is useful as a cooling agent for cooling the esophagus located near the heart in surgeries that perform electrocautery of the heart, and is particularly useful as an esophageal cooling agent (atrial fibrillation) used during catheter ablation treatment for atrial fibrillation. It is useful as an esophageal cooling agent for catheter ablation procedures.
  • FIG. 2 is a cross-sectional view schematically showing a cross section of the esophagus.
  • FIG. 2 shows the adventitia 1, longitudinal muscularis layer 2, orbicularis muscle layer 3, submucosal layer 4, muscularis mucosae 5, lamina intestinal 6, and mucosal epithelium 7 that constitute the esophagus.
  • the method for filling the esophageal coolant of the present invention into the esophagus is as described above.
  • the location of the filled esophageal coolant can be confirmed by using a 3D mapped thermometer, or by adding a contrast agent to the esophageal coolant and performing an image diagnostic test (CT scan, MRI scan, etc.) Examples include methods for checking.
  • An appropriate cooling effect can be achieved by performing the catheter ablation procedure while the esophageal cooling agent remains in the esophagus. Note that if the esophageal coolant flows down from the esophagus during catheter ablation treatment, an esophageal cooling agent may be additionally applied as necessary.
  • the catheter ablation procedure is a 5-30 second procedure at a power of 20-50W.
  • the temperature of the esophagus during treatment can be confirmed by inserting a thermometer with a 3D mapping function into the esophagus through the nose and measuring the temperature at appropriate times.
  • the patient may drink water (approximately 100 to 300 ml) to wash away the esophageal cooling agent remaining in the esophagus.
  • DSC differential scanning calorimetry
  • the amount of heat that can be calculated from the area area surrounded by the following lines (I) to (IV) in the DSC curve with the vertical axis as heat flow (W/g) and the horizontal axis as temperature (°C) is ⁇ 4 J/g or less based on the weight of the esophageal cooling agent according to [1].
  • the weight percentage of undissolved matter of the compound (A) contained in the 25°C esophageal cooling agent is 1 to 95% by weight based on the weight of the esophageal cooling agent [1] to [4].
  • the esophageal cooling agent according to any of the above.
  • the esophageal cooling agent according to any one of [1] to [8], which is an esophageal cooling agent for catheter ablation treatment for atrial fibrillation.
  • Compound (A) was carboxymethyl cellulose sodium [trade name: carboxymethyl cellulose sodium, number average molecular weight: 1,050, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., heat of dissolution in water: less than 0 J/g, specific heat: 1.6 kJ /kg ⁇ K, boiling point: 100°C or higher] was mixed with pure water at 25°C to obtain an esophageal cooling agent (A-9) containing 30% by weight of carboxymethylcellulose sodium. This was left standing in a refrigerator at 4°C for 30 minutes.
  • Example 2 was carried out in the same manner as in Example 2, except that the pure water was changed to a mixture of pure water and ethanol (95% by weight of pure water, 5% by weight of ethanol), and 70% by weight of PEG-4000N was used. An esophageal cooling agent (A-10) was obtained. This was left standing in a refrigerator at 4°C for 30 minutes.
  • Example 11 As compound (A), sorbitol [manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: less than 0 J/g, specific heat: 2.2 kJ/kg ⁇ K, boiling point: 100°C or more] was used, and polyethylene glycol [trade name: PEG-400, number average molecular weight: 400, manufactured by Sanyo Chemical Industries, Ltd.] and pure water at 25°C, containing 63% by weight of sorbitol, 10% by weight of PEG-400, and 27% by weight of pure water. Esophageal cooling agent (A-11) was obtained. This was left standing in a refrigerator at 4°C for 30 minutes.
  • Comparative example 2 Comparative esophageal coolant (A'-2), polyethylene glycol [trade name: PEG-400, number average molecular weight: 400, manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: 0 J/g, specific heat: 2.2 kJ/kg ⁇ K, boiling point: 100°C or higher] was left standing in a refrigerator at 4°C for 30 minutes.
  • PEG-400 number average molecular weight: 400, manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: 0 J/g, specific heat: 2.2 kJ/kg ⁇ K, boiling point: 100°C or higher
  • Compound (A) was polyethylene glycol [trade name: PEG-400, number average molecular weight: 400, manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: 0 J/g, specific heat: 2.2 kJ/kg K, boiling point Comparative esophageal cooling agents (A'-3) to (A'-7 ) was obtained. These were left standing in a 4°C refrigerator for 30 minutes.
  • Compound (A) was polyethylene glycol [trade name: PEG-4000N, number average molecular weight: 3100, manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: less than 0 J/g, specific heat: 2.3 kJ/kg K, Boiling point: 100°C or higher] was mixed with pure water at 25°C to obtain comparative esophageal coolants (A'-8) to (A'-9) containing 10 or 30% by weight of PEG-4000N. These were left standing in a 4°C refrigerator for 30 minutes.
  • Compound (A) was polyethylene glycol [trade name: PEG-6000P, number average molecular weight: 8600, manufactured by Sanyo Chemical Industries, Ltd., heat of dissolution in water: less than 0 J/g, specific heat: 2.3 kJ/kg K, Boiling point: 100°C or higher] was mixed with pure water at 25°C to obtain comparative esophageal coolants (A'-10) to (A'-11) containing 10 or 30% by weight of PEG-6000P. These were left standing in a 4°C refrigerator for 30 minutes.
  • kinematic viscosity of esophageal coolant was measured using an Ubbelohde viscometer in accordance with JIS-Z8803 (2011).
  • ⁇ Weight percentage of undissolved matter> At 25°C, a weight W (g) (approximately 5 g) of an esophageal coolant (previously cooled at 4°C and then temperature-controlled at 25°C) was transferred to a cellulose filter paper weighing W1 (g) (particle retention capacity: 1 ⁇ m). ), the filter residue and cellulose filter paper were dried for 15 hours, and their total weight W2 (g) was measured.
  • FIG. 4(a) is a photograph showing a state in which a temperature sensor is inserted in evaluation 1 of the cooling effect in the example.
  • FIG. 4(b) is a photograph showing a state in which the esophagus was filled with an esophageal cooling agent in evaluation 1.
  • FIG. 4(c) is a perspective view schematically showing the insertion position of the temperature sensor in the evaluation 1.
  • a test esophagus a pig's esophagus (approximately 15 cm, Kyoto Meat Market Co., Ltd.
  • FIG. 5 is a diagram schematically showing the insertion position of the temperature sensor in evaluation 2 of the cooling effect in the example.
  • Literature (Arruda MS, et al. Feasibility and safety of using an esophageal protective system to eliminate esophageal thermal inju ry: Implications on atrial-esophageal fistula following AF ablation. J Cardiovasc Electrophysiol. 2009; 20:1272-1278. doi: 10 .. 1111/j.1540-8167.2009.01536.x), the temperature of pig-derived heart tissue and esophageal tissue was controlled in a 37°C water bath. Thereafter, as shown in FIG.
  • the temperature of the temperature sensor (the highest temperature among the four temperature sensors) was measured during the current application time until the temperature rose to 39°C and during the current application time of 8 seconds and 20 seconds. Note that if the temperature did not reach 39°C even after 20 seconds, it was written as "-”. In addition, if the temperature exceeded 40° C. after 8 seconds and before 20 seconds, “interruption” was written in the “Temperature at 20 seconds of current application time (° C.)” column.
  • the esophageal cooling agent of the present invention exhibits an excellent cooling effect on the esophagus by a simple operation such as having the patient swallow the esophageal cooling agent. Therefore, it is useful as a cooling agent for cooling the esophagus located near the heart in surgeries that perform electrocautery of the heart (catheter ablation treatment for atrial fibrillation, etc.). In particular, it is useful as an esophageal cooling agent used in catheter ablation treatment for atrial fibrillation (esophageal cooling agent for catheter ablation treatment for atrial fibrillation).

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Abstract

L'objectif de la présente invention est de fournir un agent de refroidissement de l'œsophage capable de refroidir l'œsophage par un moyen simple et facile avec une charge relativement faible sur un patient. La présente invention concerne un agent de refroidissement de l'œsophage comprenant un solvant et un composé (A). Au moins une partie du composé (A) est un matériau non dissous qui n'est pas dissous dans le solvant lorsque l'agent de refroidissement de l'œsophage est à 25 °C. Lorsqu'une calorimétrie différentielle à balayage (DSC) est effectuée sur l'agent de refroidissement de l'œsophage conformément à JIS K7122-2012, un signal endothermique qui a un DDSC négatif (valeur obtenue par différenciation d'un flux de chaleur par température) dans une région où la température est dans la plage de 10 à 50 °C et où le flux de chaleur est d'au plus 0 (W/g) peut être observé, et la viscosité dynamique à 25 °C est de 100 à 5 000 mm2/s
PCT/JP2022/029643 2022-08-02 2022-08-02 Agent de refroidissement de l'œsophage Ceased WO2024028975A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006089479A (ja) * 2004-09-21 2006-04-06 Mcneil Ppc Inc 医薬用冷却エマルジョン
US20120197245A1 (en) * 2011-02-01 2012-08-02 Channel Medsystems, Inc. Methods and apparatus for cyrogenic treatment of a body cavity or lumen
US20190380761A1 (en) * 2017-02-28 2019-12-19 University Of Florida Research Foundation, Inc. Controlling esophageal temperature during cardiac ablation
JP2022112776A (ja) * 2021-01-22 2022-08-03 三洋化成工業株式会社 食道冷却剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006089479A (ja) * 2004-09-21 2006-04-06 Mcneil Ppc Inc 医薬用冷却エマルジョン
US20120197245A1 (en) * 2011-02-01 2012-08-02 Channel Medsystems, Inc. Methods and apparatus for cyrogenic treatment of a body cavity or lumen
US20190380761A1 (en) * 2017-02-28 2019-12-19 University Of Florida Research Foundation, Inc. Controlling esophageal temperature during cardiac ablation
JP2022112776A (ja) * 2021-01-22 2022-08-03 三洋化成工業株式会社 食道冷却剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LEUNG, LISA WM ET AL.: "Esophageal cooling for protection during left atrial ablation: a systematic review and meta-analysis", JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY, vol. 59, 2020, pages 347 - 355, XP037279931, DOI: 10.1007/s10840-019-00661-5 *

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